Modifying Immunity in Children With DihydROartemisinin-Piperaquine (MIC-DroP)

Summary

The MIC-DroP trial will test the hypothesis that preventing early life blood-stage malaria antigenic exposure with intermittent preventive therapy (IPT) enhances protective immunity to malaria. This study will take advantage of a unique opportunity to study infants born to mothers followed in a NIH-funded randomized controlled trial of novel intermittent preventive therapy in pregnancy (IPTp) regimens (NCT04336189). MIC-DroP will leverage the parent IPTp study to enroll 924 children who will be randomized at 8 weeks of age to receive no intermittent preventive therapy in childhood (IPTc), monthly DP from 8 weeks to 1 year of age, or monthly DP from 8 weeks to 2 years of age, and then follow children to 4 years of age. The primary outcome of this study will be to compare the incidence of malaria from 2 to 4 years of age among children randomized to receive no IPTc, monthly DP for the first year of life, or monthly DP for the first two years of life. Investigators will also leverage this trial to evaluate immune development during early childhood.

Timeline

Start

2022-02-08

Primary completion

2027-05-05

Completion

2027-05-05

Publications

• Background Dobbs KR, Jagannathan P, Dechavanne C. Editorial: Immune tolerance and human malaria. Front Immunol. 2024 Jul 4;15:1450480. doi: 10.3389/fimmu.2024.1450480. eCollection 2024. No abstract available.
• Background Nideffer J, Jagannathan P. Type I regulatory T cells in malaria: of mice and men. J Clin Invest. 2023 Jan 3;133(1):e166019. doi: 10.1172/JCI166019.
• Background 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.
• Results Li J, Wang X, Lackner AI, Narasimhan P, Li L, Mallajosyula V, Johnson MM, Hobler AL, Kirosingh AS, Braun AE, Nankya F, Musinguzi K, Kakuru A, Kamya M, Rosenthal PJ, Dorsey G, Jagannathan P, Angelo M, Pollheimer J, Gaw SL, Winn VD, Nadeau KC, Davis MM. Regulatory KIR+CD8+ T cells are elevated during human pregnancy. Sci Transl Med. 2025 Aug 6;17(810):eadm7697. doi: 10.1126/scitranslmed.adm7697. Epub 2025 Aug 6.
• Results Roh ME, Gutman J, Murphy M, Hill J, Madanitsa M, Kakuru A, Barsosio HC, Kariuki S, Lusingu JPA, Mosha F, Kajubi R, Kamya MR, Mathanga D, Chinkhumba J, Laufer MK, Mlugu E, Kamuhabwa AAR, Aklillu E, Minzi O, Okoro RN, Geidam AD, Ohieku JD, Desai M, Jagannathan P, Dorsey G, Ter Kuile FO. Dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a systematic review and individual participant data meta-analysis. medRxiv [Preprint]. 2024 Nov 26:2024.11.23.24315401. doi: 10.1101/2024.11.23.24315401.
• Results Tukwasibwe S, Lewis SN, Taremwa Y, van der Ploeg K, Press KD, Ty M, Namirimu Nankya F, Musinguzi K, Nansubuga E, Bach F, Chamai M, Okitwi M, Tumusiime G, Nakimuli A, Colucci F, Kamya MR, Nankabirwa JI, Arinaitwe E, Greenhouse B, Dorsey G, Rosenthal PJ, Ssewanyana I, Jagannathan P. Natural killer cell antibody-dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission. Clin Transl Immunology. 2024 Nov 1;13(11):e70005. doi: 10.1002/cti2.70005. eCollection 2024.
• Results Tong Y, Ratnasiri K, Hanif S, Nguyen AT, Roh ME, Dorsey G, Kakuru A, Jagannathan P, Benjamin-Chung J. Intermittent preventive treatment for malaria in pregnancy and infant growth: a mediation analysis of a randomised trial. EBioMedicine. 2024 Nov;109:105397. doi: 10.1016/j.ebiom.2024.105397. Epub 2024 Oct 16.
• Results Reyes RA, Turner L, Ssewanyana I, Jagannathan P, Feeney ME, Lavstsen T, Greenhouse B, Bol S, Bunnik EM. Differences in phenotype between long-lived memory B cells against Plasmodium falciparum merozoite antigens and variant surface antigens. PLoS Pathog. 2024 Oct 28;20(10):e1012661. doi: 10.1371/journal.ppat.1012661. eCollection 2024 Oct.
• Results Nideffer J, Ty M, Donato M, John R, Kajubi R, Ji X, Nankya F, Musinguzi K, Press KD, Yang N, Camanag K, Greenhouse B, Kamya M, Feeney ME, Dorsey G, Utz PJ, Pulendran B, Khatri P, Jagannathan P. Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells. PNAS Nexus. 2024 Aug 6;3(8):pgae325. doi: 10.1093/pnasnexus/pgae325. eCollection 2024 Aug.
• Results Boyle MJ, Engwerda CR, Jagannathan P. The impact of Plasmodium-driven immunoregulatory networks on immunity to malaria. Nat Rev Immunol. 2024 Sep;24(9):637-653. doi: 10.1038/s41577-024-01041-5. Epub 2024 Jun 11.
• Results Lee JJ, Kakuru A, Jacobson KB, Kamya MR, Kajubi R, Ranjit A, Gaw SL, Parsonnet J, Benjamin-Chung J, Dorsey G, Jagannathan P, Roh ME. Monthly Sulfadoxine-Pyrimethamine During Pregnancy Prevents Febrile Respiratory Illnesses: A Secondary Analysis of a Malaria Chemoprevention Trial in Uganda. Open Forum Infect Dis. 2024 Mar 13;11(4):ofae143. doi: 10.1093/ofid/ofae143. eCollection 2024 Apr.
• Results Kakuru A, Jagannathan P. Can we reduce malaria in pregnancy and improve birth outcomes? Lancet. 2023 Mar 25;401(10381):973-975. doi: 10.1016/S0140-6736(23)00101-0. Epub 2023 Mar 10. No abstract available.

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