Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations.

BACKGROUND: It is important to understand whether the potential impact of pyrethroid resistance on malaria control can be mitigated by switching between different pyrethroids or whether cross-resistance within this insecticide class precludes this approach. METHODS: Here we assess the relationships among pyrethroids in terms of their binding affinity to, and depletion by, key cytochrome P450 enzymes (hereafter P450s) that are known to confer metabolic pyrethroid resistance in Anopheles gambiae (s.l.) and An. funestus, in order to identify which pyrethroids may diverge from the others in their vulnerability to resistance. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations. RESULTS: We found that the type I and II pyrethroids permethrin and deltamethrin, respectively, are closely related in terms of binding affinity to key P450s, depletion by P450s and resistance within vector populations. Bifenthrin, which lacks the common structural moiety of most pyrethroids, diverged from the other pyrethroids tested in terms of both binding affinity to key P450s and depletion by P450s, but resistance to bifenthrin has rarely been tested in vector populations and was not analysed here. Etofenprox, which also lacks the common structural moiety of most pyrethroids, diverged from the more commonly deployed pyrethroids in terms of binding affinity to key P450s and resistance in vector populations, but did not diverge from these pyrethroids in terms of depletion by the P450s. The analysis of depletion by the P450s indicated that etofenprox may be more vulnerable to metabolic resistance mechanisms in vector populations. In addition, greater resistance to etofenprox was found across Aedes aegypti populations, but greater resistance to this compound was not found in any of the malaria vector species analysed. The results for pyrethroid depletion by anopheline P450s in the laboratory were largely not repeated in the findings for resistance in malaria vector populations. CONCLUSION: Importantly, the prevalence of resistance to the pyrethroids α-cypermethrin, cyfluthrin, deltamethrin, λ-cyhalothrin and permethrin was correlated across malaria vector populations, and switching between these compounds as a tool to mitigate against pyrethroid resistance is not advised without strong evidence supporting a true difference in resistance.

A new malaria vector in Africa: Predicting the expansion range of Anopheles stephensi and identifying the urban populations at risk.

In 2012, an unusual outbreak of urban malaria was reported from Djibouti City in the Horn of Africa and increasingly severe outbreaks have been reported annually ever since. Subsequent investigations discovered the presence of an Asian mosquito species; Anopheles stephensi, a species known to thrive in urban environments. Since that first report, An. stephensi has been identified in Ethiopia and Sudan, and this worrying development has prompted the World Health Organization (WHO) to publish a vector alert calling for active mosquito surveillance in the region. Using an up-to-date database of published locational records for An. stephensi across its full range (Asia, Arabian Peninsula, Horn of Africa) and a set of spatial models that identify the environmental conditions that characterize a species' preferred habitat, we provide evidence-based maps predicting the possible locations across Africa where An. stephensi could establish if allowed to spread unchecked. Unsurprisingly, due to this species' close association with man-made habitats, our maps predict a high probability of presence within many urban cities across Africa where our estimates suggest that over 126 million people reside. Our results strongly support the WHO's call for surveillance and targeted vector control and provide a basis for the prioritization of surveillance.

Global distribution and environmental suitability for chikungunya virus, 1952 to 2015.

Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted to humans by Aedes mosquitoes. Although chikungunya fever is rarely fatal, patients can experience debilitating symptoms that last from months to years. Here we comprehensively assess the global distribution of chikungunya and produce high-resolution maps, using an established modelling framework that combines a comprehensive occurrence database with bespoke environmental correlates, including up-to-date Aedes distribution maps. This enables estimation of the current total population-at-risk of CHIKV transmission and identification of areas where the virus may spread to in the future. We identified 94 countries with good evidence for current CHIKV presence and a set of countries in the New and Old World with potential for future CHIKV establishment, demonstrated by high environmental suitability for transmission and in some cases previous sporadic reports. Aedes aegypti presence was identified as one of the major contributing factors to CHIKV transmission but significant geographical heterogeneity exists. We estimated 1.3 billion people are living in areas at-risk of CHIKV transmission. These maps provide a baseline for identifying areas where prevention and control efforts should be prioritised and can be used to guide estimation of the global burden of CHIKV.

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Barriers to gene flow from oilseed rape (Brassica napus) into populations of Sinapis arvensis.

One concern over growing herbicide-tolerant crops is that herbicide-tolerance genes may be transferred into the weeds they are designed to control. Brassica napus (oilseed rape) has a number of wild relatives that cause weed problems and the most widespread of these is Sinapis arvensis (charlock). Sinapis arvensis seed was collected from 102 populations across the UK, within and outside B. napus-growing areas. These populations were tested for sexual compatibility with B. napus and it was found that none of them hybridized readily in the glasshouse. In contrast to previous studies, we have found that hybrids can be formed naturally with S. arvensis as the maternal parent. Six diverse B. napus cultivars (Capricorn, Drakkar, Falcon, Galaxy, Hobson and Regent) were tested for their compatibility with S. arvensis but no cultivar hybridized readily in the glasshouse. We were unable to detect gene transfer from B. napus to S. arvensis in the field, confirming the extremely low probability of hybridization predicted from the glasshouse work.

The ecological genetics of aliphatic glucosinolates.

Glucosinolates are plant secondary metabolites composed of a thioglucose group and an amino acid side-chain. They occur in the Brassicaceae and related families. A wide variety of glucosinolates exists owing to modification of the side-chain structure. Following tissue damage, myrosinase enzymes catalyse the decomposition of glucosinolates to a variety of volatile and nonvolatile products. The genetic control of concentration and side-chain modification of aliphatic glucosinolates, which have side-chains derived from methionine, are simple and well known from work on Arabidopsis and Brassica crops. In controlled conditions in the laboratory or in field trials, many aliphatic glucosinolates, or their degradation products, affect the behaviour of herbivores. For these reasons, we suggest that polymorphism for aliphatic glucosinolates in natural populations offers an attractive system for the study of ecological genetics of plant-herbivore interactions.

The role of spatial scale and intraspecific variation in secondary chemistry in host-plant location by Ceutorhynchus assimilis (Coleoptera: Curculionidae).

To understand the ecological role of secondary plant compounds in host location by phytophagous insects it is important to consider attraction at different scales in natural populations. The cabbage seed weevil, Ceutorhynchus assimilis, which lays eggs in pods of crucifers where the larvae feed on seed, is attracted to purified extracts of specific glucosinolate-derived volatiles. We considered the possibility that C. assimilis adults are attracted to and preferentially attack patches of plants and/or individual plants producing these volatiles. Using discrete natural populations of Brassica oleracea and Brassica nigra, we found that oviposition was highest in populations of B. oleracea producing high amounts of 3-butenylglucosinolate. No links were found between the other glucosinolates, 2-propenylglucosinolate, 2-hydroxy-3-butenylglucosinolate, 1-indolylmethylglucosinolate or 1-methoxy-3-indolylmethylglucosinolate, and oviposition in B. oleracea. B. nigra, which contains only 2-propenylglucosinolate, was not attacked by C. assimilis. Within populations of B. oleracea, neither oviposition nor the number of seeds eaten was related to the glucosinolate profiles of individual plants. We suggest that C. assimilis adults use 3-butenylglucosinolate-derived volatiles to locate host populations, whereas other cues determine oviposition on individual plants. The consequences of these results for natural selection of glucosinolate phenotypes are discussed.