ADVANCING STRATEGIES FORIDENTIFYING CLINICAL SOLUTIONS FOR
SARS-CoV-2
The COVID-19 emergency requires the urgent development of new strategies to protect the population, mainly those most at risk. Since March 2020, a dedicated team of researchers from the STI and Skin NTD Unit has worked to transfer their knowledge on epidemiology into clinical solutions for the Covid-19 pandemic. This work, still on-going, is done thanks to the contribution of citizens (channelled through the #YoMeCorono initiative), and of public and private institutions that are gathering forces to find a treatment for SARS-CoV-2.
Selected publications
In addition to the Test and Treat and the COnV-ert studies, aimed at identifying clinical solutions against SARS-CoV-2 (listed hereunder as “Therapeutics”), the Unit has performed analyses to advance knowledge in the fields of diagnostics, transmission, and risk factors.
a. Therapeutics
Nadal-Barón, Patricia; Trejo-Zahinos, Jesús; Arando, Maider; Barberan-Masegosa, Alicia; Bernat-Sole, Marta; Pérez-Ugarte, Arantxa (…); Hoyos-Mallecot, Yannick.
High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023 Journal Article
In: SCIENTIFIC REPORTS , vol. 14, iss. 1, 2024.
@article{nokey,
title = {High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023},
author = {Nadal-Barón, Patricia and Trejo-Zahinos, Jesús and Arando, Maider and Barberan-Masegosa, Alicia and Bernat-Sole, Marta and Pérez-Ugarte, Arantxa (…) and Hoyos-Mallecot, Yannick. },
doi = {10.1038/s41598-024-74355-y},
year = {2024},
date = {2024-10-08},
urldate = {2024-10-08},
journal = {SCIENTIFIC REPORTS },
volume = {14},
issue = {1},
abstract = {Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
Ubals, Maria; Nadal-Barón, Patricia; Arando, Maider; Rivero, Angel; Mendoza, Adrià; Descalzo Jorro, Victor (…); Mitjà, Oriol.
2024.
@bachelorthesis{nokey,
title = {Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial},
author = {Ubals, Maria and Nadal-Barón, Patricia and Arando, Maider and Rivero, Angel and Mendoza, Adrià and Descalzo Jorro, Victor (…) and Mitjà, Oriol. },
doi = {10.1016/S1473-3099(23)00683-7},
year = {2024},
date = {2024-04-02},
urldate = {2024-04-02},
journal = {The Lancet Infectious Diseases},
volume = {24},
issue = {4},
pages = {404-416},
abstract = {Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {bachelorthesis}
}
Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Tantalo, Lauren; Lieberman, Nicole; Perez-Mañà, Clara; Suñer, Clara; Vall-Mayans, Martí; Ubals, Maria; (…) Mitjà, Oriol
Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study Journal Article
In: The Lancet Microbe , vol. 4, iss. 12, 2023.
@article{nokey,
title = {Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study},
author = {Tantalo, Lauren and Lieberman, Nicole and Perez-Mañà, Clara and Suñer, Clara and Vall-Mayans, Martí and Ubals, Maria and (…) Mitjà, Oriol},
doi = {10.1016/S2666-5247(23)00219-7},
year = {2023},
date = {2023-12-04},
urldate = {2023-12-04},
journal = {The Lancet Microbe },
volume = {4},
issue = {12},
abstract = {Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Ávila-Nieto, Carlos; Pedreño-Lopez, Núria; Mitjà, Oriol; Clotet, Bonaventura; Blanco, Julà; Carrillo, Jorge
Syphilis vaccine: challenges, controversies and opportunities Journal Article
In: Frontiers in Immunology, vol. 14, 2023.
@article{NIETO2023SUBCUT,
title = {Syphilis vaccine: challenges, controversies and opportunities},
author = {Carlos Ávila-Nieto and Núria Pedreño-Lopez and Oriol Mitjà and Bonaventura Clotet and Julà Blanco and Jorge Carrillo},
doi = {https://doi.org/10.3389/fimmu.2023.1126170},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in Immunology},
volume = {14},
abstract = {Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.
Mitjà, Oriol; Suñer, Clara; Giacani, Lorenzo; Vall-Mayans, Martí; Tiplica, George-Sorin; Ross, Jonathan D. C.; Bradshaw, Catriona S.
Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100737, 2023, ISSN: 2666-7762.
@article{MITJA2023100737,
title = {Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis},
author = {Oriol Mitjà and Clara Suñer and Lorenzo Giacani and Martí Vall-Mayans and George-Sorin Tiplica and Jonathan D. C. Ross and Catriona S. Bradshaw},
doi = {https://doi.org/10.1016/j.lanepe.2023.100737},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100737},
abstract = {This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.
Gökengin, Deniz; Noori, Teymur; Alemany, Andrea; Bienkowski, Carlo; Liegon, Geoffroy; İnkaya, Ahmet Çağkan (…); Molina, Jean-Michel.
Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100738, 2023, ISSN: 2666-7762.
@article{GOKENGIN2023100738,
title = {Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe},
author = {Deniz Gökengin and Teymur Noori and Andrea Alemany and Carlo Bienkowski and Geoffroy Liegon and İnkaya, Ahmet Çağkan (…) and Molina, Jean-Michel.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100738},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100738},
abstract = {The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
Mitjà, Oriol; Padovese, Valeska; Folch, Cinta; Rossoni, Isotta; Marks, Michael; Rodríguez Arias, Miquel Angel (…); Casabona, Jordi.
Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100742, 2023, ISSN: 2666-7762.
@article{MITJA2023100742,
title = {Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe},
author = {Oriol Mitjà and Valeska Padovese and Cinta Folch and Isotta Rossoni and Michael Marks and Rodríguez Arias, Miquel Angel (…) and Casabona, Jordi.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100742},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100742},
abstract = {In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.
Fernández-Naval, Candela; Arando, Maider; Espasa, Mateu; Antón, Andrés; Fernández-Huerta, Miguel; Silgado, Aroa (…) Juliana Esperalba.
Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona Journal Article
In: Future Microbiology, vol. 16, no. 13, pp. 967-976, 2021.
@article{Fernandez2021,
title = {Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona},
author = {Candela Fernández-Naval and Maider Arando and Mateu Espasa and Andrés Antón and Miguel Fernández-Huerta and Silgado, Aroa (…) Juliana Esperalba.},
doi = {https://doi.org/10.2217/fmb-2021-0037},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Future Microbiology},
volume = {16},
number = {13},
pages = {967-976},
abstract = {Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.
Haynes, Austin M.; Giacani, Lorenzo; Mayans, Marti Vall; Ubals, Maria; Nieto, Carles; Pérez-Mañá, Clara; Quintó, Llorenç; Romeis, Emily; Mitjà, Oriol
Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study Journal Article
In: EBioMedicine, vol. 65, 2021, ISSN: 2352-3964.
