Evaluating the performance of Plasmodium falciparum genetics for inferring National Malaria Control Program reported incidence in Senegal.

Genetic surveillance of the parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence.

Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study.

Background: Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa.

Methods: Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems-"classic" and "integral"-are evaluated.

Vector genetics, insecticide resistance and gene drives: An agent-based modeling approach to evaluate malaria transmission and elimination.

Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness.

Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modelling study of three potential use cases.

Background: While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides, where humans or animals are treated with drugs that kill mosquitoes upon ingestion via blood meal, are therefore generating much interest. This work explores the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden.

Effectiveness of reactive case detection for malaria elimination in three archetypical transmission settings: a modelling study.

Background: Reactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages.

Incidence and admission rates for severe malaria and their impact on mortality in Africa.

Background: Appropriate treatment of life-threatening Plasmodium falciparum malaria requires in-patient care. Although the proportion of severe cases accessing in-patient care in endemic settings strongly affects overall case fatality rates and thus disease burden, this proportion is generally unknown. At present, estimates of malaria mortality are driven by prevalence or overall clinical incidence data, ignoring differences in case fatality resulting from variations in access.

Malaria Elimination Campaigns in the Lake Kariba Region of Zambia: A Spatial Dynamical Model.

As more regions approach malaria elimination, understanding how different interventions interact to reduce transmission becomes critical. The Lake Kariba area of Southern Province, Zambia, is part of a multi-country elimination effort and presents a particular challenge as it is an interconnected region of variable transmission intensities. In 2012-13, six rounds of mass test-and-treat drug campaigns were carried out in the Lake Kariba region.

Optimal Population-Level Infection Detection Strategies for Malaria Control and Elimination in a Spatial Model of Malaria Transmission.

Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.

Background: The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings.

Distribution of malaria exposure in endemic countries in Africa considering country levels of effective treatment.

Background: Malaria prevalence, clinical incidence, treatment, and transmission rates are dynamically interrelated. Prevalence is often considered a measure of malaria transmission, but treatment of clinical malaria reduces prevalence, and consequently also infectiousness to the mosquito vector and onward transmission. The impact of the frequency of treatment on prevalence in a population is generally not considered.

From puddles to planet: modeling approaches to vector-borne diseases at varying resolution and scale.

Since the original Ross-Macdonald formulations of vector-borne disease transmission, there has been a broad proliferation of mathematical models of vector-borne disease, but many of these models retain most to all of the simplifying assumptions of the original formulations. Recently, there has been a new expansion of mathematical frameworks that contain explicit representations of the vector life cycle including aquatic stages, multiple vector species, host heterogeneity in biting rate, realistic vector feeding behavior, and spatial heterogeneity. In particular, there are now multiple frameworks for spatially explicit dynamics with movements of vector, host, or both.

Dynamics of the Human Infectious Reservoir for Malaria Determined by Mosquito Feeding Assays and Ultrasensitive Malaria Diagnosis in Burkina Faso.

Background: Plasmodium falciparum gametocytes are essential for malaria transmission. Malaria control measures that aim at reducing transmission require an accurate characterization of the human infectious reservoir.

Methods: We longitudinally determined human infectiousness to mosquitoes and P.

Fun with maths: exploring implications of mathematical models for malaria eradication.

Mathematical analyses and modelling have an important role informing malaria eradication strategies. Simple mathematical approaches can answer many questions, but it is important to investigate their assumptions and to test whether simple assumptions affect the results. In this note, four examples demonstrate both the effects of model structures and assumptions and also the benefits of using a diversity of model approaches.