BACKGROUND: In the absence of a vaccine or pharmacological treatment, prevention and control of Guinea worm disease is dependent on timely identification and containment of cases to interrupt transmission. The Chad Guinea Worm Eradication Program (CGWEP) surveillance system detects and monitors Guinea worm disease in both humans and animals. Although Guinea worm cases in humans has declined, the discovery of canine infections in dogs in Chad has posed a significant challenge to eradication efforts. A foundational information system that supports the surveillance activities with modern data management practices is needed to support continued program efficacy. METHODS: We sought to assess the current CGWEP surveillance and information system to identify gaps and redundancies and propose system improvements. We reviewed documentation, consulted with subject matter experts and stakeholders, inventoried datasets to map data elements and information flow, and mapped data management processes. We used the Information Value Cycle (IVC) and Data-Information System-Context (DISC) frameworks to help understand the information generated and identify gaps. RESULTS: Findings from this study identified areas for improvement, including the need for consolidation of forms that capture the same demographic variables, which could be accomplished with an electronic data capture system. Further, the mental models (conceptual frameworks) IVC and DISC highlighted the need for more detailed, standardized workflows specifically related to information management. CONCLUSIONS: Based on these findings, we proposed a four-phased roadmap for centralizing data systems and transitioning to an electronic data capture system. These included: development of a data governance plan, transition to electronic data entry and centralized data storage, transition to a relational database, and cloud-based integration. The method and outcome of this assessment could be used by other neglected tropical disease programs looking to transition to modern electronic data capture systems.

The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections are likely. Both malaria and parasitic NTDs can alter immunologic responses to other infectious agents. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with malaria parasites and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age-groups. Enhancing surveillance platforms could provide signals that indicate whether malaria, NTDs, and COVID-19 are syndemics (synergistic epidemics). Based on the prevalence of malaria and NTDs in specific localities, efforts to characterize COVID-19 in LMICs could be expanded by adding testing for malaria and NTDs. Such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of COVID-19 in LMICs and potentially helping to mitigate its impact.

Background: Countdown to 2030 (CD2030) tracks progress in the 81 countries that account for more than 90% of under-five child deaths and 95% of maternal deaths in the world. In 2017, CD2030 identified syphilis screening and treatment during antenatal care (ANC) as priority indicators for monitoring. Methods: Country-reported data in the UNAIDS Global AIDS Monitoring System (GAM) system were used to evaluate four key syphilis indicators from CD2030 countries: (1) maternal syphilis screening and (2) treatment coverage during ANC, (3) syphilis seroprevalence among ANC attendees, and (4) national congenital syphilis (CS) case rates. A cascade analysis for CD2030 countries with coverage data for the number of women attending at least 4 antenatal care visits (ANC4), syphilis testing, seroprevalence and treatment was performed to estimate the number of CS cases that were attributable to missed opportunities for syphilis screening and treatment during antenatal care. Results: Of 81 countries, 52 (64%) reported one or more values for CS indicators into the GAM system during 2016-2017; only 53 (65%) had maternal syphilis testing coverage, 41 (51%) had screening positivity, and 40 (49%) had treatment coverage. CS case rates were reported by 13 (16%) countries. During 2016-2017, four countries reported syphilis screening and treatment coverage of >/=95% consistent with World Health Organization (WHO) targets. Sufficient data were available for 40 (49%) of countries to construct a cascade for data years 2016 and 2017. Syphilis screening and treatment service gaps within ANC4 resulted in an estimated total of 103 648 adverse birth outcomes with 41 858 of these occurring as stillbirths among women attending ANC4 (n = 31 914 408). Women not in ANC4 (n = 25 619 784) contributed an additional 67 348 estimated adverse birth outcomes with 27 198 of these occurring as stillbirths for a total of 69 056 preventable stillbirths attributable to syphilis in these 40 countries. Conclusion: These data and findings can serve as an initial baseline evaluation of antenatal syphilis surveillance and service coverage and can be used to guide improvement of delivery and monitoring of syphilis screening and treatment in ANC for these priority countries.