@article{Haynes2021,
title = {Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study},
author = {Austin M. Haynes and Lorenzo Giacani and Marti Vall Mayans and Maria Ubals and Carles Nieto and Clara Pérez-Mañá and Llorenç Quintó and Emily Romeis and Oriol Mitjà},
doi = {10.1016/j.ebiom.2021.103281},
issn = {2352-3964},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {EBioMedicine},
volume = {65},
publisher = {Elsevier},
abstract = {Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.
Hoyos-Mallecot, Yannick; Garcia, Jorge Nestor; Sulleiro, Elena; Esperalba, Juliana; Salmeron, Paula; Zarzuela, Francesc (…); Espasa, Mateu.
Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification Journal Article
In: Sexually Transmitted Infections, 2021, ISSN: 1368-4973.
@article{Hoyos-Mallecotsextrans-2020-054779,
title = {Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification},
author = {Yannick Hoyos-Mallecot and Jorge Nestor Garcia and Elena Sulleiro and Juliana Esperalba and Paula Salmeron and Zarzuela, Francesc (…) and Espasa, Mateu.},
doi = {10.1136/sextrans-2020-054779},
issn = {1368-4973},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Sexually Transmitted Infections},
publisher = {The Medical Society for the Study of Venereal Disease},
abstract = {Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.
Mitjà, Oriol; Reis, Gilmar; Boulware, David; Spivak, Adam; Ammar Sarwar, Johnston; Dunne, Michael.
Hydroxychloroquine for treatment of non-hospitalized adults wih COVID-19: A meta-analysis of individual participant data of randomized trial Journal Article
In: Clinical Translational Science , vol. 3, iss. 16, pp. 524-535, 2023.
@article{Mitja2023-wfb,
title = {Hydroxychloroquine for treatment of non-hospitalized adults wih COVID-19: A meta-analysis of individual participant data of randomized trial},
author = {Mitjà, Oriol and Reis, Gilmar and Boulware, David and Spivak, Adam and Sarwar, Ammar, Johnston, Christine (...) and Dunne, Michael.},
doi = {10.1111/cts.13468},
year = {2023},
date = {2023-03-16},
journal = {Clinical Translational Science },
volume = {3},
issue = {16},
pages = {524-535},
abstract = {Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID-19). Conventional meta-analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID-19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID-19. We evaluated the overall treatment group effect by log-likelihood ratio test (-2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (-2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614-1.610; -2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta-analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome-coronavirus 2 viral clearance and COVID-19 hospitalization did not show a clinical benefit of HCQ. Our meta-analysis provides evidence to support the interruption in the use of HCQ in mild COVID-19 outpatients to reduce progression to severe disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID-19). Conventional meta-analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID-19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID-19. We evaluated the overall treatment group effect by log-likelihood ratio test (-2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (-2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614-1.610; -2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta-analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome-coronavirus 2 viral clearance and COVID-19 hospitalization did not show a clinical benefit of HCQ. Our meta-analysis provides evidence to support the interruption in the use of HCQ in mild COVID-19 outpatients to reduce progression to severe disease.
Alemany, Andrea; Millat-Martinez, Pere; Corbacho-Monné, Marc; Suñer, Clara; Galvan-Casas, Cristina; Carrera, Caty (…); Mitjà, Oriol
In: EClinical Medicine, 2023.
@article{nokey,
title = {Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial},
author = {Alemany, Andrea and Millat-Martinez, Pere and Corbacho-Monné, Marc and Suñer, Clara and Cristina Galvan-Casas and Carrera, Caty (…) and Mitjà, Oriol},
doi = {10.1016/j.eclinm.2023.101898},
year = {2023},
date = {2023-03-10},
journal = {EClinical Medicine},
abstract = {Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection.
Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141.
Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported.
Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection.
Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141.
Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported.
Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.
Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141.
Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported.
Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.
Levine, Adam C; Fukuta, Yuriko; Huaman, Moises A; Ou, Jiangda; Meisenberg, Barry R; Patel, Bela (…); Sullivan, David J
In: Clinical Infectious Diseases, vol. 76, no. 12, pp. 2077-2086, 2023, ISSN: 1058-4838.
@article{10.1093/cid/ciad088b,
title = {Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials},
author = {Levine, Adam C and Fukuta, Yuriko and Huaman, Moises A and Ou, Jiangda and Meisenberg, Barry R and Patel, Bela (…) and Sullivan, David J},
doi = {10.1093/cid/ciad088},
issn = {1058-4838},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Clinical Infectious Diseases},
volume = {76},
number = {12},
pages = {2077-2086},
abstract = {Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results.We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022.Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%–6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%–11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer.Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results.We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022.Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%–6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%–11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer.Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.
Alemany, Andrea; Millat-Martinez, Pere; Corbacho-Monné, Marc; Malchair, Pierre; Ouchi, Dan; Ruiz-Comellas, Anna (…); Grau, Eulàlia.
In: The Lancet Respiratory Medicine, 2022, ISSN: 2213-2600.
@article{ref1,
title = {High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial},
author = {Alemany, Andrea and Millat-Martinez, Pere and Corbacho-Monné, Marc and Malchair, Pierre and Ouchi, Dan and Ruiz-Comellas, Anna (…) and Grau, Eulàlia.},
doi = {10.1016/S2213-2600(21)00545-2},
issn = {2213-2600},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {The Lancet Respiratory Medicine},
publisher = {Elsevier},
abstract = {Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19.
Mitjà, Oriol; Corbacho-Monné, Marc; Ubals, Maria; Alemany, Andrea; Suñer, Clara; Tebé, Cristian (…); Clotet, Bonaventura.
A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19 Journal Article
In: New England Journal of Medicine, vol. 384, no. 5, pp. 417-427, 2021.
@article{NEJMoa2021801b,
title = {A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19},
author = {Mitjà, Oriol and Corbacho-Monné, Marc and Ubals, Maria and Alemany, Andrea and Suñer, Clara and Tebé, Cristian (…) and Clotet, Bonaventura.},
doi = {10.1056/NEJMoa2021801},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {New England Journal of Medicine},
volume = {384},
number = {5},
pages = {417-427},
abstract = {Current strategies for preventing severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus
disease 2019 (Covid-19), but definitive evidence is lacking. (Funded by the crowdfunding campaign YoMeCorono and others;
BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Current strategies for preventing severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus
disease 2019 (Covid-19), but definitive evidence is lacking. (Funded by the crowdfunding campaign YoMeCorono and others;
BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)
(SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus
disease 2019 (Covid-19), but definitive evidence is lacking. (Funded by the crowdfunding campaign YoMeCorono and others;
BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)
Mitjà, Oriol; Corbacho-Monné, Marc; Ubals, Maria; Tebé, Cristian; Peñafiel, Judith; Tobias, Aurelio (…); Vall-Mayans, Martí.
Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial Journal Article
In: Clinical Infectious Diseases, vol. 73, no. 11, pp. e4073-e4081, 2020, ISSN: 1058-4838.
