Malaria and HIV are two of the most important Infectious diseases worldwide that are overlapping and synergistic in sub-Saharan Africa. Despite the scale up of front line prevention efforts, the burden of malaria remains staggering among pregnant women and children;and malnutrition and growth retardation are major threats to child health. The purpose of the """"""""Prevention of Malaria and HIV Disease in Tororo"""""""" (PROMOTE) program project (POI) is to evaluate promising interventions to reduce the burden of malaria and HIV and Improve maternal-child health through hypothesis based intervention studies. PROMOTE II will test the hypotheses that a) enhanced malaria chemoprevention in HIV infected and uninfected pregnant women will reduce placenta malaria;b) enhanced chemoprevention provided during both pregnancy and childhood will reduce malaria in children in the first 2 years of life and c) limiting in utero exposure to malaria antigens with enhanced malaria chemoprevention during pregnancy will reduce development of fetal immune tolerance to malaria antigens. The proposed clinical studies will evaluate chemoprevention with dihydroartemisinin-piperaquine (DP), a new artemisinin combination therapy (ACT), established as highly safe and effective for malaria treatment in pregnant women and children. PROMOTE II consists of 3 projects and 3 cores. There are 2 interlinked double blinded, randomized controlled trials in HIV-uninfected pregnant women (Project 1), and HIV-infected pregnant women (Project 2) and the children born to them with parallel structure that permits comparisons in malaria, immune responses and pharmacokinetics of DP between populations with differing HIV status and exposure. Project 3 is laboratory based, and is focused on testing central hypothesis of malaria immunity using well characterized specimens from the 2 clinical trials. Administrative, laboratory, and data cores provide infrastructure support to the projects, including the capacity to process and evaluate placental malaria using histopathology.

Public Health Relevance

Malaria and HIV are among the most important diseases adversely affecting maternal child health in Africa. The PROMOTE studies seek to advance our knowledge of interventions that reduce the burden of malaria and HIV among pregnant women and their children living in rural Sub-Saharan Africa.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
2P01HD059454-06A1
Application #
8604005
Study Section
Special Emphasis Panel (ZRG1-AARR-D (42))
Program Officer
Mofenson, Lynne M
Project Start
2008-08-01
Project End
2018-06-30
Budget Start
2013-08-01
Budget End
2014-06-30
Support Year
6
Fiscal Year
2013
Total Cost
$1,833,933
Indirect Cost
$431,732
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Odorizzi, Pamela M; Jagannathan, Prasanna; McIntyre, Tara I et al. (2018) In utero priming of highly functional effector T cell responses to human malaria. Sci Transl Med 10:
Savic, Rada M; Jagannathan, Prasanna; Kajubi, Richard et al. (2018) Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine. Clin Infect Dis 67:1079-1088
Jagannathan, Prasanna; Kakuru, Abel; Okiring, Jaffer et al. (2018) Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial. PLoS Med 15:e1002606
Jagannathan, Prasanna; Kajubi, Richard; Aweeka, Francesca T (2018) Response to ""Antiretroviral Therapy With Efavirenz in HIV-Infected Pregnant Women: Understanding the Possible Mechanisms for Drug-Drug Interaction"". Clin Pharmacol Ther 103:571
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Kapisi, James; Kakuru, Abel; Jagannathan, Prasanna et al. (2017) Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes. Malar J 16:400
Prahl, Mary; Jagannathan, Prasanna; McIntyre, Tara I et al. (2017) Sex Disparity in Cord Blood FoxP3+ CD4 T Regulatory Cells in Infants Exposed to Malaria In Utero. Open Forum Infect Dis 4:ofx022
Sonoiki, Ebere; Nsanzabana, Christian; Legac, Jennifer et al. (2017) Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1. Antimicrob Agents Chemother 61:
Kajubi, R; Huang, L; Jagannathan, P et al. (2017) Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention. Clin Pharmacol Ther 102:520-528

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