Anopheles gambiae genome: perspectives for malaria control

Malaria, a disease that infects 300 million people throughout the world and kills more than a million people, mostly children in sub-Saharan Africa, involves three organisms. The human host where the disease is seen, the protozoan Plasmodium parasite and the mosquito. The parasite is transmitted to humans only by the mosquito vector, which in sub-Saharan regions is generally Anopheles gambiae. Malaria along with AIDS and tuberculosis are killing large numbers of people and crippling the economies of the affected African countries. Though an enormous effort has been made during the past twenty years to develop vaccines to block malaria in humans, the incidence of the disease is increasing in Africa. The reasons for this development include a breakdown in mosquito control related to increased insecticide resistance, as well as increased parasite resistance to antimalarial drugs. It is clear that new methods of Anopheles mosquito control are needed to ameliorate the medical and economic situation in sub-Saharan Africa. As a step toward new malaria control methods, the international Plasmodium falciparum and Anopheles gambiae consortia have carried out the full genome sequencing of the most deadly malaria parasite and the most efficient vector. These, combined with the human genome sequence, provide the genomic infrastructure for a better understanding of the complex interactions within the malaria triad. This essay discusses possible strategies as to how the Anopheles genome can contribute to malaria control.     

Implementation of malaria control

Global trends of infant and child mortality have decreased over the last 30 years, while the proportion of malaria deaths has progressively increased due to the deteriorating situation in sub-Saharan Africa. The Global Malaria Control Strategy promoted by WHO has encountered several obstacles to its implementation. Early diagnosis and prompt treatment can reduce malaria mortality, but there is still low investment on safe and effective modalities of care delivery at the periphery, where most of the malaria burden exists. Selective vector control (indoor residual spraying and insecticide-treated nets) plays a significant role outside Africa, but its wider use is limited by cost/affordability problems and operational issues (supply, delivery and logistics). Alternative methods such as environmental management and biological control are cost-effective only under very specific epidemiological situations. In most countries forecasting, early detection and containment of malaria epidemics is deficient, and there is separation between the research and control communities, particularly in Africa. Involvement of the internal agencies, strategic investments in capacity building and institutional networking are needed to strengthen capacity for malaria and research in the countries. The major responsibility is to guide the expenditure made by the communities (which far out-weigh the limited share of national health budgets) towards the most cost-effective approaches to reduce malaria mortality and morbidity.     

The Effective Population Size of Malaria Mosquitoes: Large Impact of Vector Control

Malaria vectors in sub-Saharan Africa have proven themselves very difficult adversaries in the global struggle against malaria. Decades of anti-vector interventions have yielded mixed results—with successful reductions in transmission in some areas and limited impacts in others. These varying successes can be ascribed to a lack of universally effective vector control tools, as well as the development of insecticide resistance in mosquito populations. Understanding the impact of vector control on mosquito populations is crucial for planning new interventions and evaluating existing ones. However, estimates of population size changes in response to control efforts are often inaccurate because of limitations and biases in collection methods. Attempts to evaluate the impact of vector control on mosquito effective population size (N_e) have produced inconclusive results thus far. Therefore, we obtained data for 13–15 microsatellite markers for more than 1,500 mosquitoes representing multiple time points for seven populations of three important vector species—Anopheles gambiae, An. melas, and An. moucheti—in Equatorial Guinea. These populations were exposed to indoor residual spraying or long-lasting insecticidal nets in recent years. For comparison, we also analyzed data from two populations that have no history of organized vector control. We used Approximate Bayesian Computation to reconstruct their demographic history, allowing us to evaluate the impact of these interventions on the effective population size. In six of the seven study populations, vector control had a dramatic impact on the effective population size, reducing N_e between 55%–87%, the exception being a single An. melas population. In contrast, the two negative control populations did not experience a reduction in effective population size. This study is the first to conclusively link anti-vector intervention programs in Africa to sharply reduced effective population sizes of malaria vectors.     

