Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum
- Author(s)
- Wampfler, R; Hofmann, NE; Karl, S; Betuela, I; Kinboro, B; Lorry, L; Silkey, M; Robinson, LJ; Mueller, I; Felger, I;
- Details
- Publication Year 2017-07,Volume 11,Issue #7,Page e0005753
- Journal Title
- PLoS Negl Trop Dis
- Publication Type
- Journal Article
- Abstract
- BACKGROUND: Primaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses. METHODS: Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo. Blood samples were subsequently collected in 2-to 4-weekly intervals over 8 months. Gametocytes were detected by quantitative reverse transcription-PCR targeting pvs25 and pfs25. RESULTS: PQ treatment reduced the incidence of Pv gametocytes by 73%, which was comparable to the effect of PQ on incidence of blood-stage infections. 92% of Pv and 79% of Pf gametocyte-positive infections were asymptomatic. Pv and to a lesser extent Pf gametocyte positivity and density were associated with high blood-stage parasite densities. Multivariate analysis revealed that the odds of gametocytes were significantly reduced in mixed-species infections compared to single-species infections for both species (ORPv = 0.39 [95% CI 0.25-0.62], ORPf = 0.33 [95% CI 0.18-0.60], p<0.001). No difference between the PQ and placebo treatment arms was observed in density of Pv gametocytes or in the proportion of Pv infections that carried gametocytes. First infections after blood-stage and placebo treatment, likely caused by a relapsing hypnozoite, were equally likely to carry gametocytes than first infections after PQ treatment, likely caused by an infective mosquito bite. CONCLUSION: Pv relapses and new infections are associated with similar levels of gametocytaemia. Relapses thus contribute considerably to the Pv reservoir highlighting the importance of effective anti-hypnozoite treatment for efficient control of Pv. TRIAL REGISTRATION: ClinicalTrials.gov NCT02143934.
- Publisher
- PLOS
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 28732068
- Publisher's Version
- https://doi.org/10.1371/journal.pntd.0005753
- Open Access at Publisher's Site
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005753- NHMRC Grants
- NHMRC/1016443, NHMRC/1043345, NHMRC/1021544,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-08-30 02:22:19
Last Modified: 2017-09-04 01:33:03