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

Risk factors for mosquito house entry in the Lao PDR.

BACKGROUND: Construction of the Nam Theun 2 hydroelectric project and flooding of a 450 km(2) area of mountain plateau in south-central Lao PDR resulted in the resettlement of 6,300 people to newly built homes. We examined whether new houses would have altered risk of house entry by mosquitoes compared with traditional homes built from poorer construction materials. METHODOLOGY/PRINCIPAL FINDINGS: Surveys were carried out in the Nam Theun 2 resettlement area and a nearby traditional rice farming area in 2010. Mosquitoes were sampled in bedrooms using CDC light traps in 96 resettlement houses and 96 traditional houses and potential risk factors for mosquito house entry were recorded. Risk of mosquito house entry was more than twice as high in traditional bamboo houses compared with those newly constructed from wood (Putative Japanese Encephalitis (JE) vector incidence rate ratio (IRR) = 2.26, 95% CI 1.38-3.70, P = 0.001; Anopheline IRR = 2.35, 95% CI: 1.30-4.23, P = 0.005). Anophelines were more common in homes with cattle compared against those without (IRR = 2.32, 95% CI: 1.29-4.17, P = 0.005).Wood smoke from cooking fires located under the house or indoors was found to be protective against house entry by both groups of mosquito, compared with cooking in a separate room beside the house (Putative JE vector IRR = 0.43, 95% CI: 0.26-0.73, P = 0.002; Anopheline IRR = 0.22, 95% CI: 0.10-0.51, P<0.001). CONCLUSIONS/SIGNIFICANCE: Construction of modern wooden homes should help reduce human-mosquito contact in the Lao PDR. Reduced mosquito contact rates could lead to reduced transmission of diseases such as JE and malaria. Cattle ownership was associated with increased anopheline house entry, so zooprophylaxis for malaria control is not recommended in this area. Whilst wood smoke was protective against putative JE vector and anopheline house entry we do not recommend indoor cooking since smoke inhalation can enhance respiratory disease

Development and optimization of the Suna trap as a tool for mosquito monitoring and control

Background Monitoring of malaria vector populations provides information about disease transmission risk, as well as measures of the effectiveness of vector control. The Suna trap is introduced and evaluated with regard to its potential as a new, standardized, odour-baited tool for mosquito monitoring and control. Methods Dual-choice experiments with female Anopheles gambiae sensu lato in a laboratory room and semi-field enclosure, were used to compare catch rates of odour-baited Suna traps and MM-X traps. The relative performance of the Suna trap, CDC light trap and MM-X trap as monitoring tools was assessed inside a human-occupied experimental hut in a semi-field enclosure. Use of the Suna trap as a tool to prevent mosquito house entry was also evaluated in the semi-field enclosure. The optimal hanging height of Suna traps was determined by placing traps at heights ranging from 15 to 105 cm above ground outside houses in western Kenya. Results In the laboratory the mean proportion of An. gambiae s.l. caught in the Suna trap was 3.2 times greater than the MM-X trap (P &lt;0.001), but the traps performed equally in semi-field conditions (P = 0.615). As a monitoring tool , the Suna trap outperformed an unlit CDC light trap (P &lt;0.001), but trap performance was equal when the CDC light trap was illuminated (P = 0.127). Suspending a Suna trap outside an experimental hut reduced entry rates by 32.8% (P &lt;0.001). Under field conditions, suspending the trap at 30 cm above ground resulted in the greatest catch sizes (mean 25.8 An. gambiae s.l. per trap night). Conclusions The performance of the Suna trap equals that of the CDC light trap and MM-X trap when used to sample An. gambiae inside a human-occupied house under semi-field conditions. The trap is effective in sampling mosquitoes outside houses in the field, and the use of a synthetic blend of attractants negates the requirement of a human bait. Hanging a Suna trap outside a house can reduce An. gambiae house entry and its use as a novel tool for reducing malaria transmission risk will be evaluated in peri-domestic settings in sub-Saharan Africa

Profile : the rusinga health and demographic surveillance system, western Kenya

The health and demographic surveillance system on Rusinga Island, Western Kenya, was initiated in 2012 to facilitate a malaria intervention trial: the SolarMal project. The project aims to eliminate malaria from Rusinga Island using the nationwide adopted strategy for malaria control (insecticide-treated bed nets and case management) augmented with mass trapping of anopheline mosquitoes. The main purpose of the health and demographic surveillance is to measure the effectiveness of the trial on clinical malaria incidence, and to monitor demographic, environmental and malaria-related data variables. At the end of 2014, the 44 km(2) island had a population of approximately 25 000 individuals living in 8746 residential structures. Three times per year, all individuals are followed up and surveyed for clinical malaria. Following each round of surveillance, a randomly selected cross-section of the population is subject to a rapid diagnostic test to measure malaria. Additionally, extensive monitoring of malaria vectors is performed. Data collection and management are conducted using the OpenHDS platform, with tablet computers and applications with advanced software connected to a centralized database. Besides the general demographic information, other health-related data are collected which can be used to facilitate a range of other studies within and outside the current project. Access to the core dataset can be obtained on request from the authors

Evaluating barriers to reaching women with public health information in remote communities in Mali.

Telecommunications offers an alternative or supplement to community-based interventions as a means of extending healthcare services and improving health outcomes in remote settings but can fail to reach target communities and achieve the desired impact if barriers to access are not overcome. We conducted seven focus group discussions and 26 interviews with community health workers, community leaders, and female members of the public who declared that they had or had not previously accessed free audio health messages provided via a mobile platform in two rural communities of Mali, Koulikoro and Bougouni. A content analysis showed that participants accessed and trusted health information from a range of sources, including radio, telephone and television, as well as town criers, local relays and community health centres. Barriers to access faced by women included economic factors, lack of network or electricity, and social factors such as illiteracy, cultural restrictions and being unaware of mobile communication. Through analysis and interpretation of the participants' responses, we have made recommendations for future campaigns for the dissemination of health-related information for women in remote settings

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant