Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum

Download
Author
Wampfler, R; Hofmann, NE; Karl, S; Betuela, I; Kinboro, B; Lorry, L; Silkey, M; Robinson, LJ; Mueller, I; Felger, IDate
2017-07-01Source Title
PLoS Neglected Tropical DiseasesPublisher
PUBLIC LIBRARY SCIENCEAffiliation
Medical Biology (W.E.H.I.)Metadata
Show full item recordDocument Type
Journal ArticleCitations
Wampfler, R., Hofmann, N. E., Karl, S., Betuela, I., Kinboro, B., Lorry, L., Silkey, M., Robinson, L. J., Mueller, I. & Felger, I. (2017). Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum. PLOS NEGLECTED TROPICAL DISEASES, 11 (7), https://doi.org/10.1371/journal.pntd.0005753.Access Status
Open AccessAbstract
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.
Export Reference in RIS Format
Endnote
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
Refworks
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References