Getachew Hallelujah, Habtamu Kassahun, Abossie Ashenafi, Demissew Assalif, Tsegaye Arega, Degefa Teshome, Zhong Daibin, Wang Xiaoming, Zhou Guofa, Lee MingChieh, Kazura James W, King Christopher L, Yewhalaw Delenasaw, Yan Guiyun
Department of Medical Laboratory Technology, Arbaminch College of Health Sciences, Arbaminch, Ethiopia.
Department of Medical Laboratory Sciences, Institute of Health, Jimma University, Jimma, Ethiopia.
Malar J. 2025 Apr 17;24(1):125. doi: 10.1186/s12936-025-05365-y.
Existing malaria control strategies for Plasmodium vivax are challenging due to its dormant and relapsing liver stages, as well as the early onset of gametocytogenesis. Primaquine (PQ) effectively eliminates dormant stages and can kill gametocytes; however, it necessitates repeated dosing. In this study, the effectiveness of chloroquine (CQ) plus low-dose of PQ on recurrence and its transmission-blocking activity was evaluated.
Between September 2019 and July 2022, a prospective cohort study was conducted in the Jimma-Arjo and Dabo-Hanna districts of the Oromia region in Ethiopia. A total of 214 uncomplicated cases of P. vivax malaria were enrolled in the study. Participants were treated with either CQ alone (106) or CQ + PQ (108), based on whether their district was targeted for P. vivax elimination by the national malaria programme or not. After enrolment, participants were followed for clinical illness and parasitaemia on days 28, 42, and monthly for one year. To assess the effect of different treatment regimens on transmission-blocking activity, Anopheles arabiensis mosquitoes were used in direct membrane-feeding assays (DMFA) at baseline (pre-treatment) and on day 42 (post-treatment). Based on polymerase chain reaction (PCR) positivity, the time to the first recurrence was estimated using Kaplan-Meier survival analysis. Cox regression models were employed to assess risk factors for recurrence.
Of 3,590 individuals screened for malaria, 323 tested positive for P. vivax, and 214 were enrolled. Of these, 98.6% (211/214) completed the day 28 follow-up, and 67.3% (144/214) completed the one-year follow-up. Between days 28 and 42, 24% (95% CI 15.8-32.2%) of those individuals receiving CQ alone were PCR positive, and 10.3% (95% CI 4.5-16.0%) in those receiving CQ plus PQ. This represented a 57.3% reduction P. vivax recurrence in the CQ + PQ treatment group compared to CQ alone (risk ratio = 0.427, 95% CI 0.222-0.824, p = 0.008). During the year of follow-up at least one recurrence occurred in 70% (95% CI 59.1-80.2%) of the CQ alone and 46% (95% CI 35.5-58.1%) in the CQ + PQ treatment group (p < 0.001). Treatment regimen, high baseline parasitaemia and presence of gametocytaemia were risk factors for P. vivax recurrence. Compared to baseline DMFA at day 42, individuals showed an inhibition intensity of 39.0% in the CQ alone versus 77.8% in the CQ + PQ treatment group (p = 0.016), while inhibition prevalence was 35.2% in the CQ alone and 70.1% in the CQ + PQ treatment group (p = 0.021).
This study demonstrate that with limited supervision of CQ + PQ treatment significantly lowers the risk of P. vivax recurrence in health clinics of southwest Ethiopia compared to CQ alone. Adding PQ to CQ also reduced P. vivax transmission to mosquito vectors relative to CQ alone but did not result in a complete transmission-blocking effect by day 42 post-treatment. Therefore, improved health education on treatment adherence and bed net use could enhance the effectiveness of PQ plus CQ. Higher doses of PQ for a shorter duration may be necessary to enhance treatment adherence, reduce recurrence rates, and decrease the risk of transmission.
由于间日疟原虫存在潜伏和复发的肝期以及配子体形成较早，现有的间日疟控制策略具有挑战性。伯氨喹（PQ）可有效消除潜伏阶段并能杀死配子体；然而，它需要重复给药。在本研究中，评估了氯喹（CQ）加低剂量PQ对复发的有效性及其传播阻断活性。
2019年9月至2022年7月，在埃塞俄比亚奥罗米亚地区的吉马 - 阿尔乔和达博 - 汉纳地区进行了一项前瞻性队列研究。共有214例间日疟原虫疟疾非复杂性病例纳入研究。根据其所在地区是否被国家疟疾规划列为间日疟消除目标地区，参与者分别接受单独CQ治疗（106例）或CQ + PQ治疗（108例）。入组后，在第28天、42天以及之后一年每月对参与者进行临床疾病和寄生虫血症随访。为评估不同治疗方案对传播阻断活性的影响，在基线（治疗前）和第42天（治疗后）使用阿拉伯按蚊进行直接膜饲试验（DMFA）。基于聚合酶链反应（PCR）阳性结果，使用Kaplan - Meier生存分析估计首次复发时间。采用Cox回归模型评估复发的危险因素。
在3590名筛查疟疾的个体中，323例间日疟原虫检测呈阳性，214例纳入研究。其中，98.6%（211/214）完成了第28天的随访，67.3%（144/214）完成了一年的随访。在第28天至42天之间，单独接受CQ治疗的个体中有24%（95%CI 15.8 - 32.2%）PCR呈阳性，而接受CQ加PQ治疗的个体中为10.3%（95%CI 4.5 - 16.0%）。与单独使用CQ相比，CQ + PQ治疗组间日疟原虫复发率降低了57.3%（风险比 = 0.427，95%CI 0.222 - 0.824，p = 0.008）。在一年的随访期间，单独使用CQ治疗组中70%（95%CI 59.1 - 80.2%）至少发生一次复发，CQ + PQ治疗组为46%（95%CI 35.5 - 58.1%）（p < 0.001）。治疗方案、高基线寄生虫血症和配子体血症的存在是间日疟原虫复发的危险因素。与第42天的基线DMFA相比，单独使用CQ治疗组个体的抑制强度为39.0%，而CQ + PQ治疗组为77.8%（p = 0.016），抑制率在单独使用CQ治疗组为35.2%，CQ + PQ治疗组为70.1%（p = 0.021）。
本研究表明，在埃塞俄比亚西南部的健康诊所中，与单独使用CQ相比，在有限监督下的CQ + PQ治疗可显著降低间日疟原虫复发风险。与单独使用CQ相比，在CQ中添加PQ也降低了间日疟原虫向蚊媒的传播，但在治疗后第42天未产生完全的传播阻断效果。因此，加强关于治疗依从性和使用蚊帐的健康教育可能会提高PQ加CQ的有效性。可能需要更高剂量的PQ且疗程更短，以提高治疗依从性、降低复发率并降低传播风险。
