Heather M. Ferguson

Preventing childhood malaria in Africa by protecting adults from mosquitoes with insecticide-treated nets

Background Malaria prevention in Africa merits particular attention as the world strives toward a better life for the poorest. Insecticide-treated nets (ITNs) represent a practical means to prevent malaria in Africa, so scaling up coverage to at least 80% of young children and pregnant women by 2010 is integral to the Millennium Development Goals (MDG). Targeting individual protection to vulnerable groups is an accepted priority, but community-level impacts of broader population coverage are largely ignored even though they may be just as important. We therefore estimated coverage thresholds for entire populations at which individual- and community-level protection are equivalent, representing rational targets for ITN coverage beyond vulnerable groups. Methods and Findings Using field-parameterized malaria transmission models, we show that high (80% use) but exclusively targeted coverage of young children and pregnant women (representing <20% of the population) will deliver limited protection and equity for these vulnerable groups. In contrast, relatively modest coverage (35%–65% use, with this threshold depending on ecological scenario and net quality) of all adults and children, rather than just vulnerable groups, can achieve equitable community-wide benefits equivalent to or greater than personal protection. Conclusions Coverage of entire populations will be required to accomplish large reductions of the malaria burden in Africa. While coverage of vulnerable groups should still be prioritized, the equitable and communal benefits of wide-scale ITN use by older children and adults should be explicitly promoted and evaluated by national malaria control programmes. ITN use by the majority of entire populations could protect all children in such communities, even those not actually covered by achieving existing personal protection targets of the MDG, Roll Back Malaria Partnership, or the US Presidents Malaria Initiative.

Ecology: a prerequisite for malaria elimination and eradication

Gerry Killeen and colleagues argue that malaria eradication efforts will not be successful until a better understanding of the ecology and evolution of the mosquito vectors is gained.

Why is the effect of malaria parasites on mosquito survival still unresolved

Despite almost a century of effort, the question of whether malaria parasites kill their mosquito vectors remains open. Some direct comparisons of the longevity of infected and uninfected mosquitoes have found malaria-induced mortality, whereas others have not. Here, we use meta-analysis to show that, overall, malaria parasites do reduce mosquito survival. However, mortality effects are more likely to be detected in unnatural vector-parasite combinations and in studies of longer duration. Until these factors are systematically investigated, no firm generalities are possible.

Genetic and environmental determinants of malaria parasite virulence in mosquitoes

Models of malaria epidemiology and evolution are frequently based on the assumption that vector–parasitic associations are benign. Implicit in this assumption is the supposition that all Plasmodium parasites have an equal and neutral effect on vector survival, and thus that there is no parasite genetic variation for vector virulence. While some data support the assumption of avirulence, there has been no examination of the impact of parasite genetic diversity. We conducted a laboratory study with the rodent malaria parasite, Plasmodium chabaudi and the vector, Anopheles stephensi, to determine whether mosquito mortality varied with parasite genotype (CR and ER clones), infection diversity (single versus mixed genotype) and nutrient availability. Vector mortality varied significantly between parasite genotypes, but the rank order of virulence depended on environmental conditions. In standard conditions, mixed genotype infections were the most virulent but when glucose water was limited, mortality was highest in mosquitoes infected with CR. These genotype–by–environment interactions were repeatable across two experiments and could not be explained by variation in anaemia, gametocytaemia, blood meal size, mosquito body size, infection rate or oocyst burden. Variation in the genetic and environmental determinants of virulence may explain conflicting accounts of Plasmodium pathogenicity to mosquitoes in the malaria literature.

Ecological and evolutionary determinants of host species choice in mosquito vectors.

Insects exhibit diverse resource-exploitation strategies, including predation, herbivory and parasitism. The ecological and evolutionary factors that influence the resource selection of some insects (e.g. herbivores) have been extensively investigated because of their agricultural importance. By contrast, there has been little investigation of the selective forces that mediate host choice in haematophagous insects, despite their importance as vectors of disease. Here, we review potential determinants of host species choice in mosquitoes, the most important insect vectors of human disease, and discuss whether these could be manipulated to yield new disease-control strategies based on vector behavioural change.

Why Use of Interventions Targeting Outdoor Biting Mosquitoes will be Necessary to Achieve Malaria Elimination

By definition, elimination of malaria means permanent reduction to zero of locally incidence of infections. Achieving this goal among other reasons, it requires fully understanding on where and when persons are most exposed to malaria vectors as these are fundamental for targeting interventions to achieve maximum impact. While elimination can be possible in some settings with low malaria transmission intensity and dominated with late and indoor biting of vectors using Long Lasting Insecticidal Nets (LLIN) and Indoor Residual Spraying (IRs), it’s difficult and even impossible in areas with high and where majority of human exposure to transmission occurs outside human dwellings. Recently in response to wide spread use of LLIN and IRS, human risk of exposure to transmission is increasingly spread across the entire night so that much of it occurs outdoors and before bed time. This modification of vector populations and behaviour has now been reported from across Africa, Asia and from the Solomon Islands. Historical evidence shows that even in areas with intervention coverage exceeding 90% of human population it was so hard to even push prevalence down below the pre elimination threshold of 1% being compromised mainly with the outdoor residual transmission. Malaria control experts must however continue to deliver interventions that tackle indoor transmission but considerable amount of resources that target mosquitoes outside of houses and outside of sleeping hours will therefore be required to sustain and go beyond existing levels of malaria control and achieve elimination.

