@article{nokey,

title = {Clade IIb mpox outbreak in Sierra Leone},

author = {Oriol Mitjà and Deborah Watson-Jones and Edward M Choi and Mohamed Boi Jalloh and Foday Sahr},

doi = {10.1016/S0140-6736(25)01203-6},

year  = {2025},

date = {2025-06-20},

urldate = {2025-06-20},

journal = {The Lancet},

volume = {Online first},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Target Trial Emulation of the Modified Vaccinia Ankara-Bavarian Nordic Vaccine for Pre-Exposure Mpox Prevention in At-Risk Populations},

author = {Clara Suñer and Roser Escrig-Sarreta and Cristina Galván-Casas and Eduardo Mateos and Amanda Gabster and (…) Mitjà, Oriol},

doi = {10.3390/vaccines13060594},

year  = {2025},

date = {2025-05-30},

urldate = {2025-05-30},

journal = {Vaccines},

volume = {13},

issue = {6},

abstract = {Background:The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though no randomized trials have yet confirmed its effectiveness. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between 1 September 2022 and 15 June 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until 31 March 2024. The primary endpoint was symptomatic mpox occurrence ≥14 days post-vaccination. Results: The primary analysis included 1028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7–13.7). Mpox occurred in eight participants (0.8%): three vaccinated and five unvaccinated (HR 0.6; 95% CI 0.21–1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 450/1058 (42.5%) participants, persisting >6 months in 107 of them (23.8%). Conclusions: The low incidence of mpox during the study period resulted in a limited number of endpoint events, precluding robust conclusions on the efficacy of the MVA-BN vaccine as pre-exposure prevention for mpox. However, our analysis, which accounted for key confounders such as exposure behaviors, yielded results consistent with previous studies suggesting the effectiveness of the vaccine in the mpox setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Clinical presentation and epidemiological assessment of confirmed human mpox cases in DR Congo: a surveillance-based observational study},

author = {Emile Malembi and Roser Escrig-Sarreta and Jackie Ntumba and Robert Shongo and Justin Bengehya and (…) Mitjà, Oriol},

doi = {10.1016/S0140-6736(25)00152-7},

year  = {2025},

date = {2025-05-10},

urldate = {2025-05-10},

journal = {The Lancet},

volume = {405},

issue = {10490},

pages = {1666-1675},

abstract = {Background

Mpox, caused by the monkeypox virus, is a serious public health threat in Africa, especially in DR Congo. Previously limited to endemic areas with clade 1a, monkeypox virus has recently spread to non-endemic regions, where clade 1b has emerged. This study provides a clinical comparison of mpox cases in DR Congo regions where clade 1a and clade 1b are prevalent.

Methods

We conducted a retrospective observational study, analysing PCR-confirmed mpox cases reported from sentinel health zones in seven provinces between Oct 1, 2023, and Sept 31, 2024. Cases from the newly affected provinces (South-Kivu and Kinshasa) were described along with those from four endemic provinces (Mai-Ndombe, Tshuapa, Tshopo, South-Ubangi, and Équateur). Surveillance data, including type of exposure, demographic details, clinical presentation, complications, and outcomes were collected from national surveillance systems and local health facilities, with laboratory confirmation using quantitative PCR. All analyses were restricted to descriptive statistics.

Findings

Of 17 927 suspected cases identified, 10 986 were investigated, 5948 were PCR-positive, and 4895 met the inclusion criteria based on data completeness: 4436 in newly affected and 459 in endemic regions. In newly affected provinces, median age was 20 years (IQR 8–28), 2119 (47·8%) participants were female, and 2310 (52·1%) were male. In endemic provinces, median age was 15 years (7–26), 179 (39·0%) participants were female, and 277 (60·3%) were male. Direct or intimate human contact was reported by 1951 (44·0%) individuals in newly affected provinces versus 25 (5·4%) in endemic provinces, and zoonotic exposure in 11 (0·2%) and 99 (21·6%), respectively. The proportions of partcipants with systemic symptoms (3828 [86·3%] in newly affected provinces and 427 [93·0%] in endemic provinces) and respiratory symptoms (2450 [55·2%] and 219 [47·7%]), and median skin lesion counts (91 [IQR 37–200] and 163 [95–345]) were similar between newly affected and endemic regions. Complications included skin infections (2041 [46·0%] in newly affected provinces and 201 [43·8%] in endemic provinces), respiratory distress (82 [1·8%] and 29 [6·3%]), vision impairment (7 [0·2%] and 28 [6·1%]), and prostration (695 [15·7%] and 51 [11·1%]). The case-fatality rate was 0·7% (95% CI 0·4–1·3; 14 of 1924) in children and 0·6% (0·3–1·0; 14 of 2483) in adults in newly affected areas, compared with 5·9% (3·4–10·0; 14 of 236) in children and 2·7% (1·1–6·1; six of 222) in adults in endemic regions. Content note: this Article and its appendix contain graphic images of mpox lesions affecting various sites including the face and genitals.

Interpretation

Our study indicates concurrent mpox outbreaks in DR Congo, involving younger individuals, a higher proportion of women and girls, and distinct presentations with higher lesion counts and respiratory symptoms compared with clade 2b lineage B.1 outbreaks. The high proportion of infectious complications and case-fatality rates, especially in endemic regions, emphasise the need for timely antibiotic therapy and targeted vaccination to reduce morbidity and mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Concurrent outbreaks of mpox in Africa—an update},

author = {Camila Gonzalez-Beiras and Emile Malembi and Roser Escrig-Sarreta and Steve Ahuka and Placide Mbala and Mavoko, Hypolite (…) and Mitjà, Oriol},

