ABSTRACT
BACKGROUND: 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. METHODS: We used an in vitro culturing system of T. pallidum to perform drug susceptibility testing and applied quantitative PCR targeting the tp0574 gene to measure bacterial growth. To confirm in vivo efficacy, fifteen rabbits were infected intradermally with T. pallidum at eight sites each and randomly allocated to an experimental treatment (linezolid, moxifloxacin, clofazimine) or a control arm (benzathine penicillin G [BPG], untreated). The primary outcome was treatment efficacy defined as the time to lesion healing measured from the date of treatment start. Secondary outcomes were absence of treponemes or treponemal mRNA in injection sites, absence of seroconversion, and cerebrospinal fluid (CSF) abnormalities and negative rabbit infectivity tests (RIT). FINDINGS: Linezolid showed in vitro bactericidal activity at concentrations of 0.5 µg/mL or higher. When administered orally to experimentally infected rabbits, it induced healing of early lesions at a time similar to BPG (hazard ratio 3.84; 95% CI 2.05-7.17; p < 0.0001 compared to untreated controls). In linezolid-treated animals, dark-field microscopy and qPCR assessment showed no presence of treponemes after day 3 post-treatment start, serologic test did not convert to positive, CSF had no abnormalities, and RIT was negative. Moxifloxacin and clofazimine failed to inhibit bacterial growth in vitro and could not cure the infection in the rabbit model. INTERPRETATION: Linezolid, a low-cost oxazolidinone, has in vitro and in vivo activity against T. pallidum, with efficacy similar to BPG in treating treponemal lesions in the animal model. Our findings warrant further research to assess the efficacy of linezolid as an alternative to penicillin G to treat syphilis in human clinical trials. FUNDING: European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 850450).
Subject(s)
Linezolid/pharmacology , Treponema pallidum/drug effects , Animals , Area Under Curve , Clofazimine/pharmacology , Clofazimine/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Linezolid/therapeutic use , Male , Microbial Sensitivity Tests , Moxifloxacin/pharmacology , Moxifloxacin/therapeutic use , Penicillin G Benzathine/pharmacology , Penicillin G Benzathine/therapeutic use , ROC Curve , Rabbits , Syphilis/drug therapy , Syphilis/pathologyABSTRACT
Chancroid is a sexually acquired infection caused by Haemophilus ducreyi. The infection is characterized by one or more genital ulcers, which are soft and painful, and regional lymphadenitis, which may develop into buboes. The infection may easily be misidentified due to its rare occurrence in Europe and difficulties in detecting the causative pathogen. H. ducreyi is difficult to culture. Nucleic acid amplification tests can demonstrate the bacterium in suspected cases. Antibiotics are usually effective in curing chancroid.
Subject(s)
Chancroid , Haemophilus ducreyi/isolation & purification , Anti-Bacterial Agents/therapeutic use , Chancroid/diagnosis , Chancroid/drug therapy , Chancroid/epidemiology , Chancroid/prevention & control , Contact Tracing , Europe/epidemiology , Haemophilus ducreyi/genetics , Health Promotion , Humans , Ulcer/diagnosis , Ulcer/drug therapy , Ulcer/epidemiology , Ulcer/prevention & controlABSTRACT
INTRODUCTION: Sexually transmitted infections (STIs) and HIV are a serious global public health issue. These diseases are largely preventable, as they are directly and indirectly associated with potentially modifiable factors, including socioeconomic conditions. Sexual transmission is responsible for over 75% of new HIV infections worldwide. Moreover, commercial sex workers and their clients are two of the groups at the highest risk of acquiring and transmitting these infectious diseases, due to an extensive number of sexual encounters and the various factors related to commercial sex situations. This qualitative study aims to deepen the understanding of the risk perception of STIs and HIV and their associated factors in Nigerian commercial sex workers in the city of Barcelona. METHODS AND ANALYSIS: This is a qualitative, descriptive, interpretive study based on a social constructivist and phenomenological perspective conducted on a saturated sample of Nigerian commercial sex workers in the city of Barcelona. Data will be collected through semistructured individual and triangular group interviews. Information will be examined using a sociological discourse analysis, allowing us to understand the social and individual factors related to the risk perception of STIs and HIV in commercial sex workers. DISCUSSION: Qualitative studies are an important element in identifying individual, social and contextual factors directly or indirectly related to the health/disease process. This qualitative study will provide essential knowledge to improve health promotion, prevention strategies and effective management of STIs both for commercial sex workers and their clients. ETHICS: This study has been approved by the clinical research ethics committee (CEIC) of IDIAP Jordi Gol in Barcelona, 2012.