@article{10.1093/cid/ciaa1009b,
title = {Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial},
author = {Mitjà, Oriol and Corbacho-Monné, Marc and Ubals, Maria and Tebé, Cristian and Peñafiel, Judith and Tobias, Aurelio (…) and Vall-Mayans, Martí.},
doi = {10.1093/cid/ciaa1009},
issn = {1058-4838},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Clinical Infectious Diseases},
volume = {73},
number = {11},
pages = {e4073-e4081},
abstract = {No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days.A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported.In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days.A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported.In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.
b. Diagnostics
Nadal-Barón, Patricia; Trejo-Zahinos, Jesús; Arando, Maider; Barberan-Masegosa, Alicia; Bernat-Sole, Marta; Pérez-Ugarte, Arantxa (…); Hoyos-Mallecot, Yannick.
High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023 Journal Article
In: SCIENTIFIC REPORTS , vol. 14, iss. 1, 2024.
@article{nokey,
title = {High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023},
author = {Nadal-Barón, Patricia and Trejo-Zahinos, Jesús and Arando, Maider and Barberan-Masegosa, Alicia and Bernat-Sole, Marta and Pérez-Ugarte, Arantxa (…) and Hoyos-Mallecot, Yannick. },
doi = {10.1038/s41598-024-74355-y},
year = {2024},
date = {2024-10-08},
urldate = {2024-10-08},
journal = {SCIENTIFIC REPORTS },
volume = {14},
issue = {1},
abstract = {Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
Ubals, Maria; Nadal-Barón, Patricia; Arando, Maider; Rivero, Angel; Mendoza, Adrià; Descalzo Jorro, Victor (…); Mitjà, Oriol.
2024.
@bachelorthesis{nokey,
title = {Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial},
author = {Ubals, Maria and Nadal-Barón, Patricia and Arando, Maider and Rivero, Angel and Mendoza, Adrià and Descalzo Jorro, Victor (…) and Mitjà, Oriol. },
doi = {10.1016/S1473-3099(23)00683-7},
year = {2024},
date = {2024-04-02},
urldate = {2024-04-02},
journal = {The Lancet Infectious Diseases},
volume = {24},
issue = {4},
pages = {404-416},
abstract = {Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {bachelorthesis}
}
Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Tantalo, Lauren; Lieberman, Nicole; Perez-Mañà, Clara; Suñer, Clara; Vall-Mayans, Martí; Ubals, Maria; (…) Mitjà, Oriol
Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study Journal Article
In: The Lancet Microbe , vol. 4, iss. 12, 2023.
@article{nokey,
title = {Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study},
author = {Tantalo, Lauren and Lieberman, Nicole and Perez-Mañà, Clara and Suñer, Clara and Vall-Mayans, Martí and Ubals, Maria and (…) Mitjà, Oriol},
doi = {10.1016/S2666-5247(23)00219-7},
year = {2023},
date = {2023-12-04},
urldate = {2023-12-04},
journal = {The Lancet Microbe },
volume = {4},
issue = {12},
abstract = {Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Ávila-Nieto, Carlos; Pedreño-Lopez, Núria; Mitjà, Oriol; Clotet, Bonaventura; Blanco, Julà; Carrillo, Jorge
Syphilis vaccine: challenges, controversies and opportunities Journal Article
In: Frontiers in Immunology, vol. 14, 2023.
@article{NIETO2023SUBCUT,
title = {Syphilis vaccine: challenges, controversies and opportunities},
author = {Carlos Ávila-Nieto and Núria Pedreño-Lopez and Oriol Mitjà and Bonaventura Clotet and Julà Blanco and Jorge Carrillo},
doi = {https://doi.org/10.3389/fimmu.2023.1126170},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in Immunology},
volume = {14},
abstract = {Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.
Mitjà, Oriol; Suñer, Clara; Giacani, Lorenzo; Vall-Mayans, Martí; Tiplica, George-Sorin; Ross, Jonathan D. C.; Bradshaw, Catriona S.
Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100737, 2023, ISSN: 2666-7762.
@article{MITJA2023100737,
title = {Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis},
author = {Oriol Mitjà and Clara Suñer and Lorenzo Giacani and Martí Vall-Mayans and George-Sorin Tiplica and Jonathan D. C. Ross and Catriona S. Bradshaw},
doi = {https://doi.org/10.1016/j.lanepe.2023.100737},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100737},
abstract = {This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.
Gökengin, Deniz; Noori, Teymur; Alemany, Andrea; Bienkowski, Carlo; Liegon, Geoffroy; İnkaya, Ahmet Çağkan (…); Molina, Jean-Michel.
Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100738, 2023, ISSN: 2666-7762.
@article{GOKENGIN2023100738,
title = {Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe},
author = {Deniz Gökengin and Teymur Noori and Andrea Alemany and Carlo Bienkowski and Geoffroy Liegon and İnkaya, Ahmet Çağkan (…) and Molina, Jean-Michel.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100738},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100738},
abstract = {The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
Mitjà, Oriol; Padovese, Valeska; Folch, Cinta; Rossoni, Isotta; Marks, Michael; Rodríguez Arias, Miquel Angel (…); Casabona, Jordi.
Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100742, 2023, ISSN: 2666-7762.
@article{MITJA2023100742,
title = {Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe},
author = {Oriol Mitjà and Valeska Padovese and Cinta Folch and Isotta Rossoni and Michael Marks and Rodríguez Arias, Miquel Angel (…) and Casabona, Jordi.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100742},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100742},
abstract = {In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.
Fernández-Naval, Candela; Arando, Maider; Espasa, Mateu; Antón, Andrés; Fernández-Huerta, Miguel; Silgado, Aroa (…) Juliana Esperalba.
Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona Journal Article
In: Future Microbiology, vol. 16, no. 13, pp. 967-976, 2021.
@article{Fernandez2021,
title = {Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona},
author = {Candela Fernández-Naval and Maider Arando and Mateu Espasa and Andrés Antón and Miguel Fernández-Huerta and Silgado, Aroa (…) Juliana Esperalba.},
doi = {https://doi.org/10.2217/fmb-2021-0037},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Future Microbiology},
volume = {16},
number = {13},
pages = {967-976},
abstract = {Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.
Haynes, Austin M.; Giacani, Lorenzo; Mayans, Marti Vall; Ubals, Maria; Nieto, Carles; Pérez-Mañá, Clara; Quintó, Llorenç; Romeis, Emily; Mitjà, Oriol
Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study Journal Article
In: EBioMedicine, vol. 65, 2021, ISSN: 2352-3964.
@article{Haynes2021,
title = {Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study},
author = {Austin M. Haynes and Lorenzo Giacani and Marti Vall Mayans and Maria Ubals and Carles Nieto and Clara Pérez-Mañá and Llorenç Quintó and Emily Romeis and Oriol Mitjà},
doi = {10.1016/j.ebiom.2021.103281},
issn = {2352-3964},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {EBioMedicine},
volume = {65},
publisher = {Elsevier},
abstract = {Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.
Hoyos-Mallecot, Yannick; Garcia, Jorge Nestor; Sulleiro, Elena; Esperalba, Juliana; Salmeron, Paula; Zarzuela, Francesc (…); Espasa, Mateu.
Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification Journal Article
In: Sexually Transmitted Infections, 2021, ISSN: 1368-4973.
@article{Hoyos-Mallecotsextrans-2020-054779,
title = {Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification},
author = {Yannick Hoyos-Mallecot and Jorge Nestor Garcia and Elena Sulleiro and Juliana Esperalba and Paula Salmeron and Zarzuela, Francesc (…) and Espasa, Mateu.},
doi = {10.1136/sextrans-2020-054779},
issn = {1368-4973},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Sexually Transmitted Infections},
publisher = {The Medical Society for the Study of Venereal Disease},
abstract = {Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.
Alemany, Andrea; Perez-Zsolt, D; Raïch-Regué, D; Muñoz-Basagoiti, J; Ouchi, Dan; Laporte, Claudia (…); Mitjà, Oriol.
Cetylpyridinium Chloride Mouthwash to Reduce Shedding of Infectious SARS-CoV-2: A Double-Blind Randomized Clinical Trial Journal Article
In: Journal of Dental Research, vol. 101, no. 12, pp. 1450-1456, 2022.
@article{doi:10.1177/00220345221102310,
title = {Cetylpyridinium Chloride Mouthwash to Reduce Shedding of Infectious SARS-CoV-2: A Double-Blind Randomized Clinical Trial},
author = {Alemany, Andrea and Perez-Zsolt, D and Raïch-Regué, D and Muñoz-Basagoiti, J and Ouchi, Dan and Laporte, Claudia (…) and Mitjà, Oriol. },
doi = {10.1177/00220345221102310},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Journal of Dental Research},
volume = {101},
number = {12},
pages = {1450-1456},
abstract = {The airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via respiratory fluids and droplets suggests that mouthwashes containing substances with virucidal activity can help reduce viral spread. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to assess the virucidal activity of cetylpyridinium chloride (CPC) mouthwashes. Outpatients who tested positive for SARS-CoV-2 infection with or without symptoms were randomized to perform washes and gargles for 1 min with 15 mL of either colored distilled water or 0.07% CPC (Vitis CPC Protect) mouthwash. The study outcomes were the SARS-CoV-2 log10 viral RNA load and the nucleocapsid protein levels, both in saliva at 1 and 3 h after the intervention. In total, 118 patients were enrolled and randomized (mean [SD], age 46 [14] y). Thirteen of 118 participants (11%) did not complete follow-up or had insufficient sample volume for testing and were excluded from the analysis. The assessment of the viral load showed no significant differences between groups at any of the investigated points. However, the levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were significantly higher in the CPC group compared with the control group at 1 h (adjusted difference 269.3 pg/mL; 95% confidence interval [CI], 97.1–441.5) and at 3 h postintervention (561.1 pg/mL; 95% CI, 380.0–742.2). In nonhospitalized patients with asymptomatic or mild symptomatic SARS-CoV-2 infection, a 0.07% CPC mouthwash, compared to placebo, was associated with a significant increase of nucleocapsid protein levels in saliva, indicating enhanced disruption of viral particles.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via respiratory fluids and droplets suggests that mouthwashes containing substances with virucidal activity can help reduce viral spread. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to assess the virucidal activity of cetylpyridinium chloride (CPC) mouthwashes. Outpatients who tested positive for SARS-CoV-2 infection with or without symptoms were randomized to perform washes and gargles for 1 min with 15 mL of either colored distilled water or 0.07% CPC (Vitis CPC Protect) mouthwash. The study outcomes were the SARS-CoV-2 log10 viral RNA load and the nucleocapsid protein levels, both in saliva at 1 and 3 h after the intervention. In total, 118 patients were enrolled and randomized (mean [SD], age 46 [14] y). Thirteen of 118 participants (11%) did not complete follow-up or had insufficient sample volume for testing and were excluded from the analysis. The assessment of the viral load showed no significant differences between groups at any of the investigated points. However, the levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were significantly higher in the CPC group compared with the control group at 1 h (adjusted difference 269.3 pg/mL; 95% confidence interval [CI], 97.1–441.5) and at 3 h postintervention (561.1 pg/mL; 95% CI, 380.0–742.2). In nonhospitalized patients with asymptomatic or mild symptomatic SARS-CoV-2 infection, a 0.07% CPC mouthwash, compared to placebo, was associated with a significant increase of nucleocapsid protein levels in saliva, indicating enhanced disruption of viral particles.
Alemany, Andrea; Millat-Martinez, Pere; Ouchi, Dan; Corbacho-Monné, Marc; Bordoy, Antoni E.; Esteban, Cristina (…); Mitjà, Oriol
Self-collected mid-nasal swabs and saliva specimens, compared with nasopharyngeal swabs, for SARS-CoV-2 detection in mild COVID-19 patients Journal Article
In: Journal of Infection, vol. 83, no. 6, pp. 709-737, 2021, ISSN: 0163-4453.
@article{Alemany2021_self,
title = {Self-collected mid-nasal swabs and saliva specimens, compared with nasopharyngeal swabs, for SARS-CoV-2 detection in mild COVID-19 patients},
author = {Andrea Alemany and Pere Millat-Martinez and Dan Ouchi and Marc Corbacho-Monné and Antoni E. Bordoy and Esteban, Cristina (…) and Oriol Mitjà},
doi = {10.1016/j.jinf.2021.09.012},
issn = {0163-4453},
year = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {Journal of Infection},
volume = {83},
number = {6},
pages = {709-737},
publisher = {Elsevier},
abstract = {Self-collected nasal and saliva samples can be used for SARS-CoV-2 screening.?Self-collected nasal and saliva specimens had a 99% and 90% sensitivity, respectively.?Nasopharyngeal swab viral loads correlate better with nasal than saliva.?Viral load correlations are poorer at day 7, when lower viral loads are observed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Self-collected nasal and saliva samples can be used for SARS-CoV-2 screening.?Self-collected nasal and saliva specimens had a 99% and 90% sensitivity, respectively.?Nasopharyngeal swab viral loads correlate better with nasal than saliva.?Viral load correlations are poorer at day 7, when lower viral loads are observed.
Alemany, Andrea; Baró, Barbara; Ouchi, Dan; Rodó, Pau; Ubals, Maria; Corbacho-Monné, Marc (…); Mitjà, Oriol.
Analytical and clinical performance of the panbio COVID-19 antigen-detecting rapid diagnostic test Journal Article
In: Journal of Infection, vol. 82, no. 5, pp. 186-230, 2021, ISSN: 0163-4453.
@article{Alemany2021,
title = {Analytical and clinical performance of the panbio COVID-19 antigen-detecting rapid diagnostic test},
author = {Alemany, Andrea and Baró, Barbara and Ouchi, Dan and Rodó, Pau and Ubals, Maria and Corbacho-Monné, Marc (…) and Mitjà, Oriol.},
doi = {10.1016/j.jinf.2020.12.033},
issn = {0163-4453},
year = {2021},
date = {2021-05-01},
urldate = {2021-05-01},
journal = {Journal of Infection},
volume = {82},
number = {5},
pages = {186-230},
publisher = {Elsevier},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
c. Transmission
Nadal-Barón, Patricia; Trejo-Zahinos, Jesús; Arando, Maider; Barberan-Masegosa, Alicia; Bernat-Sole, Marta; Pérez-Ugarte, Arantxa (…); Hoyos-Mallecot, Yannick.
High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023 Journal Article
In: SCIENTIFIC REPORTS , vol. 14, iss. 1, 2024.
@article{nokey,
title = {High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023},
author = {Nadal-Barón, Patricia and Trejo-Zahinos, Jesús and Arando, Maider and Barberan-Masegosa, Alicia and Bernat-Sole, Marta and Pérez-Ugarte, Arantxa (…) and Hoyos-Mallecot, Yannick. },
doi = {10.1038/s41598-024-74355-y},
year = {2024},
date = {2024-10-08},
urldate = {2024-10-08},
journal = {SCIENTIFIC REPORTS },
volume = {14},
issue = {1},
abstract = {Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
Ubals, Maria; Nadal-Barón, Patricia; Arando, Maider; Rivero, Angel; Mendoza, Adrià; Descalzo Jorro, Victor (…); Mitjà, Oriol.
2024.
@bachelorthesis{nokey,
title = {Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial},
author = {Ubals, Maria and Nadal-Barón, Patricia and Arando, Maider and Rivero, Angel and Mendoza, Adrià and Descalzo Jorro, Victor (…) and Mitjà, Oriol. },
doi = {10.1016/S1473-3099(23)00683-7},
year = {2024},
date = {2024-04-02},
urldate = {2024-04-02},
journal = {The Lancet Infectious Diseases},
volume = {24},
issue = {4},
pages = {404-416},
abstract = {Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {bachelorthesis}
}
Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Tantalo, Lauren; Lieberman, Nicole; Perez-Mañà, Clara; Suñer, Clara; Vall-Mayans, Martí; Ubals, Maria; (…) Mitjà, Oriol
Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study Journal Article
In: The Lancet Microbe , vol. 4, iss. 12, 2023.
@article{nokey,
title = {Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study},
author = {Tantalo, Lauren and Lieberman, Nicole and Perez-Mañà, Clara and Suñer, Clara and Vall-Mayans, Martí and Ubals, Maria and (…) Mitjà, Oriol},
doi = {10.1016/S2666-5247(23)00219-7},
year = {2023},
date = {2023-12-04},
urldate = {2023-12-04},
journal = {The Lancet Microbe },
volume = {4},
issue = {12},
abstract = {Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Ávila-Nieto, Carlos; Pedreño-Lopez, Núria; Mitjà, Oriol; Clotet, Bonaventura; Blanco, Julà; Carrillo, Jorge
Syphilis vaccine: challenges, controversies and opportunities Journal Article
In: Frontiers in Immunology, vol. 14, 2023.
@article{NIETO2023SUBCUT,
title = {Syphilis vaccine: challenges, controversies and opportunities},
author = {Carlos Ávila-Nieto and Núria Pedreño-Lopez and Oriol Mitjà and Bonaventura Clotet and Julà Blanco and Jorge Carrillo},
doi = {https://doi.org/10.3389/fimmu.2023.1126170},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in Immunology},
volume = {14},
abstract = {Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.
Mitjà, Oriol; Suñer, Clara; Giacani, Lorenzo; Vall-Mayans, Martí; Tiplica, George-Sorin; Ross, Jonathan D. C.; Bradshaw, Catriona S.
Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100737, 2023, ISSN: 2666-7762.
@article{MITJA2023100737,
title = {Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis},
author = {Oriol Mitjà and Clara Suñer and Lorenzo Giacani and Martí Vall-Mayans and George-Sorin Tiplica and Jonathan D. C. Ross and Catriona S. Bradshaw},
doi = {https://doi.org/10.1016/j.lanepe.2023.100737},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100737},
abstract = {This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.
Gökengin, Deniz; Noori, Teymur; Alemany, Andrea; Bienkowski, Carlo; Liegon, Geoffroy; İnkaya, Ahmet Çağkan (…); Molina, Jean-Michel.
Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100738, 2023, ISSN: 2666-7762.
@article{GOKENGIN2023100738,
title = {Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe},
author = {Deniz Gökengin and Teymur Noori and Andrea Alemany and Carlo Bienkowski and Geoffroy Liegon and İnkaya, Ahmet Çağkan (…) and Molina, Jean-Michel.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100738},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100738},
abstract = {The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
Mitjà, Oriol; Padovese, Valeska; Folch, Cinta; Rossoni, Isotta; Marks, Michael; Rodríguez Arias, Miquel Angel (…); Casabona, Jordi.
Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100742, 2023, ISSN: 2666-7762.
@article{MITJA2023100742,
title = {Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe},
author = {Oriol Mitjà and Valeska Padovese and Cinta Folch and Isotta Rossoni and Michael Marks and Rodríguez Arias, Miquel Angel (…) and Casabona, Jordi.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100742},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100742},
abstract = {In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.
Fernández-Naval, Candela; Arando, Maider; Espasa, Mateu; Antón, Andrés; Fernández-Huerta, Miguel; Silgado, Aroa (…) Juliana Esperalba.
Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona Journal Article
In: Future Microbiology, vol. 16, no. 13, pp. 967-976, 2021.
@article{Fernandez2021,
title = {Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona},
author = {Candela Fernández-Naval and Maider Arando and Mateu Espasa and Andrés Antón and Miguel Fernández-Huerta and Silgado, Aroa (…) Juliana Esperalba.},
doi = {https://doi.org/10.2217/fmb-2021-0037},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Future Microbiology},
volume = {16},
number = {13},
pages = {967-976},
abstract = {Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.
Haynes, Austin M.; Giacani, Lorenzo; Mayans, Marti Vall; Ubals, Maria; Nieto, Carles; Pérez-Mañá, Clara; Quintó, Llorenç; Romeis, Emily; Mitjà, Oriol
Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study Journal Article
In: EBioMedicine, vol. 65, 2021, ISSN: 2352-3964.
@article{Haynes2021,
title = {Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study},
author = {Austin M. Haynes and Lorenzo Giacani and Marti Vall Mayans and Maria Ubals and Carles Nieto and Clara Pérez-Mañá and Llorenç Quintó and Emily Romeis and Oriol Mitjà},
doi = {10.1016/j.ebiom.2021.103281},
issn = {2352-3964},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {EBioMedicine},
volume = {65},
publisher = {Elsevier},
abstract = {Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.
Hoyos-Mallecot, Yannick; Garcia, Jorge Nestor; Sulleiro, Elena; Esperalba, Juliana; Salmeron, Paula; Zarzuela, Francesc (…); Espasa, Mateu.
Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification Journal Article
In: Sexually Transmitted Infections, 2021, ISSN: 1368-4973.