Establishment of a large semi-field system for experimental study of African malaria vector ecology and control in Tanzania

BackgroundMedical entomologists increasingly recognize that the ability to make inferences between laboratory experiments of vector biology and epidemiological trends observed in the field is hindered by a conceptual and methodological gap occurring between these approaches which prevents hypothesis-driven empirical research from being conducted on relatively large and environmentally realistic scales. The development of Semi-Field Systems (SFS) has been proposed as the best mechanism for bridging this gap. Semi-field systems are defined as enclosed environments, ideally situated within the natural ecosystem of a target disease vector and exposed to ambient environmental conditions, in which all features necessary for its life cycle completion are present. Although the value of SFS as a research tool for malaria vector biology is gaining recognition, only a few such facilities exist worldwide and are relatively small in size (< 100 m2).MethodsThe establishment of a 625 m2 state-of-the-art SFS for large-scale experimentation on anopheline mosquito ecology and control within a rural area of southern Tanzania, where malaria transmission intensities are amongst the highest ever recorded, is described.ResultsA greenhouse frame with walls of mosquito netting and a polyethylene roof was mounted on a raised concrete platform at the Ifakara Health Institute. The interior of the SFS was divided into four separate work areas that have been set up for a variety of research activities including mass-rearing for African malaria vectors under natural conditions, high throughput evaluation of novel mosquito control and trapping techniques, short-term assays of host-seeking behaviour and olfaction, and longer-term experimental investigation of anopheline population dynamics and gene flow within a contained environment that simulates a local village domestic setting.ConclusionThe SFS at Ifakara was completed and ready for use in under two years. Preliminary observations indicate that realistic and repeatable observations of anopheline behaviour are obtainable within the SFS, and that habitat and climatic features representative of field conditions can be simulated within it. As work begins in the SFS in Ifakara and others around the world, the major opportunities and challenges to the successful application of this tool for malaria vector research and control are discussed.

MOSQUITO MORTALITY AND THE EVOLUTION OF MALARIA VIRULENCE

Abstract Several laboratory studies of malaria parasites (Plasmodium sp.) and some field observations suggest that parasite virulence, defined as the harm a parasite causes to its vertebrate host, is positively correlated with transmission. Given this advantage, what limits the continual evolution of higher parasite virulence? One possibility is that while more virulent strains are more infectious, they are also more lethal to mosquitoes. In this study, we tested whether the virulence of the rodent malaria parasite P. chabaudi in the laboratory mouse was correlated with the fitness of mosquitoes it subsequently infected. Mice were infected with one of seven genetically distinct clones of P. chabaudi that differ in virulence. Weight loss and anemia in infected mice were monitored for 16–17 days before Anopheles stephensi mosquitoes were allowed to take a blood meal from them. Infection virulence in mice was positively correlated with transmission to mosquitoes (infection rate) and weakly associated with parasite burden (number of oocysts). Mosquito survival fell with increasing oocyst burden, but there was no overall statistically significant relationship between virulence in mice and mosquito mortality. Thus, there was no evidence that more virulent strains are more lethal to mosquitoes. Both vector survival and fecundity depended on parasite clone, and contrary to expectations, mosquitoes fed on infections more virulent to mice were more fecund. The strong parasite genetic effects associated with both fecundity and survival suggests that vector fitness could be an important selective agent shaping malaria population genetics and the evolution of phenotypes such as virulence in the vector.

Non-destructive determination of age and species of anopheles gambiae s.l. using near-infrared spectroscopy

Determining malaria vector species and age is crucial to measure malaria risk. Although different in ecology and susceptibility to control, the African malaria vectors Anopheles gambiae sensu stricto and An. arabiensis are morphologically similar and can be differentiated only by molecular techniques. Furthermore, few reliable methods exist to estimate the age of these vectors, which is a key predictor of malaria transmission intensity. We evaluated the use of near-infrared spectroscopy (NIRS) to determine vector species and age. This non-destructive technique predicted the species of field-collected mosquitoes with approximately 80% accuracy and predicted the species of laboratory-reared insects with almost 100% accuracy. The relative age of young or old females was predicted with approximately 80% accuracy, and young and old insects were predicted with > or = 90% accuracy. For applications where rapid assessment of the age structure and species composition of wild vector populations is needed, NIRS offers a valuable alternative to traditional methods.

Effect of larval crowding on mating competitiveness of Anopheles gambiae mosquitoes.

BackgroundThe success of sterile or transgenic Anopheles for malaria control depends on their mating competitiveness within wild populations. Current evidence suggests that transgenic mosquitoes have reduced fitness. One means of compensating for this fitness deficit would be to identify environmental conditions that increase their mating competitiveness, and incorporate them into laboratory rearing regimes.MethodsAnopheles gambiae larvae were allocated to three crowding treatments with the same food input per larva. Emerged males were competed against one another for access to females, and their corresponding longevity and energetic reserves measured.ResultsMales from the low-crowding treatment were much more likely to acquire the first mating. They won the first female approximately 11 times more often than those from the high-crowding treatment (Odds ratio = 11.17) and four times more often than those from the medium-crowding treatment (Odds ratio = 3.51). However, there was no overall difference in the total number of matings acquired by males from different treatments (p = 0.08). The survival of males from the low crowding treatment was lower than those from other treatments. The body size and teneral reserves of adult males did not differ between crowding treatments, but larger males were more likely to acquire mates than small individuals.ConclusionLarval crowding and body size have strong, independent effects on the mating competitiveness of adult male An. gambiae. Thus manipulation of larval crowding during mass rearing could provide a simple technique for boosting the competitiveness of sterile or transgenic male mosquitoes prior to release.