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.

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.

Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953.

Physicians deliberately inoculated marginalized patients with malaria, using them as reservoirs to facilitate malarial fever therapy for syphilitic patients. The history presents ethical questions in an evolving historical context.

High prevalence of sexually transmitted infections in HIV-infected men during routine outpatient visits in the Netherlands.

BACKGROUND: In the Netherlands, no guidelines exist for routine sexually transmitted infection (STI) screening of human immunodeficiency virus (HIV)-infected men having sex with men (MSM). We assessed prevalence and factors associated with asymptomatic STI. METHODS: MSM visiting HIV outpatient clinics of academic hospitals were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and hepatitis B and C infection. Prevalence and risk factors were studied using logistic regression. RESULTS: In total, 659 MSM were included between 2007 and 2008. STI were found in 16.0% of patients, mostly anal CT and syphilis. One new hepatitis B and 3 new hepatitis C infections were identified. In multivariate analyses, any STI (syphilis, CT, or NG) was associated with patient's age below 40 years (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.3-5.0), having had sex with 2 or more sexual partners (OR 2.1, 95% CI: 1.2-3.5), the use of the same sexual toys with a sexual partner (OR 2.2, 95% CI: 1.0-4.9), and enema use before sex (OR: 2.3, 95% 1.2-4.2). Syphilis was independently associated with fisting with gloves versus no fisting (OR: 4.9, 95% CI: 1.7-13.7) and with rimming (OR: 5.0, 95% CI: 1.7-15.0). CT or NG were associated with age below 45 years (age 40-44 years: OR: 2.4, 95% CI: 1.1-5.3; age <40 years: OR: 2.4, 95% CI: 1.1-5.4), enema use before sex (OR: 2.4, 95% CI: 1.3-4.4) and drug use during sex (OR: 2.4, 95% CI: 1.4-4.0). CONCLUSIONS: High-risk sexual behavior was very common, and 16% of HIV-infected MSM in HIV care had an asymptomatic STI, mostly anal CT and syphilis. Development of STI screening guidelines is recommended.

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.

The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS: Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS: In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS: In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Failure to infect gnotobiotic colostrum-deprived, and normal piglets with Treponema pallidum (Nichols).

Normal piglets kept at 16 degrees C. and gnotobiotic piglets kept at 32 degrees C. rapidly destroyed Treponema pallidum, while gnotobiotic piglets kept at 26 degrees C. showed slightly slower clearance. No infections were established. The high body temperature of the piglets has an important influence on the survival of T. pallidum.