Repurposing clinically approved antibacterial drugs for

Treponematoses Therapy

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Trep-AB is a five-year research project funded by a European Research Council (ERC) Starting Grant. Implemented in collaboration with the University of Washington (UW), the project aims at identifying effective, alternative therapeutic options for the two most common human treponematoses: syphilis and yaws.

The Trep-AB project will achieve this by repurposing (i.e., finding new applications for) approved antibacterial drugs, to provide a smart, affordable, and effective solution to the lack of antibiotics for these conditions. The discovery of new effective antibiotics has the potential to change treatment policies worldwide.

Publications

  • Hoyos-Mallecot Y, Garcia JN, Sulleiro E, Esperalba J, Salmeron P, Zarzuela F, et al. Drassanes Exprés: a public and confidential testing service for asymptomatic STIs with same-day result notification. Sexually Transmitted Infections. 2021. [ DOI | ePrint ]

    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: 2639 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: 23.1 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.

  • Haynes AM, Giacani L, Mayans MV, Ubals M, Nieto C, Pérez-Mañá C, et al. Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study. EBioMedicine. 2021;65. [ DOI | ePrint ]

    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 in vitro and in vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis.

  • Fernández-Naval C, Arando M, Espasa M, Antón A, Fernández-Huerta M, Silgado A, et al. Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona. Future Microbiology. 2021;16(13):967--976. [ DOI | ePrint ]

    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.

  • de Vries HJC, Nori AV, Kiellberg Larsen H, Kreuter A, Padovese V, Pallawela S, et al. 2021 European Guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens. Journal of the European Academy of Dermatology and Venereology. [ DOI | ePrint ]

    Abstract This guideline intents to offer guidance on the diagnosis and management of patients with gastrointestinal symptoms and a suspected sexually transmitted cause. Proctitis is defined as an inflammatory syndrome of the anal canal and/or the rectum. Infectious proctitis can be sexually transmitted via genital–anal mucosal contact, but some also via digital contact and toys. Neisseria gonorrhoeae, Chlamydia trachomatis (including lymphogranuloma venereum), Treponema pallidum and herpes simplex virus are the most common sexually transmitted anorectal pathogens. Shigellosis can be transferred via oral–anal contact and may lead to proctocolitis or enteritis. Although most studies on these infections have concentrated on men who have sex with men (MSM), women having anal intercourse may also be at risk. A presumptive clinical diagnosis of proctitis can be made when there are symptoms and signs, and a definitive diagnosis when the results of laboratory tests are available. The symptoms of proctitis include anorectal itching, pain, tenesmus, bleeding, constipation and discharge in and around the anal canal. The majority of rectal chlamydia and gonococcal infections are asymptomatic and can only be detected by laboratory tests. Therefore, especially when there is a history of receptive anal contact, exclusion of anorectal infections is generally indicated as part of standard screening for sexually transmitted infections (STIs). Condom use does not guarantee protection from STIs, which are often spread without penile penetration. New in this updated guideline is: (i) lymphogranuloma venereum proctitis is increasingly found in HIV-negative MSM, (ii) anorectal Mycoplasma genitalium infection should be considered in patients with symptomatic proctitis after exclusion of other common causations such N. gonorrhoeae, C. trachomatis, syphilis and herpes, (iii) intestinal spirochetosis incidentally found in colonic biopsies should not be confused with syphilis, and (iv) traumatic causes of proctitis should be considered in sexually active patients.

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This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 850450).