doi = {10.1016/S0140-6736(24)02353-5},

year  = {2025},

date = {2025-01-04},

urldate = {2025-01-04},

journal = {The Lancet},

volume = {405},

issue = {10472},

abstract = {In this Review, we examine the concurrent outbreaks of mpox in Africa, focusing on clade 1a, the newly emerged clade 1b, and clade 2b lineage A, and how they differ from the 2022 global outbreak caused by clade 2b lineage B.1. Historically, clades 1a and 2a have caused sporadic, small outbreaks in central and west Africa, respectively, primarily through zoonotic transmission. Clade 2b first caused an outbreak in Nigeria in 2017, and later spread globally via sexual contact in 2022. In August, 2024, WHO declared a global health emergency due to the newly identified clade 1b outbreak in eastern Democratic Republic of the Congo. This outbreak has now expanded to several other countries and is spreading through direct and sexual contact in urban centres and refugee camps. Clades, route of exposure, infectious dose, and host immune response are the main factors influencing clinical presentation of mpox. For clades 1a and 2a, zoonotic transmission plays an important role, whereas for clades 1b and 2b, the spread occurs through sustained human-to-human transmission without zoonotic exposure. For both clades 1a and 2a, lesions have a generalised centrifugal distribution, whereas for clade 2b they are mainly localised to the anogenital area. For clade 1b, data are still emerging, but current cases show a mix of localised lesions and centrifugal distribution. The severity of the disease is higher for clade 1a (case fatality rate up to 12%) compared with other clades (case fatality rates 0–3·6%). Diagnostic challenges include false negative results for clade 1b with existing PCR assays and poor testing access in remote areas. Tecovirimat, the primary antiviral during the 2022 outbreak, has shown reduced effectiveness against clade 1a in preliminary study results, whereas its efficacy against other clades is still under investigation. The modified vaccinia Ankara–Bavarian Nordic vaccine has been shown to be up to 90% effective against clade 2b after two doses and is safe for children, although its effectiveness drops to 20% when used as post-exposure prophylaxis. Given the evolving nature of the monkeypox virus, ongoing research and strong public health responses are key to managing potential future outbreaks.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Immune responses associated with mpox viral clearance in men with and without HIV in Spain: a multisite, observational, prospective cohort study},

author = {Moraes Cardoso, Igor and Benet, Susana and Carabelli, Julieta and Perez-Zsolt, Daniel and Mendoza, Adrià and Rivero, Angel (…) and Mothe, Beatriz},

doi = {10.1016/S2666-5247(24)00074-0 },

year  = {2024},

date = {2024-08-09},

urldate = {2024-08-09},

journal = {The Lancet Microbe },

volume = {5},

issue = {18},

abstract = {Background

Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics.

Methods

This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry.

Findings

Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4+ T-cell count median of 777 cells per μL (IQR 484–1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status.

Interpretation

Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Mpox in people with past infection or a complete vaccination course: a global case series},

author = {Aniruddha Hazra and Jason Zucker and Elizabeth Bell and John Flores and Leanna Gordon and Mitjà, Oriol (…) and Chloe Orkin},

doi = {10.1016/S1473-3099(23)00492-9},

year  = {2024},

date = {2024-01-22},

urldate = {2024-01-22},

journal = {The Lancet Infectious Diseases},

volume = {24},

issue = {1},

abstract = {Background: Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity.



Methods: In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive.



Findings: We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30-45; range 21-58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion.



Interpretation: The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak-predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Egocentric sexual network analysis among gay and bisexual men who have sex with men with and without mpox infection},

author = {Sonmez, Ibrahim and Martínez Riveros, Héctor and Cinta Folch and Clara Suñer and Yesika Diaz and Lucía Alonso and (…) Casabona, Jordi},

doi = {10.1136/sextrans-2023-055901},

year  = {2023},

date = {2023-12-13},

urldate = {2023-12-13},

journal = {Sexually Transmitted Infections},

volume = {99},

issue = {8},

abstract = {Objectives: Recent outbreaks of the mpox (monkeypox) virus have been detected in dense sexual networks of gay and bisexual men who have sex with men (GBMSM). The objective of this study is to describe and compare the epidemiological and behavioural characteristics, as well as the sexual networks, of GBMSM diagnosed with mild mpox in Spain.



Methods: A prospective case-control study was conducted in Spain from July 2022 to February 2023. The study targeted a key population of GBMSM aged 18 years or older. Study participants were categorised into cases, those who were diagnosed with mpox virus infection; and controls, those who were not diagnosed. We examined and compared the sexual network characteristics of the two groups-mpox-positive (mpox-P) and mpox-negative (mpox-N) egos-using χ2, t-test and Wilcoxon test to examine the differences between the two groups in each section. Finally, we conducted univariable and multivariable logistic regressions to determine the factors associated with mpox infection.



Results: Among the 105 participants, 35 (33.3%) were mpox-P. Compared with mpox-N, mpox-P respondents more frequently reported syphilis (mpox-P: 31.4%; mpox-N: 12.9%) and HIV (mpox-P: 45.7%; mpox-N: 18.6%), and mpox-P individuals to have had at least one sexual contact with a confirmed mpox case (mpox-P: 62.5%; mpox-N: 8.3%). In the egocentric network analysis, mpox-P respondents had a higher prevalence of group sex with alters (mpox-P: 18.5%; mpox-N: 8.9%) and one-time sexual partners (mpox-P: 46.1%; mpox-N: 31.7%). Multivariable logistic regressions showed that reporting stranger/client ties (adjusted OR (aOR)=10.3, 95% CI 1.39 to 76.6) with alters, being vaccinated for mpox (aOR=0.07, 95% CI 0.02 to 0.24) and tie strength heterogeneity (aOR=0.01, 95% CI 0.00 to 0.42) were associated with mpox infection.



Conclusions: Our findings highlight the role of demographic, epidemiological and sexual network characteristics in the transmission of mpox virus during the outbreak in Spain. These findings have important implications for future prevention efforts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ubals2022-tf,

title = {Evaluating the accuracy of self-collected swabs for the diagnoss of monkeypox},

author = {Ubals, Maria and Tarín-Vicente, Eloy José and Oller, Xènia and Mendoza, Adrià and Alemany, Andrea and Hernández-Rodríguez, Águeda (…) and Mitjà, Oriol.},

doi = {10.1093/cid/ciac889},

isbn = {1537-6591},

year  = {2023},

date = {2023-04-03},

urldate = {2023-04-03},

journal = {Clinical Infectious Diseases},

volume = {7},

number = {76},

pages = {1311-1314},

abstract = {We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{monki,

title = {Mpox in people with advanced HIV infection: a global case series},

author = {Mitjà, Oriol and Alemany, Andrea and Marks, Michael and Lezama Mora, Jezer and Rodríguez-Aldama, Juan Carlos and Torres, Mayara (…) and Villareal, Diana.},

doi = {https://doi.org/10.1016/S0140-6736(23)00273-8},

issn = {0140-6736},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {The Lancet},

