Ntuku Henry, Whittemore Brooke, Dausab Lucille, Jang Ihn Kyung, Golden Allison, Sheahan William, Wu Xue, Slater Hannah, Domingo Gonzalo J, Das Smita, Duarte Elias, Eloff Lydia, Bousema Teun, Lanke Kjerstin, Gueye Cara Smith, Prach Lisa M, Raman Jaishree, Uusiku Petrina, Katokele Stark, Gosling Roly, Greenhouse Bryan, Mumbengegwi Davis, Hsiang Michelle S
Malaria Elimination Initiative, Global Health Group, University of California, San Francisco (UCSF), San Francisco 94158, USA.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75390, USA.
EBioMedicine. 2025 Jan;111:105489. doi: 10.1016/j.ebiom.2024.105489. Epub 2024 Dec 9.
The standard malaria rapid diagnostic test (RDT) and newer ultra-sensitive RDT (uRDT) target Plasmodium falciparum histidine rich protein-2 (HRP2), which persists post-treatment. The duration of test positivity has not previously been studied in a low transmission setting.
We conducted a longitudinal cohort study in a low transmission setting in Namibia. RDT-positive individuals identified through passive and active case detection were treated and followed weekly for testing by RDT and uRDT, HRP2 quantification, quantitative PCR (qPCR) of parasitemia, and quantitative reverse transcriptase PCR (RT-PCR) of gametocytemia, until RDT and uRDT were negative for two consecutive weeks. Determinants of persistent positivity were identified using Cox proportional hazards models.
Among 137 participants with complete follow-up and no evidence of resurgence during follow-up, median duration of positivity was 42 days (range: 3-98 range) for RDT, compared to 67 days (range 12-105) for uRDT. In a sub-analysis of those with laboratory data before treatment (n = 60), drug resistance did not explain persistent positivity. Younger age (<15 years versus ≥15 years: aHR: 1.85, 95% CI 1.04-3.30, and 1.67, 95% CI 0.96-2.89, for RDT and uRDT, respectively), higher initial parasite density (highest versus lowest tertile: aHR 0.11, 95% CI 0.04-0.32 and 0.19, 95% CI 0.07-0.48 for RDT and uRDT, respectively), and persistent parasitemia (≥7 days versus reference of <7 days, aHR 0.39, 95% CI 0.20-0.76, and 0.40, 95% CI 0.21-0.76 for RDT and uRDT, respectively) were associated with longer duration of positivity.
Duration of RDT/uRDT positivity was more than double compared to reports from higher endemic settings, potentially due to lower population immunity to clear parasite DNA and antigen. Prolonged duration of positivity compromises their use to detect current infection, but increased detection of recent infection can facilitate surveillance and inform elimination efforts.
The project was funded by the Bill and Melinda Gates Foundation (A128488 and INV1135840), Horchow Family Fund (5300375400), and Chan Zuckerberg Biohub.
标准疟疾快速诊断检测（RDT）和新型超灵敏RDT（uRDT）检测的目标是恶性疟原虫富含组氨酸蛋白2（HRP2），该蛋白在治疗后仍会持续存在。此前尚未在低传播环境中研究检测阳性的持续时间。
我们在纳米比亚的一个低传播环境中开展了一项纵向队列研究。通过被动和主动病例检测确定的RDT阳性个体接受治疗，并每周进行随访，通过RDT和uRDT检测、HRP2定量、疟原虫血症的定量聚合酶链反应（qPCR）以及配子体血症的定量逆转录聚合酶链反应（RT-PCR），直至RDT和uRDT连续两周呈阴性。使用Cox比例风险模型确定持续阳性的决定因素。
在137名有完整随访且随访期间无复发证据的参与者中，RDT检测阳性的中位持续时间为42天（范围：3 - 98天），而uRDT为67天（范围12 - 105天）。在对治疗前有实验室数据的参与者（n = 60）进行的亚分析中，耐药性并不能解释持续阳性。年龄较小（<15岁与≥15岁相比：RDT和uRDT的调整后风险比分别为1.85，95%置信区间1.04 - 3.30和1.67，95%置信区间0.96 - 2.89）、初始寄生虫密度较高（最高三分位数与最低三分位数相比：RDT和uRDT的调整后风险比分别为0.11，95%置信区间0.04 - 0.32和0.19，95%置信区间0.07 - 0.48）以及持续疟原虫血症（≥7天与<7天的参考值相比：RDT和uRDT的调整后风险比分别为0.39，95%置信区间0.20 - 0.76和0.40，95%置信区间0.21 - 0.76）与阳性持续时间较长有关。
与高流行地区的报告相比，RDT/uRDT阳性持续时间增加了一倍多，这可能是由于人群清除寄生虫DNA和抗原的免疫力较低。阳性持续时间延长会影响其用于检测当前感染，但增加对近期感染的检测有助于监测并为消除疟疾工作提供信息。
该项目由比尔及梅琳达·盖茨基金会（A128488和INV1135840）、霍乔家族基金（5300375400）以及陈·扎克伯格生物中心资助。
