Sustained Malaria Transmission despite Reactive Screen-and-Treat in a Low-Transmission Area of Southern Zambia

Abstract

Malaria elimination strategies are designed to more effectively identify and treat infected individuals to interrupt transmission. One strategy, reactive screen-and-treat, starts with passive detection of symptomatic cases at health facilities. Individuals residing within the index case and neighboring households are screened with a malaria rapid diagnostic test (RDT) and treated if positive. However, it is unclear to what extent this strategy is effective in reducing transmission. Reactive screen-and-treat was implemented in Choma district, Southern Province, Zambia, in 2013, in which residents of the index case and neighboring households within 140 m were screened with an RDT. From March 2016 to July 2018, the screening radius was extended to 250-m, and additional follow-up visits at 30 and 90 days were added to evaluate the strategy. Plasmodium falciparum parasite prevalence was measured using an RDT and by quantitative PCR (qPCR). A 24-single nucleotide polymorphism molecular bar-code assay was used to genotype parasites. Eighty-four index case households with 676 residents were enrolled between March 2016 and March 2018. Within each season, parasite prevalence declined significantly in index households at the 30-day visit and remained low at the 90-day visit. However, parasite prevalence was not reduced to zero. Infections identified by qPCR persisted between study visits and were not identified by RDT. Parasites identified within the same household were most genetically related; however, overall parasite relatedness was low and similar across time and space. Thus, despite implementation of a reactive screen-and-treat program, parasitemia was not eliminated, and persisted in targeted households for at least 3 months.

Figure 1.

Study area and parasite prevalence of those sampled. (A) Location of all households sampled as part of the reactive screen-and-treat program within the catchment area of Macha Hospital within Choma district, Southern Province. Households are marked either positive (red) or negative (green) if at least one positive case (by quantitative PCR [qPCR]) was identified in that household. (B) Number of individuals enrolled in the study colored by month (1–12). (C) Parasite prevalence by rapid diagnostic test (RDT) (top row) and qPCR (bottom row) for the index household, households within 140 m, and those between 141 and 250 m. Tests were performed during initial, 30-day, and 90-day visits. Overall prevalence by RDT was lower than that by qPCR and highest in the index household. (D) Prevalence by season for the index, 140 m and 250 m households by visit number. This figure appears in color at www.ajtmh.org.

Figure 2.

Trajectory of individual infection status spanning initial and subsequent visits. Individual test results by (A) rapid diagnostic test (RDT) and (B) quantitative PCR (qPCR) on the initial, 30-day, and 90-day visits for individuals who had at least one positive test (either by qPCR or RDT). Of these individuals, much fewer were RDT positive than those who were qPCR positive. However, in both instances, there were few consecutive positive events. This figure appears in color at www.ajtmh.org.

Figure 3.

Genetic relatedness between infections. Genetic distance was calculated between infections using 24-single nucleotide polymorphism (SNP) bar codes. (A) Genetic distance of infections between all combinations of index household, households within 140 m, and households 141–250 m of the index household was calculated. In general, infections found within the same household were the most genetically related, with no clear pattern with increasing distances or within further distances (e.g., between infections all within 140 m of the index household). (B) Genetic distance between all pairs of infections by physical and temporal distance was calculated with more genetically related infections shown in red. (C) All infections were compared with the index infection, when possible, based on if the secondarily identified infection was rapid diagnostic test (RDT) and quantitative PCR (qPCR) positive or only qPCR positive. Surprisingly, infections that were only qPCR positive were more related to the index infection than those that were both RDT and qPCR positive. (D) For infections that occurred within 1 month of each other, the pairwise genetic distance was calculated. Few samples with multiple bar codes (shown in redlines) all occurred within 1 month of each other and the genetic distances are shown. Cumulative distribution function of all genetic distances for the within 1 month comparison is shown. This figure appears in color at www.ajtmh.org.