Modelling the persistence of mosquito vectors of malaria in Burkina Faso

BackgroundPopulations of the Anopheles gambiae complex are found during the rainy season throughout West Africa, even in arid areas with long dry seasons during which mosquitoes appear to be absent. Several hypotheses have been proposed to explain this apparent paradox, including aestivation, dispersal between neighbouring settlements, and long distance migration using high-altitude wind currents.MethodsAn individual-based, spatially explicit model of mosquito populations was developed for a region of West Africa centred on, and including all of, Burkina Faso. Populations associated with human settlements were linked by dispersal and the model incorporated geospatial data on the distribution of settlements, water bodies and rainfall.ResultsLocal dispersal (at rates consistent with experimental data) was necessary to explain observed patterns of rainy season populations across all of the simulation area, but by itself failed to account for the presence of populations in the arid North (the Sahel). The presence of rare dry-season larval sites could explain these northern populations, but seems inconsistent with field surveys. Aestivation by female mosquitoes explained rainy-season populations in all but the very sparsest and driest areas of human habitation, while long-distance migration based on annual wind patterns could account for all observed populations.ConclusionsModelling studies such as this can help assess the potential validity of different hypotheses and suggest priority areas for experimental study. In particular, the results highlight a shortage of empirical research on mosquito dispersal between neighbouring settlements, which may be critically important to the continued presence of many mosquito populations in West Africa. Further research that establishes the extent to which mosquitoes aestivate, and migrate using high altitude winds, is also much needed to understand Sahelian mosquito populations.

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title: The distribution and inversion polymorphism of chromosomally recognized taxa of the Anopheles gambiae complex in Mali, West Africa.
abstract: Data from polytene chromosome studies on the Anopheles gambiae complex in Mali were reviewed. The banding pattern was successfully scored in 17,705 specimens from 76 sampling sites representing the main ecological strata of the country. Two members of the complex, namely An. arabiensis and An. gambiae, were found widespread and frequently sympatric, with the latter prevalent in most localities. Population genetic analysis of the inversion polymorphisms indicated the existence of panmictic conditions for An. arabiensis only, whereas the parallel study of An. gambiae supported its splitting into at least three reproductive units, characterized by different 2R chromosome arrangements, designated Bamako, Mopti and Savanna. The chromosomal evidence was consistent with the hypothesis of complete reproductive isolation between Bamako and Mopti. Partial isolation between these two taxa and Savanna was suggested by the scoring of hypothetical hybrid 2R heterokaryotypes in various samples, but the actual hybrid origin of these specimens was not confirmed. Different patterns of geographical and seasonal distribution were shown as follows. An. arabiensis prevails in arid savannas (Sahel and Northern Sudan savanna) out of the flooded or irrigated zones; it is able to withstand the most arid conditions of Saharan localities and its breeding might extend throughout the dry season. An. gambiae Savanna and Bamako prevail in relatively humid savannas (Southern Sudan savanna) and their breeding generally occurs only during the rainy season. The Savanna taxon was almost absent in flooded or irrigated zones and in riverine localities; the Bamako taxon is distributed along the upper river Niger and its tributaries. An. gambiae Mopti extends its range in all ecological zones present in Mali including the Sahel and predesertic areas, showing high relative frequencies up to absolute dominance in flooded or irrigated areas; its breeding is highly successful also during the dry season. Rainfall at the sampling sites was found to correlate positively with the frequency of Savanna and negatively with the frequency of Mopti. The remarkable ecological flexibility of the latter was found associated with wide seasonal and geographical variations in its 2R inversion polymorphism bc/u. Higher frequencies of the bc arrangement were recorded both in the Southern localities during the dry season and in the Northern more arid localities during the rainy season. The absence or scarcity of An. arabiensis and An. gambiae Savanna in most flooded or irrigated zones suggests their competitive exclusion by An. gambiae Mopti.