@article{Hoyos-Mallecotsextrans-2020-054779,
title = {Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification},
author = {Yannick Hoyos-Mallecot and Jorge Nestor Garcia and Elena Sulleiro and Juliana Esperalba and Paula Salmeron and Zarzuela, Francesc (…) and Espasa, Mateu.},
doi = {10.1136/sextrans-2020-054779},
issn = {1368-4973},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Sexually Transmitted Infections},
publisher = {The Medical Society for the Study of Venereal Disease},
abstract = {Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.
Suñer, Clara; Coma, Ermengol; Ouchi, Dan; Hermosilla, Eduardo; Baro, Barbara; Rodríguez-Arias, Miquel Àngel (…); Mitjà., Oriol
In: The Lancet Regional Health – Europe, vol. 15, 2022, ISSN: 2666-7762.
@article{Suñer2022,
title = {Association between two mass-gathering outdoor events and incidence of SARS-CoV-2 infections during the fifth wave of COVID-19 in north-east Spain: A population-based control-matched analysis},
author = {Suñer, Clara and Coma, Ermengol and Ouchi, Dan and Hermosilla, Eduardo and Baro, Barbara and Rodríguez-Arias, Miquel Àngel (…) and Oriol Mitjà.},
doi = {10.1016/j.lanepe.2022.100337},
issn = {2666-7762},
year = {2022},
date = {2022-04-01},
urldate = {2022-04-01},
journal = {The Lancet Regional Health – Europe},
volume = {15},
publisher = {Elsevier},
abstract = {Many countries have resumed mass-gathering events like music festivals, despite the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. In this study, we aimed to assess the effect of two mass-gathering outdoor events, held during a peak of SARS-CoV-2 transmission, on COVID-19 incidence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Many countries have resumed mass-gathering events like music festivals, despite the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. In this study, we aimed to assess the effect of two mass-gathering outdoor events, held during a peak of SARS-CoV-2 transmission, on COVID-19 incidence.
Marks, Michael; Millat-Martinez, Pere; Ouchi, Dan; Roberts, Chrissy; Alemany, Andrea; Corbacho-Monné, Marc (…); Mitjà, Oriol.
Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study Journal Article
In: The Lancet Infectious Diseases, vol. 21, no. 5, pp. 629-636, 2021, ISSN: 1473-3099.
@article{Marks2021,
title = {Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study},
author = {Marks, Michael and Millat-Martinez, Pere and Ouchi, Dan and Roberts, Chrissy and Alemany, Andrea and Corbacho-Monné, Marc (…) and Mitjà, Oriol.},
doi = {10.1016/S1473-3099(20)30985-3},
issn = {1473-3099},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {The Lancet Infectious Diseases},
volume = {21},
number = {5},
pages = {629-636},
publisher = {Elsevier},
abstract = {Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2.
c. Risk factors
Nadal-Barón, Patricia; Trejo-Zahinos, Jesús; Arando, Maider; Barberan-Masegosa, Alicia; Bernat-Sole, Marta; Pérez-Ugarte, Arantxa (…); Hoyos-Mallecot, Yannick.
High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023 Journal Article
In: SCIENTIFIC REPORTS , vol. 14, iss. 1, 2024.
@article{nokey,
title = {High increase of Nichols-like clade circulating Treponema pallidum subsp. pallidum in Barcelona from 2021 to 2023},
author = {Nadal-Barón, Patricia and Trejo-Zahinos, Jesús and Arando, Maider and Barberan-Masegosa, Alicia and Bernat-Sole, Marta and Pérez-Ugarte, Arantxa (…) and Hoyos-Mallecot, Yannick. },
doi = {10.1038/s41598-024-74355-y},
year = {2024},
date = {2024-10-08},
urldate = {2024-10-08},
journal = {SCIENTIFIC REPORTS },
volume = {14},
issue = {1},
abstract = {Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Worldwide, more than 90% of contemporary syphilis strains belong to SS14-like clade. This study aimed to describe the molecular profile of circulating Treponema pallidum subsp. pallidum (TPA) strains in Barcelona, Spain, from 2021 to 2023 building upon our report in 2015 which showed that 94.8% of typed strains belonged to the SS14 clade. Multilocus sequence typing (MLST) was conducted on TPA-positive samples obtained from swab samples by sequencing the tp0136, tp0548, and tp0705 loci. Strains were classified as Nichols-like or SS14-like clade. Macrolide and tetracycline resistance‑associated mutations were determined through analysis of 23S rDNA and 16S rRNA gene sequences. Of the 96 typeable samples, 47.9% belonged to SS14-like and 52.1% to the Nichols-like. Fourteen haplotypes were identified, with ST26 representing 43.8% of the samples, distributed across 11 haplotypes in the SS14-like and 3 haplotypes in the Nichols-like. All the samples showed macrolide resistance-associated mutations, while none exhibited tetracycline-associated mutations. Our findings revealed a substantial shift in the proportion of TPA clades within the Barcelona population from 2021 to 2023, characterized by a higher proportion of Nichols-like strains compared to 2015 and international trends. The varying temporal and geographical trends underscore the need for regular surveillance to understand regional variations in syphilis and strengthen control programs.
Ubals, Maria; Nadal-Barón, Patricia; Arando, Maider; Rivero, Angel; Mendoza, Adrià; Descalzo Jorro, Victor (…); Mitjà, Oriol.
2024.
@bachelorthesis{nokey,
title = {Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial},
author = {Ubals, Maria and Nadal-Barón, Patricia and Arando, Maider and Rivero, Angel and Mendoza, Adrià and Descalzo Jorro, Victor (…) and Mitjà, Oriol. },
doi = {10.1016/S1473-3099(23)00683-7},
year = {2024},
date = {2024-04-02},
urldate = {2024-04-02},
journal = {The Lancet Infectious Diseases},
volume = {24},
issue = {4},
pages = {404-416},
abstract = {Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {bachelorthesis}
}
Background
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
Methods
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than –10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
Findings
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference –29·6, 95% CI –50·5 to –8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
Interpretation
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
Tantalo, Lauren; Lieberman, Nicole; Perez-Mañà, Clara; Suñer, Clara; Vall-Mayans, Martí; Ubals, Maria; (…) Mitjà, Oriol
Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study Journal Article
In: The Lancet Microbe , vol. 4, iss. 12, 2023.
@article{nokey,
title = {Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study},
author = {Tantalo, Lauren and Lieberman, Nicole and Perez-Mañà, Clara and Suñer, Clara and Vall-Mayans, Martí and Ubals, Maria and (…) Mitjà, Oriol},
doi = {10.1016/S2666-5247(23)00219-7},
year = {2023},
date = {2023-12-04},
urldate = {2023-12-04},
journal = {The Lancet Microbe },
volume = {4},
issue = {12},
abstract = {Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Methods: Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
Findings: Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
Interpretation: Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
Ávila-Nieto, Carlos; Pedreño-Lopez, Núria; Mitjà, Oriol; Clotet, Bonaventura; Blanco, Julà; Carrillo, Jorge
Syphilis vaccine: challenges, controversies and opportunities Journal Article
In: Frontiers in Immunology, vol. 14, 2023.
