Temporal genomic analysis of Plasmodium falciparum reveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia.

The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.

Temporal and spatial analysis of Plasmodium falciparum genomics reveals patterns of parasite connectivity in a low-transmission district in Southern Province, Zambia.

BACKGROUND: Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions and strategies in regions approaching elimination. Parasite genomics are increasingly used to monitor epidemiologic trends, including assessing residual transmission across seasons and importation of malaria into these regions. METHODS: In a low and seasonal transmission setting of southern Zambia, a total of 441 Plasmodium falciparum samples collected from 8 neighbouring health centres between 2012 and 2018 were genotyped using molecular inversion probes (MIPs n = 1793) targeting a total of 1832 neutral and geographically informative SNPs distributed across the parasite genome. After filtering for quality and missingness, 302 samples and 1410 SNPs were retained and used for downstream population genomic analyses. RESULTS: The analyses revealed most (67%, n = 202) infections harboured one clone (monogenomic) with some variation at local level suggesting low, but heterogenous malaria transmission. Relatedness identity-by-descent (IBD) analysis revealed variable distribution of IBD segments across the genome and 6% of pairs were highly-related (IBD ≥ 0.25). Some of the highly-related parasite populations persisted across multiple seasons, suggesting that persistence of malaria in this low-transmission region is fueled by parasites "seeding" across the dry season. For recent years, clusters of clonal parasites were identified that were dissimilar to the general parasite population, suggesting parasite populations were increasingly fragmented at small spatial scales due to intensified control efforts. Clustering analysis using PCA and t-SNE showed a lack of substantial parasite population structure. CONCLUSION: Leveraging both genomic and epidemiological data provided comprehensive picture of fluctuations in parasite populations in this pre-elimination setting of southern Zambia over 7 years.

Declining Age-Specific Seroprevalence and Seroconversion Rates in Plasmodium falciparum from 2009 to 2018 Documents Progress toward Malaria Elimination in Southern Zambia.

Obtaining accurate malaria surveillance data is challenging in low-transmission settings because large sample sizes are required to estimate incidence and prevalence precisely. Serology is an additional tool to document progress toward malaria elimination. An enzyme immunoassay to Plasmodium falciparum lysate was used to estimate age-specific seroprevalence among residents of southern Zambia, where malaria transmission has declined to pre-elimination levels during the past two decades. Plasma was eluted from 3,362 dried blood spots collected during five cross-sectional surveys conducted between 2009 and 2012, and again in 2018. Annual seroconversion rates (SCRs), an estimate of the force of infection, were calculated using a reversible catalytic model. The SCR decreased by two thirds from a level of approximately 0.15/year in 2009 and 2010 to approximately 0.05/year in 2011 and 2012, and then decreased 5-fold to 0.01/year by 2018, demonstrating the utility of serology in documenting progress toward elimination.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

What Heterogeneities in Individual-level Mobility Are Lost During Aggregation? Leveraging GPS Logger Data to Understand Fine-scale and Aggregated Patterns of Mobility.

Human movement drives spatial transmission patterns of infectious diseases. Population-level mobility patterns are often quantified using aggregated data sets, such as census migration surveys or mobile phone data. These data are often unable to quantify individual-level travel patterns and lack the information needed to discern how mobility varies by demographic groups. Individual-level datasets can capture additional, more precise, aspects of mobility that may impact disease risk or transmission patterns and determine how mobility differs across cohorts; however, these data are rare, particularly in locations such as sub-Saharan Africa. Using detailed GPS logger data collected from three sites in southern Africa, we explore metrics of mobility such as percent time spent outside home, number of locations visited, distance of locations, and time spent at locations to determine whether they vary by demographic, geographic, or temporal factors. We further create a composite mobility score to identify how well aggregated summary measures would capture the full extent of mobility patterns. Although sites had significant differences in all mobility metrics, no site had the highest mobility for every metric, a distinction that was not captured by the composite mobility score. Further, the effects of sex, age, and season on mobility were all dependent on site. No factor significantly influenced the number of trips to locations, a common way to aggregate datasets. When collecting and analyzing human mobility data, it is difficult to account for all the nuances; however, these analyses can help determine which metrics are most helpful and what underlying differences may be present.

The Unmeasured Burden of Febrile, Respiratory, and Diarrheal Illnesses Identified Through Active Household Surveillance in a Low Malaria Transmission Setting in Southern Zambia.