title: Patterns and seasonality of malaria transmission in the forest-savannah transitional zones of Ghana
abstract: BackgroundKnowledge of the local pattern of malaria transmission and the effect of season on transmission is essential for the planning and evaluation of malaria interventions. Therefore, entomological surveys were carried out in the forest-savannah transitional belt of Ghana (Kintampo) from November 2003 to November 2005 in preparation for drug and vaccine trials. total of 23,406 mosquitoes were caught from 919 traps over the two-year period (November 2003 to November 2005): 54.3% were Culicines, 36.2% Anopheles funestus, and 9.4% Anopheles gambiae. Infection rates with Plasmodiumfalciparum were 4.7% and 1.5% for Anopheles gambiae and Anopheles funestus, respectively. Entomological inoculation rates (EIRs) were 269 infective bites per person per year in the first year (November 2003-October 2004) and 231 the following year (November 2004-November 2005). Polymerase Chain Reaction (PCR) analysis detected only Anophelesgambiae s.s. Nineteen mosquitoes were tested by PCR in the wet season; 16 were S-molecular form, 2 M-molecular form and 1 hybrid (S/M). In the dry season, sixteen mosquitoes were tested; 11 S-molecular form, 2 M-molecular form and 3 S/M hybrids. The frequency of knock down resistance (kdr) genotypes F(R) was 0.60.ConclusionThe dynamics and seasonal abundance of malaria vectors in the Kintampo area was influenced by micro-ecology, rainfall and temperature patterns. Transmission patterns did not differ significantly between the two years (2004 and 2005) and both Anopheles gambiae and Anopheles funestus were identified as effective vectors. EIR estimates in 2004/2005 were between 231 and 269 infective bites per person per year. The information provided by the study will help in planning intensified malaria control activities as well as evaluating the impact of malaria interventions in the middle belt of Ghana.

title: Signatures of aestivation and migration in Sahelian malaria mosquito populations
abstract: During the long Sahelian dry season, mosquito vectors of malaria are expected to perish when no larval sites are available; yet, days after the first rains, mosquitoes reappear in large numbers. How these vectors persist over the 3–6-month long dry season has not been resolved, despite extensive research for over a century. Hypotheses for vector persistence include dry-season diapause (aestivation) and long-distance migration (LDM); both are facets of vector biology that have been highly controversial owing to lack of concrete evidence. Here we show that certain species persist by a form of aestivation, while others engage in LDM. Using time-series analyses, the seasonal cycles of Anopheles coluzzii, Anopheles gambiae sensu stricto (s.s.), and Anopheles arabiensis were estimated, and their effects were found to be significant, stable and highly species-specific. Contrary to all expectations, the most complex dynamics occurred during the dry season, when the density of A. coluzzii fluctuated markedly, peaking when migration would seem highly unlikely, whereas A. gambiae s.s. was undetected. The population growth of A. coluzzii followed the first rains closely, consistent with aestivation, whereas the growth phase of both A. gambiae s.s. and A. arabiensis lagged by two months. Such a delay is incompatible with local persistence, but fits LDM. Surviving the long dry season in situ allows A. coluzzii to predominate and form the primary force of malaria transmission. Our results reveal profound ecological divergence between A. coluzzii and A. gambiae s.s., whose standing as distinct species has been challenged, and suggest that climate is one of the selective pressures that led to their speciation. Incorporating vector dormancy and LDM is key to predicting shifts in the range of malaria due to global climate change, and to the elimination of malaria from Africa.

title: Survival of female Anopheles gambiae Giles through a 9-month dry season in Sudan.
abstract: The dry-season biology of a member of the Anopheles gambiae complex (probably species B) was studied in 2 areas in the Khartoum region of Sudan. It was found that in the valley of the White Nile the species maintained itself by low-level breeding, as shown by the continuing presence of larvae, male mosquitos and parous females through the dry months (9 months in the year). In the scattered villages of arid areas situated more than 20 km from the Nile Valley, on the other hand, regular sampling through the cool dry and hot dry months of the year failed to detect any An. gambiae except nulliparous females. These were found in occupied huts, deserted huts, dry wells and animal burrows.The great majority of 213 females collected in the 11 dry months between November 1966 and December 1967 had fresh or older blood-meals but the abdomen was never found fully distended in the dry season. Examination of the ovaries showed that they did not develop beyond Christophers' stage II in the period from November to February, stage III in March and April, or beyond stage IV in May. But, in June and July stage IV and V ovaries predominated and few specimens remained in stage late-II.It is inferred from these observations that the local population of An. gambiae is highly adapted to survive in the adult stage through the severe drought and heat of the arid zone of Sudan. Some feeding activity continues but ovarian development is extremely retarded, and only one batch of eggs matures during the whole 9-month period. Evidence collected in the Nile Valley indicated that female An. gambiae in that area were not subjected to similar retardation of the ovarian cycle; in fact, clear evidence was obtained there of continuous year-round breeding by the mosquito.

