Audrey Lenhart

Effective control of dengue vectors with curtains and water container covers treated with insecticide in Mexico and Venezuela: cluster randomised trials

Abstract Objectives To measure the impact on the dengue vector population (Aedes aegypti) and disease transmission of window curtains and water container covers treated with insecticide. Design Cluster randomised controlled trial based on entomological surveys and, for Trujillo only, serological survey. In addition, each site had a non-randomised external control. Setting 18 urban sectors in Veracruz (Mexico) and 18 in Trujillo (Venezuela). Participants 4743 inhabitants (1095 houses) in Veracruz and 5306 inhabitants (1122 houses) in Trujillo. Intervention Sectors were paired according to entomological indices, and one sector in each pair was randomly allocated to receive treatment. In Veracruz, the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips (an insect growth regulator). In Trujillo, the intervention comprised curtains treated with longlasting deltamethrin (PermaNet) plus water jar covers of the same material. Follow-up surveys were conducted at intervals, with the final survey after 12 months in Veracruz and nine months in Trujillo. Main outcome measures Reduction in entomological indices, specifically the Breteau and house indices. Results In both study sites, indices at the end of the trial were significantly lower than those at baseline, though with no significant differences between control and intervention arms. The mean Breteau index dropped from 60% (intervention clusters) and 113% (control) to 7% (intervention) and 12% (control) in Veracruz and from 38% to 11% (intervention) and from 34% to 17% (control) in Trujillo. The pupae per person and container indices showed similar patterns. In contrast, in nearby communities not in the trial the entomological indices followed the rainfall pattern. The intervention reduced mosquito populations in neighbouring control clusters (spill-over effect); and houses closer to treated houses were less likely to have infestations than those further away. This created a community effect whereby mosquito numbers were reduced throughout the study site. The observed effects were probably associated with the use of materials treated with insecticide at both sites because in Veracruz, people did not accept and use the pyriproxyfen chips. Conclusion Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission.

Insecticide-treated bednets to control dengue vectors: preliminary evidence from a controlled trial in Haiti.

Objectives  Insecticide‐treated bednets (ITNs) are effective in preventing nocturnally transmitted vector‐borne diseases, but their effect on diurnally active dengue vectors has never been studied. We investigated the efficacy of ITNs in reducing Aedes aegypti populations and dengue transmission.

Reducing costs and operational constraints of dengue vector control by targeting productive breeding places: a multi‐country non‐inferiority cluster randomized trial

Objectives  To test the non‐inferiority hypothesis that a vector control approach targeting only the most productive water container types gives the same or greater reduction of the vector population as a non‐targeted approach in different ecological settings and to analyse whether the targeted intervention is less costly.

Temephos Resistance in Aedes aegypti in Colombia Compromises Dengue Vector Control

Background Control and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes. In Colombia, application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy. Resistance to temephos was recently detected in the dengue-endemic city of Cucuta, leading to questions about its efficacy as a control tool. Here, we characterize the underlying mechanisms and estimate the operational impact of this resistance. Methodology/Principal Findings Larval bioassays of Ae. aegypti larvae from Cucuta determined the temephos LC50 to be 0.066 ppm (95% CI 0.06–0.074), approximately 15× higher than the value obtained from a susceptible laboratory colony. The efficacy of the field dose of temephos at killing this resistant Cucuta population was greatly reduced, with mortality rates <80% two weeks after application and <50% after 4 weeks. Neither biochemical assays nor partial sequencing of the ace-1 gene implicated target site resistance as the primary resistance mechanism. Synergism assays and microarray analysis suggested that metabolic mechanisms were most likely responsible for the temephos resistance. Interestingly, although the greatest synergism was observed with the carboxylesterase inhibitor, DEF, the primary candidate genes from the microarray analysis, and confirmed by quantitative PCR, were cytochrome P450 oxidases, notably CYP6N12, CYP6F3 and CYP6M11. Conclusions/Significance In Colombia, resistance to temephos in Ae. aegypti compromises the duration of its effect as a vector control tool. Several candidate genes potentially responsible for metabolic resistance to temephos were identified. Given the limited number of insecticides that are approved for vector control, future chemical-based control strategies should take into account the mechanisms underlying the resistance to discern which insecticides would likely lead to the greatest control efficacy while minimizing further selection of resistant phenotypes.