Fertility challenges are a personal and important part of a woman's reproductive health and are associated with health and lifestyle factors. Limited data exist on infertility among women in Palau. We describe the lifetime prevalence of self-reported infertility in a nationally representative sample of women in Palau and investigate the association between tobacco and/or betel nut use and infertility. During May-December 2016, a population-based survey of noncommunicable diseases was conducted in Palau using a geographically stratified random sample of households (N=2409). Men and women >/=18 years of age were chosen randomly from each selected household. The prevalence of a self-reported lifetime episode of infertility (having tried unsuccessfully to become pregnant for >/=12 months) was evaluated among 874 women aged >/=18 years by key health and lifestyle factors. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated. Of 315 women who ever tried to become pregnant, 39.7% (95% CI: 34.2%, 45.3%) reported a lifetime episode of infertility. Prevalence was higher in women of Palauan vs other ethnicity (PR=1.6, 95% CI: 1.1, 2.3), those who self-reported poor/not good vs. excellent/ very good health status (PR=2.1, 95% CI: 1.4, 3.3), and those with a body mass index (BMI) >/=30 vs <30 (PR=1.7, 95% CI: 1.3, 2.2). Adjusted models showed that tobacco and/or betel nut users were almost twice as likely to report infertility versus non-users (PR=1.8, 95% CI: 1.3, 2.5). More research is needed to understand the infertility experiences of women in Palau and to promote lifestyle factors contributing to optimal reproductive health.

Guidelines can help healthcare practitioners manage syphilis in pregnancy and prevent perinatal death or disability. We conducted systematic reviews to locate guidance documents describing management of syphilis in pregnancy, 2003-2017. We compared country and regional guidelines with current World Health Organization (WHO) guidelines. We found 64 guidelines with recommendations on management of syphilis in pregnancy representing 128 of the 195 WHO member countries, including the two WHO guidelines published in 2016 and 2017. Of the 62 guidelines, 16 were for countries in Africa, 21 for the Americas, two for Eastern Mediterranean, six for Europe and 17 for Asia or the Pacific. Fifty-seven (92%) guidelines recommended universal syphilis screening in pregnancy, of which 46 (81%) recommended testing at the first antenatal care visit. Also, 46 (81%) recommended repeat testing including 21 guidelines recommended this during the third pregnancy trimester and/or at delivery. Fifty-nine (95%) guidelines recommended benzathine penicillin G (BPG) as the first-line therapy for syphilis in pregnancy, consistent with WHO guidelines. Alternative regimens to BPG were listed in 42 (68%) guidelines, primarily from Africa and Asia; only 20 specified that non-penicillin regimens are not proven-effective in treating the fetus. We identified guidance recommending use of injectable penicillin in exposed infants for 112 countries. Most guidelines recommended universal syphilis testing for pregnant women, repeat testing for high-risk women and treatment of infected women with BPG; but several did not. Updating guidance on syphilis testing and treatment in pregnancy to reflect global norms could prevent congenital syphilis and save newborn lives.

In this issue of Sexually Transmitted Diseases, Arima et al.1 report on a rapid and large increase in heterosexual syphilis in Japan, with an especially concerning rate of rise among young women of reproductive age. As is true in many industrialized countries, Japan has experienced a marked upsurge in syphilis over the past 2 decades, and national surveillance since 2012 has found an increasing proportion of primary and secondary (P&S)—that is, incident—syphilis cases each year demonstrated by a 4-fold increase in case rates, from 0.7 per 100,000 in 2012 to 3.6 per 100,000 in 2016. However, unlike most high-income countries where most P&S syphilis cases are in men who have sex with men (MSM), P&S cases in Japan are most frequently reported among men who self-report only having sex with women (MSW; 48.6% of cases), followed by women (23.2%) and MSM (22.2%). On the surface, this might suggest underreporting of male homosexual contact. However, the relatively modest increase in syphilis case rates among MSM, compared with the concurrent and similarly steep rises in case rates among both MSW and women beginning in 20131 (See Arima et al, Figs. 1A, B), suggests that heterosexual syphilis is indeed on the rise in Japan.

OBJECTIVES: The WHO recommends pregnant women receive both HIV and syphilis testing at their first antenatal care visit, as untreated maternal infections can lead to severe, adverse pregnancy outcomes. One strategy for increasing testing for both HIV and syphilis is the use of point-of-care (rapid) diagnostic tests that are simple, proven effective and inexpensive. In Malawi, pregnant women routinely receive HIV testing, but only 10% are tested for syphilis at their first antenatal care visit. This evaluation explores stakeholder perceptions of a novel, dual HIV/syphilis rapid diagnostic test and potential barriers to national scale-up of the dual test in Malawi. METHODS: During June and July 2015, we conducted 15 semistructured interviews with 25 healthcare workers, laboratorians, Ministry of Health leaders and partner agency representatives working in prevention of mother-to-child transmission in Malawi. We asked stakeholders about the importance of a dual rapid diagnostic test, concerns using and procuring the dual test and recommendations for national expansion. RESULTS: Stakeholders viewed the test favourably, citing the importance of a dual rapid test in preventing missed opportunities for syphilis diagnosis and treatment, improving infant outcomes and increasing syphilis testing coverage. Primary technical concerns were about the additional procedural steps needed to perform the test, the possibility that testers may not adhere to required waiting times before interpreting results and difficulty reading and interpreting test results. Stakeholders thought national scale-up would require demonstration of cost-savings, uniform coordination, revisions to testing guidelines and algorithms, training of testers and a reliable supply chain. CONCLUSIONS: Stakeholders largely support implementation of a dual HIV/syphilis rapid diagnostic test as a feasible alternative to current antenatal testing. Scale-up will require addressing perceived barriers; negotiating changes to existing algorithms and guidelines; and Ministry of Health approval and funding to support training of staff and procurement of supplies.

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.

As the global community moves forward in implementing the 2030 Agenda for Sustainable Development, it is important that we learn from past challenges, especially those related to effectively reaching the people who are furthest behind. | | We greatly appreciated the commentary by Drs. Wu and Hawkes (1) on our article on the Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study (2) and fully agree that political will is instrumental in achieving dual elimination of mother-to-child transmission (MTCT) of HIV and syphilis. Our colleagues remarked on the “upsurge in global and national interest in controlling MTCT of syphilis that was spurred by its close alignment with the similar global goal of eliminating MTCT of HIV” (1). This interest and alignment was directly linked to evidence of continued congenital syphilis burden and the ability of countries to measure progress toward elimination. As is described in their commentary, inclusion of three core indicators into the Global AIDS Response Progress Reporting (GARPR) database in 2008 allowed, for the first time, measurement of outcomes and monitoring of national and regional progress in eliminating MTCT of syphilis, as has been done for many years in eliminating MTCT of HIV (2,3). That body of evidence, based upon country-reported data, allowed (quoting Wu and Hawkes) “accountability if national governments deem the global commitment as legitimate and comply with it” (1,4).

Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual exposure or via vertical transmission during pregnancy. T. pallidum is renowned for its invasiveness and immune-evasiveness; its clinical manifestations result from local inflammatory responses to replicating spirochaetes and often imitate those of other diseases. The spirochaete has a long latent period during which individuals have no signs or symptoms but can remain infectious. Despite the availability of simple diagnostic tests and the effectiveness of treatment with a single dose of long-acting penicillin, syphilis is re-emerging as a global public health problem, particularly among men who have sex with men (MSM) in high-income and middle-income countries. Syphilis also causes several hundred thousand stillbirths and neonatal deaths every year in developing nations. Although several low-income countries have achieved WHO targets for the elimination of congenital syphilis, an alarming increase in the prevalence of syphilis in HIV-infected MSM serves as a strong reminder of the tenacity of T. pallidum as a pathogen. Strong advocacy and community involvement are needed to ensure that syphilis is given a high priority on the global health agenda. More investment is needed in research on the interaction between HIV and syphilis in MSM as well as into improved diagnostics, a better test of cure, intensified public health measures and, ultimately, a vaccine.

OBJECTIVE: To present the findings of the Pan American Health Organization's 2014 survey on syphilis testing policies and practices in the Americas. METHODS: Representatives of national/regional reference and large, lower-level laboratories from 35 member-states were invited to participate. A semi-structured, electronically administered questionnaire collected data on syphilis tests, algorithms, equipment/commodities, challenges faced, and basic quality assurance (QA) strategies employed (i.e., daily controls, standard operating procedures, technician training, participating in external QA programs, on-site evaluations). RESULTS: The 69 participating laboratories from 30 (86%) member-states included 41 (59%) national/regio-nal reference and 28 (41%) lower-level laboratories. Common syphilis tests conducted were the rapid plasma reagin (RPR) (62% of surveyed laboratories), Venereal Disease Research Laboratory (VDRL) (54%), Fluorescent Treponemal Antibody Absorption (FTA-Abs) (41%) and Treponemal pallidum Hemagglutination Assay (TP-HA) (32%). Only three facilities reported using direct detection methods, and 28 (41% overall, 32% of lower-level facilities) used rapid tests. Most laboratories (62%) used only traditional testing algorithms (non-treponemal screening and treponemal confirmatory testing); however, 12% used only a reverse sequence algorithm (treponemal test first), and 14% employed both algorithms. Another 9 (12%) laboratories conducted only one type of serologic test. Although most reference (97%) and lower-level (89%) laboratories used at least one QA strategy, only 16% reported using all five basic strategies. Commonly reported challenges were stock-outs of essential reagents or commodities (46%), limited staff training (73%), and insufficient equipment (39%). CONCLUSIONS: Many reference and clinical laboratories in the Americas face challenges in conducting appropriate syphilis testing and in ensuring quality of testing. This article is protected by copyright. All rights reserved.

