Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study.

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).

Photograph as Skin, Skin as Wax: Indexicality and the Visualisation of Syphilis in Fin-de-Siècle France The William Bynum Prize Essay.

In early twentieth-century France, syphilis and its controversial status as a hereditary disease reigned as a chief concern for physicians and public health officials. As syphilis primarily presented visually on the surface of the skin, its study fell within the realms of both dermatologists and venereologists, who relied heavily on visual evidence in their detection, diagnosis, and treatment of the disease. Thus, in educational textbooks, atlases, and medical models, accurately reproducing the visible signposts of syphilis - the colour, texture, and patterns of primary chancres or secondary rashes - was of preeminent importance. Photography, with its potential claims to mechanical objectivity, would seem to provide the logical tool for such representations. Yet photography's relationship to syphilographie warrants further unpacking. Despite the rise of a desire for mechanical objectivity charted in the late nineteenth century, artist-produced, three-dimensional, wax-cast moulages coexisted with photographs as significant educational tools for dermatologists; at times, these models were further mediated through photographic reproduction in texts. Additionally, the rise of phototherapy complicated this relationship by fostering the clinical equation of the light-sensitive photographic plate with the patient's skin, which became the photographic record of disease and successful treatment. This paper explores these complexities to delineate a more nuanced understanding of objectivity vis-à-vis photography and syphilis. Rather than a desire to produce an unbiased image, fin-de-siècle dermatologists marshalled the photographic to exploit the verbal and visual rhetoric of objectivity, authority, and persuasion inextricably linked to culturally constructed understandings of the photograph. This rhetoric was often couched in the Peircean concept of indexicality, which physicians formulated through the language of witness, testimony, and direct connection.

Sífilis secundaria: lesiones orales como única manifestación. Informe de caso en adolescente / Secondary syphilis: oral lesions as the only physical feature: case report in an adolescent

Comunicar un caso clínico poco frecuente para contribuir al conocimiento de las características clínico-diagnósticas de las manifestaciones bucales de la sífilis y del abordaje terapéutico de esta patología. Caso clínico: una paciente femenina de 15 años de edad, sin antecedentes patológicos, fue derivada a la Cátedra de Odontología Integral Niños de la Universidad de Buenos Aires, por lesiones orales de 30 días de evolución. Clínicamente, se observaron rosáceas en filtrum, escamas en semimucosa labial, pápulas y erosiones; además, se hallaron adenopatías submaxilares bilaterales y occipitales. Se solicitaron hemograma completo, eritrosedimentación, VDRI cuantitativa y cualitativa, FTA-abs y prueba de Elisa para VIH. Tras los resultados, la paciente fue derivada a un servicio de infectología, con diagnóstico presuntivo de secundarismo sifilítico. Allí recibió tratamiento con penicilina G benzatínica 2.400.000 Ul en dosis única. Conclusión: el diagnóstico oportuno y un tratamiento precoz evitan las complicaciones serias y la diseminación de la enfermedad...

[Syphilis and pregnancy]. / Syphilis au cours de la grossesse.

Consequences of syphilis for mother, pregnancy, fetus and child are considerable, but preventable. Serological screening must be offered at the first prenatal visit, using both a treponemal (eg. TPHA) and a non treponemal (eg. VDRL or RPR) test. When the results are compatible with any type of active syphilis, treatment is required. The treatment of choice is penicillin: benzathine penicillin G, 2.4 million units intramuscular, repeated one week later, and most authors recommend a third dose if a late latent syphilis is suspected, or in case of coinfection with HIV. Women with a proven penicillin allergy can be desensitized. Alternative therapies, such as macrolids, are less well evaluated. Follow-up during and after therapy must not be neglected. In case of Jarisch-Herxheimer reaction, the mother should be managed on an inpatient basis, and the fetus carefully monitored. The VDRL should be repeated (usually every trimester), and therapy be renewed if there is not a significant decrease in titer. The fetus should be followed by serial ultrasound examinations. Finally, the child must be followed up clinically and biologically, and treated in case of congenital syphilis. The residual risk of adverse outcome is increased in case of reinfection, lack of maternal therapy or incomplete treatment, or when diagnosis and therapy are performed late in pregnancy.

