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      Global burden of maternal and congenital syphilis and associated adverse birth outcomes—Estimates for 2016 and progress since 2012

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          Abstract

          Background

          In 2007 the World Health Organization (WHO) launched the global initiative to eliminate mother-to-child transmission of syphilis (congenital syphilis, or CS). To assess progress towards the goal of <50 CS cases per 100,000 live births, we generated regional and global estimates of maternal and congenital syphilis for 2016 and updated the 2012 estimates.

          Methods

          Maternal syphilis estimates were generated using the Spectrum-STI model, fitted to sentinel surveys and routine testing of pregnant women during antenatal care (ANC) and other representative population data. Global and regional estimates of CS used the same approach as previous WHO estimates.

          Results

          The estimated global maternal syphilis prevalence in 2016 was 0.69% (95% confidence interval: 0.57–0.81%) resulting in a global CS rate of 473 (385–561) per 100,000 live births and 661,000 (538,000–784,000) total CS cases, including 355,000 (290,000–419,000) adverse birth outcomes (ABO) and 306,000 (249,000–363,000) non-clinical CS cases (infants without clinical signs born to un-treated mothers). The ABOs included 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth weight births, and 109,000 infants with clinical CS. Of these ABOs– 203,000 (57%) occurred in pregnant women attending ANC but not screened for syphilis; 74,000 (21%) in mothers not enrolled in ANC, 55,000 (16%) in mothers screened but not treated, and 23,000 (6%) in mothers enrolled, screened and treated. The revised 2012 estimates were 0.70% (95% CI: 0.63–0.77%) maternal prevalence, and 748,000 CS cases (539 per 100,000 live births) including 397,000 (361,000–432,000) ABOs. The estimated decrease in CS case rates between 2012 and 2016 reflected increased access to ANC and to syphilis screening and treatment.

          Conclusions

          Congenital syphilis decreased worldwide between 2012 and 2016, although maternal prevalence was stable. Achieving global CS elimination, however, will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC.

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          Most cited references26

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          Early antenatal care visit: a systematic analysis of regional and global levels and trends of coverage from 1990 to 2013

          Summary Background The timing of the first antenatal care visit is paramount for ensuring optimal health outcomes for women and children, and it is recommended that all pregnant women initiate antenatal care in the first trimester of pregnancy (early antenatal care visit). Systematic global analysis of early antenatal care visits has not been done previously. This study reports on regional and global estimates of the coverage of early antenatal care visits from 1990 to 2013. Methods Data were obtained from nationally representative surveys and national health information systems. Estimates of coverage of early antenatal care visits were generated with linear regression analysis and based on 516 logit-transformed observations from 132 countries. The model accounted for differences by data sources in reporting the cutoff for the early antenatal care visit. Findings The estimated worldwide coverage of early antenatal care visits increased from 40·9% (95% uncertainty interval [UI] 34·6–46·7) in 1990 to 58·6% (52·1–64·3) in 2013, corresponding to a 43·3% increase. Overall coverage in the developing regions was 48·1% (95% UI 43·4–52·4) in 2013 compared with 84·8% (81·6–87·7) in the developed regions. In 2013, the estimated coverage of early antenatal care visits was 24·0% (95% UI 21·7–26·5) in low-income countries compared with 81·9% (76·5–87·1) in high-income countries. Interpretation Progress in the coverage of early antenatal care visits has been achieved but coverage is still far from universal. Substantial inequity exists in coverage both within regions and between income groups. The absence of data in many countries is of concern and efforts should be made to collect and report coverage of early antenatal care visits to enable better monitoring and evaluation. Funding Department of Reproductive Health and Research, WHO and UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.
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            Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality

            Background Globally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity. Objectives This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality. Methods We conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken. Results Moderate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 – 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 – 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 – 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 – 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong. Conclusion Detection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.
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              Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews

              Background 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. Methods and findings Country-level data about BPG shortages were collected using 3 survey approaches. First, a survey designed by the WHO Department of Reproductive Health and Research was distributed to 41 countries and territories in the Americas and 41 more in Africa. Second, WHO conducted an email survey of 28 US Centers for Disease Control and Prevention country directors. An additional 13 countries were in contact with WHO for related congenital syphilis prevention activities and also reported on BPG shortages. Third, the Clinton Health Access Initiative (CHAI) collected data from 14 countries (where it has active operations) to understand the extent of stock-outs, in-country purchasing, usage behavior, and breadth of available purchasing options to identify stock-outs worldwide. CHAI also conducted in-person interviews in the same 14 countries to understand the extent of stock-outs, in-country purchasing and usage behavior, and available purchasing options. CHAI also completed a desk review of 10 additional high-income countries, which were also included. BPG shortages were attributable to shortfalls in supply, demand, and procurement in the countries assessed. This assessment should not be considered globally representative as countries not surveyed may also have experienced BPG shortages. Country contacts may not have been aware of BPG shortages when surveyed or may have underreported medication substitutions due to desirability bias. Funding for the purchase of BPG by countries was not evaluated. In all, 114 countries and territories were approached to provide information on BPG shortages occurring during 2014–2016. Of unique countries and territories, 95 (83%) responded or had information evaluable from public records. Of these 95 countries and territories, 39 (41%) reported a BPG shortage, and 56 (59%) reported no BPG shortage; 10 (12%) countries with and without BPG shortages reported use of antibiotic alternatives to BPG for treatment of maternal syphilis. Market exits, inflexible production cycles, and minimum order quantities affect BPG supply. On the demand side, inaccurate forecasts and sole sourcing lead to under-procurement. Clinicians may also incorrectly prescribe BPG substitutes due to misperceptions of quality or of the likelihood of adverse outcomes. Conclusions Targets for improvement include drug forecasting and procurement, and addressing provider reluctance to use BPG. Opportunities to improve global supply, demand, and use of BPG should be prioritized alongside congenital syphilis elimination efforts.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Formal analysisRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Writing – original draft
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 February 2019
                2019
                : 14
                : 2
                : e0211720
                Affiliations
                [1 ] Avenir Health, Geneva, Switzerland
                [2 ] Independent consultant, London, United Kingdom
                [3 ] Department of Communicable Diseases and Environmental Determinants of Health, Pan-American Health Organization, Washington DC, United States of America
                [4 ] Independent Consultant, Atlanta, Georgia, United States of America
                [5 ] Avenir Health, Glastonbury, Connecticut, United States of America
                [6 ] World Health Organization, Regional Office for the Western Pacific, Manila, the Philippines
                [7 ] World Health Organization, Sub-Saharan Africa Office, Brazzaville, Republic of Congo
                [8 ] Independent Consultant, Leiden, The Netherlands
                [9 ] USA Centers for Disease Control and Prevention, Cambodia Country Office, Phnom Penh, Cambodia
                [10 ] USA Centers for Disease Control and Prevention, Division of STD Prevention, Atlanta, Georgia, United States of America
                [11 ] World Health Organization, Dept. of Reproductive Health and Research, Geneva, Switzerland
                BITS Pilani, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-5301-8461
                http://orcid.org/0000-0003-3447-0222
                http://orcid.org/0000-0002-2701-6892
                http://orcid.org/0000-0002-1786-6295
                Article
                PONE-D-18-26271
                10.1371/journal.pone.0211720
                6392238
                30811406
                3ff846c4-3572-4997-b9fd-e65811227ac7

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 19 September 2018
                : 26 October 2018
                Page count
                Figures: 2, Tables: 2, Pages: 17
                Funding
                Funded by: World Health Organization, Dept. of Reproductive Health and Research
                Award Recipient :
                The project was funded by the World Health Organization, Department of Reproductive Health and Research/Human Reproduction Programme. The analysis was furthermore supported by a cooperative agreement from the U.S. Centers for Disease Control and Prevention in support of prevention of mother-to-child transmission of syphilis, and by the Department of International Development (DfID) of the United Kingdom. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the World Health Organization, or the U.S. Centers for Disease Control and Prevention.
                Categories
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