Prenatal screening and treatment for sexually transmitted infections (STIs) can prevent adverse perinatal outcomes. In Guam, the largest of the three U.S. territories in the Pacific, primary and secondary syphilis rates among women increased 473%, from 1.1 to 6.3 per 100,000 during 2009-2013 (1). In 2013, the first congenital syphilis case after no cases since 2008 was reported (1,2). Little is known about STI screening coverage and factors associated with inadequate screening among pregnant women in Guam. This study evaluated the prevalence of screening for syphilis, human immunodeficiency virus (HIV), chlamydia, and gonorrhea, and examined correlates of inadequate screening among pregnant women in Guam. Data came from the medical records of a randomly selected sample of mothers with live births in 2014 at a large public hospital. Bivariate analyses and multivariable models using Poisson regression were conducted to determine factors associated with inadequate screening for syphilis and other STIs. Although most (93.5%) women received syphilis screening during pregnancy, 26.8% were not screened sufficiently early to prevent adverse pregnancy outcomes. Many women were not screened for HIV infection (31.1%), chlamydia (25.3%), or gonorrhea (25.7%). Prenatal care and insurance were important factors affecting STI screening during pregnancy. Prenatal care providers play an important role in preventing congenital infections. Policies and programs increasing STI and HIV services for pregnant women and improved access to and use of prenatal care are essential for promoting healthy mothers and infants.

A qualitative inquiry was used to assess if incentives consisting of a hygiene kit, protein-fortified flour, and delivery kit reduced barriers to antenatal care and delivery services in Nyanza Province, Kenya. We conducted 40 interviews (baseline: five nurses, six mothers, one focus group of five mothers; follow-up: nine nurses, 19 mothers) to assess perceptions of these services. Mothers and nurses identified poor quality of care, fear of HIV diagnosis and stigma, inadequate transport, and cost of care as barriers. Nurses believed incentives encouraged women to use services; mothers described wanting good birth outcomes as their motivation. While barriers to care did not change during the study, incentives may have increased service use. These findings suggest that structural improvements-upgraded infrastructure, adequate staffing, improved treatment of women by nurses, low or no-cost services, and provision of transport-could increase satisfaction with and use of services, improving maternal and infant health.

The World Health Organization (WHO) estimates that each year 150,000 [110,000–190,000] infants are born with human immunodeficiency virus (HIV)1 and 350,000 perinatal deaths are caused by untreated maternal syphilis at the global level.2 Results from HIV clinical trials demonstrated effectiveness of antiretroviral therapy for prevention of HIV transmission from mother to child.3,4 However, the goal of elimination of mother-to-child transmission (EMTCT) of HIV remained largely aspirational until the adoption of the HIV elimination target by the Americas region in 20105 and the launch of the Global Plan for EMTCT of HIV in 2011.6 | An effective intervention against congenital syphilis—early serologic detection of infection in women before or during pregnancy, and treatment of syphilis-infected women with parenteral penicillin—has been available for 70 years.7 However, until recently, syphilis testing in antenatal care (ANC) remained limited in countries with constrained laboratory capacity. In 2007, WHO launched a strategy for the elimination of congenital syphilis as a public health problem.8 Congenital syphilis elimination had already been established as a priority in the Americas a decade before the launch of the global strategy.9

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.

