Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection.

Mavuto Mukaka,Francois H Nosten,Thomas J Peto,Thuy-Nhien Nguyen,Koukeo Phommasone,Pimnara Peerawaranun,Nicholas J White,Arjen M Dondorp,Tran Tinh Hien,Daniel M Parker,Paul N Newton,Lorenz Von Seidlein,Mallika Imwong,Nicholas P J Day,Ladda Kajeechiwa,Rupam Tripura,Mayfong Mayxay

doi:10.1186/s12936-021-03879-9

Abstract

BackgroundMalaria 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.MethodsData 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).ResultsAt 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.ConclusionReactive 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.

Highlights

Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases
This approach was supported in sub-Saharan Africa by a recent analysis of Demographic and Health Surveys (DHS) data which found strong evidence of household clustering of Plasmodium falciparum infections in children [13]
50% (869/1753) were in villages where mass drug administration (MDA) were conducted, and the remainder were in control villages

Summary

Introduction

Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. After index cases of malaria are identified, their household members, neighbours, and other contacts are screened by RDT or microscopy and treated with anti-malarials if they test positive [12] This approach was supported in sub-Saharan Africa by a recent analysis of Demographic and Health Surveys (DHS) data which found strong evidence of household clustering of Plasmodium falciparum infections in children [13]. A recent study from Namibia found that indoor residual insecticide spraying and presumptive anti-malarial treatment of household members of a P. falciparum malaria index case significantly reduced malaria transmission [14] This is at least in part because in sub-Saharan Africa the endophilic–endophagic and mainly nocturnal Anopheles species tend to stay within human habitations after a blood meal and infect other household and community members during subsequent blood meals. An adaptation of the “1-3-7” approach, named “case investigation focus investigation and response” (CIFIR) is being strongly promoted in South-East Asia, there is only weak evidence in its support, and there are many important differences in malaria epidemiology, accessibility and control programme resources and capability between China and the South-East Asian region

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