Genetic differentiation of Anopheles gambiae s.s. populations in Mali,West Africa,using microsatellite loci

Anopheles gambiae sensu stricto is a principal vector of malaria through much of sub-Saharan Africa, where this disease is a major cause of morbidity and mortality in human populations. Accordingly, population sizes and gene flow in this species have received special attention, as these parameters are important in attempts to control malaria by impacting its mosquito vector. Past measures of genetic differentiation have sometimes yielded conflicting results, in some cases suggesting that gene flow is extensive over vast distances (6000 km) and is disrupted only by major geological disturbances and/or barriers. Using microsatellite DNA loci from populations in Mali, West Africa, we measured genetic differentiation over uniform habitats favorable to the species across distances ranging from 62 to 536 km. Gene flow was strongly correlated with distance (r(2) = 0.77), with no major differences among chromosomes. We conclude that in this part of Africa, at least, genetic differentiation for microsatellite DNA loci is consistent with traditional models of isolation by distance.     

The epidemiology of yellow fever in Africa

Yellow fever (YF) is still a major public heath problem, particularly in Africa, despite the availability of a very efficacious vaccine. The World Health Organization estimates that there are 200,000 cases of YF annually, including 30,000 deaths, of which over 90% occur in Africa. In the past 15 years, the number of YF cases has increased tremendously, with most of the YF activity in West Africa. This increase in YF activity is in part due to a breakdown in YF vaccination and mosquito control programs. Five genotypes of YF virus have been found in Africa, and each genotype circulates in a distinct geographical region. West Africa genotype I, found in Nigeria and surrounding areas, is associated with frequent epidemics, whereas the three genotypes in East and Central Africa are in regions where YF outbreaks are rare. Other factors, including genetic and behavioral variation among vector species, are also thought to play a role in the epidemiology of YF in Africa.     

Epidemiology of groundnut rosette virus disease: current status and future research needs@

Rosette is the most destructive virus disease of groundnut in sub-Saharan Africa. It is caused by a complex of three agents, namely groundnut rosette assistor virus, groundnut rosette virus and its satellite RNA. The disease appears to be indigenous to Africa as it has not been recorded elsewhere. Thus rosette represents a new-encounter situation as the disease is thought to have spread to the introduced groundnut from indigenous host plants. Rosette has been known since 1907 and much information has been obtained on the main features of the disease, viz. its biology, transmission, viral aetiology and diagnosis, and the impact of chemical control of the aphid vector, cultural practices and virus-resistant varieties on disease management. However, there are still many gaps in the available knowledge, especially the reasons for the large and unpredictable fluctuations in the incidence and severity of rosette disease throughout sub-Saharan Africa. Three unresolved issues of particular importance concern the nature of the primary source(s) of inoculum, the means of survival of virus and vector during unfavourable periods, and the distances over which the aphid vector can disperse and disseminate virus. Now that the aetiology of the disease is understood and diagnostic tools have been developed, the time is opportune for new initiatives in understanding the ecology and epidemiology of rosette. Substantial progress can be made by developing a co-ordinated multi-disciplinary research programme and making full use of the latest techniques, approaches and experience gained elsewhere with other insect-borne viruses. This information would help to explain the sporadic disease epidemics that cause serious crop losses and sometimes total crop failure, and would also facilitate the development of disease forecasting methods and sustainable integrated disease management strategies.     

Culicoides species as potential vectors of African horse sickness virus in the southern regions of South Africa

African horse sickness (AHS), a disease of equids caused by the AHS virus, is of major concern in South Africa. With mortality reaching up to 95% in susceptible horses and the apparent reoccurrence of cases in regions deemed non‐endemic, most particularly the Eastern Cape, epidemiological research into factors contributing to the increase in the range of this economically important virus became imperative. The vectors, Culicoides (Diptera: Ceratopogonidae), are considered unable to proliferate during the unfavourable climatic conditions experienced in winter in the province, although the annual occurrence of AHS suggests that the virus has become established and that vector activity continues throughout the year. Surveillance of Culicoides within the province is sparse and little was known of the diversity of vector species or the abundance of known vectors, Culicoides imicola and Culicoides bolitinos. Surveillance was performed using light trapping methods at selected sites with varying equid species over two winter and two outbreak seasons, aiming to determine diversity, abundance and vector epidemiology of Culicoides within the province. The research provided an updated checklist of Culicoides species within the Eastern Cape, contributing to an increase in the knowledge of AHS vector epidemiology, as well as prevention and control in southern Africa.     

Controlling Malaria Using Livestock-Based Interventions: A One Health Approach

Where malaria is transmitted by zoophilic vectors, two types of malaria control strategies have been proposed based on animals: using livestock to divert vector biting from people (zooprophylaxis) or as baits to attract vectors to insecticide sources (insecticide-treated livestock). Opposing findings have been obtained on malaria zooprophylaxis, and despite the success of an insecticide-treated livestock trial in Pakistan, where malaria vectors are highly zoophilic, its effectiveness is yet to be formally tested in Africa where vectors are more anthropophilic. This study aims to clarify the different effects of livestock on malaria and to understand under what circumstances livestock-based interventions could play a role in malaria control programmes. This was explored by developing a mathematical model and combining it with data from Pakistan and Ethiopia. Consistent with previous work, a zooprophylactic effect of untreated livestock is predicted in two situations: if vector population density does not increase with livestock introduction, or if livestock numbers and availability to vectors are sufficiently high such that the increase in vector density is counteracted by the diversion of bites from humans to animals. Although, as expected, insecticide-treatment of livestock is predicted to be more beneficial in settings with highly zoophilic vectors, like South Asia, we find that the intervention could also considerably decrease malaria transmission in regions with more anthropophilic vectors, like Anopheles arabiensis in Africa, under specific circumstances: high treatment coverage of the livestock population, using a product with stronger or longer lasting insecticidal effect than in the Pakistan trial, and with small (ideally null) repellency effect, or if increasing the attractiveness of treated livestock to malaria vectors. The results suggest these are the most appropriate conditions for field testing insecticide-treated livestock in an Africa region with moderately zoophilic vectors, where this intervention could contribute to the integrated control of malaria and livestock diseases.     

Onchocerciasis control: Moving towards the millennium

The recognition of onchocerciasis as a major public health problem in the savanna belts of West Africa resulted in the establishment of the Onchocerciasis Control Programme (OCP) in 1974. Control was initially based on vector control by weekly larviciding. The OCP is now in transition towards its final phase in which repeated treatment with ivermectin, a safe and effective microfilaricide, is incorporated with vector control, or in certain circumstances is used alone. Ivermectin distribution hingeing on sustainable community systems is the basis of a new programme in endemic African countries outside the OCP and in the Americas. David Molyneux and John Davies describe the latest trends and developments related to onchocerciasis control.     

An island within an island: genetic differentiation of Anopheles gambiae in São Tomé, West Africa, and its relevance to malaria vector control

Islands are choice settings for experimental studies of vector control strategies based on transgenic insects. Before considering this approach, knowledge of the population structure of the vector is essential. Genetic variation at 12 microsatellite loci was therefore studied in samples of the malaria vector Anopheles gambiae s.s., collected from six localities of S?o Tomé island (West Africa). The objectives were (i) to assess the demographic stability and effective population size of A. gambiae from these sites, (ii) to determine population differentiation and (iii) to relate the observed patterns of population structure with geographic, ecological and historical aspects of the vector on the island. Significant population differentiation, revealed by FST and RST statistics, was found between the southernmost site, Porto Alegre, and northern localities. The observed patterns of population substructure are probably a result of restrictions to gene flow in the less inhabited, more densely forested and mountainous south. In all localities surveyed, A. gambiae appeared to be experiencing a demographic expansion, consistent with a relatively recent (ca. 500 years) founder effect. The results are discussed with respect to current and future prospects of malaria vector control.     