BACKGROUND: Congenital syphilis continues to be a preventable cause of global stillbirth and neonatal morbidity and mortality. Shortages of injectable penicillin, the only recommended treatment for pregnant women and infants with syphilis, have been reported by high-morbidity countries. We sought to estimate current and projected annual needs for benzathine penicillin in antenatal care settings for 30 high morbidity countries that account for approximately 33% of the global burden of congenital syphilis. METHODS: Proportions of antenatal care attendance, syphilis screening coverage in pregnancy, syphilis prevalence among pregnant women, and adverse pregnancy outcomes due to untreated maternal syphilis reported to WHO were applied to 2012 birth estimates for 30 high syphilis burden countries to estimate current and projected benzathine penicillin need for prevention of congenital syphilis. RESULTS: Using current antenatal care syphilis screening coverage and seroprevalence, we estimated the total number of women requiring treatment with at least one injection of 2.4 MU of benzathine penicillin in these 30 countries to be 351,016. Syphilis screening coverage at or above 95% for all 30 countries would increase the number of women requiring treatment with benzathine penicillin to 712,030. Based on WHO management guidelines, 351,016 doses of weight-based benzathine penicillin would also be needed for the live-born infants of mothers who test positive and are treated for syphilis in pregnancy. Assuming availability of penicillin and provision of treatment for all mothers diagnosed with syphilis, an estimated 95,938 adverse birth outcomes overall would be prevented including 37,822 stillbirths, 15,814 neonatal deaths, and 34,088 other congenital syphilis cases. CONCLUSION: Penicillin need for maternal and infant syphilis treatment is high among this group of syphilis burdened countries. Initiatives to ensure a stable and adequate supply of benzathine penicillin for treatment of maternal syphilis are important for congenital syphilis prevention, and will be increasingly critical in the future as more countries move toward elimination targets.

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. OBJECTIVES: To describe congenital syphilis (CS) morbidity and mortality during 1999-2013. STUDY DESIGN: National CS case data reported to CDC during 1999-2013 were analyzed. Cases were classified as "dead cases" (stillbirths and deaths up to twelve months after delivery), "morbid cases" (cases with "strong" (physical, radiographic, and/or non-serologic laboratory) evidence of CS), and "non-morbid" cases (cases with a normal physical examination reported, but without strong evidence of infection). Annual rates of these cases were calculated. Cases were compared using selected maternal and infant criteria. RESULTS: During 1999-2013, 6,383 cases of CS were reported: 6.5% (dead), 33.6% (morbid), 53.9% (non-morbid), and 5.9% (unknown morbidity); 81.8% of dead cases were stillbirths. Rates of dead, morbid, and non-morbid cases all decreased over this time period, but the overall proportions that were dead or morbid cases did not significantly change. The overall case fatality ratio during 1999-2013 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, less than ten prenatal visits, and maternal non-treponemal titer ≥ 1:8 increased the likelihood of a dead case; risk of being a dead case increased with maternal non-treponemal titer (chi2 for trend p<0.001). Infants with CS born alive at <28 weeks gestation (RR=107.4, p<0.001) or born weighing <1,500 grams (RR=43.9, p<0.001) were at greatly increased risk of death. CONCLUSIONS: CS remains an important preventable cause of perinatal morbidity and mortality, with comparable case fatality ratios during 1999-2013 (6.5%) and 1992-1998 (6.4%). Detection and treatment of syphilis early during pregnancy remain crucial to reducing CS morbidity and mortality.

BACKGROUND: Global guidelines recommend universal syphilis and HIV screening for pregnant women. Rapid syphilis testing (RST) may contribute toward achievement of universal screening. OBJECTIVES: To examine the impact of RST on syphilis and HIV screening among pregnant women. SEARCH STRATEGY: We searched MEDLINE for English- and non-English language articles published through November, 2014. SELECTION CRITERIA: We included studies that used a comparative design and reported on syphilis and HIV test uptake among pregnant women in low- and middle-income countries (LMICs) following introduction of RST. DATA COLLECTION AND ANALYSIS: Data were extracted from six eligible articles presenting findings from Asia, Africa, and Latin America. MAIN RESULTS: All studies reported substantial increases in antenatal syphilis testing following introduction of RST; the latter did not appear to adversely impact antenatal HIV screening levels at sites already offering rapid HIV testing and may increase HIV screening among pregnant women in some settings. Qualitative data revealed that women were highly satisfied with RST. Nevertheless, ensuring adequate training for healthcare workers and supplies of commodities were cited as key implementation barriers. CONCLUSIONS: RST may increase antenatal syphilis and HIV screening and contribute to the improvement of antenatal care in LMICs.