Malaria incidence has declined in southern Zambia over recent decades, leading to efforts to achieve and sustain malaria elimination. Understanding the remaining disease burden is key to providing optimal health care. A longitudinal study conducted in a rural area of Choma District, Southern Province, Zambia, assessed the prevalence of and factors associated with symptoms of non-malarial illnesses and treatment-seeking behavior. We analyzed data collected monthly between October 2018 through September 2020 from 1,174 individuals from 189 households. No incident malaria cases were detected by rapid diagnostic tests among febrile participants. Mixed-effects logistic regression identified factors associated with cough, fever, diarrhea, and treatment-seeking. Incidence rates of cough (192 of 1,000 person-months), fever (87 of 1,000 person-months), and fever with cough (37 of 1,000 person-months) were highest among adults older than 65 years. Diarrhea incidence (37 of 1,000 person-months) was highest among children younger than 5 years. For every additional symptomatic household member, one's odds of experiencing symptoms increased: cough by 47% (95% CI, 40-55), fever by 31% (95% CI, 23-40), diarrhea by 31% (95% CI, 17-46), and fever with cough by 112% (95% CI, 90-137), consistent with household clustering of illnesses. However, between 35% and 75% of participants did not seek treatment for their symptoms. Treatment-seeking was most common for children 5 to 9 years old experiencing diarrhea (adjusted odds ratio, 3.61; 95% CI, 1.42-9.18). As malaria prevalence reduces, respiratory and diarrheal infections persist, particularly among young children but, notably, also among adults older than 65 years. Increasing awareness of the disease burden and treatment-seeking behavior are important for guiding resource re-allocation as malaria prevalence declines in this region.

Understudied Anophelines Contribute to Malaria Transmission in a Low-Transmission Setting in the Choma District, Southern Province, Zambia.

Malaria transmission has declined substantially in Southern Province, Zambia, which is considered a low-transmission setting. The Zambian government introduced a reactive test-and-treat strategy to identify active zones of transmission and treat parasitemic residents. This study was conducted in the Choma District, Southern Province, Zambia, concurrently with an evaluation of this strategy to identify vectors responsible for sustaining transmission, and to identify entomological, spatial, and ecological risk factors associated with increased densities of mosquitoes. Anophelines were collected with CDC light traps indoors and near animal pens in index cases and neighboring households. Outdoor collections captured significantly more anophelines than indoor traps, and 10 different anopheline species were identified. Four species (Anopheles arabiensis, An. rufipes, An. squamosus, and An. coustani) were positive for Plasmodium falciparum circumsporozoite protein by ELISA, and 61% of these 26 anophelines were captured outdoors. Bloodmeal assays confirm plasticity in An. arabiensis foraging, feeding both on humans and animals, whereas An. rufipes, An. squamosus, and An. coustani were largely zoophilic and exophilic. Linear regression of count data for indoor traps revealed that households with at least one parasitemic resident by polymerase chain reaction testing was associated with higher female anopheline counts. This suggests that targeting households with parasitemic individuals for vector interventions may reduce indoor anopheline populations. However, many vectors species responsible for transmission may not be affected by indoor interventions because they are primarily exophilic and forage opportunistically. These data underscore the necessity for further evaluation of vector surveillance and control tools that are effective outdoors, in conjunction with current indoor-based interventions.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency and Gametocytemia in a Pre-Elimination, Low Malaria Transmission Setting in Southern Zambia.

The WHO recommends single low-dose (SLD) primaquine as a gametocytocide to reduce Plasmodium falciparum transmission in areas of low transmission. Despite this recommendation, uptake of SLD primaquine has been low because of concerns of glucose-6-phosphate dehydrogenase (G6PD) deficiency. Individuals with G6PD deficiency can experience hemolysis when exposed to primaquine. In Southern Province, Zambia, malaria transmission has declined significantly over the past decade. Single low-dose primaquine may be an effective tool, but there is limited information on G6PD deficiency. We screened 137 residents in Macha, Southern Province, Zambia, and the prevalence of G6PD (A-) was 15%. We also revisited data collected from 2008 to 2013 in the same area and found the highest gametocyte burden among those aged 5-15 years. The findings from this study suggest that SLD primaquine targeted to school-aged children may be an effective tool to help achieve malaria elimination in southern Zambia.

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

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.

Improving the efficiency of reactive case detection for malaria elimination in southern Zambia: a cross-sectional study.

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.

Distinct Antibody Signatures Associated with Different Malaria Transmission Intensities in Zambia and Zimbabwe.