publisher = {Elsevier},

abstract = {BackgroundPeople living with HIV have accounted for 38?50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sunyer2023,

title = {Viral dynamics in patients with monkeypox infection: a prospective cohort study in Spain},

author = {Suñer, Clara and Ubals, Maria and Tarín-Vicente, Eloy José and Mendoza, Adrià and Alemany, Andrea and Hernández-Rodríguez, Agueda (…) and Mitjà, Oriol.},

doi = {https://doi.org/10.1016/S1473-3099(22)00794-0},

issn = {1473-3099},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {The Lancet Infectious Diseases},

publisher = {Elsevier},

abstract = {BackgroundMonkeypox DNA has been detected in skin lesions, saliva, oropharynx, urine, semen, and stool of patients infected during the 2022 clade IIb outbreak; however, the viral dynamics within these compartments remain unknown. We aimed to characterise the viral load kinetics over time in various parts of the body.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series},

author = {John P Thornhill and Romain Palich and Jade Ghosn and Sharon Walmsley and Davide Moschese and Cortes, Claudia P (…) and Orkin, Chloe},

doi = {10.1016/S0140-6736(22)02187-0},

year  = {2022},

date = {2022-12-03},

journal = {The Lancet},

volume = {400},

issue = {10367},

pages = {1953-1965},

abstract = {Background

Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors.

Methods

International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections.

Findings

Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28–40; range 19–84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1–200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported.

Interpretation

The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tarín-Vicente2022,

title = {Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study},

author = {Tarín-Vicente, Eloy José and Alemany, Andrea and Agud-Dios, Manuel and Ubals, Maria and Suñer, Clara and Antón, Andrés (…) and Mitjà, Oriol.},

doi = {https://doi.org/10.1016/S0140-6736(22)01436-2},

issn = {0140-6736},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {The Lancet},

volume = {400},

number = {10353},

pages = {661-669},

publisher = {Elsevier},

abstract = {In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ref1_mitjas,

title = {Monkeypox},

author = {Oriol Mitjà and Dimie Ogoina and Boghuma K. Titanji and Cristina Galvan and Jean-Jacques Muyembe and Michael Marks and Chloe M. Orkin},

doi = {https://doi.org/10.1016/S0140-6736(22)02075-X},

issn = {0140-6736},

year  = {2022},

date = {2022-01-01},

journal = {The Lancet},

publisher = {Elsevier},

abstract = {Monkeypox is a zoonotic illness caused by the monkeypox virus, an Orthopoxvirus in the same genus as the variola, vaccinia, and cowpox viruses. Since the detection of the first human case in the Democratic Republic of the Congo in 1970, the disease has caused sporadic infections and outbreaks, mainly restricted to some countries in west and central Africa. In July, 2022, WHO declared monkeypox a Public Health Emergency of International Concern, on account of the unprecedented global spread of the disease outside previously endemic countries in Africa and the need for global solidarity to address this previously neglected disease. The 2022 outbreak has been primarily associated with close intimate contact (including sexual activity) and most cases have been diagnosed among men who have sex with men, who often present with novel epidemiological and clinical characteristics. In the 2022 outbreak, the incubation period ranges from 7 days to 10 days and most patients present with a systemic illness that includes fever and myalgia and a characteristic rash, with papules that evolve to vesicles, pustules, and crusts in the genital, anal, or oral regions and often involve the mucosa. Complications that require medical treatment (eg, antiviral therapy, antibacterials, and pain control) occur in up to 40% of patients and include rectal pain, odynophagia, penile oedema, and skin and anorectal abscesses. Most patients have a self-limited illness; between 1% and 13% require hospital admission (for treatment or isolation), and the case-fatality rate is less than 0·1%. A diagnosis can be made through the presence of Orthopoxvirus DNA in PCRs from lesion swabs or body fluids. Patients with severe manifestations and people at risk of severe disease (eg, immunosuppressed people) could benefit from antiviral treatment (eg, tecovirimat). The current strategy for post-exposure prophylaxis or pre-exposure prophylaxis for people at high risk is vaccination with the non-replicating modified vaccinia Ankara. Antiviral treatment and vaccines are not yet available in endemic countries in Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@article{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 = {article}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@article{nokey,

title = {Human and entomological determinants of malaria transmission in the Lihir Islands of Papua New Guinea: A cross-sectional study},

author = {Millat-Martínez, P and Katusele, M and Kasian, B and Omera, E and Jamea, E and Lorry, L (…) and Baró, B. },

doi = {10.1371/journal.pntd.0012277},

year  = {2025},

date = {2025-01-03},

urldate = {2025-01-03},

journal = {PLOS Neglected Tropical Diseases},

volume = {19},

issue = {1},

abstract = {Background

The Lihir Islands of Papua New Guinea, located in an area with high burden of malaria and hosting a large mining operation, offer a unique opportunity to study transmission. There, we investigated human and vector factors influencing malaria transmission.



Methods

In 2019, a cross-sectional study was conducted on 2,914 individuals assessing malaria prevalence through rapid diagnostic tests (RDT), microscopy, and quantitative PCR (qPCR). A logistic regression analysis identified infection-associated factors. Anopheles species distribution, biting behaviours, and sporozoite carriage were assessed through human landing catches and larval surveys.



Results

Overall malaria prevalence (any species) was 3.6% by RDT, 4.5% by microscopy, and 15.0% by qPCR. P. vivax accounted for 37.1% of infections, P. falciparum for 34.6%, P. malariae for 3.0%, P. ovale 0.2%, and mixed infections for 24.5%. Prevalence (qPCR) varied across geographic areas, from 8.5% in the mine-impacted zone (MIZ) to 27.0% in the non-MIZ. Other factors independently associated with infection risk included cohabiting with an infected individual (aOR = 1.94, 95%CI: 1.56–2.42), and residing in traditional housing (aOR = 1.65, 95%CI: 1.21–2.25). Children had double the infection risk compared to adults, and the use of long-lasting insecticidal-treated nets did not decrease risk of infection. An. punctulatus was the major vector in one of the four geographical areas; while An. farauti was predominant in the rest of them, both with an early biting behaviour but with different biting intensities by geographical area. Entomological inoculation rates ranged from 26.9 (95%CI: 12.3–45.2) infective bites per person-year in the MIZ to 441.3 (95%CI: 315.7–572.1) in the non-MIZ.



