A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences

Insecticides have played a major role in the prevention, control, and elimination of vector-borne diseases, but insecticide resistance threatens the efficacy of available vector control tools. A global survey was conducted to investigate vector control insecticide use from 2010 to 2019. Out of 140 countries selected as sample for the study, 87 countries responded. Also, data on ex-factory deliveries of insecticide-treated nets (ITNs) were analyzed. Insecticide operational use was highest for control of malaria, followed by dengue, leishmaniasis and Chagas disease. Vector control relied on few insecticide classes with pyrethroids the most used overall. Results indicated that IRS programs have been slow to react to detection of pyrethroid resistance, while proactive resistance management using insecticides with unrelated modes of action was generally weak. The intensive use of recently introduced insecticide products raised concern about product stewardship regarding the preservation of insecticide susceptibility in vector populations. Resistance management was weakest for control of dengue, leishmaniasis or Chagas disease. Therefore, it will be vital that vector control programs coordinate on insecticide procurement, planning, implementation, resistance monitoring, and capacity building. Moreover, increased consideration should be given to alternative vector control tools that prevent the development of insecticide resistance.

Malaria epidemics in regions with seasonal windows of transmission can vary greatly in size from year to year. A central question has been whether these interannual cycles are driven by climate, are instead generated by the intrinsic dynamics of the disease, or result from the resonance of these two mechanisms. This corresponds to the more general inverse problem of identifying the respective roles of external forcings vs. internal feedbacks from time series for nonlinear and noisy systems. We propose here a quantitative approach to formally compare rival hypotheses on climate vs. disease dynamics, or external forcings vs. internal feedbacks, that combines dynamical models with recently developed, computational inference methods. The interannual patterns of epidemic malaria are investigated here for desert regions of northwest India, with extensive epidemiological records for Plasmodium falciparum malaria for the past two decades. We formulate a dynamical model of malaria transmission that explicitly incorporates rainfall, and we rely on recent advances on parameter estimation for nonlinear and stochastic dynamical systems based on sequential Monte Carlo methods. Results show a significant effect of rainfall in the inter-annual variability of epidemic malaria that involves a threshold in the disease response. The model exhibits high prediction skill for yearly cases in the malaria transmission season following the monsoonal rains. Consideration of a more complex model with clinical immunity demonstrates the robustness of the findings and suggests a role of infected individuals that lack clinical symptoms as a reservoir for transmission. Our results indicate that the nonlinear dynamics of the disease itself play a role at the seasonal, but not the interannual, time scales. They illustrate the feasibility of forecasting malaria epidemics in desert and semi-arid regions of India based on climate variability. This approach should be applicable to malaria in other locations, to other infectious diseases, and to other nonlinear systems under forcing. Malaria epidemics can exhibit pronounced variation from year to year that can be driven by external forcings, such as climate, or can be generated instead by dynamic feedbacks within the disease system itself. For example, levels of immunity in the population (or control efforts) can rise and fall as the result of past levels of infection. This type of feedback is found in the dynamics of all (nonlinear) biological systems. Feedbacks can interact in complex ways with external drivers, for example by creating refractory periods. It remains a challenge to identify internal feedbacks vs. external forcings from available temporal records of aggregated reported cases and forcing variables. We propose a quantitative approach that can statistically compare the hypotheses of feedbacks vs. forcings (epidemiological vs. climate) based on dynamical and mechanistic models. Our approach is computational, based on a large number of computer simulations of the different models. We illustrate and apply the approach to the analysis of extensive monthly records for malaria incidence in desert regions of India that span two decades. Our analyses confirm the strong role of rainfall, and quantify this effect with transmission model(s) for malaria that include rainfall and are shown to exhibit a remarkable prediction skill.

Due to the rapid extension of pyrethroid resistance in malaria vectors worldwide, manufacturers are developing new vector control tools including insecticide mixtures containing at least two active ingredients with different mode of action as part of insecticide resistance management. Olyset® Plus is a new long-lasting insecticidal net (LLIN) incorporating permethrin and a synergist, piperonyl butoxide (PBO), into its fibres in order to counteract metabolic-based pyrethroid resistance of mosquitoes. In this study, we evaluated the efficacy of Olyset® Plus both in laboratory and field against susceptible and multi-resistant malaria vectors and compared with Olyset Net, which is a permethrin incorporated into polyethylene net. In laboratory, Olyset® Plus performed better than Olyset® Net against susceptible Anopheles gambiae strain with a 2-day regeneration time owing to an improved permethrin bleeding rate with the new incorporation technology. It also performed better than Olyset® Net against multiple resistant populations of An. gambiae in experimental hut trials in West Africa. Moreover, the present study showed evidence for a benefit of incorporating a synergist, PBO, with a pyrethroid insecticide into mosquito netting. These results need to be further validated in a large-scale field trial to assess the durability and acceptability of this new tool for malaria vector control.

Pesticide lifecycle management encompasses a range of elements from legislation, regulation, manufacturing, application, risk reduction, monitoring, and enforcement to disposal of pesticide waste. A survey was conducted in 2017-2018 to describe the contemporary global status of pesticide lifecycle management, to identify where the gaps are found. A three-tiered questionnaire was distributed to government entities in 194 countries. The response rate was 29%, 27% and 48% to the first, second and third part of the questionnaire, respectively. The results showed gaps for most of the selected indicators of pesticide management, suggesting that pesticide efficacy and safety to human health and the environment are likely being compromised at various stages of the pesticide lifecycle, and at varying degrees across the globe. Low-income countries generally had the highest incidence of gaps. Particular shortcomings were deficiencies in pesticide legislation, inadequate capacity for pesticide registration, protection against occupational exposure to pesticides, consumer protection against residues in food, and environmental protection against pesticide contamination. Policy support for, and implementation of, pesticide use-reduction strategies such as integrated pest management and integrated vector management has been inadequate across regions. Priority actions for structural improvement in pesticide lifecycle management are proposed, including pesticide use-reduction strategies, targeted interventions, and resource mobilization.

Background: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both. Methods: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration–response curves for each insecticide–species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC₅₀ and LC₉₉, respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI₅₀ and OI₉₉), to measure mortality and the sterilizing effect, respectively. Results: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC₅₀/LC₉₉ or OI₅₀/OI₉₉ values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species–insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were < 10% for most mosquito species-insecticide combinations. Conclusion: Our findings, based on the largest susceptibility dataset ever produced on mosquitoes, showed that the new WHO bottle bioassay is adequate for evaluating mosquito susceptibility to new and promising public health insecticides currently deployed for vector control. The datasets presented in this study have been used recently by the WHO to establish 17 new insecticide discriminating concentrations (DCs) for either Aedes spp. or Anopheles spp. The bottle bioassay and DCs can now be widely used to monitor baseline insecticide susceptibility of wild populations of vectors of malaria and Aedes-borne diseases worldwide. Graphical