Antibodies to Plasmodium falciparum are specific biomarkers that can be used to monitor parasite exposure over broader time frames than microscopy, rapid diagnostic tests, or molecular assays. Consequently, seroprevalence surveys can assist with monitoring the impact of malaria control interventions, particularly in the final stages of elimination, when parasite incidence is low. The protein array format to measure antibodies to diverse P. falciparum antigens requires only small sample volumes and is high throughput, permitting the monitoring of malaria transmission on large spatial and temporal scales. We expanded the use of a protein microarray to assess malaria transmission in settings beyond those with a low malaria incidence. Antibody responses in children and adults were profiled, using a P. falciparum protein microarray, through community-based surveys in three areas in Zambia and Zimbabwe at different stages of malaria control and elimination. These three epidemiological settings had distinct serological profiles reflective of their malaria transmission histories. While there was little correlation between transmission intensity and antibody signals (magnitude or breadth) in adults, there was a clear correlation in children younger than 5 years of age. Antibodies in adults appeared to be durable even in the absence of significant recent transmission, whereas antibodies in children provided a more accurate picture of recent levels of transmission intensity. Seroprevalence studies in children could provide a valuable marker of progress toward malaria elimination.IMPORTANCE As malaria approaches elimination in many areas of the world, monitoring the effect of control measures becomes more important but challenging. Low-level infections may go undetected by conventional tests that depend on parasitemia, particularly in immune individuals, who typically show no symptoms of malaria. In contrast, antibodies persist after parasitemia and may provide a more accurate picture of recent exposure. Only a few parasite antigens-mainly vaccine candidates-have been evaluated in seroepidemiological studies. We examined antibody responses to 500 different malaria proteins in blood samples collected through community-based surveillance from areas with low, medium, and high malaria transmission intensities. The breadth of the antibody responses in adults was broad in all three settings and was a poor correlate of recent exposure. In contrast, children represented a better sentinel population for monitoring recent malaria transmission. These data will help inform the use of multiplex serology for malaria surveillance.

Genetic Evidence of Focal Plasmodium falciparum Transmission in a Pre-elimination Setting in Southern Province, Zambia.

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.

Characteristics of Subpatent Malaria in a Pre-Elimination Setting in Southern Zambia.

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.

Efficiency of a Malaria Reactive Test-and-Treat Program in Southern Zambia: A Prospective, Observational Study.

To improve malaria surveillance and achieve elimination, the Zambian National Malaria Elimination Program implemented a reactive test-and-treat program in Southern Province in 2013 in which individuals with rapid diagnostic test (RDT)-confirmed malaria are followed-up at their home within 1 week of diagnosis. Individuals present at the index case household and those residing within 140 m of the index case are tested with an RDT and treated with artemether-lumefantrine if positive. This study evaluated the efficiency of this reactive test-and-treat strategy by characterizing infected individuals missed by the RDT and the current screening radius. The radius was expanded to 250 m, and a quantitative polymerase chain reaction (qPCR) test was performed on dried blood spot specimens. From January 2015 through March 2016, 145 index cases were identified at health centers and health posts. A total of 3,333 individuals residing in 525 households were screened. Excluding index cases, the parasite prevalence was 1.1% by RDT (33 positives of 3,016 participants) and 2.4% by qPCR (73 positives of 3,016 participants). Of the qPCR-positive cases, 62% of 73 individuals tested negative by RDT. Approximately half of the infected individuals resided within the index case household (58% of RDT-positive individuals and 48% of qPCR-positive individuals). The low sensitivity of the RDT and the high proportion of secondary cases within the index case household decreased the efficiency of this reactive test-and-treat strategy. Reactive focal drug administration in index case households would be a more efficient approach to treating infected individuals associated with a symptomatic case.

Malaria knowledge and bed net use in three transmission settings in southern Africa.

BACKGROUND: Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality in endemic areas. Despite increasing availability, the use of ITNs remains limited in some settings. Poor malaria knowledge is a barrier to the widespread use of ITNs. The goal of this study was to assess the levels of malaria knowledge and evaluate factors associated with bed net use among individuals residing in three regions of southern Africa with different levels of malaria transmission and control. METHODS: A cross-sectional study was conducted on a sample of 7535 residents recruited from 2066 households in Mutasa District, Zimbabwe (seasonal malaria transmission), Choma District, Zambia (low transmission) and Nchelenge District, Zambia (high transmission), between March 2012 and March 2017. A standardized questionnaire was used to collect data on demographics, malaria-related knowledge and use of preventive measures. Multivariate logistic regression analyses were used to assess determinants of bed net use. RESULTS: Most of the 3836 adult participants correctly linked mosquito bites to malaria (85.0%), mentioned at least one malaria symptom (95.5%) and knew of the benefit of sleeping under an ITN. Bed net ownership and use were highest in Choma and Nchelenge Districts and lowest in Mutasa District. In multivariate analyses, knowledge of ITNs was associated with a 30-40% increased likelihood of bed net use after adjusting for potential confounders across all sites. Other factors significantly associated with bed net use were age, household size and socioeconomic status, although the direction, strength and size of association varied by study site. Importantly, participants aged 5-14 years had reduced odds of sleeping under a bed net compared to children younger than 5 years. CONCLUSION: Relevant knowledge of ITNs translated into the expected preventive behaviour of sleeping under a bed net, underscoring the need for continued health messaging on malaria prevention. The implementation and delivery of malaria control and elimination interventions needs to consider socioeconomic equity gaps, and target school-age children to ensure access to and improve utilization of ITNs.

