Potential Causes and Consequences of Behavioural Resilience and Resistance in Malaria Vector Populations: A Mathematical Modelling Analysis

The ability of mosquitoes to evade fatal exposure to insecticidal nets and sprays represents the primary obstacle to eliminating malaria. However, it remains unclear which behaviours are most important for buffering mosquito and parasite populations against vector control. Simulated life histories were used to compare the impact of alternative feeding behavior strategies upon overall lifetime feeding success, and upon temporal distributions of successful feeds and biting rates experienced by unprotected humans, in the presence and absence of insecticidal nets. Strictly nocturnal preferred feeding times were contrasted with 1) a wider preference window extending to dawn and dusk, and 2) crepuscular preferences wherein foraging is suppressed when humans sleep and can use nets but is maximal immediately before and after. Simulations with diversion and mortality parameters typical of endophagic, endophilic African vectors, such as Anopheles gambiae and Anopheles funestus, were compared with those for endophagic but exophilic species, such as Anopheles arabiensis, thatalso enter houses but leave earlier before lethal exposure to insecticide-treated surfaces occurs. Insecticidal nets were predicted to redistribute successful feeding events to dawn and dusk where these were included in the profile of innately preferred feeding times. However, predicted distributions of biting unprotected humans, were unaffected because extended hostseeking activity was redistributed to innately preferred feeding times. Recently observed alterations of biting activity distributions therefore reflect processes not captured in this model, such as evolutionary selection of heritably modified feeding time preferences or phenotypically plastic expression of feeding time preference caused by associative learning. Surprisingly, endophagy combined with exophily, among mosquitoes that enter houses but then feed and/or rest briefly before rapidly exiting, consistently attenuated predicted insecticide impact more than any feeding time preference trait. Regardless of underlying cause, recent redistributions of host-biting activity to dawn and dusk necessitate new outdoor control strategies. However, persistently indoor-feeding vectors, that evade intradomiciliary insecticide exposure, are at least equally important. Fortunately, recent evaluations of occupied houses or odour-baited stations, with baffled entrances that retain An. arabiensis within insecticide-treated structures, illustrate how endophagic but exophilic vectors may be more effectively tackled using existing insecticides

Rationalizing Historical Successes of Malaria Control in Africa in Terms of Mosquito Resource Availability Management.

Environmental management of mosquito resources is a promising approach with which to control malaria, but it has seen little application in Africa for more than half a century. Here we present a kinetic model of mosquito foraging for aquatic habitats and vertebrate hosts that allows estimation of malaria transmission intensity by defining the availability of these resources as the rate at which individual mosquitoes encounter and use them. The model captures historically observed responses of malaria transmission to environmental change, highlights important gaps in current understanding of vector ecology, and suggests convenient solutions. Resource availability is an intuitive concept that provides an adaptable framework for models of mosquito population dynamics, gene flow, and pathogen transmission that can be conveniently parameterized with direct field measurements. Furthermore, the model presented predicts that drastic reductions of malaria transmission are possible with environmental management and elucidates an ecologic basis for previous successes of integrated malaria control in Africa before the advent of DDT or chloroquine. Environmental management for malaria control requires specialist skills that are currently lacking in sub-Saharan Africa where they are needed most. Infrastructure and human capacity building in clinical, public health, and environmental disciplines should therefore be prioritized so that growing financial support for tackling malaria can be translated into truly integrated control programs

Exploring the contributions of bed nets, cattle, insecticides and excitorepellency to malaria control: a deterministic model of mosquito host-seeking behaviour and mortality

Domestic and personal protection measures against malaria exposure either divert host-seeking vectors to other hosts or kill those attempting to feed. Here, we explicitly model mosquito host-seeking processes in the context of local host availability and elucidate the impacts and mechanisms of pyrethroid-treated bed nets in Africa. It has been suggested that excitorepellent insecticides could increase exposure of unprotected humans by concentrating mosquito biting activity on this vulnerable group. This worst-case scenario is confirmed as a possibility where vector populations lack alternative hosts, but an approximate ‘break-even' scenario, with users experiencing little overall change in exposure, is more likely because of increased mosquito mortality while foraging for resources. Insecticidal nets are predicted to have epidemiologically significant impacts on transmission experienced by users and non-users at levels of coverage that can be achieved by sustainable net distribution systems, regardless of excitorepellency or the ecological setting. The results are consistent with the outcome of several randomised controlled trials, predicting enormous reductions in transmission at individual and community levels. As financial support, technology and distribution systems for insecticide-treated nets improve, massive reductions in malaria transmission could be realise

Pushing past the tipping points in containment trajectories of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics: A simple arithmetic rationale for crushing the curve instead of merely flattening it

Countries with ambitious national strategies to crush the curve of their Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic trajectories include China, Korea, Japan, Taiwan, New Zealand and Australia. However, the United States and many hard-hit European countries, like Ireland, Italy, Spain, France and the United Kingdom, currently appear content to merely flatten the curve of their epidemic trajectories so that transmission persists at rates their critical care services can cope with. Here I present a simple set of arithmetic modelling analyses that are accessible to non-specialists and explain why preferable crush the curve strategies, to eliminate transmission within months, would require only a modest amount of additional containment effort relative to the tipping point targeted by flatten the curve strategies, which allow epidemics to persist at supposedly steady, manageable levels for years, decades or even indefinitely

Advantages of larval control for African malaria vectors: Low mobility and behavioural responsiveness of immature mosquito stages allow high effective coverage

BACKGROUND: Based on sensitivity analysis of the MacDonald-Ross model, it has long been argued that the best way to reduce malaria transmission is to target adult female mosquitoes with insecticides that can reduce the longevity and human-feeding frequency of vectors. However, these analyses have ignored a fundamental biological difference between mosquito adults and the immature stages that precede them: adults are highly mobile flying insects that can readily detect and avoid many intervention measures whereas mosquito eggs, larvae and pupae are confined within relatively small aquatic habitats and cannot readily escape control measures. PRESENTATION OF THE HYPOTHESIS: We hypothesize that the control of adult but not immature mosquitoes is compromised by their ability to avoid interventions such as excito-repellant insecticides. TESTING THE HYPOTHESIS: We apply a simple model of intervention avoidance by mosquitoes and demonstrate that this can substantially reduce effective coverage, in terms of the proportion of the vector population that is covered, and overall impact on malaria transmission. We review historical evidence that larval control of African malaria vectors can be effective and conclude that the only limitations to the effective coverage of larval control are practical rather than fundamental. IMPLICATIONS OF THE HYPOTHESIS: Larval control strategies against the vectors of malaria in sub-Saharan Africa could be highly effective, complementary to adult control interventions, and should be prioritized for further development, evaluation and implementation as an integral part of Rolling Back Malaria

Insecticide-Treated Nets Can Reduce Malaria Transmission by Mosquitoes Which Feed Outdoors

Insecticide treated nets (ITNs) represent a powerful means for controlling malaria in Africa because the mosquito vectors feed primarily indoors at night. The proportion of human exposure that occurs indoors, when people are asleep and can conveniently use ITNs, is therefore very high. Recent evidence suggests behavioral changes by malaria mosquito populations to avoid contact with ITNs by feeding outdoors in the early evening. We adapt an established mathematical model of mosquito behavior and malaria transmission to illustrate how ITNs can achieve communal suppression of malaria transmission exposure, even where mosquito evade them and personal protection is modest. We also review recent reports from Tanzania to show that conventional mosquito behavior measures can underestimate the potential of ITNs because they ignore the importance of human movements

Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria.

We propose a stochastic model for the relationship between the entomologic inoculation rate (EIR) for Plasmodium falciparum malaria and the force of infection in endemic areas. The model incorporates effects of increased exposure to mosquito bites as a result of the growth in body surface area with the age of the host, naturally acquired pre-erythrocytic immunity, and the reduction in the proportion of entomologically assessed inoculations leading to infection, as the EIR increases. It is fitted to multiple datasets from field studies of the relationship between malaria infection and the EIR. We propose that this model can account for non-monotonic relationships between the age of the host and the parasite prevalence and incidence of disease. It provides a parsimonious explanation for the faster acquisition of natural immunity in adults than in children exposed to high EIRs. This forms one component of a new stochastic model for the entire transmission cycle of P. falciparum that we have derived to estimate the potential epidemiologic impact of malaria vaccines and other malaria control interventions

Biologically meaningful coverage indicators for eliminating malaria transmission.

Mosquitoes, which evade contact with long-lasting insecticidal nets and indoor residual sprays, by feeding outdoors or upon animals, are primary malaria vectors in many tropical countries. They can also dominate residual transmission where high coverage of these front-line vector control measures is achieved. Complementary strategies, which extend insecticide coverage beyond houses and humans, are required to eliminate malaria transmission in most settings. The overwhelming diversity of the world's malaria transmission systems and optimal strategies for controlling them can be simply conceptualized and mapped across two-dimensional scenario space defined by the proportion of blood meals that vectors obtain from humans and the proportion of human exposure to them which occurs indoors