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Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection
Malaria Journal ( IF 2.4 ) Pub Date : 2021-08-26 , DOI: 10.1186/s12936-021-03879-9
Mavuto Mukaka 1, 1 , Pimnara Peerawaranun 1 , Daniel M Parker 2 , Ladda Kajeechiwa 3 , Francois H Nosten 3, 4 , Thuy-Nhien Nguyen 4, 5 , Tran Tinh Hien 4, 5 , Rupam Tripura 1, 4, 6 , Thomas J Peto 1, 4 , Koukeo Phommasone 7, 8 , Mayfong Mayxay 7, 9 , Paul N Newton 4, 7 , Mallika Imwong 1, 10 , Nicholas P J Day 1, 4 , Arjen M Dondorp 1, 4 , Nicholas J White 1, 4 , Lorenz von Seidlein 1, 4
Affiliation  

Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources. Data from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL). At baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected. Reactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.

中文翻译:

大湄公河次区域家庭中的疟疾聚集:对反应性病例检测的操作影响

疟疾反应性病例检测是对指示病例的密切接触者进行检测,如果呈阳性,则对其进行治疗。它被纳入大湄公河次区域国家的国家疟疾控制计划,以加速消除疟疾。然而,由于产量低、影响证据有限以及对资源的高需求,反应性病例检测在控制和消除疟疾方面的价值仍然存在争议。分析了来自缅甸、越南、柬埔寨和老挝的大规模药物管理 (MDA) 研究的流行病学评估数据,以探索家庭中的疟疾感染聚集情况。然后确定在假设的反应性病例检测程序中筛查的接触者中疟疾阳性病例的比例。假设用于快速诊断测试 (RDT) 检测的寄生虫密度阈值 > 50/µL (50,000/mL),基于干血斑 (DBS) 的 PCR > 5/µL (5000/mL) 和超灵敏PCR (uPCR) 的验证检测限为 0.0022/µL (22/mL)。在基线时,在 MDA 之前,uPCR 在 693 个家庭中检测到 1223 例疟原虫感染。存在聚集的疟原虫感染。在 637 个无症状感染的家庭中,44% (278/637) 有一名以上的成员感染了疟原虫。在有症状感染的 132 户家庭中,65% (86/132) 有一名以上的成员感染了疟原虫。在基线时,4% 的家庭感染了一种以上的恶性疟原虫,但在 MDA 后三个月,没有一个家庭感染过一种以上的恶性疟原虫。使用 DBS PCR 进行的反应性病例检测将在 6 个家庭中检测到另外 10 个病例,而 RDT 筛查将在 169 个至少有一个 RDT 阳性病例的家庭中的三个家庭中检测到另外 5 个病例。这意味着每 1000 人筛查中分别发现 19 例和 9 例额外病例。总体而言,假设所有发热的 RDT 阳性患者都将寻求治疗并使用 RDT 引发反应性病例检测,那么这些社区中 1052 例 (99.5%) 疟原虫感染中的 1047 例将未被发现。预计大湄公河次区域的反应性病例检测对疟疾负担的影响可以忽略不计,但在人力和财政资源方面会产生大量成本。在 169 户至少有一个 RDT 阳性病例的家庭中,RDT 屏幕会在三个家庭中检测到另外五个病例。这意味着每 1000 人筛查中分别发现 19 例和 9 例额外病例。总体而言,假设所有发热的 RDT 阳性患者都将寻求治疗并使用 RDT 引发反应性病例检测,那么这些社区中 1052 例 (99.5%) 疟原虫感染中的 1047 例将未被发现。预计大湄公河次区域的反应性病例检测对疟疾负担的影响可以忽略不计,但在人力和财政资源方面会产生大量成本。在 169 户至少有一个 RDT 阳性病例的家庭中,RDT 屏幕会在三个家庭中检测到另外五个病例。这意味着每 1000 人筛查中分别发现 19 例和 9 例额外病例。总体而言,假设所有发热的 RDT 阳性患者都将寻求治疗并使用 RDT 引发反应性病例检测,那么这些社区中 1052 例 (99.5%) 疟原虫感染中的 1047 例将未被发现。预计大湄公河次区域的反应性病例检测对疟疾负担的影响可以忽略不计,但在人力和财政资源方面会产生大量成本。假设所有发热的 RDT 阳性患者都将寻求治疗并使用 RDT 引起反应性病例检测,那么这些社区中 1052 例 (99.5%) 疟原虫感染中的 1047 例将未被发现。预计大湄公河次区域的反应性病例检测对疟疾负担的影响可以忽略不计,但在人力和财政资源方面会产生大量成本。假设所有发热的 RDT 阳性患者都将寻求治疗并使用 RDT 引起反应性病例检测,那么这些社区中 1052 例 (99.5%) 疟原虫感染中的 1047 例将未被发现。预计大湄公河次区域的反应性病例检测对疟疾负担的影响可以忽略不计,但在人力和财政资源方面会产生大量成本。
更新日期:2021-08-27
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