Wampfler Rahel, Hofmann Natalie E, Karl Stephan, Betuela Inoni, Kinboro Benson, Lorry Lina, Silkey Mariabeth, Robinson Leanne J, Mueller Ivo, Felger Ingrid
Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.
PLoS Negl Trop Dis. 2017 Jul 21;11(7):e0005753. doi: 10.1371/journal.pntd.0005753. eCollection 2017 Jul.
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.
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.
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.
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.
ClinicalTrials.gov NCT02143934.
伯氨喹（PQ）是目前唯一获得许可的预防间日疟原虫（Pv）复发的抗疟药物。它还能清除成熟的恶性疟原虫（Pf）配子体，从而减少治疗后的传播。在巴布亚新几内亚儿童的治疗至再感染队列中进行随机PQ治疗，有助于研究根治后Pv和Pf配子体携带情况，并调查Pv复发的作用。
儿童接受氯喹、蒿甲醚-本芴醇联合PQ或安慰剂进行根治。随后在8个月内每隔2至4周采集血样。通过靶向pvs25和pfs25的定量逆转录聚合酶链反应检测配子体。
PQ治疗使Pv配子体的发生率降低了73%，这与PQ对血期感染发生率的影响相当。92%的Pv和79%的Pf配子体阳性感染无症状。Pv以及在较小程度上Pf配子体的阳性率和密度与高血期寄生虫密度相关。多变量分析显示，与单物种感染相比，混合物种感染中两种物种的配子体几率均显著降低（ORPv = 0.39 [95% CI 0.25 - 0.62]，ORPf = 0.33 [95% CI 0.18 - 0.60]，p<0.001）。在Pv配子体密度或携带配子体的Pv感染比例方面，未观察到PQ治疗组和安慰剂治疗组之间存在差异。血期和安慰剂治疗后的首次感染可能由复发的休眠子引起，与PQ治疗后的首次感染（可能由感染性蚊虫叮咬引起）携带配子体的可能性相同。
Pv复发和新感染与相似水平的配子血症相关。因此，复发对Pv储存库有很大贡献，突出了有效的抗休眠子治疗对有效控制Pv的重要性。
ClinicalTrials.gov NCT02143934。
