Antimalarial drugs are frequently used to prevent malaria in pregnancy, when infection can threaten the health of mothers and their unborn babies. We propose to conduct a randomized controlled trial comparing two very different drug intervention strategies that have both been shown to prevent the sequelae of malaria in pregnancy: continuous weekly prophylaxis and intermittent preventive treatment (IPT). These strategies have never been assessed using the same drug in a direct comparative trial in the absence of significant drug resistance. We have a unique opportunity to compare these strategies in Malawi, where we recently discovered that twelve years after chloroquine was withdrawn due to high rates of resistance, chloroquine-susceptible parasites predominate and chloroquine is once again an effective agent to treat malaria. Chloroquine can be used during pregnancy as weekly prophylaxis or intermittent preventive therapy. In the proposed study, our aims are (1) to compare the efficacy of chloroquine as weekly prophylaxis vs. IPT in the prevention of pregnancy-associated malaria and its sequelae, (2) to compare the effect of these treatment strategies on antimalarial drug resistance and (3) to assess the impact of the origin and timing of malaria infections the sequelae of malaria in pregnancy.

Public Health Relevance

This study will provide important information for the future use of antimalarial medication and other interventions for the prevention of malaria in pregnancy. We will examine how and when to prevent pregnancy-associated malaria to protect mothers and their newborns and also avoid the spread of drug resistance.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAI1-BLG-M (J1))
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Rogers, Martin J
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University of Maryland Baltimore
Schools of Medicine
United States
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Divala, Titus H; Mungwira, Randy G; Mawindo, Patricia M et al. (2018) Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial. Lancet Infect Dis 18:1097-1107
Boudová, Sarah; Walldorf, Jenny A; Bailey, Jason A et al. (2017) Mother-Newborn Pairs in Malawi Have Similar Antibody Repertoires to Diverse Malaria Antigens. Clin Vaccine Immunol 24:
Laurens, Matthew B; Mungwira, Randy G; Nyirenda, Osward M et al. (2016) TSCQ study: a randomized, controlled, open-label trial of daily trimethoprim-sulfamethoxazole or weekly chloroquine among adults on antiretroviral therapy in Malawi: study protocol for a randomized controlled trial. Trials 17:322
Mwanza, Sydney; Joshi, Sudhaunshu; Nambozi, Michael et al. (2016) The return of chloroquine-susceptible Plasmodium falciparum malaria in Zambia. Malar J 15:584
Divala, Titus H; Mungwira, Randy G; Laufer, Miriam K (2015) Moving targets: The challenges of studying infectious diseases among pregnant women in resource limited settings. Vaccine 33:6401-5
Boudová, Sarah; Divala, Titus; Mawindo, Patricia et al. (2015) The prevalence of malaria at first antenatal visit in Blantyre, Malawi declined following a universal bed net campaign. Malar J 14:422
Boudová, Sarah; Cohee, Lauren M; Kalilani-Phiri, Linda et al. (2014) Pregnant women are a reservoir of malaria transmission in Blantyre, Malawi. Malar J 13:506
Kalilani-Phiri, Linda; Thesing, Phillip C; Nyirenda, Osward M et al. (2013) Timing of malaria infection during pregnancy has characteristic maternal, infant and placental outcomes. PLoS One 8:e74643
Mathanga, Don P; Walker, Edward D; Wilson, Mark L et al. (2012) Malaria control in Malawi: current status and directions for the future. Acta Trop 121:212-7
Frosch, Anne E P; Venkatesan, Meera; Laufer, Miriam K (2011) Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data. Malar J 10:116

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