Cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries: a modelling study.

BACKGROUND: Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence. METHODS: In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya,$750 in South Africa, $3000 in Colombia, and$1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective. FINDINGS: Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya,$260 in South Africa, $2207 in Colombia, and$205 in Ukraine). INTERPRETATION: Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis. FUNDING: WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation

Impact of maternal ART on mother-to-child transmission (MTCT) of HIV at six weeks postpartum in Rwanda

BACKGROUND: In 2010, Rwanda adopted ART for prevention of mother to child transmission of HIV from pregnant women living with HIV during pregnancy and breasfeeding period. This study examines rates of mother-to-childtransmission of HIV at 6–10 weeks postpartum and risk factors for mother-to-child transmission of HIV (MTCT) among HIV infected women on ART during pregnancy and breastfeeding. METHODS: A cross-sectional survey study was conducted between July 2011–June 2012 among HIV-exposed infants aged 6–10 weeks and their mothers/caregivers. Stratified multi-stage, probability proportional to size and systematic sampling to select a national representative sample of clients. Consenting mothers/caregivers were interviewed on demographic and program interventions. Dry blood spots from HIV-exposed infants were collected for HIV testing using DNA PCR technique. Results are weighted for sample realization. Univariable analysis of socio-demographic and programmatic determinants of early mother-to-child transmission of HIV was conducted. Variables were retained for final multivariable models if they were either at least of marginal significance (p-value < 0.10) or played a confounding role (the variable had a noticeable impact > 10% change on the effect estimate). RESULTS: The study sample was 1639 infants with HIV test results. Twenty-six infants were diagnosed HIV-positive translating to a weighted MTCT estimate of 1.58% (95% CI 1.05–2.37%). Coverage of most elimination of MTCT (EMTCT) program interventions, was above 80, and 90.4% of mother-infant pairs received antiretroviral treatment or prophylaxis. Maternal ART and infant antiretroviral prophylaxis (OR 0.01; 95%CI 0.001–0.17) and maternal age older than 25 years were significantly protective (OR 0.33; 95%CI 0.14–0.78). No disclosure of HIV status, not testing for syphilis during pregnancy and preterm birth were significant risk factors for MTCT. Factors suggesting higher sociodemographic status (flush toilet, mother self-employed) were borderline risk factors for MTCT. CONCLUSION: ART for all women during pregnancy and breastfeeding was associated with the estimated low MTCT rate of 1.58%. Mothers who did not receive a full package of anti-retroviral therapy according to the Rwanda EMTCT protocol, and young and single mothers were at higher risk of MTCT and should be targeted for support in preventing HIV infection

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

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

Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews

<div><p>Background</p><p>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.</p><p>Methods and findings</p><p>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.</p><p>Conclusions</p><p>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.</p></div

Identified drivers of BPG stock-outs across the value chain.

<p>*API, active pharmaceutical ingredient; BPG, benzathine penicillin G; FDF, final dose formulator; GMP, Good Manufacturing Practice.</p

Select responses from providers describing barriers to administration of BPG.

<p>Select responses from providers describing barriers to administration of BPG.</p

Countries with reported shortages of benzathine penicillin G (BPG) during 2014–2016.

<p>Countries with reported shortages of benzathine penicillin G (BPG) during 2014–2016.</p

Number of countries included in surveys reporting BPG shortage and/or medication substitution for treatment of maternal syphilis.

<p>Number of countries included in surveys reporting BPG shortage and/or medication substitution for treatment of maternal syphilis.</p