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Concept: Syphilis


Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs) averted.

Concepts: Pharmacoeconomics, Sahara, Southern Africa, Syphilis, North Africa, Malaria, Sub-Saharan Africa, Africa


Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic.

Concepts: Anal sex, Syphilis, Immune system, Epidemiology, Antiretroviral drug, Chlamydia infection, AIDS, HIV


In 2015, the rate of reported primary and secondary syphilis in the United States was 7.5 cases per 100,000 population, nearly four times the previous lowest documented rate of 2.1 in 2000 (1). In 2015, 81.7% of male primary and secondary syphilis cases with information on the sex of the sex partner were among gay, bisexual, and other men who have sex with men (collectively referred to as MSM) (1). These data suggest a disproportionate incidence of disease among MSM. However, attempts to quantify this disparity have been hindered by limited data on the size of the MSM population at the state level. To produce the first estimates of state-specific rates of primary and secondary syphilis among MSM, CDC used MSM population estimates based on a new methodology (2) and primary and secondary syphilis case counts reported in 2015 to the National Notifiable Diseases Surveillance System. Among 44 states reporting information on the sex of sex partners for ≥70% of male cases, the overall rate of primary and secondary syphilis among all men (aged ≥18 years) in the United States in 2015 was 17.5 per 100,000, compared with 309.0 among MSM and 2.9 among men who reported sex with women only. The overall rate of primary and secondary syphilis among MSM was 106.0 times the rate among men who have sex with women only and 167.5 times the rate among women.* These data highlight the disproportionate impact of syphilis among MSM and underscore the need for innovative and targeted syphilis prevention measures at the state and local level, especially among MSM. It is important that health care providers recognize the signs and symptoms of syphilis, screen sexually active MSM for syphilis at least annually, and provide timely treatment according to national sexually transmitted diseases treatment guidelines (3).

Concepts: Sexual intercourse, Syphilis, Oral sex, United States, Human sexuality, Sexually transmitted disease, Human sexual behavior


Clinical and experimental studies have shown that estradiol (E2) confers protection against HIV and other sexually transmitted infections. Here, we investigated the underlying mechanism. Better protection in E2-treated mice, immunized against genital HSV-2, coincided with earlier recruitment and higher proportions of Th1 and Th17 effector cells in the vagina post-challenge, compared to placebo-treated controls. Vaginal APCs isolated from E2-treated mice induced 10-fold higher Th17 and Th1 responses, compared to APCs from progesterone-treated, placebo-treated, and estradiol-receptor knockout mice in APC-T cell co-cultures. CD11c+ DCs in the vagina were the predominant APC population responsible for priming these Th17 responses, and a potent source of IL-6 and IL-1β, important factors for Th17 differentiation. Th17 responses were abrogated in APC-T cell co-cultures containing IL-1β KO, but not IL-6 KO vaginal DCs, showing that IL-1β is a critical factor for Th17 induction in the genital tract. E2 treatment in vivo directly induced high expression of IL-1β in vaginal DCs, and addition of IL-1β restored Th17 induction by IL-1β KO APCs in co-cultures. Finally, we examined the role of IL-17 in anti-HSV-2 memory T cell responses. IL-17 KO mice were more susceptible to intravaginal HSV-2 challenge, compared to WT controls, and vaginal DCs from these mice were defective at priming efficient Th1 responses in vitro, indicating that IL-17 is important for the generation of efficient anti-viral memory responses. We conclude that the genital mucosa has a unique microenvironment whereby E2 enhances CD4+ T cell anti-viral immunity by priming vaginal DCs to induce Th17 responses through an IL-1-dependent pathway.

Concepts: B cell, Human sexuality, AIDS, Syphilis, Immune system, Chlamydia infection, T cells, Sexual intercourse


Background Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. Methods We performed repeated clinical surveys for active yaws, serologic surveys for latent yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious yaws in the entire population and the prevalence of latent yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. Results At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P<0.001). The prevalence of high-titer latent yaws among children was reduced from 18.3% to 6.5% (difference, 11.8 percentage points; P<0.001) with a near-absence of high-titer seroreactivity in children 1 to 5 years of age. Adverse events identified within 1 week after administration of the medication occurred in approximately 17% of the participants, included nausea, diarrhea, and vomiting, and were mild in severity. No evidence of emergence of resistance to macrolides against Treponema pallidum subspecies pertenue was seen. Conclusions The prevalence of active and latent yaws infection fell rapidly and substantially 12 months after high-coverage mass treatment with azithromycin, with the reduction perhaps aided by subsequent activities to identify and treat new cases of yaws. Our results support the WHO strategy for the eradication of yaws. (Funded by Newcrest Mining and International SOS; YESA-13 number, NCT01955252 .).

