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Background  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.    Methods  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).    Results  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.    Conclusion  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.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12936-021-03879-9.

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