Bacillus thuringiensis israelensis (Bti) for the control of dengue vectors: systematic literature review.

To systematically review the literature on the effectiveness of Bacillus thuringiensis israelensis (Bti), when used as a single agent in the field, for the control of dengue vectors.

Insecticide resistance status of Aedes aegypti (L.) from Colombia

BACKGROUND To evaluate the insecticide susceptibility status of Aedes aegypti (L.) in Colombia, and as part of the National Network of Insecticide Resistance Surveillance, 12 mosquito populations were assessed for resistance to pyrethroids, organophosphates and DDT. Bioassays were performed using WHO and CDC methodologies. The underlying resistance mechanisms were investigated through biochemical assays and RT-PCR. RESULTS All mosquito populations were susceptible to malathion, deltamethrin and cyfluthrin, and highly resistant to DDT and etofenprox. Resistance to lambda-cyhalothrin, permethrin and fenitrothion ranged from moderate to high in some populations from Chocó and Putumayo states. In Antioquia state, the Santa Fe population was resistant to fenitrothion. Biochemical assays showed high levels of both cytochrome P450 monooxygenases (CYP) and non-specific esterases (NSE) in some of the fenitrothion- and pyrethroid-resistant populations. All populations showed high levels of glutathione-S-transferase (GST) activity. GSTe2 gene was found overexpressed in DDT-resistant populations compared with Rockefeller susceptible strain. CONCLUSIONS Differences in insecticide resistance status were observed between insecticides and localities. Although the biochemical assay results suggest that CYP and NSE could play an important role in the pyrethroid and fenitrothion resistance detected, other mechanisms remain to be investigated, including knockdown resistance. Resistance to DDT was high in all populations, and GST activity is probably the main enzymatic mechanism associated with this resistance. The results of this study provide baseline data on insecticide resistance in Colombian A. aegypti populations, and will allow comparison of changes in susceptibility status in this vector over time.

Time-varying, serotype-specific force of infection of dengue virus

Significance Using mathematical models to extend knowledge of pathogen transmission and recommend optimized control efforts is dependent on the accuracy of model parameters. The rate at which susceptible individuals become infected [the force of infection (FoI)] is one of the most important parameters, but due to data constraints it is often incorrectly assumed to be constant over time. Using a bespoke method for a 12-y longitudinal dataset of serotype-specific dengue virus (DENV) infections, we estimated time-varying, serotype-specific FoIs for all four DENV serotypes. The FoI varied markedly in time, which implies that DENV transmission dynamics are complex and are best summarized using time-dependent transmission parameters. Our results provide more accurate measures of virus transmission dynamics and a basis for improving selection of control and disease prevention strategies. Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission parameters such as the force of infection (FoI), which is the per-capita risk of a susceptible person being infected. The FoI captures the fundamental dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne, multiserotype pathogen that currently infects ∼390 million people a year. Existing estimates of the DENV FoI are inaccurate because they rely on the unrealistic assumption that risk is constant over time. Dengue models are thus unreliable for designing vaccine deployment strategies. Here, we present to our knowledge the first time-varying (daily), serotype-specific estimates of DENV FoIs using a spline-based fitting procedure designed to examine a 12-y, longitudinal DENV serological dataset from Iquitos, Peru (11,703 individuals, 38,416 samples, and 22,301 serotype-specific DENV infections from 1999 to 2010). The yearly DENV FoI varied markedly across time and serotypes (0–0.33), as did daily basic reproductive numbers (0.49–4.72). During specific time periods, the FoI fluctuations correlated across serotypes, indicating that different DENV serotypes shared common transmission drivers. The marked variation in transmission intensity that we detected indicates that intervention targets based on one-time estimates of the FoI could underestimate the level of effort needed to prevent disease. Our description of dengue virus transmission dynamics is unprecedented in detail, providing a basis for understanding the persistence of this rapidly emerging pathogen and improving disease prevention programs.