Conclusions

Malaria transmission and infection was lower in the MIZ compared to other areas. Measures focusing on at-risk groups, including vector-control and transmission interruption methods, could be taken into account by the mine and the healthcare authorities to reduce malaria burden outside the MIZ.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {A loop-mediated isothermal amplification test for yaws: a multi-country diagnostic accuracy evaluation},

author = {Handley, Becca and González-Beiras, Camila and Tchatchouang, Serges and Hugues, Kouadio Aboh and Basing, Laud Antony and Sylla, Aboubacar (…) and Marks, Michael. },

doi = {10.1016/S2214-109X(24)00324-3     },

year  = {2024},

date = {2024-11-12},

urldate = {2024-11-12},

journal = {The Lancet Global Health  },

volume = {12},

issue = {11},

pages = {e1891-e1898},

abstract = {Background: To meet the WHO target of eradicating yaws by 2030, highly sensitive and specific diagnostic tools are needed. A multiplex Treponema pallidum-Haemophilus ducreyi loop-mediated isothermal amplification (TPHD-LAMP) test holds promise as a near-patient diagnostic tool for yaws and H ducreyi. We conducted a prospective evaluation in Cameroon, Côte d'Ivoire, Ghana, and the Republic of the Congo to determine the diagnostic accuracy of the TPHD-LAMP test, as well as to assess its acceptability, feasibility, and cost.



Methods: Active case searching within schools and communities was used to locate participants with clinically suspicious laws-like lesions. Individuals with serologically confirmed active yaws provided paired lesion swabs between March, 2021, and April, 2023. For each participant, one swab was tested with the TPHD-LAMP at a local district laboratory and the other with reference quantitative PCR (qPCR) tests conducted at national reference laboratories. The primary outcome was TPHD-LAMP test sensitivity and specificity compared with qPCR. Laboratory technicians were interviewed using a multiple-choice survey to gauge acceptability and feasibility of the TPHD-LAMP test. Costs of each test were calculated.



Findings: Of 3085 individuals with at least one suspected yaws lesion, 531 (17%) were serologically confirmed. We enrolled 493 participants with seropositive yaws and a further 32 with negative serology. The sensitivity of the TPHD-LAMP test for detecting T pallidum was 63% (95% CI 56-70) and the specificity was 66% (95% CI 61-71). Sensitivity and specificity for T pallidum improved to 73% (63-82; p=0·0065) and 75% (68-80; p=0·0003), respectively, in H ducreyi-negative samples. Interviews highlighted challenges in user-friendliness and practicality of the TPHD-LAMP test. The cost of the test per sample was one third of that of qPCR, although the TPHD-LAMP test entailed higher costs to establish the assay.



Interpretation: This was the first multi-country diagnostic evaluation of a molecular test for yaws. The TPHD-LAMP testing, in its current form, falls short of the WHO target product profile criteria for yaws diagnostics. These findings highlight the importance of assessing new diagnostics in real-world conditions to ensure their suitability for programmatic use.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {An integrated active case detection and management of skin NTDs in yaws endemic health districts in Cameroon, Côte d'Ivoire and Ghana},

author = {Tchatchouang, Serges and Basing, Laud Antony and Hugues, Kouadio Aboh and Handley, Becca and Gonzalez-Beiras, Camila and Amanor, Ivy (…) and Marks, Michael. },

doi = {10.1371/journal.pntd.0011790},

year  = {2024},

date = {2024-10-04},

urldate = {2024-10-04},

journal = {PLOS Neglected Tropical Diseases},

volume = {18},

issue = {10},

abstract = {Background: Integrated approaches to mapping skin Neglected Tropical Diseases (NTDs) may be cost-effective way to guide decisions on resource mobilization. Pilot studies have been carried out, but large-scale data covering multiple countries endemic for skin NTDs are lacking. Within the LAMP4YAWS project, we collected integrated data on the burden of multiple skin NTDs.



Methods: From March 2021 to March 2023, integrated case searches for yaws alongside other skin conditions were performed in endemic health districts of yaws in Cameroon, Côte d'Ivoire, and Ghana. Integrated activities included training, social mobilization and active case detection. Initial screening involved a brief clinical examination of participants to determine if any skin conditions were suspected. Cases of skin NTDs were then referred to a health facility for appropriate management.



Results: Overall 61,080 individuals screened, 11,387 (18.6%) had skin lesions. The majority of individuals (>90%) examined were children aged 15 years old and under. The proportion of serologically confirmed yaws cases was 8.6% (18/210) in Cameroon, 6.8% (84/1232) in Côte d'Ivoire, and 26.8% (440/1643) in Ghana. Other skin conditions based on clinical examination included: scabies, Buruli ulcer, leprosy, lymphatic filariasis (lymphoedema and hydrocele), tungiasis, and fungal infections. The most common conditions were scabies and superficial fungal infections. In Cameroon, scabies and superficial fungal infections accounted for 5.1% (214/4204) and 88.7% (3730/4204) respectively, 25.2% (1285/5095) and 50.4% (2567/5095) in Côte d'Ivoire. In Ghana, 20% (419/2090) of individuals had scabies but superficial fungal infections were not routinely recorded and were reported in only 1.3% (28/2090). Other skin NTDs were less common across all three countries.



Conclusion: This study confirms that integrated screening allows simultaneous detection of multiple skin NTDs, maximising use of scarce resources.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Sequence typing of Haemophilus ducreyi isolated from patients in the Namatanai region of Papua New Guinea: Infections by Class I and Class II strain types differ in ulcer duration and resurgence of infection after azithromycin treatment},

author = {Monica Medappa and Petra Popisilova and Lucy N. John and Camila Gonzalez-Beiras and Martí Vall-Mayans and Oriol Mitjà and David Smajs},

