Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity

Summary

This study specifically seeks to quantify the contribution of relapes to the burden of P. vivax infections and disease by determining on the effect of radical pre-erythrocytic and erythrocytic clearance on subsequent rates of Plasmodium spp. infection and disease in children aged 5-10 years in a treatment to re-infection study design. In order the clear liver-stage/blood-stages G6PD-normal children were randomised to receive Chloroquine (3 days, standard dose) and Coartem (3 days, standard dose) plus either i) primaquine (20 days, 0.5mg/kg) or ii) placebo (20days). These drugs were administered over a period of 4 weeks. In addition to this epidemiological data, the study will assess the natural acquisition of cellular and humoral immune responses to P. falciparum and P. vivax, thus assisting in the determination of correlates of clinical immunity to P. falciparum and P. vivax in PNG children aged 5-10 years. These data will not only be essential for development of future vaccines against P. vivax and P falciparum but provide invaluable insight into the contribution of long-lasting liver-stages to the force of infection with P. vivax that will contribute towards designing more rational approaches to the treatment of P. vivax both in the context of case management and future attempts at elimination.

Timeline

Start

2009-08

Primary completion

2010-05

Completion

2014-05

Publications

• Potter GE, Callier V, Shrestha B, Joshi S, Dwivedi A, Silva JC, Laurens MB, Follmann DA, Deye GA. Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials? Malar J. 2023 Dec 19;22(1):383. doi: 10.1186/s12936-023-04802-0.
• Potter GE, Callier V, Shrestha B, Joshi S, Dwivedi A, Silva JC, Laurens MB, Follmann DA, Deye GA. Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials? Res Sq [Preprint]. 2023 Sep 22:rs.3.rs-3370731. doi: 10.21203/rs.3.rs-3370731/v1.
• Stadler E, Cromer D, Mehra S, Adekunle AI, Flegg JA, Anstey NM, Watson JA, Chu CS, Mueller I, Robinson LJ, Schlub TE, Davenport MP, Khoury DS. Population heterogeneity in Plasmodium vivax relapse risk. PLoS Negl Trop Dis. 2022 Dec 19;16(12):e0010990. doi: 10.1371/journal.pntd.0010990. eCollection 2022 Dec.
• Holzschuh A, Gruenberg M, Hofmann NE, Wampfler R, Kiniboro B, Robinson LJ, Mueller I, Felger I, White MT. Co-infection of the four major Plasmodium species: Effects on densities and gametocyte carriage. PLoS Negl Trop Dis. 2022 Sep 13;16(9):e0010760. doi: 10.1371/journal.pntd.0010760. eCollection 2022 Sep.
• Hofmann NE, Karl S, Wampfler R, Kiniboro B, Teliki A, Iga J, Waltmann A, Betuela I, Felger I, Robinson LJ, Mueller I. The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea. Elife. 2017 Sep 1;6:e23708. doi: 10.7554/eLife.23708.
• Wampfler R, Hofmann NE, Karl S, Betuela I, Kinboro B, Lorry L, Silkey M, Robinson LJ, Mueller I, Felger I. Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum. PLoS Negl Trop Dis. 2017 Jul 21;11(7):e0005753. doi: 10.1371/journal.pntd.0005753. eCollection 2017 Jul.
• Robinson LJ, Wampfler R, Betuela I, Karl S, White MT, Li Wai Suen CS, Hofmann NE, Kinboro B, Waltmann A, Brewster J, Lorry L, Tarongka N, Samol L, Silkey M, Bassat Q, Siba PM, Schofield L, Felger I, Mueller I. Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model. PLoS Med. 2015 Oct 27;12(10):e1001891. doi: 10.1371/journal.pmed.1001891. eCollection 2015 Oct.

Drugs

Indications