title: Dry Season Biology of Anopheles gambiae Giles in the Sudan
abstract: COLLECTIONS of mosquitoes have been made regularly throughout the dry season in the desert west of Omdurman, Sudan, by means of pyrethrum-spraying, well-traps and hand catching. The results indicate that adult female Anopheles gambiae (sp. B ?) Giles survive throughout the dry season, but with a change in their physiology and behaviour. The insects were found to hide in dwelling huts (87.7 per cent), in cracks down dry wells (8.5 per cent), in disused or ruined houses (3.2 per cent) and in rabbit and rodent burrows (0.5 per cent). Dissection showed that 77.1 per cent of the nulliparous females captured were engorged with blood. Of these, 90.6 per cent contained human blood. The ovaries evidently undergo only one gonotrophic cycle during the dry season, developing extremely slowly so that, when the rains come, the gravid females are ready to oviposit. These mosquitoes are apparently unable to lay eggs during the dry season.

title: Aestivation of the African Malaria Mosquito, Anopheles gambiae in the Sahel
abstract: The African malaria mosquito, Anopheles gambiae, inhabits diverse environments including dry savannas, where surface waters required for larval development are absent for 4–8 months per year. Under such conditions, An. gambiae virtually disappears. Whether populations survive the long dry season by aestivation (a dormant state promoting extended longevity during the summer) or are reestablished by migrants from distant locations where larval sites persist has remained an enigma for over 60 years. Resolving this question is important, because fragile dry season populations may be more susceptible to control. Here, we show unequivocally that An. gambiae aestivates based on a demographic study and a mark release–recapture experiment spanning the period from the end of one wet season to the beginning of the next. During the dry season, An. gambiae was barely detectable in Sahelian villages of Mali. Five days after the first rain, before a new generation of adults could be produced, mosquito abundance surged 10-fold, implying that most mosquitoes were concealed locally until the rain. Four days after the first rain, a marked female An. gambiae s.s. was recaptured. Initially captured, marked, and released at the end of the previous wet season, she has survived the 7-month-long dry season. These results provide evidence that An. gambiae persists throughout the dry season by aestivation and open new questions for mosquito and parasite research. Improved malaria control by targeting aestivating mosquitoes using existing or novel strategies may be possible.

title: The contribution of aestivating mosquitoes to the persistence of Anopheles gambiae in the Sahel
abstract: BackgroundPersistence of African anophelines throughout the long dry season (4-8 months) when no surface waters are available remains one of the enduring mysteries of medical entomology. Recent studies demonstrated that aestivation (summer diapause) is one mechanism that allows the African malaria mosquito, Anopheles gambiae, to persist in the Sahel. However, migration from distant localities - where reproduction continues year-round - might also be involved.MethodsTo assess the contribution of aestivating adults to the buildup of populations in the subsequent wet season, two villages subjected to weekly pyrethrum sprays throughout the dry season were compared with two nearby villages, which were only monitored. If aestivating adults are the main source of the subsequent wet-season population, then the subsequent wet-season density in the treated villages will be lower than in the control villages. Moreover, since virtually only M-form An. gambiae are found during the dry season, the reduction should be specific to the M form, whereas no such difference is predicted for S-form An. gambiae or Anopheles arabiensis. On the other hand, if migrants arriving with the first rain are the main source, no differences between treated and control villages are expected across all members of the An. gambiae complex.ResultsThe wet-season density of the M form in treated villages was 30% lower than that in the control (P < 10-4, permutation test), whereas no significant differences were detected in the S form or An. arabiensis.ConclusionsThese results support the hypothesis that the M form persist in the arid Sahel primarily by aestivation, whereas the S form and An. arabiensis rely on migration from distant locations. Implications for malaria control are discussed.

title: Dry season reproductive depression of Anopheles gambiae in the Sahel.
abstract: The African malaria mosquito, Anopheles gambiae, is widespread south of the Sahara including in dry savannahs and semi-arid environments where no surface water exists for several months a year. Adults of the M form of An. gambiae persist through the long dry season, when no surface waters are available, by increasing their maximal survival from 4 weeks to 7 months. Dry season diapause (aestivation) presumably underlies this extended survival. Diapause in adult insects is intrinsically linked to depressed reproduction. To determine if reproduction of the Sahelian M form is depressed during the dry season, we assessed seasonal changes in oviposition, egg batch size, and egg development, as well as insemination rate and blood feeding in wild caught mosquitoes. Results from xeric Sahelian and riparian populations were compared. Oviposition response in the Sahelian M form dropped from 70% during the wet season to 20% during the dry season while the mean egg batch size among those that laid eggs fell from 173 to 101. Correspondingly, the fraction of females that exhibited gonotrophic dissociation increased over the dry season from 5% to 45%, while a similar fraction of the population retained developed eggs despite having access to water. This depression in reproduction the Sahelian M form was not caused by a reduced insemination rate. Seasonal variation in these reproductive parameters of the riparian M form population was less extreme and the duration of reproductive depression was shorter. Blood feeding responses did not change with the season in either population. Depressed reproduction during the dry season in the Sahelian M form of An. gambiae provides additional evidence for aestivation and illuminates the physiological processes involved. The differences between the Sahelian and riparian population suggest an adaptive cline in aestivation phenotypes between populations only 130 km apart.

