Gillian Stresman

A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia

BackgroundAsymptomatic reservoirs of malaria parasites are common yet are difficult to detect, posing a problem for malaria control. If control programmes focus on mosquito control and treatment of symptomatic individuals only, malaria can quickly resurge if interventions are scaled back. Foci of parasite populations must be identified and treated. Therefore, an active case detection system that facilitates detection of asymptomatic parasitaemia and gametocyte carriers was developed and tested in the Macha region in southern Zambia.MethodsEach week, nurses at participating rural health centres (RHC) communicated the number of rapid diagnostic test (RDT) positive malaria cases to a central research team. During the dry season when malaria transmission was lowest, the research team followed up each positive case reported by the RHC by a visit to the homestead. The coordinates of the location were obtained by GPS and all consenting residents completed a questionnaire and were screened for malaria using thick blood film, RDT, nested-PCR, and RT-PCR for asexual and sexual stage parasites. Persons who tested positive by RDT were treated with artemether/lumefantrine (Coartem®). Data were compared with a community-based study of randomly selected households to assess the prevalence of asymptomatic parasitaemia in the same localities in September 2009.ResultsIn total, 186 and 141 participants residing in 23 case and 24 control homesteads, respectively, were screened. In the case homesteads for which a control population was available (10 of the 23), household members of clinically diagnosed cases had a 8.0% prevalence of malaria using PCR compared to 0.7% PCR positive individuals in the control group (p = 0.006). The case and control groups had a gametocyte prevalence of 2.3% and 0%, respectively but the difference was not significant (p = 0.145).ConclusionsThis pilot project showed that active case detection is feasible and can identify reservoirs of asymptomatic infection. A larger sample size, data over multiple low transmission seasons, and in areas with different transmission dynamics are needed to further validate this approach.

Quantifying travel behavior for infectious disease research: a comparison of data from surveys and mobile phones

Human travel impacts the spread of infectious diseases across spatial and temporal scales, with broad implications for the biological and social sciences. Individual data on travel patterns have been difficult to obtain, particularly in low-income countries. Travel survey data provide detailed demographic information, but sample sizes are often small and travel histories are hard to validate. Mobile phone records can provide vast quantities of spatio-temporal travel data but vary in spatial resolution and explicitly do not include individual information in order to protect the privacy of subscribers. Here we compare and contrast both sources of data over the same time period in a rural area of Kenya. Although both data sets are able to quantify broad travel patterns and distinguish regional differences in travel, each provides different insights that can be combined to form a more detailed picture of travel in low-income settings to understand the spread of infectious diseases.

Rural health centres communities and malaria case detection in Zambia using mobile telephones: a means to detect potential reservoirs of infection in unstable transmission conditions.

BackgroundEffective malaria control depends on timely acquisition of information on new cases, their location and their frequency so as to deploy supplies, plan interventions or focus attention on specific locations appropriately to intervene and prevent an upsurge in transmission. The process is known as active case detection, but because the information is time sensitive, it is difficult to carry out. In Zambia, the rural health services are operating effectively and for the most part are provided with adequate supplies of rapid diagnostic tests (RDT) as well as effective drugs for the diagnosis and treatment of malaria. The tests are administered to all prior to treatment and appropriate records are kept. Data are obtained in a timely manner and distribution of this information is important for the effective management of malaria control operations. The work reported here involves combining the process of positive diagnoses in rural health centres (passive case detection) to help detect potential outbreaks of malaria and target interventions to foci where parasite reservoirs are likely to occur.MethodsTwelve rural health centres in the Choma and Namwala Districts were recruited to send weekly information of rapid malaria tests used and number of positive diagnoses to the Malaria Institute at Macha using mobile telephone SMS. Data were entered in excel, expressed as number of cases per rural health centre and distributed weekly to interested parties.ResultsThese data from each of the health centres which were mapped using geographical positioning system (GPS) coordinates were used in a time sensitive manner to plot the patterns of malaria case detection in the vicinity of each location. The data were passed on to the appropriate authorities. The seasonal pattern of malaria transmission associated with local ecological conditions can be seen in the distribution of cases diagnosed.ConclusionsAdequate supplies of RDT are essential in health centres and the system can be expanded throughout the country to support strategic targeting of interventions by the National Malaria Control Programme. Participation by the health centre staff was excellent.

Beyond temperature and precipitation: ecological risk factors that modify malaria transmission.

Being able to identify the ecological factors that impact risk for malaria would confer important predictive capacity to target malaria control interventions in a community. Temperature and water available for breeding habitats have been shown to be important primary ecological factors that impact the distribution of the malaria vectors and the rate at which the mosquito and parasite develop. However, to this point, studies focusing on the local level have been met with many inconsistent results when assessing malaria risk using both temperature and precipitation. This paper reviewed existing literature to determine if other ecological factors beyond temperature and water are present that may be modifying any associations present between ecological factors and malaria risk. It was found that the ability for water to pool and persist, water quality, elevation, deforestation, and agriculture have all been associated with malaria and may be modifying risk. Using the primary and modifying ecological variables, identifying the interactions between these factors and specific thresholds for increased malaria risk is critical: filling this knowledge gap would enable communities to develop tailored malaria control interventions targeted to their specific circumstances.

