Redefining the treponemal history through pre-Columbian genomes from Brazil.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3-6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

Acute syphilitic posterior placoid chorioretinopathy presenting as atypical multiple evanescent white dot syndrome.

BACKGROUND: This paper reports the case of a young man who presented with syphilis masquerading as multiple evanescent white dots syndrome (MEWDS), which turned out to be an acute syphilitic posterior placoid chorioretinopathy (ASPPC) during follow-up. CASE PRESENTATION: A 59-year-old healthy male consulted for a three days' history of visual impairment in both eyes. On multimodal imaging, he was diagnosed as MEWDS. Fundus fluorescein angiography (FFA) showed early peripheral bilateral granular hyperfluorescence that correlated with the yellow-white dots found on fundus exam. Indocyanine green angiography (ICGA) depicted hypofluorescent dots on late phase. Spectral-domain optical coherence tomography (SD-OCT) revealed numerous inner retinal highly reflective deposits in the outer nuclear layer and disruption of the ellipsoid zone. After initial improvement, he presented again for a sudden visual loss at 3 weeks. FFA, ICGA and SD-OCT demonstrated the same but more numerous and outer lesions suggesting an ASPPC. A full inflammatory work-up revealed highly positive titers of rapid plasma regain (RPR) and fluorescent treponemal antibody absorption (FTA-Abs), suggesting a syphilis infection. The ophthalmological manifestations dramatically improved after the patient was admitted for high-dose intravenous penicillin G 24 million per day for 2 weeks. CONCLUSION: This is the first case that reports an ocular syphilitic infection masquerading as MEWDS at presentation and that turns to be an ASPPC. Syphilis serology should be routinely done in every case of atypical MEWDS especially when unusually presented in a young healthy man, with bilateral involvement and a bad clinical evolution.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Antenatal testing for anaemia, HIV and syphilis in Indonesia - a health systems analysis of low coverage.

BACKGROUND: Adverse pregnancy outcomes can be prevented through the early detection and treatment of anaemia, HIV and syphilis during the antenatal period. Rates of testing for anaemia, HIV and syphilis among women attending antenatal services in Indonesia are low, despite its mandate in national guidelines and international policy. METHODS: Midwife-held antenatal care records for 2015 from 8 villages in 2 sub-districts within Cianjur district were reviewed, alongside the available sub-district Puskesmas (Community Health Centre) maternity and laboratory records. We conducted four focus group discussions with kaders (community health workers) (n = 16) and midwives (n = 9), and 13 semi-structured interviews with laboratory and counselling, public sector maternity and HIV management and relevant non-governmental organisation staff. Participants were recruited from village, sub-district, district and national level as relevant to role. RESULTS: We were unable to find a single recorded result of antenatal testing for HIV, syphilis or anaemia in the village (566 women) or Puskesmas records (2816 women) for 2015. Laboratory records did not specifically identify antenatal women. Participants described conducting and reporting testing in a largely ad hoc manner; relying on referral to health facilities based on clinical suspicion or separate non-maternity voluntary counselling and testing programs. Participants recognized significant systematic challenges with key differences between the more acceptable (and reportedly more often implemented) haemoglobin testing and the less acceptable (and barely implemented) HIV and syphilis testing. However, a clear need for leadership and accountability emerged as an important factor for prioritizing antenatal testing and addressing these testing gaps. CONCLUSIONS: Practical solutions such as revised registers, availability of point-of-care tests and capacity building of field staff will therefore need to be accompanied by both funding and political will to coordinate, prioritize and be accountable for testing in pregnancy.

Treponema pallidum putative novel drug target identification and validation: rethinking syphilis therapeutics with plant-derived terpenoids.

Syphilis, a slow progressive and the third most common sexually transmitted disease found worldwide, is caused by a spirochete gram negative bacteria Treponema pallidum. Emergence of antibiotic resistant T. pallidum has led to a search for novel drugs and their targets. Subtractive genomics analyses of pathogen T. pallidum and host Homo sapiens resulted in identification of 126 proteins essential for survival and viability of the pathogen. Metabolic pathway analyses of these essential proteins led to discovery of nineteen proteins distributed among six metabolic pathways unique to T. pallidum. One hundred plant-derived terpenoids, as potential therapeutic molecules against T. pallidum, were screened for their drug likeness and ADMET (absorption, distribution, metabolism, and toxicity) properties. Subsequently the resulting nine terpenoids were docked with five unique T. pallidum targets through molecular modeling approaches. Out of five targets analyzed, D-alanine:D-alanine ligase was found to be the most promising target, while terpenoid salvicine was the most potent inhibitor. A comparison of the inhibitory potential of the best docked readily available natural compound, namely pomiferin (flavonoid) with that of the best docked terpenoid salvicine, revealed that salvicine was a more potent inhibitor than that of pomiferin. To the best of our knowledge, this is the first report of a terpenoid as a potential therapeutic molecule against T. pallidum with D-alanine:D-alanine ligase as a novel target. Further studies are warranted to evaluate and explore the potential clinical ramifications of these findings in relation to syphilis that has public health importance worldwide.

Yaws, syphilis, sexuality, and the circulation of medical knowledge in the British Caribbean and the Atlantic world.

This history of the disease categories "yaws" and "syphilis" explores the interplay between European and African medical cultures in the early modern Atlantic world. The assertion made by both early modern and modern medical authorities, that yaws and syphilis are the same disease, prompts a case study of the history of disease that reflects on a variety of issues in the history of medicine: the use of ideas about contagion to demarcate racial and sexual difference at sites around the British Empire; the contrast between persistently holistic ideas about disease causation in the Black Atlantic and the growth of ontological theories of disease among Europeans and Euro-Americans; and the controversy over the African practice of yaws inoculation, which may once have been an effective treatment but was stamped out by plantation owners who viewed it as a waste of their enslaved laborers' valuable time.

Colitis and gastroparesis associated with syphilis in an HIV-infected person with an undetectable viral load.

We present a patient with fully controlled HIV disease and a normal CD4 count whose initial treatment for syphilis failed. Biopsy-proven syphilitic colitis and severe gastroparesis developed, requiring the insertion of a temporary percutaneous gastrostomy tube. The patient responded to a course of high-dose aqueous crystalline penicillin followed by doxycycline, and he completely recovered. The occurrence of failure of conventional syphilis treatment in HIV-infected patients is discussed.

A randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya.

A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.

[Indication of mycoplasmas in the synovial fluid of rheumatoid arthritis patients]. / Indikatsiia mikoplazm v sinovial'noi zhidkosti bol'nykh revmatoidnym artritom.

Specimens of synovial fluid taken from patients with rheumatoid arthritis were tested for the presence of mycoplasmas and mycoplasmic antigens. In 30% of cases the direct inoculation into cell-free media permitted the detection of mycoplasma-like agents which could not be subcultured on solid media for identification. Mycoplasmic antigens were detected in the tested material with the same frequency by means of the immunofluorescence test. The use of cell cultures made it possible to isolate and identify mycoplasmas. M. arthritidis and M. fermentans, as well as their association, were identified in the immunofluorescence test and in cell cultures.

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.