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Background: Reactive case detection (RCD) seeks to enhance malaria surveillance and control by identifying and treating parasitaemic individuals residing near index cases. In Zambia, this strategy starts with passive detection of symptomatic incident malaria cases at local health facilities or by community health workers, with subsequent home visits to screen-and-treat residents in the index case and neighbouring (secondary) households within a 140-m radius using rapid diagnostic tests (RDTs). However, a small circular radius may not be the most efficient strategy to identify parasitaemic individuals in low-endemic areas with hotspots of malaria transmission. To evaluate if RCD efficiency could be improved by increasing the probability of identifying parasitaemic residents, environmental risk factors and a larger screening radius (250 m) were assessed in a region of low malaria endemicity. Methods: Between January 12, 2015 and July 26, 2017, 4170 individuals residing in 158 index and 531 secondary households were enrolled and completed a baseline questionnaire in the catchment area of Macha Hospital in Choma District, Southern Province, Zambia. Plasmodium falciparum prevalence was measured using PfHRP2 RDTs and quantitative PCR (qPCR). A Quickbird™ high-resolution satellite image of the catchment area was used to create environmental risk factors in ArcGIS, and generalized estimating equations were used to evaluate associations between risk factors and secondary households with parasitaemic individuals. Results: The parasite prevalence in secondary (non-index case) households was 0.7% by RDT and 1.8% by qPCR. Overall, 8.5% (n = 45) of secondary households had at least one resident with parasitaemia by qPCR or RDT. The risk of a secondary household having a parasitaemic resident was significantly increased in proximity to higher order streams and marginally with increasing distance from index households. The adjusted OR for proximity to third- and fifth-order streams were 2.97 (95% CI 1.04–8.42) and 2.30 (95% CI 1.04–5.09), respectively, and that for distance to index households for each 50 m was 1.24 (95% CI 0.98–1.58). Conclusion: Applying proximity to streams as a screening tool, 16% (n = 3) more malaria-positive secondary households were identified compared to using a 140-m circular screening radius. This analysis highlights the potential use of environmental risk factors as a screening strategy to increase RCD efficiency. [ABSTRACT FROM AUTHOR]

Background: Southern Province, Zambia has experienced a dramatic decline in Plasmodium falciparum malaria transmission in the past decade and is targeted for elimination. Zambia's National Malaria Elimination Program recommends reactive case detection (RCD) within 140 m of index households to enhance surveillance and eliminate remaining transmission foci.Methods: To evaluate whether RCD captures local transmission, we genotyped 26 microsatellites from 106 samples collected from index (n = 27) and secondary (n = 79) cases detected through RCD in the Macha Hospital catchment area between January 2015 and April 2016.Results: Participants from the same RCD event harbored more genetically related parasites than those from different RCD events, suggesting that RCD captures, at least in part, infections related through local transmission. Related parasites clustered in space and time, up to at least 250 m from index households. Spatial analysis identified a putative focal transmission hotspot.Conclusions: The current RCD strategy detects focal transmission events, although programmatic guidelines to screen within 140 m of index households may fail to capture all secondary cases. This study highlights the utility of parasite genetic data in assessing programmatic interventions, and similar approaches may be useful to malaria elimination programs seeking to tailor intervention strategies to the underlying transmission epidemiology. [ABSTRACT FROM AUTHOR]

Background: Substantial reductions in the burden of malaria have been documented in parts of sub-Saharan Africa, with elimination strategies and goals being formulated in some regions. Within this context, understanding the epidemiology of low-level malaria transmission is crucial to achieving and sustaining elimination. A 24 single-nucleotide-polymorphism Plasmodium falciparum molecular barcode was used to characterize parasite populations from infected individuals identified through passive and active case detection in an area approaching malaria elimination in southern Zambia. Methods: The study was conducted in the catchment area of Macha Hospital in Choma District, Southern Province, Zambia, where the parasite prevalence declined over the past decade, from 9.2% in 2008 to less than 1% in 2013. Parasite haplotypes from actively detected, P. falciparum-infected participants enrolled in a serial cross-sectional, community-based cohort study from 2008 to 2013 and from passively detected, P. falciparum-infected individuals enrolled at five rural health centres from 2012 to 2015 were compared. Changes in P. falciparum genetic relatedness, diversity and complexity were analysed as malaria transmission declined. Results: Actively detected cases identified in the community were most commonly rapid diagnostic test negative, asymptomatic and had submicroscopic parasitaemia. Phylogenetic reconstruction using concatenated 24 SNP barcode revealed a separation of parasite haplotypes from passively and actively detected infections, consistent with two genetically distinct parasite populations. For passively detected infections identified at health centres, the proportion of detectable polyclonal infections was consistently low in all seasons, in contrast with actively detected infections in which the proportion of polyclonal infections was high. The mean genetic divergence for passively detected infections was 34.5% for the 2012-2013 transmission season, 37.8% for the 2013-2014 season, and 30.8% for the 2014-2015 season. The mean genetic divergence for actively detected infections was 22.3% in the 2008 season and 29.0% in the 2008-2009 season and 9.9% across the 2012-2014 seasons. Conclusions: Distinct parasite populations were identified among infected individuals identified through active and passive surveillance, suggesting that infected individuals detected through active surveillance may not have contributed substantially to ongoing transmission. As parasite prevalence and diversity within these individuals declined, resource-intensive efforts to identify the chronically infected reservoir may not be necessary to eliminate malaria in this setting. [ABSTRACT FROM AUTHOR]