doi = {10.1371/journal.pntd.0012398},

year  = {2024},

date = {2024-08-15},

urldate = {2024-08-15},

journal = {PLOS Neglected Tropical Diseases},

volume = {18},

issue = {8},

abstract = {Haemophilus ducreyi (HD) is an important cause of cutaneous ulcers in several endemic regions, including the Western Pacific Region, especially among children. An HD sequence typing on swab samples taken from 1,081 ulcers in the Namatanai district of Papua New Guinea, during the pilot study for treatment of yaws, has been performed using the Grant typing system. Of the 363 samples that tested positive for the 16S rDNA of HD, the dsrA sequences of 270 samples were determined. Altogether they revealed 8 HD strain types circulating in Namatanai, including seven strain types of Class I (I.3, I.4, I.5, I.9, I.10, I.11, I.12) and one strain of Class II (II.3); four Class I types (I.9, I.10, I.11, I.12) were novel. The southern region of Namatanai (Matalai Rural) was identified as the region with the lowest genotype diversity and with most infections caused by HD Class II. The middle and northern subdistricts were affected mainly by HD Class I. Analysis of patient characteristics revealed that Class II HD infections were more often represented by longer-lasting ulcers than Class I HD infections. An increase in the prevalence of the I.10 strain was found after azithromycin administration compared to the untreated population at baseline likely reflecting higher infectivity of HD Class I, and more specifically strain type I.10.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = { Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d'Ivoire},

author = {González-Beiras, Camila and Adingra, Tano and Handley, Becca and Arhinful, Daniel and Tchatchouang, Serges and Houndji, Ahouansou (…) and Marks, Michael. },

doi = {10.1371/journal.pntd.0012224},

year  = {2024},

date = {2024-06-20},

urldate = {2024-06-20},

journal = {PLOS Neglected Tropical Diseases},

volume = {18},

issue = {6},

abstract = {aws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation. In this study, conducted in three endemic countries of West Africa where yaws remains a significant public health concern (Ghana, Cameroon, and Côte d'Ivoire), we aimed to assess the knowledge, attitudes, and practices related to yaws among community members, community health workers (CHWs), and traditional healers. The study revealed variations in the perception of causes of yaws among community members: the majority or participants in Ghana attributed yaws to germs (60.2%); in Cameroon the most reported form of transmission was contact with or drinking infected water sources (44.6%); and in Côte d'Ivoire both of these answers were also the most prevalent (60.3% germs and 93.% water sources). A substantial proportion of participants in Côte d'Ivoire also associated yaws with witchcraft and divine punishment (44.8%). Only a small proportion of individuals in Ghana and Côte d'Ivoire correctly identified contact with an infected person as a form of transmission (11.9% and 20.7%, respectively) and less than half in Cameroon (42.6%), although more than 98% of all participants reported avoidance behaviours towards yaws infected people due to fear of getting infected. Most participants expressed a preference for seeking care at hospitals (49.2%, 60.6%, 86.2%) or health care professionals including doctors and nurses (58.5%, 41,5% and 17.2%) if they were diagnosed with yaws, although a quarter of participants in Côte d'Ivoire also sought support from traditional healers. The CHWs interviewed were generally well-trained on yaws causes and treatment options, although they often reported low availability of treatment and diagnostic tests for yaws. Our findings underscore the need for community education, awareness campaigns, ongoing CHW training, and improved access to yaws treatment and diagnostic resources. The data also suggest that collaboration with traditional healers, who usually hold a highly esteemed position in the society, such as giving training on yaws causes and transmission or exchanging knowledge on treatment options, could be beneficial in certain regions, particularly in Côte d'Ivoire.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients' ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes},

author = {Monica Medappa and Petra Popisilova and María Paula Madruga and Lucy N. John and Camila Gonzalez-Beiras and Grillova, Linda (…) and Smajs, David},

doi = {10.1371/journal.pntd.0011831},

year  = {2024},

date = {2024-01-02},

urldate = {2024-01-02},

journal = {PLOS Neglected Tropical Diseases},

volume = {18},

issue = {1},

abstract = {Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics. The endemic character of yaws infections and the expected exclusive reservoir of TPE in humans opened a new opportunity to start a yaws eradication campaign. We have developed a multi-locus sequence typing (MLST) scheme for TPE isolates combining the previously published (TP0548, TP0488) and new (TP0858) chromosomal loci, and we compared this typing scheme to the two previously published MLST schemes. We applied this scheme to TPE-containing clinical isolates obtained during a mass drug administration study performed in the Namatanai District of Papua New Guinea between June 2018 and December 2019. Of 1081 samples collected, 302 (28.5%) tested positive for TPE DNA, from which 255 (84.4%) were fully typed. The TPE PCR-positivity in swab samples was higher in younger patients, patients with single ulcers, first ulcer episodes, and with ulcer duration less than six months. Non-treponemal serological test positivity correlated better with PCR positivity compared to treponema-specific serological tests. The MLST revealed a low level of genetic diversity among infecting TPE isolates, represented by just three distinct genotypes (JE11, SE22, and TE13). Two previously used typing schemes revealed similar typing resolutions. Two new alleles (one in TP0858 and one in TP0136) were shown to arise by intragenomic recombination/deletion events. Compared to samples genotyped as JE11, the minor genotypes (TE13 and SE22) were more frequently detected in samples from patients with two or more ulcers and patients with higher values of specific TP serological tests. Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Prevalence and risk factors associated with Haemophilus ducreyi cutaneous ulcers in Cameroon},

author = {Ndzomo, Philippe and Tchatchouang, Serges and Tabah, Ernest and Njamsshi, Theophilus and Noah Tsanga, Mireille Victorine and Bondi, Jules Alexis (…) and Eyangoh, Sara},