@article{NIETO2023SUBCUT,
title = {Syphilis vaccine: challenges, controversies and opportunities},
author = {Carlos Ávila-Nieto and Núria Pedreño-Lopez and Oriol Mitjà and Bonaventura Clotet and Julà Blanco and Jorge Carrillo},
doi = {https://doi.org/10.3389/fimmu.2023.1126170},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in Immunology},
volume = {14},
abstract = {Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.
Mitjà, Oriol; Suñer, Clara; Giacani, Lorenzo; Vall-Mayans, Martí; Tiplica, George-Sorin; Ross, Jonathan D. C.; Bradshaw, Catriona S.
Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100737, 2023, ISSN: 2666-7762.
@article{MITJA2023100737,
title = {Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis},
author = {Oriol Mitjà and Clara Suñer and Lorenzo Giacani and Martí Vall-Mayans and George-Sorin Tiplica and Jonathan D. C. Ross and Catriona S. Bradshaw},
doi = {https://doi.org/10.1016/j.lanepe.2023.100737},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100737},
abstract = {This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.
Gökengin, Deniz; Noori, Teymur; Alemany, Andrea; Bienkowski, Carlo; Liegon, Geoffroy; İnkaya, Ahmet Çağkan (…); Molina, Jean-Michel.
Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100738, 2023, ISSN: 2666-7762.
@article{GOKENGIN2023100738,
title = {Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe},
author = {Deniz Gökengin and Teymur Noori and Andrea Alemany and Carlo Bienkowski and Geoffroy Liegon and İnkaya, Ahmet Çağkan (…) and Molina, Jean-Michel.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100738},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100738},
abstract = {The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
Mitjà, Oriol; Padovese, Valeska; Folch, Cinta; Rossoni, Isotta; Marks, Michael; Rodríguez Arias, Miquel Angel (…); Casabona, Jordi.
Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe Journal Article
In: The Lancet Regional Health – Europe, vol. 34, pp. 100742, 2023, ISSN: 2666-7762.
@article{MITJA2023100742,
title = {Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe},
author = {Oriol Mitjà and Valeska Padovese and Cinta Folch and Isotta Rossoni and Michael Marks and Rodríguez Arias, Miquel Angel (…) and Casabona, Jordi.},
doi = {https://doi.org/10.1016/j.lanepe.2023.100742},
issn = {2666-7762},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {The Lancet Regional Health - Europe},
volume = {34},
pages = {100742},
abstract = {In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.
Fernández-Naval, Candela; Arando, Maider; Espasa, Mateu; Antón, Andrés; Fernández-Huerta, Miguel; Silgado, Aroa (…) Juliana Esperalba.
Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona Journal Article
In: Future Microbiology, vol. 16, no. 13, pp. 967-976, 2021.
@article{Fernandez2021,
title = {Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona},
author = {Candela Fernández-Naval and Maider Arando and Mateu Espasa and Andrés Antón and Miguel Fernández-Huerta and Silgado, Aroa (…) Juliana Esperalba.},
doi = {https://doi.org/10.2217/fmb-2021-0037},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Future Microbiology},
volume = {16},
number = {13},
pages = {967-976},
abstract = {Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aim: To implement the multilocus sequence typing (MLST) methodology in syphilis samples previously characterized by enhanced CDC typing (ECDCT) and macrolide resistance. Materials & methods: MLST was performed on genital ulcer and blood samples by analyzing a region of the tp0136, tp0548 and tp0705 loci using Sanger sequencing. Results: Up to 59/85 (69.4%) of genital ulcer and 4/39 (10.3%) of whole blood samples were fully typed. The most frequent profiles were 1.3.1 (56%) and 1.1.1 (11%). All the 1.3.1 samples typed carried the A2058G mutation, responsible for macrolide resistance. MLST and ECDCT showed similar overall typing yields. Conclusion: Several allelic profiles of T. pallidum subsp. pallidum were identified and classified into two major genetic clades in Barcelona. Our results were similar to that described in Europe.
Haynes, Austin M.; Giacani, Lorenzo; Mayans, Marti Vall; Ubals, Maria; Nieto, Carles; Pérez-Mañá, Clara; Quintó, Llorenç; Romeis, Emily; Mitjà, Oriol
Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study Journal Article
In: EBioMedicine, vol. 65, 2021, ISSN: 2352-3964.
@article{Haynes2021,
title = {Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study},
author = {Austin M. Haynes and Lorenzo Giacani and Marti Vall Mayans and Maria Ubals and Carles Nieto and Clara Pérez-Mañá and Llorenç Quintó and Emily Romeis and Oriol Mitjà},
doi = {10.1016/j.ebiom.2021.103281},
issn = {2352-3964},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {EBioMedicine},
volume = {65},
publisher = {Elsevier},
abstract = {Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both textitin vitro and textitin vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.
Hoyos-Mallecot, Yannick; Garcia, Jorge Nestor; Sulleiro, Elena; Esperalba, Juliana; Salmeron, Paula; Zarzuela, Francesc (…); Espasa, Mateu.
Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification Journal Article
In: Sexually Transmitted Infections, 2021, ISSN: 1368-4973.
@article{Hoyos-Mallecotsextrans-2020-054779,
title = {Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification},
author = {Yannick Hoyos-Mallecot and Jorge Nestor Garcia and Elena Sulleiro and Juliana Esperalba and Paula Salmeron and Zarzuela, Francesc (…) and Espasa, Mateu.},
doi = {10.1136/sextrans-2020-054779},
issn = {1368-4973},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Sexually Transmitted Infections},
publisher = {The Medical Society for the Study of Venereal Disease},
abstract = {Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background STIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.Methods The Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.Results Between 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.Conclusions Drassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.Data are available upon reasonable request. All data relevant to the study are included in the article, however more detailed protocols are available upon request.
Alemany, Andrea; Balanza, Núria; Millat-Martínez, Pere; Ouchi, Dan; Corbacho-Monné, Marc; Morales-Indiano, C (…); Baró, Bàrbara.
Prognostic performance of early immune and endothelial activation markers in mild-to-moderate COVID-19 outpatients: a nested case-control study Journal Article
In: Frontiers of Immunology, vol. 15, 2024.
@article{nokey,
title = {Prognostic performance of early immune and endothelial activation markers in mild-to-moderate COVID-19 outpatients: a nested case-control study},
author = {Alemany, Andrea and Balanza, Núria and Millat-Martínez, Pere and Ouchi, Dan and Corbacho-Monné, Marc and Morales-Indiano, C (…) and Baró, Bàrbara.},
doi = {10.3389/fimmu.2024.1501872},
year = {2024},
date = {2024-11-27},
urldate = {2024-11-27},
journal = {Frontiers of Immunology},
volume = {15},
abstract = {Introduction: Evidence on the association of biomarkers of host response to infection with COVID-19 clinical outcomes has focused mainly on hospitalized patients. We investigated the prognostic performance of 39 immune and endothelial activation markers measured early in the course of disease to predict the development of severe COVID-19 and hospitalization.