OBJECTIVE: To asses laboratory syphilis testing policies and practices among laboratories in the Americas. METHODS: Laboratory directors or designees from PAHO member countries were invited to participate in a structured, electronically-delivered survey between March and August, 2014. Data on syphilis tests, algorithms, and quality control (QC) practices were analyzed, focusing on laboratories receiving specimens from antenatal clinics (ANCs). RESULTS: Surveys were completed by 69 laboratories representing 30 (86%) countries. Participating laboratories included 36 (52%) national or regional reference labs and 33 (48%) lower-level laboratories. Most (94%) were public sector facilities and 71% reported existence of a national algorithm for syphilis testing in pregnancy, usually involving both treponemal and non-treponemal testing (72%). Less than half (41%) used rapid syphilis tests (RSTs); and only seven laboratories representing five countries reported RSTs were included in the national algorithm for pregnant women. Most (83%) laboratories serving ANCs reported using some type of QC system; 68% of laboratories reported participation in external QC. Only 36% of laboratories reported data to national/local surveillance. Half of all laboratories serving ANC settings reported a stockout of one or more essential supplies during the previous year (median duration, 30days). CONCLUSION: Updating laboratory algorithms, improving testing standards, integrating data into existing surveillance, and improved procurement and distribution of commodities may be needed to ensure elimination of MTCT of syphilis in the Americas.

OBJECTIVE: To describe the capacity of Peru's Perinatal Information System (Sistema Informatico Perinatal, SIP) to provide estimates for monitoring the proportion of stillbirths and other adverse birth outcomes attributable to maternal syphilis. METHODS: A descriptive study was conducted to assess the quality and completeness of SIP data from six Peruvian public hospitals that used the SIP continuously from 2000 - 2010 and had maternal syphilis prevalence of at least 0.5% during that period. In-depth interviews were conducted with Peruvian stakeholders about their experiences using the SIP. RESULTS: Information was found on 123 575 births from 2000 - 2010 and syphilis test results were available for 99 840 births. Among those 99 840 births, there were 1 075 maternal syphilis infections (1.1%) and 619 stillbirths (0.62%). Among women with syphilis infection in pregnancy, 1.7% had a stillbirth, compared to 0.6% of women without syphilis infection. Much of the information needed to estimate the proportion of stillbirths attributable to maternal syphilis was available in the SIP, with the exception of syphilis treatment information, which was not collected. However, SIP data collection is complex and time-consuming for clinicians. Data were unlinked across hospitals and not routinely used or quality-checked. Despite these limitations, the SIP data examined were complete and valid; in 98% of records, information on whether or not the infant was stillborn was the same in both the SIP and clinical charts. Nearly 89% of women had the same syphilis test result in clinical charts and the SIP. CONCLUSIONS: The large number of syphilis infections reported in Peru's SIP and the ability to link maternal characteristics to newborn outcomes make the system potentially useful for monitoring the proportion of stillbirths attributable to congenital syphilis in Peru. To ensure good data quality and sustainability of Peru's SIP, data collection should be simplified and information should be continually quality-checked and used for the benefit of participating facilities.

BACKGROUND: Screening and treatment for syphilis among pregnant women is the primary means of prevention of congenital syphilis. Sentinel surveillance for syphilis can inform these prevention efforts. METHODS: We reviewed antenatal syphilis screening results to assess trends and to identify correlates of seropositivity among women attending antenatal care clinics in the Democratic Republic of Congo during 2011. RESULTS: Syphilis seropositivity among the 17,669 women attending the antenatal care clinics during 2011 was 4.2% (range 0.4%-16.9%). Syphilis seropositivity was significantly higher among women attending rural clinics (5.0%) as compared to urban clinics (3.0%) and those tested in antenatal care clinics in the provinces of Equateur (7.6%) and Orientale (7.7%) as compared to other provinces (p < 0.001). Based on the ANC syphilis seroprevalence and national pregnancy estimates, we estimate that approximately 128,591 pregnant women countrywide would have tested seropositive for syphilis during 2011. Over 85,000 adverse pregnancy outcomes would have resulted from these maternal infections, assuming prenatal syphilis diagnosis and treatment were not available. CONCLUSION: The prevalence of syphilis was highest in rural areas, but exceeded 1% in every area, indicating a need to assure screening and treatment throughout Democratic Republic of Congo. These sentinel surveillance estimates can be used to guide national congenital syphilis prevention efforts.