title: Seasonal variation in metabolic rate, flight activity and body size of Anopheles gambiae in the Sahel
abstract: Malaria in Africa is vectored primarily by the Anopheles gambiae complex. Although the mechanisms of population persistence during the dry season are not yet known, targeting dry season mosquitoes could provide opportunities for vector control. In the Sahel, it appears likely that M-form A. gambiae survive by aestivation (entering a dormant state). To assess the role of eco-physiological changes associated with dry season survival, we measured body size, flight activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a Sahelian locality, far from permanent water sources, and at a riparian location adjacent to the Niger River. We found significant seasonal variation in body size at both the Sahelian and riparian sites, although the magnitude of the variation was greater in the Sahel. For flight activity, significant seasonality was only observed in the Sahel, with increased flight activity in the wet season when compared with that just prior to and throughout the dry season. Whole-organism metabolic rate was affected by numerous biotic and abiotic factors, and a significant seasonal component was found at both locations. However, assay temperature accounted completely for seasonality at the riparian location, while significant seasonal variation remained after accounting for all measured variables in the Sahel. Interestingly, we did not find that mean metabolic rate was lowest during the dry season at either location, contrary to our expectation that mosquitoes would conserve energy and increase longevity by reducing metabolism during this time. These results indicate that mosquitoes may use mechanisms besides reduced metabolic rate to enable survival during the Sahelian dry season.

title: Tracing the origin of the early wet‐season Anopheles coluzzii in the Sahel
abstract: In arid environments, the source of the malaria mosquito populations that re‐establish soon after first rains remains a puzzle and alternative explanations have been proposed. Using genetic data, we evaluated whether the early rainy season (RS) population of Anopheles coluzzii is descended from the preceding late RS generation at the same locality, consistent with dry season (DS) dormancy (aestivation), or from migrants from distant locations. Distinct predictions derived from these two hypotheses were assessed, based on variation in 738 SNPs in eleven A. coluzzii samples, including seven samples spanning 2 years in a Sahelian village. As predicted by the “local origin under aestivation hypothesis,” temporal samples from the late RS and those collected after the first rain of the following RS were clustered together, while larger genetic distances were found among samples spanning the RS. Likewise, multilocus genotype composition of samples from the end of the RS was similar across samples until the following RS, unlike samples that spanned the RS. Consistent with reproductive arrest during the DS, no genetic drift was detected between samples taken over that period, despite encompassing extreme population minima, whereas it was detected between samples spanning the RS. Accordingly, the variance in allele frequency increased with time over the RS, but not over the DS. However, not all the results agreed with aestivation. Large genetic distances separated samples taken a year apart, and during the first year, within‐sample genetic diversity declined and increased back during the late RS, suggesting a bottleneck followed by migration. The decline of genetic diversity followed by a mass distribution of insecticide‐treated nets was accompanied by a reduced mosquito density and a rise in the mutation conferring resistance to pyrethroids, indicating a bottleneck due to insecticidal selection. Overall, our results support aestivation in A. coluzzii during the DS that is accompanied by long‐distance migration in the late RS.