First comprehensive analysis of Aedes aegypti bionomics during an arbovirus outbreak in west Africa: Dengue in Ouagadougou,Burkina Faso, 2016–2017

BackgroundDengue’s emergence in West Africa was typified by the Burkina Faso outbreaks in 2016 and 2017, the nation’s largest to date. In both years, we undertook three-month surveys of Aedes populations in or near the capital city Ouagadougou, where the outbreaks were centered.MethodologyIn 1200LG (urban), Tabtenga (peri-urban) and Goundry (rural) localities, we collected indoor and outdoor resting mosquito adults, characterized larval habitats and containers producing pupae and reared immature stages to adulthood in the laboratory for identification. All mosquito adults were identified morphologically. Host species (from which bloodmeals were taken) were identified by PCR. Generalized mixed models were used to investigate relationships between adult or larval densities and multiple explanatory variables.ResultsFrom samples in 1,780 houses, adult Ae. aegypti were significantly more abundant in the two urban localities (Tabtenga and 1200 LG) in both years than in the rural site (Goundry), where Anopheles spp. were far more common. Results from adult collections indicated a highly exophilic and anthropophilic (>90% bloodmeals of human origin) vector population, but with a relatively high proportion of bloodfed females caught inside houses. Habitats producing most pupae were waste tires (37% of total pupae), animal troughs (44%) and large water barrels (30%).While Stegomyia indices were not reliable indicators of adult mosquito abundance, shared influences on adult and immature stage densities included rainfall and container water level, collection month and container type/purpose. Spatial analysis showed autocorrelation of densities, with a partial overlap in adult and immature stage hotspots.ConclusionResults provide an evidence base for the selection of appropriate vector control methods to minimize the risk, frequency and magnitude of future outbreaks in Ouagadougou. An integrated strategy combining community-driven practices, waste disposal and insecticide-based interventions is proposed. The prospects for developing a regional approach to arbovirus control in West Africa or across Africa are discussed.     

Elimination of Lymphatic Filariasis in The Gambia

BackgroundThe prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission.ConclusionsWe conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF.     

Genetic Structure of a Local Population of the Anopheles gambiae Complex in Burkina Faso

Members of the Anopheles gambiae species complex are primary vectors of human malaria in Africa. Population heterogeneities for ecological and behavioral attributes expand and stabilize malaria transmission over space and time, and populations may change in response to vector control, urbanization and other factors. There is a need for approaches to comprehensively describe the structure and characteristics of a sympatric local mosquito population, because incomplete knowledge of vector population composition may hinder control efforts. To this end, we used a genome-wide custom SNP typing array to analyze a population collection from a single geographic region in West Africa. The combination of sample depth (n = 456) and marker density (n = 1536) unambiguously resolved population subgroups, which were also compared for their relative susceptibility to natural genotypes of Plasmodium falciparum malaria. The population subgroups display fluctuating patterns of differentiation or sharing across the genome. Analysis of linkage disequilibrium identified 19 new candidate genes for association with underlying population divergence between sister taxa, A. coluzzii (M-form) and A. gambiae (S-form).     

Large-scale use of mosquito larval source management for malaria control in Africa: a cost analysis

Background

At present, large-scale use of two malaria vector control methods, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) is being scaled up in Africa with substantial funding from donors. A third vector control method, larval source management (LSM), has been historically very successful and is today widely used for mosquito control globally, except in Africa. With increasing risk of insecticide resistance and a shift to more exophilic vectors, LSM is now under re-evaluation for use against afro-tropical vector species. Here the costs of this intervention were evaluated.

Methods

The 'ingredients approach' was used to estimate the economic and financial costs per person protected per year (pppy) for large-scale LSM using microbial larvicides in three ecologically diverse settings: (1) the coastal metropolitan area of Dar es Salaam in Tanzania, (2) a highly populated Kenyan highland area (Vihiga District), and (3) a lakeside setting in rural western Kenya (Mbita Division). Two scenarios were examined to investigate the cost implications of using alternative product formulations. Sensitivity analyses on product prices were carried out.