doi = {10.1371/journal.pntd.0011553},

year  = {2023},

date = {2023-12-27},

journal = {PLOS Neglected Tropical Diseases},

volume = {17},

issue = {12},

abstract = {Epidemics of yaws-like cutaneous ulcers are regularly documented in children in the tropics. They occur mainly in poor and remote communities without access to health facilities. The integration of molecular tools into yaws control efforts has made it possible to describe Haemophilus ducreyi (HD) as a major cause of cutaneous ulcers. The objective of this study was to determine the prevalence of HD as cause of cutaneous ulcers, investigate its presence in asymptomatic individuals and identify associated risk factors. A cross-sectional study was conducted in yaws endemic districts of Cameroon. Participants included people presenting yaws-like ulcers and asymptomatic individuals. Swab samples were collected from each participant and tested for HD and Treponema pallidum (TP) using an established qPCR method. Additionally, demographic, habitat, proximity, and hygiene characteristics were collected using a structured questionnaire. A total of 443 individuals participated in the study, including 271 ulcer cases and 172 asymptomatic contacts. The prevalence of HD in ulcers was 30.3% (Confidence Interval (CI) 95% [24.8-35.7]) and the prevalence of asymptomatic HD carriage was 8.6% (CI95% [4.5-12.9]). TP was also detected in our sample among ulcer cases but in lower proportion (5.2% CI95% [2.5-7.8]) compared to HD. The adjusted logistic regression model showed that women were as much at risk of having HD cutaneous ulcer as men regardless of age. Physical proximity to a confirmed ulcer case was the major factor identified favouring HD transmission. HD ulcers were more likely to be present on Bantu individuals compared to Baka as well as HD colonization. These findings highlight HD as the most common cause of cutaneous ulcers in yaws-endemic communities in Cameroon. The exact implications of detecting HD on intact skin are not yet clear. Further studies are needed to understand the significance of this carriage in the spread dynamics of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Rapid Serologic Test for Diagnosis of Yaws in Patients with Suspicious Skin Ulcers},

author = {Clara Suñer and Lucy N John and Wendy Houinei and Maria Ubals and Dan Ouchi and Alemany, Andrea (…) and González-Beiras, Camila},

doi = {10.3201/eid2908.230608},

year  = {2023},

date = {2023-08-29},

urldate = {2023-08-29},

journal = {Emerging Infectious Diseases},

volume = {29},

issue = {8},

abstract = {The Chembio DPP (Dual Path Platform) Syphilis Screen & Confirm kit (https://chembio.com) is a rapid serologic test that can be used to diagnose yaws. We evaluated its capacity to detect patients with ulcers that tested PCR positive for Treponema pallidum subsp. pertenue. DPP detected 84% of ulcers that were positive by PCR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1371/journal.pntd.0011319b,

title = {Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis},

author = {Abdullah Alshehri and Yashpal S. Chhonker and Veenu Bala and Constant Edi and Catherine M. Bjerum and Koudou, Benjamin G (…) and Murry, Daryl.},

doi = {10.1371/journal.pntd.0011319},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {PLOS Neglected Tropical Diseases},

volume = {17},

number = {6},

pages = {1-17},

publisher = {Public Library of Science},

abstract = {Background Ivermectin (IVM) is a broad–spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple–drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub–Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single–oral dose in LF–infected subjects and healthy individuals. Methodology / Principal findings In this analysis, 724 samples were collected from treatment–naïve Wuchereria bancrofti–infected (n = 32) and uninfected (n = 24) adults living in Côte d’Ivoire who had received one dose of IVM as a part of triple–drug therapy. PopPK analysis was conducted using Phoenix NLME 8.3 software. The Monte Carlo simulation based on the final model was performed to simulate drug exposure among different dosing groups (200 μg/kg, 18 mg, and 36 mg). A two–compartment model with zero–order dose input into the absorption compartment with a lag time function followed by first–order absorption and linear elimination best described the IVM’s pharmacokinetic (PK) parameters. The final model identifies that the PK parameters of IVM are not affected by LF infection. Sex was a significant covariate on the peripheral volume of distribution (Vp/F, 53% lower in men than in women). IVM drug exposure shows linear pharmacokinetic behavior among the simulated dosing groups with similar drug exposure based on sex. Conclusion/Significance We have developed a PopPk model to describe and identify possible sources of the variability of IVM exposure. To our knowledge, this is the first PopPK study of IVM in patients with LF. Trial registration NCT02845713; NCT03664063},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lucy2022b,

title = {Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication},

author = {Lucy N. John and Camila G. Beiras and Wendy Houinei and Monica Medappa and Maria Sabok and Kolmau, Reman (…) and Mitjà, Oriol.},

doi = {https://doi.org/10.1056/NEJMoa2109449},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {New England Journal of Medicine},

volume = {386},

number = {1},

pages = {47-56},

abstract = {textitTreponema pallidum subspecies textitpertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed. In an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lucy2021,

title = {Safety of mass drug coadministration with ivermectin, diethylcarbamazine, albendazole, and azithromycin for the integrated treatment of neglected tropical diseases: a cluster randomized community trial},

author = {Lucy N. John and Camila Gonzalez-Beiras and Marti Vall-Mayans and Reman Kolmau and Wendy Houinei and James Wangi and Michael Marks and Mitjà, Oriol},

doi = {https://doi.org/10.1016/j.lanwpc.2021.100293},

issn = {2666-6065},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {The Lancet Regional Health – Western Pacific},

publisher = {Elsevier},

abstract = {Neglected tropical diseases control programmes run separately. For settings with more than one endemic disease, combined mass drug administration (MDA) has potential practical advantages compared with separate programmes but needs confirmation of safety. We assessed the safety of combined MDA for multiple neglected tropical diseases using ivermectin, diethylcarbamazine, albendazole (IDA) and azithromycin (AZI).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/cid/ciy343,

title = {Multiple Class I and Class II Haemophilus ducreyi Strains Cause Cutaneous Ulcers in Children on an Endemic Island},

author = {Jacob C Grant and Camila González-Beiras and Kristen M Amick and Kate R Fortney and Dharanesh Gangaiah and Humphreys, Tricia L (…) and Spinola, Stanley M.},

doi = {10.1093/cid/ciy343},

year  = {2018},

date = {2018-11-13},

urldate = {2018-11-13},

journal = {Clinical Infectious Diseases},

volume = {11},

issue = {67},

pages = {1768-1774},

abstract = {Background: Together with Treponema pallidum subspecies pertenue, Haemophilus ducreyi is a major cause of exudative cutaneous ulcers (CUs) in children. For H. ducreyi, both class I and class II strains, asymptomatic colonization, and environmental reservoirs have been found in endemic regions, but the epidemiology of this infection is unknown.



Methods: Based on published whole-genome sequences of H. ducreyi CU strains, a single-locus typing system was developed and applied to H. ducreyi-positive CU samples obtained prior to, 1 year after, and 2 years after the initiation of a mass drug administration campaign to eradicate CU on Lihir Island in Papua New Guinea. DNA from the CU samples was amplified with class I and class II dsrA-specific primers and sequenced; the samples were classified into dsrA types, which were geospatially mapped. Selection pressure analysis was performed on the dsrA sequences.