House Structure Is Associated with Plasmodium falciparum Infection in a Low-Transmission Setting in Southern Zambia.

House structure may influence the risk of malaria by affecting mosquito entry and indoor resting. Identification of construction features associated with protective benefits could inform vector control approaches, even in low-transmission settings. We examined the association between house structure and malaria prevalence in a cross-sectional analysis of 2,788 children and adults residing in 866 houses in a low-transmission area of Southern Province, Zambia, over the period 2008-2012. Houses were categorized according to wall (brick/cement block or mud/grass) and roof (metal or grass) material. Malaria was assessed by point-of-care rapid diagnostic test (RDT) for Plasmodium falciparum. We identified 52 RDT-positive individuals residing in 41 houses, indicating an overall prevalence in the sample of 1.9%, ranging from 1.4% to 8.8% among the different house types. Occupants of higher quality houses had reduced odds of P. falciparum malaria compared with those in the lowest quality houses after controlling for bed net use, indoor insecticide spraying, clustering by house, cohabitation with another RDT-positive individual, transmission season, ecologic risk defined as nearest distance to a Strahler-classified third-order stream, education, age, and gender (adjusted odds ratio [OR]: 0.26, 95% confidence interval [CI]: 0.09-0.73, P = 0.01 for houses with brick/cement block walls and metal roof; OR: 0.22, 95% CI: 0.09-0.52, P < 0.01 for houses with brick/cement block walls and grass roof). Housing improvements offer a promising approach to vector control in low-transmission settings that circumvents the threat posed by insecticide resistance, and may confer a protective benefit of similar magnitude to current vector control strategies.

Characterizing and quantifying human movement patterns using GPS data loggers in an area approaching malaria elimination in rural southern Zambia.

In areas approaching malaria elimination, human mobility patterns are important in determining the proportion of malaria cases that are imported or the result of low-level, endemic transmission. A convenience sample of participants enrolled in a longitudinal cohort study in the catchment area of Macha Hospital in Choma District, Southern Province, Zambia, was selected to carry a GPS data logger for one month from October 2013 to August 2014. Density maps and activity space plots were created to evaluate seasonal movement patterns. Time spent outside the household compound during anopheline biting times, and time spent in malaria high- and low-risk areas, were calculated. There was evidence of seasonal movement patterns, with increased long-distance movement during the dry season. A median of 10.6% (interquartile range (IQR): 5.8-23.8) of time was spent away from the household, which decreased during anopheline biting times to 5.6% (IQR: 1.7-14.9). The per cent of time spent in malaria high-risk areas for participants residing in high-risk areas ranged from 83.2% to 100%, but ranged from only 0.0% to 36.7% for participants residing in low-risk areas. Interventions targeted at the household may be more effective because of restricted movement during the rainy season, with limited movement between high- and low-risk areas.

Evaluation of the operational challenges in implementing reactive screen-and-treat and implications of reactive case detection strategies for malaria elimination in a region of low transmission in southern Zambia.

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.

Spatial and temporal changes in household structure locations using high-resolution satellite imagery for population assessment: an analysis in southern Zambia, 2006-2011.

Satellite imagery is increasingly available at high spatial resolution and can be used for various purposes in public health research and programme implementation. Comparing a census generated from two satellite images of the same region in rural southern Zambia obtained four and a half years apart identified patterns of household locations and change over time. The length of time that a satellite image-based census is accurate determines its utility. Households were enumerated manually from satellite images obtained in 2006 and 2011 of the same area. Spatial statistics were used to describe clustering, cluster detection, and spatial variation in the location of households. A total of 3821 household locations were enumerated in 2006 and 4256 in 2011, a net change of 435 houses (11.4% increase). Comparison of the images indicated that 971 (25.4%) structures were added and 536 (14.0%) removed. Further analysis suggested similar household clustering in the two images and no substantial difference in concentration of households across the study area. Cluster detection analysis identified a small area where significantly more household structures were removed than expected; however, the amount of change was of limited practical significance. These findings suggest that random sampling of households for study participation would not induce geographic bias if based on a 4.5-year-old image in this region. Application of spatial statistical methods provides insights into the population distribution changes between two time periods and can be helpful in assessing the accuracy of satellite imagery.