Results

The results show that for programmes using the same granular formulation larviciding costs the least pppy in Dar es Salaam (US$0.94), approximately 60% more in Vihiga District (US$1.50) and the most in Mbita Division (US$2.50). However, these costs are reduced substantially if an alternative water-dispensable formulation is used; in Vihiga, this would reduce costs to US$0.79 and, in Mbita Division, to US$1.94. Larvicide and staff salary costs each accounted for approximately a third of the total economic costs per year. The cost pppy depends mainly on: (1) the type of formulation required for treating different aquatic habitats, (2) the human population density relative to the density of aquatic habitats and (3) the potential to target the intervention in space and/or time.

Conclusion

Costs for LSM compare favourably with costs for IRS and LLINs, especially in areas with moderate and focal malaria transmission where mosquito larval habitats are accessible and well defined. LSM presents an attractive tool to be integrated in ongoing malaria control effort in such settings. Further data on the epidemiological health impact of larviciding is required to establish cost effectiveness.     

Onchocerciasis in West Africa after 2002: a challenge to take up

Initially planned for a 20 year life time, the Onchocerciasis Control Programme in West Africa (OCP) will have finally continued its activities for nearly three decades (vector control alone from 1975 to 1989, then vector control and/or therapeutic treatment until 2002). Although onchocerciasis is no longer a problem of public health importance nor an obstacle to socio-economic development in the OCP area, the control of this filariasis is not over because OCP never aimed at eradication, neither of the parasite (Onchocerca volvulus), nor of its vector (Simulium damnosum s.l.). In 2003, the eleven Participating countries of OCP will take over the responsibility of carrying out the residual activities of monitoring and the control of this disease. This mission is of great importance because any recrudescence of the transmission could lead in the long run to the reappearance of the clinical signs of onchocerciasis, if not its most serious manifestations. For epidemiological and operational reasons, and given the disparity in national health policies and infrastructures, the capacities of the countries to take over the residual activities of monitoring and control of onchocerciasis are very unequal. Indeed, the interventions to be carried out are very different from one country to another and the process of integrating the residual activities into the national health systems is not taking place at the same pace. This inequality among the countries vis-a-vis the challenges to be met does not, however, prejudge the epidemiological situation after 2002 whose evolution will also depend on the effectiveness of the provisions made before that date by OCP, then after 2002, by the Regional Office for Africa of the World Health Organization which is currently setting up a sub-regional multidisease surveillance centre.     

The WHO Onchocerciasis Control Programme: retrospect and prospects

The history of onchocerciasis control in Africa and the genesis of the WHO Onchocerciasis Control Programme in West Africa (OCP) are briefly reviewed. The importance of experience gained in anti-locust campaigns in helping to plan the OCP is stressed. Members of the Simulium damnosum species complex are the vectors of onchocerciasis, which OCP is controlling with insecticide treatments on the stretches of rivers where the Simulium breed. Migrations of flies have been responsible for reinfestations of controlled areas and the spread of insecticide resistance. The management of these problems and related research are described, but it is emphasized that despite setbacks OCP is achieving its aims. A strategy for the future is outlined: vector control supplemented by chemotherapy is expected to continue until the year 2004.     