title: Dry season ecology of Anopheles gambiae complex mosquitoes in The Gambia
abstract: BackgroundMalaria in The Gambia is highly seasonal, with transmission occurring as Anopheles gambiae s.l. populations expand during and immediately after a single annual rainy season that lasts from June to October. There has been very limited investigation of the ecology of vectors during the dry season, when numbers are very limited and distributions may be restricted.MethodsWeekly adult mosquito collections (pyrethrum spray, light trap, and search collections from rooms, as well as light trap collections from animal shelters, abandoned wells and grain stores), and artificial sentinel breeding site surveys were performed in four villages near the upper tidal and partially saline part of the Gambia River in the last four months of an annual dry season (March to June). Mosquito species were identified by morphological and DNA analysis, and ELISA assays were performed to test for Plasmodium falciparum sporozoites and human blood meal components.ResultsAdults of An. gambiae s.l. were collected throughout the period, numbers increasing towards the end of the dry season when humidity was increasing. Adult collections were dominated by An. melas (86%), with An. gambiae s.s. (10%) and An. arabiensis (3%) also present throughout. Most females collected in room search and spray collections contained blood meals, but most from light traps were unfed. None of the females tested (n = 1709) contained sporozoites. Larvae (mostly An. gambiae s.s.) were recovered from artificial sentinel breeding sites in the two villages that had freshwater pools. These two villages had the highest proportions of An. gambiae s.s. adults, and experienced the most substantial increase in proportions of An. gambiae s.s. after the onset of rains.ConclusionDuring the dry season population minimum, An. melas was the predominant vector species, but differences among villages in availability of fresh-water breeding sites correlate with egg laying activity and relative numbers of An. gambiae s.s. adults, and with the increase in this species immediately after the beginning of the rains. Local variation in dry season vector persistence is thus likely to influence spatial heterogeneity of transmission intensity in the early part of the rainy season.

title: Dry season refugia of malaria-transmitting mosquitoes in a dry savannah zone of east Africa.
abstract: Dry season survival of Anopheles funestus, Anopheles gambiae and Anopheles arabiensis in the Kilombero valley a dry savannah zone of east Africa, was investigated with over 400 collections from 23 areas, covering 300 sq km of the valley. Anopheles gambiae was found only in association with humans, in forested areas of high annual rainfall, while An. funestus occurred at high densities at the valley edge where large non-moving bodies of water remained. A large population of An. arabiensis was present along the river system throughout the middle of the valley, and mosquitoes probably derived from this population were occasionally caught in villages bordering the valley. No evidence was obtained of aestivation in any mosquito species. Anopheles gambiae was the most long lived, 6.3% compared to 2.0% of the An. arabiensis and 4% of the An. funestus surviving for four or more gonotrophic cycles, the approximate duration of the extrinsic cycle of most malaria parasites. Oocysts of malaria parasites were found in 5.4% of An. funestus and 2.3% of An. arabiensis from villages. Oocyst rates in An. funestus differed significantly between areas but not between houses within areas. Anopheles funestus is the most important dry season malaria vector in the valley, and remains in foci closely associated with groups of houses. All three species survive at high densities but as otherwise hidden refugia populations.

title: Anopheline Mosquito Survival Strategies During the Dry Period in Western Kenya
abstract: The dry season survival mechanism of Anopheles gambiae Giles is one of the most vexing deficiencies in our understanding of the biology of the major malaria vectors. In this study, we examined the dynamics of anopheline adult mosquitoes, their larval habitats, and egg survival potential during the dry season in the basin region of Lake Victoria, western Kenya. Through field surveys, we demonstrated two survival strategies of An. gambiae sensu stricto during the dry season: continuous reproduction throughout the year and embryo dormancy in moist soil for at least several days. We further demonstrated that An. gambiae shows a strong preference for moist soil as an oviposition substrate rather than dry soil substrate under the insectary conditions. The observation that anopheline eggs remain a dormant stage to resist desiccation clearly contrasts the conventional wisdom that anopheline eggs hatch shortly after they are laid. Our results from western Kenya are consistent with the suggestion that anopheline mosquitoes do not necessarily suffer a severe population bottleneck during the dry season and thus maintain a large effective population size.