Evaluation of the effectiveness of insecticide treated materials for household level dengue vector control

Objective To assess the operational effectiveness of long-lasting insecticide treated materials (ITMs), when used at household level, for the control of Aedes aegypti in moderately infested urban and suburban areas. Methods In an intervention study, ITMs consisting of curtains and water jar-covers (made from PermaNet) were distributed under routine field conditions in 10 clusters (5 urban and 5 suburban), with over 4000 houses, in Trujillo, Venezuela. Impact of the interventions were determined by comparing pre-and post-intervention measures of the Breteau index (BI, number of positive containers/100 houses) and pupae per person index (PPI), and by comparison with indices from untreated areas of the same municipalities. The effect of ITM coverage was modeled. Results At distribution, the proportion of households with ≥1 ITM curtain was 79.7% in urban and 75.2% in suburban clusters, but decreased to 32.3% and 39.0%, respectively, after 18 months. The corresponding figures for the proportion of jars using ITM covers were 34.0% and 50.8% at distribution and 17.0% and 21.0% after 18 months, respectively. Prior to intervention, the BI was 8.5 in urban clusters and 42.4 in suburban clusters, and the PPI was 0.2 and 0.9, respectively. In both urban and suburban clusters, the BI showed a sustained 55% decrease, while no discernable pattern was observed at the municipal level. After controlling for confounding factors, the percentage ITM curtain coverage, but not ITM jar-cover coverage, was significantly associated with both entomological indices (Incidence Rate Ratio = 0.98; 95%CI 0.97–0.99). The IRR implied that ITM curtain coverage of at least 50% was necessary to reduce A. aegypti infestation levels by 50%. Conclusion Deployment of insecticide treated window curtains in households can result in significant reductions in A. aegypti levels when dengue vector infestations are moderate, but the magnitude of the effect depends on the coverage attained, which itself can decline rapidly over time.

Use of the pupal/demographic-survey technique to identify the epidemiologically important types of containers producing Aedes aegypti (L.) in a dengue-endemic area of Venezuela

Abstract As dengue continues to emerge as a major public-health problem world-wide, efforts to control the dengue vector Aedes aegypti must become more effective and efficient. Results from larval and pupal surveys applied in Venezuela illustrate the uniqueness of the information gained from pupal surveys; information that is lost when traditional Stegomyia indices are calculated. As most Ae. aegypti pupae will emerge to become adults, controlling the containers that produce the most pupae could have the greatest impact on the adult population. Pupal-survey results in Venezuela showed that large (150- to 200-litre) water drums produce the greatest number of pupae throughout the year. In the rainy season, approximately 70% of all pupae are found in these drums or in tyres, buckets and tanks. Over 80% of pupae in the dry season are found in drums and tanks alone. By targeting only those domestic breeding containers that produce the greatest number of pupae, control efforts may be streamlined to have the greatest impact on reducing the local adult Ae. aegypti population.

A Cluster-Randomized Trial of Insecticide-Treated Curtains for Dengue Vector Control in Thailand

The efficacy of insecticide-treated window curtains (ITCs) for dengue vector control was evaluated in Thailand in a cluster-randomized controlled trial. A total of 2,037 houses in 26 clusters was randomized to receive the intervention or act as control (no treatment). Entomological surveys measured Aedes infestations (Breteau index, house index, container index, and pupae per person index) and oviposition indices (mean numbers of eggs laid in oviposition traps) immediately before and after intervention, and at 3-month intervals over 12 months. There were no consistent statistically significant differences in entomological indices between intervention and control clusters, although oviposition indices were lower (P < 0.01) in ITC clusters during the wet season. It is possible that the open housing structures in the study reduced the likelihood of mosquitoes making contact with ITCs. ITCs deployed in a region where this house design is common may be unsuitable for dengue vector control.