BACKGROUND: Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts. METHODS AND FINDINGS: We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 - $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 - 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 - $111 in the four scenarios with net costs. Results were robust in sensitivity analyses. CONCLUSIONS: Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be tailored to countries using local epidemiologic and programmatic data.

BACKGROUND: In China, recent rises in syphilis and HIV cases have increased the focus on preventing mother-to-child transmission of these infections. We assess the health and economic outcomes of different strategies of prenatal HIV and syphilis screening from the local health department's perspective. METHODS: A Markov cohort decision analysis model was used to estimate the health and economic outcomes of pregnancy using disease prevalence and cost data from local sources and, if unavailable, from published literature. Adverse pregnancy outcomes included induced abortion, stillbirth, low birth weight, neonatal death, congenital syphilis in live-born infants, and perinatal HIV infection. We examined 4 screening strategies: no screening, screening for HIV only, for syphilis only, and for both HIV and syphilis. We estimated disability-adjusted life years (DALYs) for each health outcome using life expectancies and infections for mothers and newborns. RESULTS: For a simulated cohort of 10,000 pregnant women (0.07% prevalence for HIV and 0.25% for syphilis; 10% of HIV-positives were coinfected with syphilis), the estimated costs per DALY prevented were as follows: syphilis-only, $168; HIV-and-syphilis, $359; and HIV-only, $5636. The estimated incremental cost-effectiveness ratio if an existing HIV-only strategy added syphilis screening (i.e., move from the HIV-only strategy to the HIV-and-syphilis strategy) was $140 per additional DALY prevented. CONCLUSIONS: Given the increasing prevalence of syphilis and HIV among pregnant women in China, prenatal HIV screening programs that also include syphilis screening are likely to be substantially more cost-effective than HIV screening alone and prevent many more adverse pregnancy outcomes.

BACKGROUND: South Africa recommends universal syphilis and HIV testing in pregnancy, with prompt antiretroviral therapy or penicillin treatment for women testing positive. METHODS: We used a multistage, purposeful sampling strategy to retrospectively identify clinical records from a sample (7.3%) of 32,518 women delivering from January 2005 to June 2006 at 6 public clinics in the Northern Cape and Gauteng. Descriptive analyses and logistic regression were used to assess coverage and factors related to testing and treatment of HIV and syphilis. RESULTS: Of 2379 women sampled, 93% accessed antenatal care (ANC) services during pregnancy and 71% before the third pregnancy trimester. Testing during pregnancy or delivery was 74% for HIV and 84% for syphilis; testing at the first ANC visit was 41% and 71%; and infection prevalence at delivery was 14% and 5%, respectively. Of 243 women with reactive HIV tests, 104 (43%) had treatment documented (single-dose nevirapine) before delivery. Of 98 women with reactive syphilis tests, 73% had documented receipt of 1 penicillin injection and 36% had all 3 recommended injections. Multivariable analysis found women tested for syphilis were almost 4 times more likely to have had no HIV test compared with those without syphilis testing (adjusted odds ratios, 3.9; 95% confidence interval, 1.7-5.5). CONCLUSIONS: Integration and provision of a package of HIV and syphilis testing at the first ANC visit and decentralizing treatments of both infections to primary care settings could increase the coverage of testing and treatment services, thus enhancing the effectiveness of current programs eliminating mother-to-child transmission of HIV and syphilis.

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 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]; = 91.8%; < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; = 95.9%; < 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.

BACKGROUND: To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. METHODS: Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. RESULTS: Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P < 0.001), reported more STIs in the past year (65.5% vs. 56.5%; P = 0.002), had more urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). CONCLUSIONS: Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.

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.