title: Distribution of the African malaria vectors of the Anopheles gambiae complex.
abstract: The Anopheles gambiae complex contains what many consider to be the most efficient malaria vector mosquito species in the world: A. gambiae s.s. There are currently six named and one unnamed species recognized within the complex and excellent evidence for at least three species within A. gambiae itself in west Africa. The identification of the species and concomitant distribution records are not simply of academic interest, but are vital to effective malaria control. With species identification comes the associated knowledge of the biology of that species which, in turn, dictates appropriate control measures. For example, in Zimbabwe in 1977 a malaria outbreak occurred in the southeastern lowveld areas and members of the A. gambiae complex were collected inside benzene hexachloride (BHC) (organochlorine)−sprayed dwellings. Species identification showed that all survivors on World Health Organization susceptibility tests were A. arabiensis, while most of those that died were the non-vector species A. quadriannulatus. The realization that A. arabiensis, a major vector in southern Africa, was resistant to the insecticide used for house spraying led to a change in policy and BHC was replaced with DDT, to good effect. A similar situation arose in South Africa where DDT was replaced by pyrethroids in 1996 because of environmental concerns, objections by the community to DDT residues on the walls of their houses, and increased bed bug biting activity. Unbeknown to the control program authorities, populations of the very efficient vector A. funestus across the border in southern Mozambique had developed resistance to pyrethroids. Four years after stopping DDT spraying, South Africa experienced the worst malaria epidemic since house spraying was first introduced in the 1950s. Appropriate trapping techniques and species identification confirmed the presence of A. funestus inside pyrethroid-sprayed houses and enzyme-linked immunosorbent assays showed a Plasmodium falciparum infectivity rate of 5.4% in these samples. Current research is aimed at determining the extent and distribution of resistant populations. Insecticide resistance is now a major problem facing malaria vector control programs in most African countries with all three important vector species, A. gambiae, A. arabiensis (of the A. gambiae complex), and A. funestus, showing resistance to one or more of the insecticide classes used in vector control. There is obvious concern regarding the spread of this resistance and gene flow studies and distribution predictive modeling provide valuable data for use in control programs. Early distribution maps reflected the distribution of entomologists rather than mosquito species and this has long been recognized as a limitation of these maps. More recent studies have also not adequately addressed this issue. Coetzee and others did not attempt to predict species distribution beyond actual collection points, but simply overlaid the collection data with temperature data. Lindsay and others used climatic and distributional data to predict species occurrence, but this resulted in maps with limitations that were obvious at the periphery of the species distributions, for example, A. arabiensis in South Africa was predicted to occur in areas of semi-desert with no rivers and extending down the southern coast to Cape Town. Discrepancies in such predictive models are obvious at the distributional limits of a species, but variation in species composition would not be easily detected in areas with large numbers of mosquitoes without real data to support the models. The paper by Levine and others in this issue is an improvement on previous studies using spatial imaging. However, again there is a discrepancy between the predictions and reality, particularly obvious when A. quadriannulatus is considered. From what is currently known about A. quadriannulatus species A and B, it would appear that the former is restricted to southern Africa, south of the Zambezi River, while the latter is known only from the highlands of Ethiopia. Records from the islands of Zanzibar and Pemba are historical and it is doubtful whether the taxon still occurs there, if it ever did. However, the maps presented by Levine and others show that suitable habitats for these species occur widely throughout southern, eastern, and central Africa. The investigators’ suggestion that unknown biological species requirements determine distribution seems logical at first, considering that known climatic factors are not sensitive enough to correlate precisely with actual collection data. However, in southern Africa, much of central Botswana is semi-desert, unsuitable for A. quadriannulatus breeding and yet the predictive models do not detect this. It illustrates the limitation of computer modeling for species distribution, particularly where breeding sites in arid areas are highly localized at permanent springs, river edges, or irrigational projects, and are not affected by local rainfall. There is no doubt that geographic information systems and distribution modeling are useful components of an efficient malaria control program where models are based on verified distributional data. They are best used at the regional level (www.malaria.org) for practical program management rather than on a continent-wide scale where resolution is coarse and applicability limited. The extrapolation of African data to South America (Levine and others) to predict in retrospect which member of the A. gambiae complex was imported into Brazil during the 1930s was very interesting. Most African malariologists have always assumed that it was A. gambiae s.s. because of the ferocity of the epidemic. This is confirmed by the predictive model of Levine and others, and the consequences had Soper failed to eradicate the species, aptly summarized.

title: The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis
abstract: BackgroundThis is the second in a series of three articles documenting the geographical distribution of 41 dominant vector species (DVS) of human malaria. The first paper addressed the DVS of the Americas and the third will consider those of the Asian Pacific Region. Here, the DVS of Africa, Europe and the Middle East are discussed. The continent of Africa experiences the bulk of the global malaria burden due in part to the presence of the An. gambiae complex. Anopheles gambiae is one of four DVS within the An. gambiae complex, the others being An. arabiensis and the coastal An. merus and An. melas. There are a further three, highly anthropophilic DVS in Africa, An. funestus, An. moucheti and An. nili. Conversely, across Europe and the Middle East, malaria transmission is low and frequently absent, despite the presence of six DVS. To help control malaria in Africa and the Middle East, or to identify the risk of its re-emergence in Europe, the contemporary distribution and bionomics of the relevant DVS are needed.ResultsA contemporary database of occurrence data, compiled from the formal literature and other relevant resources, resulted in the collation of information for seven DVS from 44 countries in Africa containing 4234 geo-referenced, independent sites. In Europe and the Middle East, six DVS were identified from 2784 geo-referenced sites across 49 countries. These occurrence data were combined with expert opinion ranges and a suite of environmental and climatic variables of relevance to anopheline ecology to produce predictive distribution maps using the Boosted Regression Tree (BRT) method.ConclusionsThe predicted geographic extent for the following DVS (or species/suspected species complex*) is provided for Africa: Anopheles (Cellia) arabiensis, An.  These maps are presented alongside a bionomics summary for each species relevant to its control.

