Prevention of Malaria in HIV-uninfected Pregnant Women and Infants

Summary

This will be a double-blinded randomized controlled phase III trial of 782 HIV uninfected pregnant women and the children born to them. HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of two intermittent preventive treatment in pregnancy (IPTp) treatment arms: 1) monthly sulfadoxine-pyrimethamine (SP), or 2) monthly dihydroartemisinin-piperaquine (DP). Both interventions arms will have either SP or DP placebo to ensure adequate blinding is achieved in the study. Follow-up for the pregnant women will end approximately 6 weeks after giving birth. All children born to mothers enrolled in the study will be followed from birth until they reach 12 months of age.

Timeline

Start

2016-09

Primary completion

2018-12-04

Completion

2018-12-04

Publications

• Results Kajubi R, Ochieng T, Kakuru A, Jagannathan P, Nakalembe M, Ruel T, Opira B, Ochokoru H, Ategeka J, Nayebare P, Clark TD, Havlir DV, Kamya MR, Dorsey G. Monthly sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trial. Lancet. 2019 Apr 6;393(10179):1428-1439. doi: 10.1016/S0140-6736(18)32224-4. Epub 2019 Mar 22.
• Results Harrington WE, Kakuru A, Jagannathan P. Malaria in pregnancy shapes the development of foetal and infant immunity. Parasite Immunol. 2019 Mar;41(3):e12573. doi: 10.1111/pim.12573. Epub 2018 Aug 28.
• Results Briggs J, Ategeka J, Kajubi R, Ochieng T, Kakuru A, Ssemanda C, Wasswa R, Jagannathan P, Greenhouse B, Rodriguez-Barraquer I, Kamya M, Dorsey G. Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda. J Infect Dis. 2019 Jul 2;220(3):457-466. doi: 10.1093/infdis/jiz130.
• Results Okiring J, Olwoch P, Kakuru A, Okou J, Ochokoru H, Ochieng TA, Kajubi R, Kamya MR, Dorsey G, Tusting LS. Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: a prospective cohort study. Malar J. 2019 Apr 23;18(1):144. doi: 10.1186/s12936-019-2779-x.
• Results Kakuru A, Jagannathan P, Kajubi R, Ochieng T, Ochokoru H, Nakalembe M, Clark TD, Ruel T, Staedke SG, Chandramohan D, Havlir DV, Kamya MR, Dorsey G. Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial. BMC Med. 2020 Aug 10;18(1):207. doi: 10.1186/s12916-020-01675-x.
• Results Savic RM, Jagannathan P, Kajubi R, Huang L, Zhang N, Were M, Kakuru A, Muhindo MK, Mwebaza N, Wallender E, Clark TD, Opira B, Kamya M, Havlir DV, Rosenthal PJ, Dorsey G, Aweeka FT. Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine. Clin Infect Dis. 2018 Sep 14;67(7):1079-1088. doi: 10.1093/cid/ciy218.
• Results Ategeka J, Kakuru A, Kajubi R, Wasswa R, Ochokoru H, Arinaitwe E, Yeka A, Jagannathan P, Kamya MR, Muehlenbachs A, Chico RM, Dorsey G. Relationships Between Measures of Malaria at Delivery and Adverse Birth Outcomes in a High-Transmission Area of Uganda. J Infect Dis. 2020 Aug 4;222(5):863-870. doi: 10.1093/infdis/jiaa156.
• Results Roh ME, Kuile FOT, Rerolle F, Glymour MM, Shiboski S, Gosling R, Gutman J, Kakuru A, Desai M, Kajubi R, L'Ianziva A, Kamya MR, Dorsey G, Chico RM. Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis. Lancet Glob Health. 2020 Jul;8(7):e942-e953. doi: 10.1016/S2214-109X(20)30119-4.
• Vaaben AV, Levan J, Nguyen CBT, Callaway PC, Prahl M, Warrier L, Nankya F, Musinguzi K, Kakuru A, Muhindo MK, Dorsey G, Kamya MR, Feeney ME. In Utero Activation of Natural Killer Cells in Congenital Cytomegalovirus Infection. J Infect Dis. 2022 Sep 4;226(4):566-575. doi: 10.1093/infdis/jiac307.
• Hughes E, Wallender E, Kajubi R, Jagannathan P, Ochieng T, Kakuru A, Kamya MR, Clark TD, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women. Clin Infect Dis. 2022 Aug 31;75(3):406-415. doi: 10.1093/cid/ciab965.
• Zehner N, Adrama H, Kakuru A, Andra T, Kajubi R, Conrad M, Nankya F, Clark TD, Kamya M, Rodriguez-Barraquer I, Dorsey G, Jagannathan P. Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait. Clin Infect Dis. 2021 Nov 16;73(10):1887-1895. doi: 10.1093/cid/ciab245.
• Kakuru A, Roh ME, Kajubi R, Ochieng T, Ategeka J, Ochokoru H, Nakalembe M, Clark TD, Ruel T, Staedke SG, Chandramohan D, Havlir DV, Kamya MR, Dorsey G, Jagannathan P. Infant sex modifies associations between placental malaria and risk of malaria in infancy. Malar J. 2020 Dec 3;19(1):449. doi: 10.1186/s12936-020-03522-z.

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Indications