This issue features a retrospective study of clinical | records from one health facility in rural Tanzania in | which the investigators uncovered an unexpected | number of congenital syphilis cases among infants | (Page 125-131). The authors point out that congenital | syphilis is an age-old disease that has fallen off the | priority list of the global health agenda, yet continues | to cause substantial morbidity in countries with limited | resources. They further note that syphilis can be cheaply | and easily cured with penicillin anywhere in the world, | supporting that the most important reason that this | infection continues to kill and maim infants is through | simple neglect. | The evidence supports that the authors' assertions | are correct. The World Health Orgnization (WHO) | estimates that each year between 715 000 and 1 575 000 | pregnant women are infected with syphilis, and most | of them (up to 80%) will suffer a serious adverse | pregnancy outcome.[1] Among live-born infants of | infected mothers, about half go on to have congenital | syphilis infection as depicted in this article; but these | surviving children represent just the tip of the iceberg. | In low income settings, syphilis is the most common | infection associated with fetal loss or stillbirth, occurring | in up to 40% of pregnancies among infected women | who are inadequately treated.[1-3] Syphilis infection also | contributes importantly to preterm delivery, affecting | 20%-33% of infants born to untreated mothers, and | through this means cause a substantial source of early | neonatal death.[1,3] Morbidity aside, the global perinatal | mortality associated with syphilis is estimated at about | 327 000 cases each year—similar to or exceeding the | perinatal deaths estimated for HIV, malaria or tetanus— | and almost all these cases could be prevented.[4

OBJECTIVE: To assess L-tryptophan (LT) dose, age, sex, and immunogenetic markers as possible risk or protective factors for the development of LT-associated eosinophilia-myalgia syndrome (EMS) and related clinical findings. METHODS: HLA-DRB1 and DQA1 allele typing and Gm/Km phenotyping were performed on a cohort of 94 white subjects with documented LT ingestion and standardized evaluations. Multivariate analyses compared LT dose, age, sex, and alleles among groups of subjects who ingested LT and subsequently developed surveillance criteria for EMS, developed EMS or characteristic features of EMS (EMS spectrum disorder), or developed no features of EMS (unaffected). RESULTS: Considering all sources of LT, higher LT dose (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8), age >45 years (OR 3.0, 95% CI 1.0-8.8), and HLA-DRB1*03 (OR 3.9, 95% CI 1.2-15.2), DRB1*04 (OR 3.9, 95% CI 1.1-16.4), and DQA1*0601 (OR 13.7, 95% CI 1.3-1.8) were risk factors for the development of EMS, whereas DRB1*07 (OR 0.12, 95% CI 0.02-0.48) and DQA1*0501 (OR 0.23, 95% CI 0.05-0.85) were protective. Similar risk and protective factors were seen for developing EMS following ingestion of implicated LT, except that DRB1*03 was not a risk factor and DQA1*0201 was an additional protective factor. EMS spectrum disorder also showed similar findings, but with DRB1*04 being a risk factor and DRB1*07 and DQA1*0201 being protective. There were no differences in sex distribution, Gm/Km allotypes, or Gm/Km phenotypes among any groups. CONCLUSION: In addition to the xenobiotic dose and subject age, polymorphisms in immune response genes may underlie the development of certain xenobiotic-induced immune-mediated disorders, and these findings may have implications for future related epidemics.

OBJECTIVE: Project RESPECT's brief risk reduction counseling (BRRC) reduced sexual risk and bacterial STIs among at-risk heterosexuals and has been packaged for use with this population. We assessed BRRC's efficacy with RESPECT participants who used drugs and examined BRRC's applicability to present-day users of heroin, cocaine, speedball, or crack. METHODS: We compared baseline demographic and economic variables, risk behaviors, and prevalence and correlates of bacterial STIs for ever-injectors ([EIs], N=335) and never-injectors ([NIs], N=3963). We assessed changes in risk behaviors and bacterial STIs for EIs and NIs at 12 months. We compared prevalence of HSV-2, hepatitis B core antigen virus (HBV), hepatitis C virus (HCV), and trichomonas among EIs with recently reported rates among drug users. RESULTS: At baseline, 19% of EIs and 29% of NIs had bacterial STIs. Both groups had similar baseline STI correlates. At 12 months, 4% of EIs and 7% of NIs had bacterial STIs. Twelve-month cumulative incidence of bacterial STIs in BRRC was 21% lower among EIs and 18% lower among NIs compared to the informational condition. At 12 months, EIs reported fewer sexual risk behaviors than at baseline. Baseline positivity rates of trichomoniasis in EIs (female: 15%) and in male and female EIs of HSV-2 (39%, 68%), HBV (41%, 37%), and HCV (60%, 58%) were similar to rates in present-day drug users. CONCLUSION: Efficacy of BRRC in reducing sexual risk and bacterial STIs in EIs, and similar profiles for EIs and present-day drug users suggest evaluating BRRC with present-day drug users.