Planning of the control of Plasmodium falciparum malaria leads to a need for models of malaria epidemiology that provide realistic quantitative prediction of likely epidemiological outcomes of a wide range of control strategies. Predictions of the effects of control often ignore medium-and long-term dynamics. The complexities of the Plasmodium life-cycle, and of within-host dynamics, limit the applicability of conventional deterministic malaria models. We use individual-based stochastic simulations of malaria epidemiology to predict the impacts of interventions on infection, morbidity, mortality, health services use and costs. Individual infections are simulated by stochastic series of parasite densities, and naturally acquired immunity acts by reducing densities. Morbidity and mortality risks, and infectiousness to vectors, depend on parasite densities. The simulated infections are nested within simulations of individuals in human populations, and linked to models of interventions and health systems. We use numerous field datasets to optimise parameter estimates. By using a volunteer computing system we obtain the enormous computational power required for model fitting, sensitivity analysis, and exploration of many different intervention strategies. The project thus provides a general platform for comparing, fitting, and evaluating different model structures, and for quantitative prediction of effects of different interventions and integrated control programmes.

Although some malaria-control programs are beginning to combine insecticide-treated nets (ITNs) and indoor residual spraying (IRS), little is known about the effectiveness of such combinations. We use a mathematical model to compare the effectiveness of ITNs and IRS with dichlorodiphenyltrichloroethane (DDT) or bendiocarb, applied singly and in combination, in an epidemiological setting based in Namawala, Tanzania, with Anopheles gambiae as the primary vector. Our model indicates that although both IRS (with DDT) and ITNs provide personal protection, humans with only ITNs are better protected than those with only IRS, and suggests that high coverage of IRS with bendiocarb may interrupt transmission, as can simultaneous high coverage of ITNs and IRS with DDT. When adding a second vector-control intervention, it is more effective to cover the unprotected population first. Although our model includes some assumptions and approximations that remain to be addressed, these findings should be useful for prioritizing and designing future field research.

Insecticide-treated mosquito nets (ITN) provide excellent protection against malaria; however, they have a number of shortcomings that are particularly evident in politically unstable countries or countries at war: not everyone at risk can necessarily afford a net, nets may be difficult to obtain or import, nets may not be suitable for migrants or refugees sleeping under tents or plastic shelter. There is a need to develop cheaper, locally appropriate alternatives for the most impoverished and for victims of complex emergencies. Afghan women, in common with many Muslim peoples of Asia, wear a veil or wrap known as a chaddar to cover the head and upper body. This cloth doubles as a sheet at night, when they are used by both sexes. A randomized controlled trial was undertaken in which 10% of the families of an Afghan refugee camp (population 3950) in north-western Pakistan had their chaddars and top-sheets treated with permethrin insecticide at a dosage of 1 g/m2 while a further 10% had their chaddars treated with placebo formulation. Malaria episodes were recorded by passive case detection at the camp's health centre. From August to November the odds of having a falciparum or vivax malaria episode were reduced by 64% in children aged 0-10 years and by 38% in refugees aged < 20 years in the group using permethrin-treated chaddars and top-sheets. Incidence in refugees over 20 years of age was not significantly reduced. The cost of the permethrin treatment per person protected (US$0.17) was similar to that for treating bednets (and cost only 10-20% of the price of a new bednet). An entomological study simulating real-life conditions indicated that host-seeking mosquitoes were up to 70% less successful at feeding on men sleeping under treated chaddars and some were killed by the insecticide. Permethrin-treated top-sheets and blankets should provide appropriate and effective protection from malaria in complex emergencies. In Islamic and non-Islamic countries in Asia, treated chaddars and top-sheets should offer a satisfactory solution for the most vulnerable who cannot afford treated nets.

BackgroundA number of different malaria vaccine candidates are currently in pre-clinical or clinical development. Even though they vary greatly in their characteristics, it is unlikely that any of them will provide long-lasting sterilizing immunity against the malaria parasite. There is great uncertainty about what the minimal vaccine profile should be before registration is worthwhile; how to allocate resources between different candidates with different profiles; which candidates to consider combining; and what deployment strategies to consider.Methods and FindingsWe use previously published stochastic simulation models, calibrated against extensive epidemiological data, to make quantitative predictions of the population effects of malaria vaccines on malaria transmission, morbidity and mortality. The models are fitted and simulations obtained via volunteer computing. We consider a range of endemic malaria settings with deployment of vaccines via the Expanded program on immunization (EPI), with and without additional booster doses, and also via 5-yearly mass campaigns for a range of coverages. The simulation scenarios account for the dynamic effects of natural and vaccine induced immunity, for treatment of clinical episodes, and for births, ageing and deaths in the cohort. Simulated pre-erythrocytic vaccines have greatest benefits in low endemic settings (EIR of 84) PEV may lead to increased incidence of severe disease in the long term, if efficacy is moderate to low (<70%). Blood stage vaccines (BSV) are most useful in high transmission settings, and are comparable to PEV for low transmission settings. Combinations of PEV and BSV generally perform little better than the best of the contributing components. A minimum half-life of protection of 2–3 years appears to be a precondition for substantial epidemiological effects. Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.ConclusionsWe present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings. The results raise several issues for vaccine clinical development, in particular appropriateness of vaccine types for different transmission settings; the need to assess transmission to the vector and duration of protection; and the importance of deployment additional to the EPI, which again may make the issue of number of doses required more critical. To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced ...

There is a long history of considering the constituent components of malaria risk and the malaria transmission cycle via the use of mathematical models, yet strategic planning in endemic countries tends not to take full advantage of available disease intelligence to tailor interventions. National malaria programmes typically make operational decisions about where to implement vector control and surveillance activities based upon simple categorizations of annual parasite incidence. With technological advances, an enormous opportunity exists to better target specific malaria interventions to the places where they will have greatest impact by mapping and evaluating metrics related to a variety of risk components, each of which describes a different facet of the transmission cycle. Here, these components and their implications for operational decision-making are reviewed. For each component, related mappable malaria metrics are also described which may be measured and evaluated by malaria programmes seeking to better understand the determinants of malaria risk. Implementing tailored programmes based on knowledge of the heterogeneous distribution of the drivers of malaria transmission rather than only consideration of traditional metrics such as case incidence has the potential to result in substantial improvements in decision-making. As programmes improve their ability to prioritize their available tools to the places where evidence suggests they will be most effective, elimination aspirations may become increasingly feasible.