Date Published: December 27, 2017
Publisher: Public Library of Science
Author(s): Stephen Nurse-Findlay, Melanie M. Taylor, Margaret Savage, Maeve B. Mello, Sanni Saliyou, Manuel Lavayen, Frederic Seghers, Michael L. Campbell, Françoise Birgirimana, Leopold Ouedraogo, Morkor Newman Owiredu, Nancy Kidula, Lee Pyne-Mercier, Nicola Low
Abstract: BackgroundBenzathine 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 findingsCountry-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.ConclusionsTargets 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.
Partial Text: The World Health Organization (WHO) estimates that there are 5.6 million new cases of syphilis annually and 18 million prevalent cases . In 2012, WHO estimated that there were 930,000 pregnant women with syphilis, resulting in 350,000 adverse pregnancy outcomes, with over half of these being stillbirth or neonatal death . Both screening and treatment for syphilis remain suboptimal in low- and middle-income countries (LMICs) , despite the diagnosis and prevention of mother-to-child transmission (MTCT) of syphilis being feasible, inexpensive, and cost-effective . Benzathine penicillin G (BPG) is the only recommended treatment for syphilis in pregnant women to prevent MTCT, as other drugs are contraindicated, do not cross the placenta to treat the fetus, or are less effective than BPG . Treatment of syphilis-infected pregnant women with 2.4 million international units (IU) of intramuscular of BPG given at least 28 days prior to delivery can result in an 82% reduced risk of stillbirth and 80% reduction in neonatal mortality . In recognition of this, WHO published The Global Elimination of Congenital Syphilis: Rationale and Strategy for Action  and set country targets for the elimination of MTCT of HIV and syphilis, which will bring BPG shortages into sharp focus.
In this evaluation, 39 countries of 95 (41%) responding to surveys reported shortages or stock-outs of BPG occurring during 2014–2016 (114 countries/territories surveyed). Both high-income countries and LMICs were affected.