Results: Thirty-seven samples contained class I sequences, 27 contained class II sequences, and 13 contained both. There were 5 class I and 4 class II types circulating on the island; 3 types accounted for approximately 87% of the strains. The composition and geospatial distribution of the types varied little over time and there was no evidence of selection pressure.



Conclusions: Multiple strains of H. ducreyi cause CU on an endemic island and coinfections are common. In contrast to recent findings with T. pallidum pertenue, strain composition is not affected by antibiotic pressure, consistent with environmental reservoirs of H. ducreyi. Such reservoirs must be addressed to achieve eradication of H. ducreyi.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2018,

title = {Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study},

author = {Oriol Mitjà and Charmie Godornes and Wendy Houinei and August Kapa and Raymond Paru and Abel, Haina (…) and Lukehart, Sheila A.},

doi = {10.1016/S0140-6736(18)30204-6},

issn = {0140-6736},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {The Lancet},

volume = {391},

number = {10130},

pages = {1599-1607},

publisher = {Elsevier},

abstract = {Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of yaws. We assessed the long-term efficacy of the WHO strategy for yaws eradication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marks2018,

title = {Comparative efficacy of low-dose versus standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea},

author = {Michael Marks and Oriol Mitjà and Christian Bottomley and Cynthia Kwakye and Wendy Houinei and Bauri, Mathias (…) and Wanaom, Augustine.},

doi = {10.1016/S2214-109X(18)30023-8},

issn = {2214-109X},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {The Lancet Global Health},

volume = {6},

number = {4},

pages = {e401-e410},

publisher = {Elsevier},

abstract = {A dose of 30 mg/kg of azithromycin is recommended for treatment of yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of azithromycin is recommended for the elimination of trachoma as a public health problem. In some settings, these diseases are co-endemic. We aimed to determine the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for the treatment of active and latent yaws.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/cid/cix723,

title = {Single-Dose Azithromycin for the Treatment of Haemophilus ducreyi Skin Ulcers in Papua New Guinea},

author = {Camila González-Beiras and August Kapa and Marti Vall-Mayans and Raymond Paru and Sergi Gavilán and Houinei, Wendy (…) and Mitjà, Oriol. },

doi = {10.1093/cid/cix723},

year  = {2017},

date = {2017-08-16},

urldate = {2017-08-16},

journal = {Clinical Infectious Diseases},

volume = {65},

issue = {12},

pages = {2085–2090},

abstract = {Background

Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue (TP) are major causative agents of cutaneous ulcer (CU) in the tropics. Azithromycin is recommended to treat sexually transmitted HD infections and has good in vitro activity against HD strains from both genital and skin ulcers. We investigated the efficacy of oral single-dose azithromycin on HD-CU.



Methods

We conducted a community-based cohort study in Lihir Island, Papua New Guinea, from October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in diameter were eligible for this study and had collected a lesional swab for polymerase chain reaction (PCR). All participants were treated with single-dose azithromycin (30 mg/kg) and were followed up for assessment of clinical resolution. We retrospectively classified patients according to PCR results into HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU at 14 days after treatment.



Results

We obtained full outcome data from 246 patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78 (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence interval [CI], .82–.93) in the HD group, 78.4% [95% CI, .63–.89] in the TP group, and 74.4% (95% CI, .64–.83) in the PCR-negative group. If we included the participants with improved ulcers, the healing rates increased to 94.7%, 97.3%, and 89.7% respectively. HD cases classified as not healed all converted to HD-negative PCR.



Conclusions

Based upon clinical resolution and PCR conversion to HD negative, a single oral dose of azithromycin is efficacious for the treatment of HD-CU. These results have implications for the treatment of individual patients and for the use of antibiotics in public health strategies to control CU in the tropics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2017,

title = {Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study},

author = {Oriol Mitjà and Camila González-Beiras and Charmie Godornes and Reman Kolmau and Wendy Houinei and Abel, Haina (…) and Bassat, Quique.},

doi = {10.1016/S2214-109X(17)30388-1},

issn = {2214-109X},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {The Lancet Global Health},

volume = {5},

number = {12},

pages = {e1268-e1274},

publisher = {Elsevier},

abstract = {Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1371/journal.pntd.0004958,

title = {Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea},

author = {Wendy Houinei and Charmie Godornes and August Kapa and Sascha Knauf and Eric Q. Mooring and González-Beiras, Camila (…) and Mitjà, Oriol. },

doi = {10.1371/journal.pntd.0004958},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {PLOS Neglected Tropical Diseases},

volume = {11},

number = {5},

pages = {1-10},

publisher = {Public Library of Science},

abstract = {Author summary Children in rural communities of tropical countries often suffer skin ulcers that are caused by the bacteria Haemophilus ducreyi–causative agent of chancroid- and Treponema pallidum subsp. pertenue -causative agent of yaws-. The currently recommended strategy for yaws eradication is one round of mass drug administration (MDA) with azithromycin. We attempted to find reasons for the limited impact of yaws MDA on the prevalence of H. ducreyi leg ulcers by examining potential sources of infection in healthy carriers, flies, and bed linen. H. ducreyi DNA was found in skin swabs from 20% of asymptomatic children, in 9/10 flies, and 3/6 bed sheets from the houses of children with ulcers. While H. ducreyi DNA has been detected in the genital tract of asymptomatic women without genital ulcers, this is the first report of such detection on the skin of asymptomatic individuals. Importantly, skin cultures obtained from two asymptomatic children yielded viable H. ducreyi, confirming colonization and a potential reservoir of infection. If confirmed to contain viable bacteria, flies and fomites may also contribute to the continued presence of this infection after mass treatment with azithromycin. Our findings provide evidence that persistence of H. ducreyi ulcers after antibiotic MDA is due to the ubiquity of the organism in the environment. Improved hygiene and additional strategies such as repeated rounds of MDA could be able to control such a reservoir.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gonzalez2016,

title = {Epidemiology of Haemophilus ducreyi Infections},

author = {Camila González-Beiras and Michael Marks and Cheng Chen and Sally Roberts and Oriol Mitjà},

doi = {10.3201/eid2201.150425},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Emerging Infectious Diseases},

