Background The impact of chemoprophylaxis targeting Plasmodium falciparum on Plasmodium vivax and Plasmodium ovale, which may remain quiescent as hypnozoites in the liver, is debated. Methods We conducted a nested case-control analysis of the outcomes of P. vivax and P. ovale infections in imported malaria cases in France among civilian travellers from January 1st, 2006, to December 31st, 2017. Using adjusted logistic regression, we assessed the effect of chemoprophylaxis on the incubation period, time from symptoms to diagnosis, management, blood results, symptoms, and hospitalization duration. We analysed the effect of blood-stage drugs (doxycycline, mefloquine, chloroquine, chloroquine-proguanil) or atovaquone-proguanil on the incubation period. We used a counterfactual approach to ascertain the causal effect of chemoprophylaxis on postinfection characteristics. Results Among 247 P. vivax- and 615 P. ovale-infected travellers, respectively, 30% and 47% used chemoprophylaxis, and seven (3%) and eight (1%) were severe cases. Chemoprophylaxis users had a greater risk of presenting symptoms more than two months after returning for both species (P. vivax odds ratio (OR), 2.91 [95% confidence interval (CI), 1.22–6.95], P= .02, P. ovale OR, 2.28 [95% CI, 1.47–3.53], P< .001). Using drugs only acting on the blood stage was associated with delayed symptom onset after 60 days, while using atovaquone-proguanil was not. Conclusions Civilian travellers infected with P. vivax or P. ovale reporting chemoprophylaxis use, especially of blood-stage agents, had a greater risk of delayed onset of illness. The impact of chemoprophylaxis on the outcomes of infection with relapse-causing species calls for new chemoprophylaxis acting against erythrocytic and liver stages.

中文翻译：

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化学预防对平民旅行者间日疟原虫和卵形疟原虫感染的影响：一项针对 862 名患者的巢式病例对照研究，采用反事实方法

背景 针对恶性疟原虫的化学预防对间日疟原虫和卵形疟原虫的影响存在争议，这些疟原虫可能作为休眠体在肝脏中保持静止。方法 我们对 2006 年 1 月 1 日至 2017 年 12 月 31 日期间法国输入性疟疾病例中间日疟原虫和卵形疟原虫感染的结果进行了巢式病例对照分析。使用调整后的逻辑回归，我们评估了化学预防对潜伏期、从症状到诊断的时间、管理、血液结果、症状和住院时间的影响。我们分析了血期药物（多西环素、甲氟喹、氯喹、氯喹-氯胍）或阿托伐醌-氯胍对潜伏期的影响。我们使用反事实方法来确定化学预防对感染后特征的因果影响。结果 在 247 名 P. vivax 和 615 名 P. ovale 感染的旅行者中，分别有 30% 和 47% 使用了化学预防，其中 7 例 (3%) 和 8 例 (1%) 为重症病例。对于这两个物种，化学预防使用者在返回两个多月后出现症状的风险更大（间日疟原虫比值比 (OR)，2.91 [95% 置信区间 (CI)，1.22–6.95]，P=.02，P.卵形 OR，2.28 [95% CI，1.47–3.53]，P<.001）。使用仅作用于血液阶段的药物与 60 天后症状发作延迟有关，而使用阿托瓦醌-氯胍则不然。结论 感染间日疟原虫或卵形疟原虫的平民旅行者报告使用了化学预防措施，尤其是血液阶段试剂，延迟发病的风险更大。化学预防对导致复发的物种感染结果的影响要求新的化学预防作用于红细胞和肝阶段。