title: Geographical distributions of African malaria vector sibling species and evidence for insecticide resistance
abstract: BackgroundMany of the mosquito species responsible for malaria transmission belong to a sibling complex; a taxonomic group of morphologically identical, closely related species. Sibling species often differ in several important factors that have the potential to impact malaria control, including their geographical distribution, resistance to insecticides, biting and resting locations, and host preference. The aim of this study was to define the geographical distributions of dominant malaria vector sibling species in Africa so these distributions can be coupled with data on key factors such as insecticide resistance to aid more focussed, species-selective vector control.ResultsWithin the Anopheles gambiae species complex and the Anopheles funestus subgroup, predicted geographical distributions for Anopheles coluzzii, An. gambiae (as now defined) and An. funestus (distinct from the subgroup) have been produced for the first time. Improved predicted geographical distributions for Anopheles arabiensis, Anopheles melas and Anopheles merus have been generated based on records that were confirmed using molecular identification methods and a model that addresses issues of sampling bias and past changes to the environment. The data available for insecticide resistance has been evaluated and differences between sibling species are apparent although further analysis is required to elucidate trends in resistance.ConclusionsSibling species display important variability in their geographical distributions and the most important malaria vector sibling species in Africa have been mapped here for the first time. This will allow geographical occurrence data to be coupled with species-specific data on important factors for vector control including insecticide resistance. Species-specific data on insecticide resistance is available for the most important malaria vectors in Africa, namely An. arabiensis, An. coluzzii, An. gambiae and An. funestus. Future work to combine these data with the geographical distributions mapped here will allow more focussed and resource-efficient vector control and provide information to greatly improve and inform existing malaria transmission models.

title: Living at the edge: biogeographic patterns of habitat segregation conform to speciation by niche expansion in Anopheles gambiae
abstract: BackgroundOngoing lineage splitting within the African malaria mosquito Anopheles gambiae is compatible with ecological speciation, the evolution of reproductive isolation by divergent natural selection acting on two populations exploiting alternative resources. Divergence between two molecular forms (M and S) identified by fixed differences in rDNA, and characterized by marked, although incomplete, reproductive isolation is occurring in West and Central Africa. To elucidate the role that ecology and geography play in speciation, we carried out a countrywide analysis of An. gambiae M and S habitat requirements, and that of their chromosomal variants, across Burkina Faso.ResultsMaps of relative abundance by geostatistical interpolators produced a distinct pattern of distribution: the M-form dominated in the northernmost arid zones, the S-form in the more humid southern regions. Maps of habitat suitability, quantified by Ecological Niche Factor Analysis based on 15 eco-geographical variables revealed less contrast among forms. M was peculiar as it occurred proportionally more in habitat of marginal quality. Measures of ecological niche breadth and overlap confirmed the mismatch between the fundamental and realized patterns of habitat occupation: forms segregated more than expected from the extent of divergence of their environmental envelope – a signature of niche expansion. Classification of chromosomal arm 2R karyotypes by multilocus genetic clustering identified two clusters loosely corresponding to molecular forms, with 'mismatches' representing admixed individuals due to shared ancestral polymorphism and/or residual hybridization. In multivariate ordination space, these karyotypes plotted in habitat of more marginal quality compared to non-admixed, 'typical', karyotypes. The distribution of 'typical' karyotypes along the main eco-climatic gradient followed a consistent pattern within and between forms, indicating an adaptive role of inversions at this geographical scale.ConclusionEcological segregation between M and S is consistent with niche expansion into marginal habitats by chromosomal inversion variants during early lineage divergence; presumably, this process is promoted by inter-karyotype competition in the higher-quality core habitat. We propose that the appearance of favourable allelic combinations in other regions of suppressed recombination (e.g. pericentromeric portions defining speciation islands in An. gambiae) fosters development of reproductive isolation to protect linkage between separate chromosomal regions.

