Eliminating mother-to-child transmission of human immunodeficiency virus, syphilis and hepatitis B in sub-Saharan Africa.

Triple elimination is an initiative supporting the elimination of mother-to-child transmission of three diseases - human immunodeficiency virus (HIV) infection, syphilis and hepatitis B. Significant progress towards triple elimination has been made in some regions, but progress has been slow in sub-Saharan Africa, the region with the highest burden of these diseases. The shared features of the three diseases, including their epidemiology, disease interactions and core interventions for tackling them, enable an integrated health-systems approach for elimination of mother-to-child transmission. Current barriers to triple elimination in sub-Saharan Africa include a lack of policies, strategies and resources to support the uptake of well established preventive and treatment interventions. While much can be achieved with existing tools, the development of new products and models of care, as well as a prioritized research agenda, are needed to accelerate progress on triple elimination in sub-Saharan Africa. In this paper we aim to show that health systems working together with communities in sub-Saharan Africa could deliver rapid and sustainable results towards the elimination of mother-to-child transmission of all three diseases. However, stronger political support, expansion of evidence-based interventions and better use of funding streams are needed to improve efficiency and build on the successes in prevention of mother-to-child transmission of HIV. Triple elimination is a strategic opportunity to reduce the morbidity and mortality from HIV infection, syphilis and hepatitis B for mothers and their infants within the context of universal health coverage.

La triple élimination est une initiative visant à soutenir l'éradication de la transmission mère-enfant de trois maladies ­ l'infection au virus de l'immunodéficience humaine (VIH), la syphilis et l'hépatite B. Bien que des avancées considérables aient été observées en ce sens dans certaines régions, les progrès demeurent lents en Afrique subsaharienne, pourtant durement touchée par ces maladies. Les caractéristiques communes aux trois affections, notamment leur épidémiologie, les interactions entre elles et les principales interventions nécessaires à leur prise en charge permettent aux systèmes de santé d'adopter une approche intégrée pour éviter la transmission mère-enfant. Plusieurs obstacles entravent actuellement la triple élimination en Afrique subsaharienne, parmi lesquels l'absence de politiques, de stratégies et de ressources pour garantir la disponibilité de traitements préventifs et curatifs bien établis. Les outils existants offrent déjà de nombreuses solutions; mais pour accélérer la progression de cette triple élimination en Afrique subsaharienne, il est indispensable de développer de nouveaux produits et modèles de soins, ainsi qu'un programme de recherche prioritaire. Dans le présent document, nous voulons montrer que si les systèmes de santé collaborent avec les communautés en Afrique subsaharienne, ils pourront obtenir des résultats rapides et durables en vue d'éradiquer la transmission mère-enfant des trois maladies susmentionnées. Néanmoins, une telle démarche implique un soutien politique massif, l'expansion des interventions fondées sur des données scientifiques, et une meilleure utilisation des sources de financement afin d'améliorer l'efficacité et de s'appuyer sur les réussites en matière de prévention de la transmission du VIH de la mère à l'enfant. La triple élimination représente une occasion stratégique de réduire la morbidité et la mortalité liées à l'infection au VIH, à la syphilis et à l'hépatite B, tant chez les mères que chez les nourrissons, dans un contexte de couverture maladie universelle.

La triple eliminación es una iniciativa que apoya la eliminación de la transmisión maternoinfantil de tres enfermedades: la infección por el virus de la inmunodeficiencia humana (VIH), la sífilis y la hepatitis B. En algunas regiones se han logrado avances significativos hacia la triple eliminación, pero los progresos se han desarrollado con mayor lentitud en el África subsahariana, la región con la mayor carga de estas enfermedades. Las características comunes de las tres enfermedades, como su epidemiología, las interacciones entre ellas y las intervenciones básicas para combatirlas, permiten un enfoque integrado de los sistemas de salud para la eliminación de la transmisión maternoinfantil. Los obstáculos actuales para la triple eliminación en el África subsahariana incluyen la falta de políticas, estrategias y recursos para apoyar la adopción de intervenciones preventivas y de tratamiento bien establecidas. Aunque se puede lograr mucho con las herramientas existentes, se necesita el desarrollo de nuevos productos y modelos de atención, así como una agenda de investigación prioritaria, para acelerar el progreso de la triple eliminación en el África subsahariana. En este documento pretendemos demostrar que los sistemas de salud que trabajan conjuntamente con las comunidades del África subsahariana podrían obtener resultados rápidos y sostenibles hacia la eliminación de la transmisión maternoinfantil de las tres enfermedades. Sin embargo, se necesita un mayor apoyo político, la ampliación de las intervenciones basadas en la evidencia y un mejor uso de los flujos de financiación para mejorar la eficiencia y aprovechar los éxitos en la prevención de la transmisión maternoinfantil del VIH. La triple eliminación es una oportunidad estratégica para reducir la morbilidad y la mortalidad de la infección por el VIH, la sífilis y la hepatitis B para las madres y sus hijos en el contexto de la cobertura sanitaria universal.

Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil.

BACKGROUND: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage. METHODS: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018. RESULTS: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens. CONCLUSION: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.

Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action.

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.