Design of trials for interrupting the transmission of endemic pathogens

Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up.; A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor-baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial.; Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial.; The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors

Host-specific cues cause differential attractiveness of Kenyan men to the African malaria vector Anopheles gambiae

BACKGROUND: Many studies have suggested that variability in the attractiveness of humans to host-seeking mosquitoes is caused by differences in the make-up of body emanations, and olfactory signals in particular. Most investigations have either been laboratory-based, utilising odour obtained from sections of the body, or have been done in the field with sampling methods that do not discriminate between visual, physical and chemical cues of the host. Accordingly, evidence for differential attractiveness based on body emanations remains sparse in spite of the far-reaching epidemiological implications of this phenomenon. METHODS: A new three-port olfactometer that accommodates complete human beings as sources of host-seeking stimuli was used to study behavioural responses of Anopheles gambiae Giles sensu stricto (hereafter An. gambiae) under semi-field conditions in western Kenya. Differential attractiveness of nine male Kenyans was assessed by simultaneously exposing the mosquitoes to (a mixture of) total body emanations of 3 people occupying separate tents. Controls (empty tents) were included and the effect of residual odours following tent occupation was also examined. RESULTS: Trap catches increased significantly (P < 0.001) when a tent was occupied. Based on 'competition' experiments, the nine persons were classified into least, medium and most attractive groups. There was no significant interaction between person and trap (P = 0.302) or person and test period (P = 0.223). Presence (P < 0.001) or absence (P = 0.949) of significant differences in the number of mosquitoes caught per trap when tents were simultaneously occupied by one person in each or left empty, respectively, demonstrated that residual odours following tent occupation did not affect behavioural responses of the mosquitoes. CONCLUSION: We provide evidence that in the vicinity of humans, when exposed to a blend of physical and olfactory signals from more than one host, An. gambiae can effectively and consistently express host-selection behaviour that results in non-random biting

An exploratory study of community factors relevant for participatory malaria control on Rusinga Island, western Kenya

<p>Abstract</p> <p>Background</p> <p>Capacity strengthening of rural communities, and the various actors that support them, is needed to enable them to lead their own malaria control programmes. Here the existing capacity of a rural community in western Kenya was evaluated in preparation for a larger intervention.</p> <p>Methods</p> <p>Focus group discussions and semi-structured individual interviews were carried out in 1,451 households to determine (1) demographics of respondent and household; (2) socio-economic status of the household; (3) knowledge and beliefs about malaria (symptoms, prevention methods, mosquito life cycle); (4) typical practices used for malaria prevention; (5) the treatment-seeking behaviour and household expenditure for malaria treatment; and (6) the willingness to prepare and implement community-based vector control.</p> <p>Results</p> <p>Malaria was considered a major threat to life but relevant knowledge was a chimera of scientific knowledge and traditional beliefs, which combined with socio-economic circumstances, leads to ineffective malaria prevention. The actual malaria prevention behaviour practiced by community members differed significantly from methods known to the respondents. Beside bednet use, the major interventions implemented were bush clearing and various hygienic measures, even though these are ineffective for malaria prevention. Encouragingly, most respondents believed malaria could be controlled and were willing to contribute to a community-based malaria control program but felt they needed outside assistance.</p> <p>Conclusion</p> <p>Culturally sensitive but evidence-based education interventions, utilizing participatory tools, are urgently required which consider traditional beliefs and enable understanding of causal connections between mosquito ecology, parasite transmission and the diagnosis, treatment and prevention of disease. Community-based organizations and schools need to be equipped with knowledge through partnerships with national and international research and tertiary education institutions so that evidence-based research can be applied at the grassroots level.</p

A Push-Pull System to Reduce House Entry of Malaria Mosquitoes.

Mosquitoes are the dominant vectors of pathogens that cause infectious diseases such as malaria, dengue, yellow fever and filariasis. Current vector control strategies often rely on the use of pyrethroids against which mosquitoes are increasingly developing resistance. Here, a push-pull system is presented, that operates by the simultaneous use of repellent and attractive volatile odorants. Experiments were carried out in a semi-field set-up: a traditional house which was constructed inside a screenhouse. The release of different repellent compounds, para-menthane-3,8-diol (PMD), catnip oil e.o. and delta-undecalactone, from the four corners of the house resulted in significant reductions of 45% to 81.5% in house entry of host-seeking malaria mosquitoes. The highest reductions in house entry (up to 95.5%), were achieved by simultaneously repelling mosquitoes from the house (push) and removing them from the experimental set-up using attractant-baited traps (pull). The outcome of this study suggests that a push-pull system based on attractive and repellent volatiles may successfully be employed to target mosquito vectors of human disease. Reductions in house entry of malaria vectors, of the magnitude that was achieved in these experiments, would likely affect malaria transmission. The repellents used are non-toxic and can be used safely in a human environment. Delta-undecalactone is a novel repellent that showed higher effectiveness than the established repellent PMD. These results encourage further development of the system for practical implementation in the field

Plasmodium-associated changes in human odor attract mosquitoes.