volume = {22},

number = {1},

pages = {1-8},

publisher = {CDC},

abstract = {The global epidemiology of emphHaemophilus ducreyi infections is poorly documented because of difficulties in confirming microbiological diagnoses. We evaluated published data on the proportion of genital and nongenital skin ulcers caused by emphH. ducreyi before and after introduction of syndromic management for genital ulcer disease (GUD). Before 2000, the proportion of GUD caused by emphH. ducreyi ranged from 0.0% to 69.0% (35 studies in 25 countries). After 2000, the proportion ranged from 0.0% to 15.0% (14 studies in 13 countries). In contrast, emphH. ducreyi has been recently identified as a causative agent of skin ulcers in children in the tropical regions; proportions ranged from 9.0% to 60.0% (6 studies in 4 countries). We conclude that, although there has been a sustained reduction in the proportion of GUD caused by emphH. ducreyi, this bacterium is increasingly recognized as a major cause of nongenital cutaneous ulcers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Oriol2015,

title = {Mass Treatment with Single-Dose Azithromycin for Yaws},

author = {Oriol Mitjà and Wendy Houinei and Penias Moses and August Kapa and Raymond Paru and Hays, Russell (…) and Bassat, Quique. },

doi = {10.1056/NEJMoa1408586},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {New England Journal of Medicine},

volume = {372},

number = {8},

pages = {703-710},

abstract = {Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marks2015,

title = {Challenges and key research questions for yaws eradication},

author = {Michael Marks and Oriol Mitjà and Lasse S. Vestergaard and Allan Pillay and Sascha Knauf and Chen, Cheng-Yen (…) and Asiedu, Kingsley B.},

doi = {10.1016/S1473-3099(15)00136-X},

issn = {1473-3099},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {The Lancet Infectious Diseases},

volume = {15},

number = {10},

pages = {1220-1225},

publisher = {Elsevier},

abstract = {Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that emphHaemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2015,

title = {Global epidemiology of yaws: a systematic review},

author = {Oriol Mitjà and Michael Marks and Diby J. P. Konan and Gilbert Ayelo and Camila Gonzalez-Beiras and Boua, Bernard (…) and Asiedu, Kingsley B. },

doi = {10.1016/S2214-109X(15)00011-X},

issn = {2214-109X},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {The Lancet Global Health},

volume = {3},

number = {6},

pages = {e324-e331},

publisher = {Elsevier},

abstract = {To achieve yaws eradication, the use of the new WHO strategy of initial mass treatment with azithromycin and surveillance twice a year needs to be extended everywhere the disease occurs. However, the geographic scope of the disease is unknown. We aimed to synthesise published and unpublished work to update the reported number of people with yaws at national and subnational levels and to estimate at-risk populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2014,

title = {Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study},

author = {Oriol Mitjà and Sheila A. Lukehart and Gideon Pokowas and Penias Moses and August Kapa and Godornes, Charmie (…) and Bassat, Quique. },

doi = {10.1016/S2214-109X(14)70019-1},

issn = {2214-109X},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {The Lancet Global Health},

volume = {2},

number = {4},

pages = {e235-e241},

publisher = {Elsevier},

abstract = {Skin infections with ulceration are a major health problem in countries of the south Pacific region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacific islands emphHaemophilus ducreyi as causes of skin ulceration in a yaws-endemic region. Additionally, we identified specific signs and symptoms associated with these causative agents of cutaneous ulcers and compared these findings with laboratory-based diagnoses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ayove2014,

title = {Sensitivity and specificity of a rapid point-of-care test for active yaws: a comparative study},

author = {Ayove, Telek and Houniei, Wendy and Wangnapi, Regina and Bieb, Sibauk V. and Kazadi, Walter and Luke, Lisol-Nirau (…) and Mitjà, Oriol.},

doi = {10.1016/S2214-109X(14)70231-1},

issn = {2214-109X},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {The Lancet Global Health},

volume = {2},

number = {7},

pages = {e415-e421},

publisher = {Elsevier},

abstract = {To eradicate yaws, national control programmes use the Morges strategy (initial mass treatment and biannual resurveys). The resurvey component is designed to actively detect and treat remaining yaws cases and is initiated on the basis of laboratory-supported reactive non-treponemal serology (using the rapid plasma reagin [RPR] test). Unfortunately, the RPR test is available rarely in yaws-endemic areas. We sought to assess a new point-of-care assay?the Dual Path Platform (DPP) syphilis assay, which is based on simultaneous detection of antibodies to treponemal and non-treponemal antigens?for guiding use of antibiotics for yaws eradication. A secondary goal was to ascertain at what timepoint the DPP assay line reverted to negative after treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2013,

title = {Yaws},

author = {Oriol Mitjà and Kingsley Asiedu and David Mabey},

doi = {10.1016/S0140-6736(12)62130-8},

issn = {0140-6736},

year  = {2013},

date = {2013-01-01},

journal = {The Lancet},

volume = {381},

number = {9868},

pages = {763-773},

publisher = {Elsevier},

abstract = {Yaws is an infectious disease caused by Treponema pallidum pertenue?a bacterium that closely resembles the causative agent of syphilis?and is spread by skin-to-skin contact in humid tropical regions. Yaws causes disfiguring, and sometimes painful lesions of the skin and bones. As with syphilis, clinical manifestations can be divided into three stages; however, unlike syphilis, mother-to-child transmission does not occur. A major campaign to eradicate yaws in the 1950s and 1960s, by mass treatment of affected communities with longacting, injectable penicillin, reduced the number of cases by 95% worldwide, but yaws has reappeared in recent years in Africa, Asia, and the western Pacific. In 2012, one oral dose of azithromycin was shown to be as effective as intramuscular penicillin in the treatment of the disease, and WHO launched a new initiative to eradicate yaws by 2020.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mitjà2012,

title = {Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial},

author = {Oriol Mitjà and Russell Hays and Anthony Ipai and Moses Penias and Raymond Paru and David Fagaho and Elisa Lazzari and Quique Bassat},

doi = {10.1016/S0140-6736(11)61624-3},

issn = {0140-6736},

year  = {2012},

date = {2012-01-01},

journal = {The Lancet},

volume = {379},

number = {9813},

pages = {342-347},

publisher = {Elsevier},

abstract = {Yaws is an endemic treponematosis and, as such, a neglected tropical disease?is re-emerging in children in rural, tropical areas. Oral azithromycin is effective for syphilis. We assessed the efficacy of azithromycin compared with intramuscular long-acting penicillin to treat patients with yaws.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}