Chrispin Owaga, Jonathan Cox, Jennifer C. Stevenson, Pauline China, Will Stone, Philip A. Knight, Chris Drakeley, Victor Osoti, Ogobara K. Doumbo, Shehu Shagari, Teun Bousema, Simon Kariuki, Robert W. Sauerwein, Gillian Stresman, John S. Bradley, Euniah Makori, Wycliffe Odongo, and Amrish Baidjoe
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, In a cluster-randomized controlled trial, Teun Bousema and colleagues investigate whether interventions targeted to malaria hotspots in the western Kenyan highlands can reduce transmission in surrounding areas., Editors' Summary Background In 2015, there were about 200 million cases of malaria (a mosquito-borne parasitic disease) worldwide and about 438,000 malaria-related deaths. Most of these deaths were caused by Plasmodium falciparum, which is transmitted to people by night-flying Anopheles mosquitoes. When infected mosquitoes bite people, they inject “sporozoites,” a parasitic form that replicates in the liver. After a few days, the liver releases “merozoites,” which invade red blood cells, where they replicate before bursting out and infecting more red blood cells. This increase in parasitic burden causes recurring flu-like symptoms and can cause organ damage and death if not treated promptly with antimalarial drugs. Infected red blood cells also release “gametocytes,” which infect mosquitoes when they take a blood meal. In the mosquito, gametocytes multiply and develop into sporozoites, which completes the parasite’s life cycle. Malaria can be prevented by controlling Anopheles mosquitoes and by avoiding mosquito bites. Methods for controlling mosquitoes include treating stagnant water with “larvicides” to kill immature mosquitoes and spraying houses with insecticides (indoor residual spraying); sleeping under insecticide-treated bednets is an effective way to avoid mosquito bites. Treatment with antimalarial drugs also decreases malaria transmission. Why Was This Study Done? Improved malaria prevention has reduced malaria-related deaths over recent years, and experts are now trying to devise strategies to eradicate malaria. Targeting malaria transmission hotspots—regions where the intensity of transmission is higher than in surrounding areas—is one potential strategy for reducing malaria transmission. Mosquito densities are highest in hotspots, and people living in hotspots may transmit malaria parasites to a large number of mosquitoes that can then spread malaria transmission to wider areas. Targeting malaria hotspots might, therefore, benefit communities in both the targeted region and the surrounding area. Here, the researchers look for malaria hotspots in Rachuonyo South District in the western Kenyan highlands, an area where malaria transmission intensity is generally low, and undertake a cluster-randomized controlled trial to determine the impact of hotspot-targeted malaria control interventions on malaria transmission inside hotspots and in surrounding communities. A cluster-randomized trial compares outcomes in groups (clusters) of people (here, people living in different malaria hotspots) randomly assigned to receive different interventions. What Did the Researchers Do and Find? Using survey results and spatial scanning techniques, the researchers detected 27 serologically defined malaria hotpots (clusters of people with antibodies to the malaria parasite) in Rachuonyo South District. Of these, ten hotspots were at least 1.5 kilometers from the nearest neighboring hotspot (allowing space for evaluation zones and a buffer between hotspots). During the following peak malaria transmission period, they randomly allocated five of these hotspots to targeted interventions (larvicide treatment of stagnant water, community distribution of insecticide-treated bednets, indoor residual spraying, and mass drug administration) and five hotspots to the control intervention (the Kenyan national policy of annual indoor residual spraying, routine case management at clinics, and bednet distribution at antenatal clinics). Intervention coverage exceeded 87% for all the components of the targeted intervention. However, the intervention did not change the prevalence of parasites (the proportion of the population carrying parasites) at 8 or 16 weeks post-intervention in the evaluation zones—the areas 1–500 meters from the border of the hotspots (the study’s primary outcome). There was a statistically significant reduction in parasite prevalence inside intervention hotspots at 8 but not 16 weeks post-intervention (a statistically significant change is one unlikely to have happened by chance). Finally, similar numbers of individuals from the intervention and control clusters attended local health facilities and were found to have confirmed clinical malaria, and there was no significant difference between intervention and control clusters in the number of mosquitoes caught within hotspots or evaluation zones. What Do These Findings Mean? These findings show that, despite high coverage, the impact of interventions targeting malaria hotspots in Rachuonyo South District on parasite prevalence was modest, transient, and restricted to the targeted hotspot. It may be that the number of clusters included in this study was too small to detect any subtle effects of hotspot-targeted interventions. Moreover, the effect of the targeted interventions may have been masked by other ongoing interventions in the region. However, these findings suggest that malaria transmission in Rachuonyo South District may not occur primarily from hotspots to the surrounding areas. Thus, areas where malaria transmission is widespread but includes hotspots might benefit most from an untargeted community-wide approach to malaria prevention. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001993. Information is available from the World Health Organization on malaria (in several languages); its Global Technical Strategy for Malaria 2016–2030 provides a framework to guide countries towards malaria elimination; the World Malaria Report 2015 describes the current global malaria situation and includes information on malaria in individual African countries and recommended policies and strategies for malaria control The US Centers for Disease Control and Prevention provides information on malaria (in English and Spanish), including information about malaria prevention and personal stories about malaria The UK National Health Service Choices website also provides information about malaria, including a personal story Information is available from the Roll Back Malaria Partnership on the global control of malaria (in English and French) MedlinePlus provides links to additional information on malaria (in English and Spanish) More information about this trial is available