Concepts: World Health Organization, Infectious disease, Scientific method, Azithromycin, Malaria, Papua New Guinea, Syphilis, Clinical trial


The population of Sikkim is a unique blend of multi-tribal and metropolitan culture. However, till date, no data regarding prevalence of sexually transmitted diseases (henceforth abbreviated as STDs) among this population is available and hence requires attention. Hence the objective is to determine the prevalence of STDs in Sikkim and to describe associated risk factors. A cross-sectional study involving ‘Questionnaire-based anonymous feedback system’ was followed to collect data from 2,000 individuals across the society. The four most common STDs, gonorrhea, syphilis, chlamydia and HIV, were considered for the study. Total 69 (3.6 %) cases of STDs were found in 1,918 individuals was affected by at least one of the STDs, out of which 43 were males and 26 were females. Cases of gonorrhea, syphilis, chlamydiasis and HIV were 25, 22, 4 and 18 respectively. Out of total 69 cases of STDs, 20 individuals were also suffering from some kind of hepatitis. Addictions like alcoholism, smoking and drugs were also found in significant number, with 1,019 (>50 %) individuals with at least one of these addictions. Relative risk analysis indicates that gender-wise females are more vulnerable to STDs than males. The number of partners, addictions, especially alcohol and drug abuse, also contribute to STD cases. STDs act as a significant risk factor in transmitting some of the types of hepatitis. In such cases, females are more vulnerable than males. The results suggest that new community health programs are essential for both, HIV and non-HIV STDs in Sikkim.

Concepts: Syphilis, Drug addiction, Human sexual behavior, Sexually transmitted diseases and infections, Chlamydia infection, Oral sex, Sexually transmitted disease, Epidemiology


The aim of this study was to investigate clinical features and outcomes of children treated for congenital syphilis (CS).

Concepts: Syphilis


BACKGROUND: Serologic tests are widely used for the diagnosis of syphilis. However, conventional methods require well-trained technicians to produce reliable results. We compared automated nontreponemal and treponemal tests with conventional methods. METHODS: The HiSens Auto Rapid Plasma Reagin (AutoRPR) and Treponema Pallidum Particle Agglutination (AutoTPPA) tests, which utilize latex turbidimetric immunoassay, were assessed. A total of 504 sera were assayed by AutoRPR, AutoTPPA, conventional VDRL and FTA-ABS. Among them, 250 samples were also tested by conventional TPPA. RESULTS: The concordance rate between the results of VDRL and AutoRPR was 67.5%, and 164 discrepant cases were all VDRL reactive but AutoRPR negative. In the 164 cases, 133 showed FTA-ABS reactivity. Medical records of 106 among the 133 cases were reviewed, and 82 among 106 specimens were found to be collected from patients already treated for syphilis. The concordance rate between the results of AutoTPPA and FTA-ABS was 97.8%. The results of conventional TPPA and AutoTPPA for 250 samples were concordant in 241 cases (96.4%). AutoRPR showed higher specificity than that of VDRL, while VDRL demonstrated higher sensitivity than that of AutoRPR regardless of whether the patients had been already treated for syphilis or not. Both FTA-ABS and AutoTPPA showed high sensitivities and specificities greater than 98.0%. CONCLUSIONS: Automated RPR and TPPA tests could be alternatives to conventional syphilis tests, and AutoRPR would be particularly suitable in treatment monitoring, since results by AutoRPR in cases after treatment became negative more rapidly than by VDRL.

Concepts: Spirochaete, Sensitivity and specificity, FTA-ABS, Rapid plasma reagin, Treponema, Blood tests, Treponema pallidum, Syphilis


Benzathine penicillin G (BPG) is the only recommended treatment to prevent mother-to-child transmission of syphilis. Due to recent reports of country-level shortages of BPG, an evaluation was undertaken to quantify countries that have experienced shortages in the past 2 years and to describe factors contributing to these shortages.

Concepts: Prevention, Beta-lactam antibiotics, Benzylpenicillin, Benzathine benzylpenicillin, Syphilis, Penicillin


The growing shale gas (“fracking”) industry depends on a mobile workforce, whose influx could have social impacts on host communities. Sexually transmitted infections (STIs) can increase through sexual mixing patterns associated with labor migration. No prior studies have quantified the relationship between shale gas activity and rates of three reportable STIs: chlamydia, gonorrhea, and syphilis.

Concepts: Treponema pallidum, Neisseria gonorrhoeae, Oral sex, Syphilis, Sexually transmitted diseases and infections, Human sexual behavior, Chlamydia infection, Sexually transmitted disease