Malaria parasites (Plasmodium) can change the attractiveness of their vertebrate hosts to Anopheles vectors, leading to a greater number of vector-host contacts and increased transmission. Indeed, naturally Plasmodium-infected children have been shown to attract more mosquitoes than parasite-free children. Here, we demonstrate Plasmodium-induced increases in the attractiveness of skin odor in Kenyan children and reveal quantitative differences in the production of specific odor components in infected vs. parasite-free individuals. We found the aldehydes heptanal, octanal, and nonanal to be produced in greater amounts by infected individuals and detected by mosquito antennae. In behavioral experiments, we demonstrated that these, and other, Plasmodium-induced aldehydes enhanced the attractiveness of a synthetic odor blend mimicking "healthy" human odor. Heptanal alone increased the attractiveness of "parasite-free" natural human odor. Should the increased production of these aldehydes by Plasmodium-infected humans lead to increased mosquito biting in a natural setting, this would likely affect the transmission of malaria

An assessment of participatory integrated vector management for malaria control in Kenya

BACKGROUND : The World Health Organization (WHO) recommends integrated vector management (IVM) as a strategy to improve and sustain malaria vector control. However, this approach has not been widely adopted. OBJECTIVES : We comprehensively assessed experiences and findings on IVM in Kenya with a view to sharing lessons that might promote its wider application. METHODS : The assessment used information from a qualitative external evaluation of two malaria IVM projects implemented between 2006 and 2011 and an analysis of their accumulated entomological and malaria case data. The project sites were Malindi and Nyabondo, located in coastal and western Kenya, respectively. The assessment focused on implementation of five key elements of IVM: integration of vector control methods, evidence-based decision making, intersectoral collaboration, advocacy and social mobilization, and capacity building. RESULTS : IVM was more successfully implemented in Malindi than in Nyabondo owing to greater community participation and multistakeholder engagement. There was a significant decline in the proportion of malaria cases among children admitted to Malindi Hospital, from 23.7% in 2006 to 10.47% in 2011 (p < 0.001). However, the projects’ operational research methodology did not allow statistical attribution of the decline in malaria and malaria vectors to specific IVM interventions or other factors. CONCLUSIONS : Sustaining IVM is likely to require strong participation and support from multiple actors, including community-based groups, non-governmental organizations, international and national research institutes, and various government ministries. A cluster-randomized controlled trial would be essential to quantify the effectiveness and impact of specific IVM interventions, alone or in combination.Grants from the Biovision Foundation (Switzerland) through the International Centre of Insect Physiology and Ecology (ICIPE).http://ehp.niehs.nih.govam2016School of Health Systems and Public Health (SHSPH

Host choice and multiple blood feeding behaviour of malaria vectors and other anophelines in Mwea rice scheme, Kenya

<p>Abstract</p> <p>Background</p> <p>Studies were conducted between April 2004 and February 2006 to determine the blood-feeding pattern of <it>Anopheles </it>mosquitoes in Mwea Kenya.</p> <p>Methods</p> <p>Samples were collected indoors by pyrethrum spay catch and outdoors by Centers for Disease Control light traps and processed for blood meal analysis by an Enzyme-linked Immunosorbent Assay.</p> <p>Results</p> <p>A total of 3,333 blood-fed <it>Anopheles </it>mosquitoes representing four <it>Anopheles </it>species were collected and 2,796 of the samples were assayed, with <it>Anopheles arabiensis </it>comprising 76.2% (n = 2,542) followed in decreasing order by <it>Anopheles coustani </it>8.9% (n = 297), <it>Anopheles pharoensis </it>8.2% (n = 272) and <it>Anopheles funestus </it>6.7% (n = 222). All mosquito species had a high preference for bovine (range 56.3–71.4%) over human (range 1.1–23.9%) or goat (0.1–2.2%) blood meals. Some individuals from all the four species were found to contain mixed blood meals. The bovine blood index (BBI) for <it>An. arabiensis </it>was significantly higher for populations collected indoors (71.8%), than populations collected outdoors (41.3%), but the human blood index (HBI) did not differ significantly between the two populations. In contrast, BBI for indoor collected <it>An. funestus </it>(51.4%) was significantly lower than for outdoor collected populations (78.0%) and the HBI was significantly higher indoors (28.7%) than outdoors (2.4%). Anthropophily of <it>An. funestus </it>was lowest within the rice scheme, moderate in unplanned rice agro-ecosystem, and highest within the non-irrigated agro-ecosystem. Anthropophily of <it>An. arabiensis </it>was significantly higher in the non-irrigated agro-ecosystem than in the other agro-ecosystems.</p> <p>Conclusion</p> <p>These findings suggest that rice cultivation has an effect on host choice by <it>Anopheles </it>mosquitoes. The study further indicate that zooprophylaxis may be a potential strategy for malaria control, but there is need to assess how domestic animals may influence arboviruses epidemiology before adapting the strategy.</p