Reliability of School Surveys in Estimating Geographic Variation in Malaria Transmission in the Western Kenyan Highlands

Background School surveys provide an operational approach to assess malaria transmission through parasite prevalence. There is limited evidence on the comparability of prevalence estimates obtained from school and community surveys carried out at the same locality. Methods Concurrent school and community cross-sectional surveys were conducted in 46 school/community clusters in the western Kenyan highlands and households of school children were geolocated. Malaria was assessed by rapid diagnostic test (RDT) and combined seroprevalence of antibodies to bloodstage Plasmodium falciparum antigens. Results RDT prevalence in school and community populations was 25.7% (95% CI: 24.4-26.8) and 15.5% (95% CI: 14.4-16.7), respectively. Seroprevalence in the school and community populations was 51.9% (95% CI: 50.5-53.3) and 51.5% (95% CI: 49.5-52.9), respectively. RDT prevalence in schools could differentiate between low (<7%, 95% CI: 0-19%) and high (>39%, 95% CI: 25-49%) transmission areas in the community and, after a simple adjustment, were concordant with the community estimates. Conclusions Estimates of malaria prevalence from school surveys were consistently higher than those from community surveys and were strongly correlated. School-based estimates can be used as a reliable indicator of malaria transmission intensity in the wider community and may provide a basis for identifying priority areas for malaria control.

The impact of hotspot-targeted interventions on malaria transmission: study protocol for a cluster-randomized controlled trial.

BackgroundMalaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community.Methods/designHotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations.DiscussionThis study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection.Trial registrationNCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012.

The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial.

Background Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities. Methods and Findings Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June–6 July 2012) and 16 wk (21 August–10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons. Conclusions Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear. Trial registration ClinicalTrials.gov NCT01575613

Malaria research challenges in low prevalence settings

The prevalence of malaria has reduced significantly in some areas over the past decade. These reductions have made local elimination possible and the research agenda has shifted to this new priority. However, there are critical issues that arise when studying malaria in low transmission settings, particularly identifying asymptomatic infections, accurate detection of individuals with microparasitaemic infections, and achieving a sufficient sample size to have an adequately powered study. These challenges could adversely impact the study of malaria elimination if they remain unanswered.

Focal Screening to Identify the Subpatent Parasite Reservoir in an Area of Low and Heterogeneous Transmission in the Kenya Highlands

BACKGROUND Mass screening and treatment currently fails to identify a considerable fraction of low parasite density infections, while mass treatment exposes many uninfected individuals to antimalarial drugs. Here we test a hybrid approach to screen a sentinel population to identify clusters of subpatent infections in the Kenya highlands with low, heterogeneous malaria transmission. METHODS Two thousand eighty-two inhabitants were screened for parasitemia by nested polymerase chain reaction (nPCR). Children aged ≤ 15 years and febrile adults were also tested for malaria by rapid diagnostic test (RDT) and served as sentinel members to identify subpatent infections within the household. All parasitemic individuals were assessed for multiplicity of infections by nPCR and gametocyte carriage by nucleic acid sequence-based amplification. RESULTS Households with RDT-positive individuals in the sentinel population were more likely to have nPCR-positive individuals (odds ratio: 1.71, 95% confidence interval, 1.60-1.84). The sentinel population identified 64.5% (locality range: 31.6%-81.2%) of nPCR-positive households and 77.3% (locality range: 24.2%-91.0%) of nPCR-positive individuals. The sensitivity of the sentinel screening approach was positively associated with transmission intensity (P = .037). CONCLUSIONS In this low endemic area, a focal screening approach with RDTs prior to the high transmission season was able to identify the majority of the subpatent parasite reservoirs.

High Levels of Asymptomatic and Subpatent Plasmodium falciparum Parasite Carriage at Health Facilities in an Area of Heterogeneous Malaria Transmission Intensity in the Kenyan Highlands

In endemic settings, health facility surveys provide a convenient approach to estimating malaria transmission intensity. Typically, testing for malaria at facilities is performed on symptomatic attendees, but asymptomatic infections comprise a considerable proportion of the parasite reservoir. We sampled individuals attending five health facilities in the western Kenyan highlands. Malaria prevalence by rapid diagnostic test (RDT) was 8.6-32.9% in the health facilities. Of all polymerase chain reaction-positive participants, 46.4% (95% confidence interval [95% CI] = 42.6-50.2%) of participants had infections that were RDT-negative and asymptomatic, and 55.9% of those infections consisted of multiple parasite clones as assessed by merozoite surface protein-2 genotyping. Subpatent infections were more common in individuals reporting the use of non-artemisinin-based antimalarials in the 2 weeks preceding the survey (odds ratio = 2.49, 95% CI = 1.04-5.92) compared with individuals not reporting previous use of antimalarials. We observed a large and genetically complex pool of subpatent parasitemia in the Kenya highlands that must be considered in malaria interventions.