Quantifying and preventing Plasmodium vivax recurrences in primaquine-untreated pregnant women: An observational and modeling study in Brazil

Autor(es)

Corder, Rodrigo M. ; de Lima, Antonio C. P. ; Khoury, David S. ; Docken, Steffen S. ; Davenport, Miles P. ; Ferreira, Marcelo U.

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 14, n. 7, p. 16-pg., 2020-07-01.

Resumo

Author summary Plasmodium vivax, a malaria parasite that can stay dormant in the liver and originate relapses within months after a single mosquito inoculation, causes 76% of the malaria burden in Latin America. Pregnant women are ineligible for primaquine (PQ), the only currently available drug that is able to preventP.vivaxrelapses. Here we apply a mathematical model to real-life data from Brazil's main malaria transmission hotspot and estimate that, once infected withP.vivax, 23% of the pregnant women will have one or more vivax malaria recurrences over the next 12 weeks. Significantly, 86% of these earlyP.vivaxrecurrences are attributable to relapses or late recrudescences, which could be prevented by PQ administration. Repeated vivax malaria infections during pregnancy are associated with adverse effects on maternal and neonatal health. We show that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk ofP.vivaxrecurrences over the next 12 months by 20% to 65%, and should be investigated as a measure to lower the burden of repeated vivax malaria during pregnancy. Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean.Plasmodium vivaxcauses 76% of the regional malaria burden and appears to be less affected thanP.falciparumby current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supressP.vivaxrelapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Jurua Valley, Brazil ' s main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primaryP.vivaxinfections in 158 pregnant women treated with CQ only and 316P.vivaxinfections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected withP.vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these earlyP.vivaxrecurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk ofP.vivaxrecurrences over the next 12 months by 20% to 65%. We conclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health. (AU)

• Processo FAPESP: 17/50292-9 - Modeling the relative contribution of relapses to Plasmodium vivax infection in Brazil
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/21728-2 - Uso de modernas técnicas de autópsia na investigação de doenças humanas (MODAU)
• Beneficiário: Paulo Hilário Nascimento Saldiva
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/18740-9 - Bases científicas para a eliminação da malária residual na Amazônia Brasileira
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático