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In more academic terms, an active focus of malaria transmission is a geographical area that supports malaria transmission, where the local Anopheles population sustains the basic reproductive rate (R0; average number of secondary infections arising in a susceptible population as a result of a single individual with malaria over the course of their malaria infection) at a level above 1 [16]. The most inclusive approach to clear infections in humans, including those that are present at densities below the detection limit of rapid diagnostic tests or microscopy [55] is to give mass drug administration (MDA) where a full therapeutic dose of drugs are administered to a population without prior screening. Because all age groups contribute to malaria transmission [57], VIMT may need to be administered to all age groups to see an impact.

Long lasting pyrethroid treated bednets are the most important tool for preventing malaria. Pyrethroid resistant Anopheline mosquitoes are now ubiquitous in Africa, though the public health impact remains unclear, impeding the deployment of more expensive nets. Meta-analyses of bioassay studies and experimental hut trials are used to characterise how pyrethroid resistance changes the efficacy of standard bednets, and those containing the synergist piperonyl butoxide (PBO), and assess its impact on malaria control. New bednets provide substantial personal protection until high levels of resistance, though protection may wane faster against more resistant mosquito populations as nets age. Transmission dynamics models indicate that even low levels of resistance would increase the incidence of malaria due to reduced mosquito mortality and lower overall community protection over the life-time of the net. Switching to PBO bednets could avert up to 0.5 clinical cases per person per year in some resistance scenarios. In recent years, widespread use of insecticide-treated bednets has prevented hundreds of thousands cases of malaria in Africa. Insecticide-treated bednets protect people in two ways: they provide a physical barrier that prevents the insects from biting and the insecticide kills mosquitos that come into contact with the net while trying to bite. Unfortunately, some mosquitoes in Africa are evolving so that they can survive contact with the insecticide currently used on bednets. How this emerging insecticide resistance is changing the number of malaria infections in Africa is not yet clear and it is difficult for scientists to study. To help mitigate the effects of insecticide resistance, scientists are testing new strategies to boost the effects of bednets, such as adding a second chemical that makes the insecticide on bednets more deadly to mosquitoes. In some places, adding this second chemical makes the nets more effective, but in others it does not. Moreover, these doubly treated, or “combination”, nets are more expensive and so it can be hard for health officials to decide whether and where to use them. Now, Churcher et al. have used computer modeling to help predict how insecticide resistance might change malaria infection rates and help determine when it makes sense to switch to the combination net. Insecticide-treated bednets provide good protection for individuals sleeping under them until relatively high levels of resistance are achieved, as measured using a simple test. As more resistant mosquitos survive encounters with the nets, the likelihood of being bitten before bed or while sleeping unprotected by a net increases. This is expected to increase malaria infections. As bednets age and are washed multiple times, they lose some of their insecticide and this problem becomes worse. Churcher et al. also show that the combination bednets may provide some additional protection against resistant mosquitos and reduce the number of malaria infections in some cases. The experiments show a simple test could help health officials determine which type of net would be most beneficial. The experiments and the model Churcher et al. created also may help scientists studying how to prevent increased spread of malaria in communities where mosquitos are becoming resistant to insecticide-treated nets.

Despite concern that climate change could increase the human risk to malaria in certain areas, the temperature dependency of malaria transmission is poorly characterized. Here, we use a mechanistic model fitted to experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae , is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, parasite development rate, and overall vector competence. We use these data, together with estimates of the survival of infected blood-fed mosquitoes, to explore the theoretical influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted. Malaria transmission is affected by temperature but this relationship is not well characterised. Here, the authors experimentally determine the effect of temperature on parasite development in the mosquito and model how it impacts malaria transmission in Kenya under current and future climate scenarios.

Long lasting insecticidal nets (LLINs) provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance. Long lasting insecticide treated mosquito nets (LLINs) provide protection from malaria through both direct effects to the user and indirect community-level effects. Here, the authors use mathematical modelling to assess the relative contributions of these effects under different insecticide resistance and LLIN usage scenarios.

Mating causes dramatic changes in female physiology, behaviour, and immunity in many insects, inducing oogenesis, oviposition, and refractoriness to further mating. Females from the Anopheles gambiae species complex typically mate only once in their lifetime during which they receive sperm and seminal fluid proteins as well as a mating plug that contains the steroid hormone 20-hydroxyecdysone. This hormone, which is also induced by blood-feeding, plays a major role in activating vitellogenesis for egg production. Here we show that female Anopheles coluzzii susceptibility to Plasmodium falciparum infection is significantly higher in mated females compared to virgins. We also find that mating status has a major impact on the midgut transcriptome, detectable only under sugar-fed conditions: once females have blood-fed, the transcriptional changes that are induced by mating are likely masked by the widespread effects of blood-feeding on gene expression. To determine whether increased susceptibility to parasites could be driven by the additional 20E that mated females receive from males, we mimicked mating by injecting virgin females with 20E, finding that these females are significantly more susceptible to human malaria parasites than virgin females injected with the control 20E carrier. Further RNAseq was carried out to examine whether the genes that change upon 20E injection in the midgut are similar to those that change upon mating. We find that 79 midgut-expressed genes are regulated in common by both mating and 20E, and 96% (n = 76) of these are regulated in the same direction (up vs down in 20E/mated). Together, these findings show that male Anopheles mosquitoes induce changes in the female midgut that can affect female susceptibility to P. falciparum. This implies that in nature, males might contribute to malaria transmission in previously unappreciated ways, and that vector control strategies that target males may have additional benefits towards reducing transmission.

Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of the number of parasites they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections of humans and mice and demonstrate a dose-dependency for probability of infection and the length of the host pre-patent period. Mosquitoes with a higher numbers of sporozoites in their salivary glands following blood-feeding are more likely to have caused infection (and have done so quicker) than mosquitoes with fewer parasites. A similar dose response for the probability of infection was seen for humans given a pre-erythrocytic vaccine candidate targeting circumsporozoite protein (CSP), and in mice with and without transfusion of anti-CSP antibodies. These interventions prevented infection more efficiently from bites made by mosquitoes with fewer parasites. The importance of parasite number has widespread implications across malariology, ranging from our basic understanding of the parasite, how vaccines are evaluated and the way in which transmission should be measured in the field. It also provides direct evidence for why the only registered malaria vaccine RTS,S was partially effective in recent clinical trials.

Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness. Indoor residual spraying is a commonly used method for mosquito, and malaria, control and there are a number of available insecticides that are available for this. Here, the authors evaluate the efficacy of widely-used and novel insecticides against pyrethroid-resistant mosquitoes.

During sporogony, malaria-causing parasites infect a mosquito, reproduce and migrate to the mosquito salivary glands where they can be transmitted the next time blood feeding occurs. The time required for sporogony, known as the extrinsic incubation period (EIP), is an important determinant of malaria transmission intensity. The EIP is typically estimated as the time for a given percentile, x , of infected mosquitoes to develop salivary gland sporozoites (the infectious parasite life stage), which is denoted by EIP x . Many mechanisms, however, affect the observed sporozoite prevalence including the human-to-mosquito transmission probability and possibly differences in mosquito mortality according to infection status. To account for these various mechanisms, we present a mechanistic mathematical model, which explicitly models key processes at the parasite, mosquito and observational scales. Fitting this model to experimental data, we find greater variation in the EIP than previously thought: we estimated the range between EIP 10 and EIP 90 (at 27°C) as 4.5 days compared to 0.9 days using existing statistical methods. This pattern holds over the range of study temperatures included in the dataset. Increasing temperature from 21°C to 34°C decreased the EIP 50 from 16.1 to 8.8 days. Our work highlights the importance of mechanistic modelling of sporogony to (1) improve estimates of malaria transmission under different environmental conditions or disease control programs and (2) evaluate novel interventions that target the mosquito life stages of the parasite.

A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment of population-wide malaria transmission potential based on 1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across both sites, we identified 39 infectious individuals. In high endemicity settings, infectious individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one of three infectious individuals in the lowest endemicity setting was detected by molecular techniques alone. The percentages of infected mosquitoes in the different surveys ranged from 0.05 (4/7716) to 1.6% (121/7749), and correlate positively with transmission intensity. We also estimated exposure to malaria vectors through genetic matching of blood from 1094 wild-caught bloodfed mosquitoes with that of humans resident in the same houses. Although adults transmitted fewer parasites to mosquitoes than children, they received more mosquito bites, thus balancing their contribution to the infectious reservoir. Heterogeneity in the transmission potential of individual hosts is an important feature of malaria. Here, the authors perform a multi-regional study of the human infectious reservoir in malaria-endemic regions of Burkina Faso and Kenya.

Background Pyrethroid-PBO nets were conditionally recommended for control of malaria transmitted by mosquitoes with oxidase-based pyrethroid-resistance based on epidemiological evidence of additional protective effect with Olyset Plus compared to a pyrethroid-only net (Olyset Net). Entomological studies can be used to assess the comparative performance of other brands of pyrethroid-PBO ITNs to Olyset Plus. Methods An experimental hut trial was performed in Cové, Benin to compare PermaNet 3.0 (deltamethrin plus PBO on roof panel only) to Olyset Plus (permethrin plus PBO on all panels) against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) following World Health Organization (WHO) guidelines. Both nets were tested unwashed and after 20 standardized washes compared to Olyset Net. Laboratory bioassays were also performed to help explain findings in the experimental huts. Results With unwashed nets, mosquito mortality was higher in huts with PermaNet 3.0 compared to Olyset Plus (41% vs. 28%, P < 0.001). After 20 washes, mortality declined significantly with PermaNet 3.0 (41% unwashed vs. 17% after washing P < 0.001), but not with Olyset Plus (28% unwashed vs. 24% after washing P = 0.433); Olyset Plus induced significantly higher mortality than PermaNet 3.0 and Olyset Net after 20 washes. PermaNet 3.0 showed a higher wash retention of PBO compared to Olyset Plus. A non-inferiority analysis performed with data from unwashed and washed nets together using a margin recommended by the WHO, showed that PermaNet 3.0 was non-inferior to Olyset Plus in terms of mosquito mortality (25% with Olyset Plus vs. 27% with PermaNet 3.0, OR = 1.528, 95%CI = 1.02–2.29) but not in reducing mosquito feeding (25% with Olyset Plus vs. 30% with PermaNet 3.0, OR = 1.192, 95%CI = 0.77–1.84). Both pyrethroid-PBO nets were superior to Olyset Net. Conclusion Olyset Plus outperformed PermaNet 3.0 in terms of its ability to cause greater margins of improved mosquito mortality compared to a standard pyrethroid net, after multiple standardized washes. However, using a margin of non-inferiority defined by the WHO, PermaNet 3.0 was non-inferior to Olyset Plus in inducing mosquito mortality. Considering the low levels of mortality observed and increasing pyrethroid-resistance in West Africa, it is unclear whether either of these nets would demonstrate the same epidemiological impact observed in community trials in East Africa.