Contributions of Anopheles larval control to malaria suppression in tropical Africa: review of achievements and potential

Malaria vector control targeting the larval stages of mosquitoes was applied successfully against many species of Anopheles (Diptera: Culicidae) in malarious countries until the mid-20th Century. Since the introduction of DDT in the 1940s and the associated development of indoor residual spraying (IRS), which usually has a more powerful impact than larval control on vectorial capacity, the focus of malaria prevention programmes has shifted to the control of adult vectors. In the Afrotropical Region, where malaria is transmitted mainly by Anopheles funestus Giles and members of the Anopheles gambiae Giles complex, gaps in information on larval ecology and the ability of An. gambiae sensu lato to exploit a wide variety of larval habitats have discouraged efforts to develop and implement larval control strategies. Opportunities to complement adulticiding with other components of integrated vector management, along with concerns about insecticide resistance, environmental impacts, rising costs of IRS and logistical constraints, have stimulated renewed interest in larval control of malaria vectors. Techniques include environmental management, involving the temporary or permanent removal of anopheline larval habitats, as well as larviciding with chemical or biological agents. This present review covers large-scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years. Although such studies are limited in number and scope, their results suggest that targeting larvae, particularly in human-made habitats, can significantly reduce malaria transmission in appropriate settings. These approaches are especially suitable for urban areas, where larval habitats are limited, particularly when applied in conjunction with IRS and other adulticidal measures, such as the use of insecticide treated bednets.     

Shift in species composition in the Anopheles gambiae complex after implementation of long‐lasting insecticidal nets in Dielmo,Senegal

Long‐lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the cornerstones of malaria vector control. However, the effectiveness of these control tools depends on vector ecology and behaviour, which also largely determine the efficacy of certain Anopheles mosquitoes (Diptera: Culicidae) as vectors. Malaria vectors in sub‐Saharan Africa are primarily species of the Anopheles gambiae complex, which present intraspecific differences in behaviour that affect how they respond to vector control tools. The focus of this study is the change in species composition in the An. gambiae complex after the implementation of LLINs in Dielmo, Senegal. The main findings referred to dramatic decreases in the proportions of Anopheles coluzzii and An. gambiae after the introduction of LLINs, and an increase in the proportion of Anopheles arabiensis. Two years after LLINs were first introduced, An. arabiensis remained the most prevalent species and An. gambiae had begun to rebound. This indicated a need to develop additional vector control tools that can target the full range of malaria vectors.     

Effectiveness of vector control methods for the control of cutaneous and visceral leishmaniasis: A meta-review

Elimination of visceral leishmaniasis (VL) in Southeast Asia and global control of cutaneous leishmaniasis (CL) and VL are priorities of the World Health Organization (WHO). But is the existing evidence good enough for public health recommendations? This meta-review summarises the available and new evidence for vector control with the aims of establishing what is known about the value of vector control for the control of CL and VL, establishing gaps in knowledge, and particularly focusing on key recommendations for further scientific work. This meta-review follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria, including (1) systematic reviews and meta-analyses (SRs/MAs) for (2) vector control methods and strategies and (3) for the control of CL and/or VL. Nine SRs/MAs were included, with different research questions and inclusion/exclusion criteria. The methods analysed for vector control can be broadly classified into (1) indoor residual spraying (IRS); (2) insecticide-treated nets (ITNs; including insecticide-impregnated bednets); (3) insecticide-treated curtains (ITCs; including insecticide-treated house screening); (4) insecticide-treated bedsheets (ITSs) and insecticide-treated fabrics (ITFs; including insecticide-treated clothing) and (5) durable wall lining (treated with insecticides) and other environmental measures to protect the house; (6) control of the reservoir host; and (7) strengthening vector control operations through health education. The existing SRs/MAs include a large variation of different primary studies, even for the same specific research sub-question. Also, the SRs/MAs are outdated, using available information until earlier than 2018 only. Assessing the quality of the SRs/MAs, there is a considerable degree of variation. It is therefore very difficult to summarise the results of the available SRs/MAs, with contradictory results for both vector indices and—if available—human transmission data. Conclusions of this meta-review are that (1) existing SRs/MAs and their results make policy recommendations for evidence-based vector control difficult; (2) further work is needed to establish efficacy and community effectiveness of key vector control methods with specific SRs and MAs (3) including vector and human transmission parameters; and (4) attempting to conclude with recommendations in different transmission scenarios.