A Road Map for the Global Elimination of Congenital Syphilis

Congenital syphilis is the oldest recognized congenital infection, and continues to account for extensive global perinatal morbidity and mortality today. Serious adverse pregnancy outcomes caused by maternal syphilis infection are prevented with screening early in pregnancy and prompt treatment of women testing positive. Intramuscular penicillin, an inexpensive antibiotic on the essential medicine list of nations all over the world, effectively cures infection and prevents congenital syphilis. In fact, at a cost of $11–15 per disability adjusted life year (DALY) averted, maternal syphilis screening and treatment is among the most cost-effective public health interventions in existence. Yet implementation of this basic public health intervention is sporadic in countries with highest congenital syphilis burden. We discuss the global burden of this devastating disease, current progress and ongoing challenges for its elimination in countries with highest prevalence, and next steps in ensuring a world free of preventable perinatal deaths caused by syphilis

A systematic review and meta-analysis of studies evaluating the performance and operational characteristics of dual point-of-care tests for HIV and syphilis.

BACKGROUND: Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality. OBJECTIVES: To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched seven electronic bibliographic databases from 2012 to December 2016 with no language restrictions. Search keywords included HIV, syphilis and diagnosis. REVIEW METHODS: We included studies that evaluated the operational characteristics of dual HIV/syphilis RDTs. Outcomes included diagnostic test accuracy, cost effectiveness, ease of use and interpretation and acceptability. All studies were assessed against quality criteria and assessed for risk of bias. RESULTS: Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost and the requirement of a single finger prick as important characteristics of dual RDTs. CONCLUSION: The results of this systematic review and meta-analysis can be used by policy-makers and national programme managers who are considering implementing dual RDTs for HIV and syphilis. TRIAL REGISTRATION NUMBER: PROSPERO 2016:CRD42016049168

Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study

Background: In 2007, WHO launched a global initiative for the elimination of mother-to-child transmission of syphilis (congenital syphilis). An important aspect of the initiative is strengthening surveillance to monitor progress towards elimination. In 2008, using a health systems model with country data inputs, WHO estimated that 1·4 million maternal syphilis infections caused 520 000 adverse pregnancy outcomes. To assess progress, we updated the 2008 estimates and estimated the 2012 global prevalence and cases of maternal and congenital syphilis. Methods: We used a health systems model approved by the Child Health Epidemiology Reference Group. WHO and UN databases provided inputs on livebirths, antenatal care coverage, and syphilis testing, seropositivity, and treatment in antenatal care. For 2012 estimates, we used data collected between 2009 and 2012. We updated the 2008 estimates using data collected between 2000 and 2008, compared these with 2012 estimates using data collected between 2009 and 2012, and performed subanalyses to validate results. Findings: In 2012, an estimated 930 000 maternal syphilis infections caused 350 000 adverse pregnancy outcomes including 143 000 early fetal deaths and stillbirths, 62 000 neonatal deaths, 44 000 preterm or low weight births, and 102 000 infected infants worldwide. Nearly 80% of adverse outcomes (274 000) occurred in women who received antenatal care at least once. Comparing the updated 2008 estimates with the 2012 estimates, maternal syphilis decreased by 38% (from 1 488 394 cases in 2008 to 927 936 cases in 2012) and congenital syphilis decreased by 39% (from 576 784 to 350 915). India represented 65% of the decrease. Analysis excluding India still showed an 18% decrease in maternal and congenital cases of syphilis worldwide. Interpretation: Maternal and congenital syphilis decreased worldwide from 2008 to 2012, which suggests progress towards the elimination of mother-to-child transmission of syphilis. Nonetheless, maternal syphilis caused substantial adverse pregnancy outcomes, even in women receiving antenatal care. Improved access to quality antenatal care, including syphilis testing and treatment, and robust data are all important for achieving the elimination of mother-to child transmission of syphilis. Funding: The UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction in WHO, and the US Centers for Disease Control and Prevention

Male Circumcision for Prevention of HIV Transmission: What the New Data Mean for HIV Prevention in the United States

Recent clinical trials in Africa found that male circumcision reduces the risk of acquiring HIV from heterosexual sex--what are the implications of these studies for the United States

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. METHODS: PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. FINDINGS: Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). CONCLUSION: Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women

Congenital syphilis: trends in mortality and morbidity in the United States, 1999 through 2013

BACKGROUND: Congenital syphilis (CS) results when an infected pregnant mother transmits syphilis to her unborn child prior to or at delivery. The severity of infection can range from a delivery at term without signs of infection to stillbirth or death after delivery. OBJECTIVE: We sought to describe CS morbidity and mortality during 1999 through 2013. STUDY DESIGN: National CS case data reported to Centers for Disease Control and Prevention during 1999 through 2013 were analyzed. Cases were classified as dead (stillbirths and deaths up to 12 months after delivery), morbid (cases with strong [physical, radiographic, and/or nonserologic laboratory] evidence of CS), and nonmorbid (cases with a normal physical examination reported, without strong evidence of infection). Annual rates of these cases were calculated. Cases were compared using selected maternal and infant criteria. RESULTS: During 1999 through 2013, 6383 cases of CS were reported: 6.5% dead, 33.6% morbid, 53.9% nonmorbid, and 5.9% unknown morbidity; 81.8% of dead cases were stillbirths. Rates of dead, morbid, and nonmorbid cases all decreased over this time period, but the overall proportions that were dead ormorbid cases did not significantly change. The overall case fatality ratio during 1999 through 2013 was 6.5%. Among cases of CS, maternal race/ethnicity was not associated with increased morbidity or death, although most cases (83%) occurred among black or Hispanic mothers. No or inadequate treatment for maternal syphilis, \u3c10 prenatal visits, and maternal nontreponemal titer \u3e1:8 increased the likelihood of a dead case; risk of a dead case increased with maternal nontreponemal titer (x2 for trend P \u3c .001). Infants with CS born alive at \u3c28 weeks’ gestation (relative risk, 107.4; P\u3c .001) or born weighing\u3c1500 g (relative risk, 43.9; P \u3c .001) were at greatly increased risk of death. CONCLUSION: CS remains an important preventable cause of perinatal morbidity and mortality, with comparable case fatality ratios during 1999 through 2013 (6.5%) and 1992 through 1998 (6.4%). Detection and treatment of syphilis early during pregnancy remain crucial to reducing CS morbidity and mortality

Toward global prevention of sexually transmitted infections (STIs): The need for STI vaccines.

An estimated 499 million curable sexually transmitted infections (STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In addition, well over 500 million people are estimated to have a viral STI such as herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in time. STIs result in a large global burden of sexual, reproductive, and maternal-child health consequences, including genital symptoms, pregnancy complications, cancer, infertility, and enhanced HIV transmission, as well as important psychosocial consequences and financial costs. STI control strategies based primarily on behavioral primary prevention and STI case management have had clear successes, but gains have not been universal. Current STI control is hampered or threatened by several behavioral, biological, and implementation challenges, including a large proportion of asymptomatic infections, lack of feasible diagnostic tests globally, antimicrobial resistance, repeat infections, and barriers to intervention access, availability, and scale-up. Vaccines against HPV and hepatitis B virus offer a new paradigm for STI control. Challenges to existing STI prevention efforts provide important reasons for working toward additional STI vaccines. We summarize the global epidemiology of STIs and STI-associated complications, examine challenges to existing STI prevention efforts, and discuss the need for new STI vaccines for future prevention efforts