Methods: We conducted a nested case-control study from a randomized clinical trial evaluating the efficacy of COVID-19 convalescent plasma in outpatients aged 50 years or older presenting with mild-to-moderate COVID-19. We selected participants who were hospitalized within 28 days (cases) and who were not (controls) to compare their biomarker levels in plasma samples collected at enrolment.
Results: A total of 42 cases and 42 controls were included in this study. The levels of CRP, IL6, IP10, ferritin, IFNα, IL8, IL1RA, MCP1, and RANTES, determined within 7 days of symptoms onset, showed good individual prognostic performance for COVID-19 associated hospitalization by day 28. The biomarkers CRP, IL6, IP10, IL8, IL1RA, and suPAR showed good individual prognostic performance for severe COVID-19. CRP, IL6 and IP10 had the most robust association with both hospitalization and severe COVID-19, with CRP having the highest discriminatory capacity with hospitalization, and IL6 for severe COVID-19.
Discussion: Our study shows good prognostic performance of CRP and IL6 for 28-day hospitalization in patients with mild-to-moderate COVID-19, in the absence of clinical criteria for admission upon enrolment. These findings confirm the value of these biomarkers at early stages of COVID-19 disease in the outpatient setting to support management decisions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction: Evidence on the association of biomarkers of host response to infection with COVID-19 clinical outcomes has focused mainly on hospitalized patients. We investigated the prognostic performance of 39 immune and endothelial activation markers measured early in the course of disease to predict the development of severe COVID-19 and hospitalization.
Methods: We conducted a nested case-control study from a randomized clinical trial evaluating the efficacy of COVID-19 convalescent plasma in outpatients aged 50 years or older presenting with mild-to-moderate COVID-19. We selected participants who were hospitalized within 28 days (cases) and who were not (controls) to compare their biomarker levels in plasma samples collected at enrolment.
Results: A total of 42 cases and 42 controls were included in this study. The levels of CRP, IL6, IP10, ferritin, IFNα, IL8, IL1RA, MCP1, and RANTES, determined within 7 days of symptoms onset, showed good individual prognostic performance for COVID-19 associated hospitalization by day 28. The biomarkers CRP, IL6, IP10, IL8, IL1RA, and suPAR showed good individual prognostic performance for severe COVID-19. CRP, IL6 and IP10 had the most robust association with both hospitalization and severe COVID-19, with CRP having the highest discriminatory capacity with hospitalization, and IL6 for severe COVID-19.
Discussion: Our study shows good prognostic performance of CRP and IL6 for 28-day hospitalization in patients with mild-to-moderate COVID-19, in the absence of clinical criteria for admission upon enrolment. These findings confirm the value of these biomarkers at early stages of COVID-19 disease in the outpatient setting to support management decisions.
Methods: We conducted a nested case-control study from a randomized clinical trial evaluating the efficacy of COVID-19 convalescent plasma in outpatients aged 50 years or older presenting with mild-to-moderate COVID-19. We selected participants who were hospitalized within 28 days (cases) and who were not (controls) to compare their biomarker levels in plasma samples collected at enrolment.
Results: A total of 42 cases and 42 controls were included in this study. The levels of CRP, IL6, IP10, ferritin, IFNα, IL8, IL1RA, MCP1, and RANTES, determined within 7 days of symptoms onset, showed good individual prognostic performance for COVID-19 associated hospitalization by day 28. The biomarkers CRP, IL6, IP10, IL8, IL1RA, and suPAR showed good individual prognostic performance for severe COVID-19. CRP, IL6 and IP10 had the most robust association with both hospitalization and severe COVID-19, with CRP having the highest discriminatory capacity with hospitalization, and IL6 for severe COVID-19.
Discussion: Our study shows good prognostic performance of CRP and IL6 for 28-day hospitalization in patients with mild-to-moderate COVID-19, in the absence of clinical criteria for admission upon enrolment. These findings confirm the value of these biomarkers at early stages of COVID-19 disease in the outpatient setting to support management decisions.
Suñer, Clara; Ouchi, Dan; Mas, Miquel Àngel; Lopez Alarcon, Rosa; Massot Mesquida, Mireia; Prat, Nuria (…); Mitjà, Oriol.
A retrospective cohort study of risk factors for mortality among nursing homes exposed to COVID-19 in Spain Journal Article
In: Nature Aging, vol. 1, no. 7, pp. 579-584, 2021, ISSN: 2662-8465.
@article{Suñer2021,
title = {A retrospective cohort study of risk factors for mortality among nursing homes exposed to COVID-19 in Spain},
author = {Suñer, Clara and Ouchi, Dan and Mas, Miquel Àngel and Lopez Alarcon, Rosa and Massot Mesquida, Mireia and Prat, Nuria (…) and Mitjà, Oriol.},
doi = {10.1038/s43587-021-00079-7},
issn = {2662-8465},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Nature Aging},
volume = {1},
number = {7},
pages = {579-584},
abstract = {Long-term care (LTC) facilities have shown remarkably high mortality rates during the coronavirus disease 2019 (COVID-19) outbreak in many countries1, and different risk factors for mortality have been identified in this setting2–5. Using facilities as the unit of analysis, we investigated multiple variables covering facility characteristics and socioeconomic characteristics of the geographic location to identify risk factors for excess mortality from a comprehensive perspective. Furthermore, we used a clustering approach to detect patterns in datasets and generate hypotheses regarding potential relationships between types of nursing homes and mortality trends. Our retrospective analysis included 167 nursing homes providing LTC to 8,716 residents during the COVID-19 outbreak in Catalonia (northeast Spain). According to multiple regression analysis, COVID-19-related and overall mortality at the facility level were significantly associated with a higher percentage of patients with complex diseases, lower scores on pandemic preparedness measures and higher population incidence of COVID-19 in the surrounding population. When grouping nursing homes into eight clusters based on common features, we found higher mortality rates in four clusters, mainly characterized by a higher proportion of residents with complex chronic conditions or advanced diseases, lower scores on pandemic preparedness, being located in rural areas and larger capacity, respectively.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Long-term care (LTC) facilities have shown remarkably high mortality rates during the coronavirus disease 2019 (COVID-19) outbreak in many countries1, and different risk factors for mortality have been identified in this setting2–5. Using facilities as the unit of analysis, we investigated multiple variables covering facility characteristics and socioeconomic characteristics of the geographic location to identify risk factors for excess mortality from a comprehensive perspective. Furthermore, we used a clustering approach to detect patterns in datasets and generate hypotheses regarding potential relationships between types of nursing homes and mortality trends. Our retrospective analysis included 167 nursing homes providing LTC to 8,716 residents during the COVID-19 outbreak in Catalonia (northeast Spain). According to multiple regression analysis, COVID-19-related and overall mortality at the facility level were significantly associated with a higher percentage of patients with complex diseases, lower scores on pandemic preparedness measures and higher population incidence of COVID-19 in the surrounding population. When grouping nursing homes into eight clusters based on common features, we found higher mortality rates in four clusters, mainly characterized by a higher proportion of residents with complex chronic conditions or advanced diseases, lower scores on pandemic preparedness, being located in rural areas and larger capacity, respectively.