Diseases of the skull in pre-Columbian South American mummies.

OBJECTIVE: The majority of paleopathological investigations focus on the study of the skull. This is because the skull is the most frequently preserved part of the human body recovered from archaeological excavations. From studying the skull, a variety of information can be obtained regarding the individual, such as sex, age, nutritional status, and other disease processes, if present. METHODS: This study represents the examination of more than 700 human skulls recovered from archaeological excavations from the Andean region of southern Peru and northern Chile and dating back more than 8000 years. RESULTS: A variety of skull abnormalities were encountered. The nonmetric variables of Huschke's foramina and palatine tori were common. Cranial deformation was observed in more than 85% of the cases. There were two cases of sagittal synostosis. Iron deficiency anemia resulting in porotic hyperostosis of the skull was evident in certain cultures. Exostoses of the external auditory canal resulting from chronic otitis was evident only among coastal populations. One skull demonstrated a periostitis consistent with Treponema infection. Trephination was encountered only in the skulls from Peru. Fifty-four cases of skull fractures were observed, half of which showed evidence of healing. Finally, only two cases of neoplastic skull lesions were encountered. CONCLUSION: The study of the human skull alone provides a large amount of information regarding the health and diseases of ancient populations.

Treponematosis and Lyme borreliosis connections: explanation for Tchefuncte disease syndromes?

A convergence of evidence from macroscopic, radiographic and histologic examination indicates that treponemal infection was present in the 16ST1 Tchefuncte Indian burial population, dated 500 B.C. to 300 A.D. Pattern and nature of lesions suggests that chronic infection induced by variants of the spirochete Treponema pallidum, causing endemic syphilis and/or yaws, resulted in third-stage osseous response. It is suggested that Tchefuncte Indians acquired partial immunity to treponemal infection by exposure to a variant of the related spirochete, Borrelia burgdorferi, the causative agent of Lyme disease. Partial immunity would help explain the relatively mild expression of the treponemal disease process in the 16ST1 skeletal population and the apparent absence of venereal syphilis. Presence of the Borrelia burgdorferi spirochete might be linked to a single incidence of juvenile rheumatoid arthritis.

[The cytoarchitectonics of hard chancre in rabbits with experimental syphilis exposed to soliusul'fon and cefamezine]. / Tsitoarkhitektonika tverdogo shankra u krolikov s éksperimental'nym sifilisom pri vozdeistvii soliusul'fonom i tsefamezinom.

Twenty rabbits were infected with Treponema pallidum suspension. Ten animals were injected with solusulfone, the rest with cefamezin. Specific features of syphilis induced by a pool of Treponemas are described, such as T. pallidum ultrastructure, formation of a specific granule, form of the agent aggression. Solusulfone treatment was associated with activation of phagocytosis, that manifested by a shift of the incomplete/complete phagocytosis ratio towards the reaction completion; however, intact T. pallidum were detectable even in 72 hrs after the drug injection. Cefamezin had no effect on the cysts and cyst-like formations at the beginning of the treatment course but these forms of the agent were already undetectable in 48 hours.

Treponema pallidum in early syphilitic lesions in humans during high-dosage penicillin therapy. An electron microscopical study.

The alterations of early syphilitic infection occuring in the course of high dosage penicillin (120 mega IU, 36 h) as clinical experimental trial has been studied both from the clinical and the electron microscopical views. By electron microscopical studies, findings revealing the localization and the status of treponemes before and during penicillin treatment could be established. Before treatment started, the majority of treponemes was of intercellular localization. In the course of treatment various forms of destruction could be differentiated. The most striking change in the host tissue after 7-8 h of penicillin therapy was an elimination of treponemes by penetrating phagocytes. 24 h after the beginning of treatment, treponemes could not be demonstrated any more. The clinical and serological findings after the high dosage penicilline will produce results comparable to those of conventional therapie.