Background: As malaria transmission declines in many regions of sub-Saharan Africa, interventions to identify the asymptomatic reservoir are being deployed with the goals of improving surveillance and interrupting transmission. Reactive case detection strategies, in which individuals with clinical malaria are followed up at their home and household residents and neighbours are screened and treated for malaria, are increasingly used as part of malaria elimination programmes. Methods: A reactive screen-and-treat programme was implemented by the National Malaria Control Centre in Southern Province, Zambia, in which individuals residing within 140 m of an index case were screened with a malaria rapid diagnostic test (RDT) and treated if positive. The operational challenges during the early stages of implementing this reactive screen-and-treat programme in the catchment area of Macha Hospital in Southern Province, Zambia were assessed using rural health centre records, ground truth evaluation of community health worker performance, and data from serial cross-sectional surveys. The proportion of individuals infected with Plasmodium falciparum who were identified and treated was estimated by simulating reactive screen-and-treat and focal drug administration cascades. Results: Within the 1st year of implementation, community health workers followed up 32 % of eligible index cases. When index cases were followed up, 66 % of residents were at home in the index households and 58 % in neighbouring households. Forty-one neighbouring households of 26 index households were screened, but only 13 (32 %) were within the 140-m screening radius. The parasite prevalence by RDT was 22 % in index households and 5 % in neighbouring households. In a simulation model with complete follow-up, 22 % of the total infected population would be detected with reactive screen-and-treat but 57 % with reactive focal drug administration. Conclusions: With limited resources, coverage and diagnostic tools, reactive screen-and-treat will likely not be sufficient to achieve malaria elimination in this setting. However, high coverage with reactive focal drug administration could be efficient at decreasing the reservoir of infection and should be considered as an alternative strategy. [ABSTRACT FROM AUTHOR]

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.

To achieve and sustain malaria elimination, identification and treatment of the asymptomatic infectious reservoir is critical. Malaria rapid diagnostic tests (RDTs) are frequently used to identify asymptomatic, Plasmodium -infected individuals through test-and-treat strategies, but their sensitivity is low when used in low transmission settings. Characteristics of individuals with subpatent (RDT-negative but polymerase chain reaction [PCR]-positive) Plasmodium parasitemia were evaluated in southern Zambia where malaria transmission has declined and efforts to achieve malaria elimination are underway. Simple random sampling based on satellite imagery was used to select households for participation in community-based, cross-sectional surveys between 2008 and 2013. Questionnaires were administered to collect information on age, gender, recent history of malaria symptoms, and recent antimalarial drug use. Blood samples were collected by finger prick for Plasmodium falciparum histidine-rich protein 2 RDT, blood smears for microscopy, and dried blood spots for molecular analysis to detect malaria parasites and their sexual stage. Of 3,863 participants with complete data, 102 (2.6%) were positive by microscopy, RDT, or PCR. Of these, 48 (47%) had subpatent parasitemia. Most individuals with subpatent parasitemia were asymptomatic (85%). Compared with individuals without parasitemia, individuals with subpatent parasitemia were significantly more likely to be aged 5-25 years. Approximately one quarter (27%) of those with subpatent parasitemia had detectable gametocytemia. These findings suggest that strategies based on active or reactive case detection can identify asymptomatic individuals positive by RDT, but more sensitive diagnostic tests or focal drug administration may be necessary to target individuals with subpatent parasitemia to achieve malaria elimination.

Viral load monitoring for HIV treatment is recommended but not feasible in many settings. A point-of-care test using capillary blood would increase access but may require up to 200 μL of blood to achieve a lower limit of detection of 1000 copies/mL. This cross-sectional study evaluated the feasibility of collecting 200 μL of capillary blood and blood collection preferences among adults in rural Zambia. Adults seeking HIV counseling and testing at Macha Hospital were recruited in 2015. Capillary blood was collected in four 50 μL tubes. Blood collection was categorized as complete (200 μL collected), partial (all tubes filled but <200 μL obtained due to collection techniques), or incomplete (1-4 tubes attempted; <200 μL obtained due to insufficient blood flow). One fingerstick was required for 90% of the 201 participants. A median blood volume of 196 μL was collected. Complete, partial and incomplete collection was achieved in 34%, 59% and 6% of participants. The majority of participants (95%) preferred fingerstick over venous blood collection. A point-of-care viral load test requiring up to 200 μL of blood is feasible in a rural setting but would require training and supervision to ensure that sufficient blood was collected.