title: Ecological niche partitioning between Anopheles gambiae molecular forms in Cameroon: the ecological side of speciation
abstract: BackgroundSpeciation among members of the Anopheles gambiae complex is thought to be promoted by disruptive selection and ecological divergence acting on sets of adaptation genes protected from recombination by polymorphic paracentric chromosomal inversions. However, shared chromosomal polymorphisms between the M and S molecular forms of An. gambiae and insufficient information about their relationship with ecological divergence challenge this view. We used Geographic Information Systems, Ecological Niche Factor Analysis, and Bayesian multilocus genetic clustering to explore the nature and extent of ecological and chromosomal differentiation of M and S across all the biogeographic domains of Cameroon in Central Africa, in order to understand the role of chromosomal arrangements in ecological specialisation within and among molecular forms.ResultsSpecies distribution modelling with presence-only data revealed differences in the ecological niche of both molecular forms and the sibling species, An. arabiensis. The fundamental environmental envelope of the two molecular forms, however, overlapped to a large extent in the rainforest, where they occurred in sympatry. The S form had the greatest niche breadth of all three taxa, whereas An. arabiensis and the M form had the smallest niche overlap. Correspondence analysis of M and S karyotypes confirmed that molecular forms shared similar combinations of chromosomal inversion arrangements in response to the eco-climatic gradient defining the main biogeographic domains occurring across Cameroon. Savanna karyotypes of M and S, however, segregated along the smaller-scale environmental gradient defined by the second ordination axis. Population structure analysis identified three chromosomal clusters, each containing a mixture of M and S specimens. In both M and S, alternative karyotypes were segregating in contrasted environments, in agreement with a strong ecological adaptive value of chromosomal inversions.ConclusionOur data suggest that inversions on the second chromosome of An. gambiae are not causal to the evolution of reproductive isolation between the M and S forms. Rather, they are involved in ecological specialization to a similar extent in both genetic backgrounds, and most probably predated lineage splitting between molecular forms. However, because chromosome-2 inversions promote ecological divergence, resulting in spatial and/or temporal isolation between ecotypes, they might favour mutations in other ecologically significant genes to accumulate in unlinked chromosomal regions. When such mutations occur in portions of the genome where recombination is suppressed, such as the pericentromeric regions known as speciation islands in An. gambiae, they would contribute further to the development of reproductive isolation.

title: Larval habitat segregation between the molecular forms of the mosquito Anopheles gambiae in a rice field area of Burkina Faso, West Africa
abstract: In West Africa, lineage splitting between the M and S molecular forms of the major Afro‐tropical malaria mosquito, Anopheles gambiae (Diptera: Culicidae), is thought to be driven by ecological divergence, occurring mainly at the larval stage. Here, we present evidence for habitat segregation between the two molecular forms in and around irrigated rice fields located within the humid savannahs of western Burkina Faso. Longitudinal sampling of adult mosquitoes emerging from a range of breeding sites distributed along a transect extending from the heart of the rice field area into the surrounding savannah was conducted from June to November 2009. Analysis revealed that the two molecular forms and their sibling species Anopheles arabiensis are not randomly distributed in the area. A major ecological gradient was extracted in relation to the perimeter of the rice fields. The M form was associated with larger breeding sites mostly consisting of rice paddies, whereas the S form and An. arabiensis were found to depend upon temporary, rain‐filled breeding sites. These results support hypotheses about larval habitat segregation and confirm the suggestion that the forms have different larval habitat requirements. Segregation appears to be clearly linked to anthropogenic permanent habitats and the community structure they support.

title: Chromosomal differentiation and adaptation to human environments in the Anopheles gambiae complex.
abstract: Speciation in the Anopheles gambiae complex is reviewed and discussed with emphasis on the patterns of chromosomal differentiation, particularly at the intraspecific level. The significance of inversion polymorphism in gambiae and arabiensis (the two species of greatest medical importance) is evaluated with reference to recent field investigations carried out in Nigeria. In both sibling species some of the inversions show clinical geographical changes in frequencies, with evident correlations with climatic conditions and vegetation zones. Microgeographical variations in species distribution and in intraspecific inversion frequencies are also present, which appear mostly related to man-made environmental contrasts. Parallel indoor-/outdoor collections of samples from polymorphic populations of arabiensis and gambiae show that adult mosquitoes carrying certain inversion karyotypes do not distribute at random in relation to the human environment, being significantly more frequent in outdoor than in indoor samples, or vice-versa. Optimal habitat choice appears to be involved in such variations of indoor resting behaviour, since the chromosomal types carried by less endophilic individuals are those more adapted to humid climates, i.e. those which tend to avoid the higher nocturnal saturation deficit of the indoor environment. This phenomenon, producing non-uniform exposure of the vector population to residual insecticides sprayed in houses, might explain the mediocrity of the results of malaria control projects based on house-spraying against endophilic vectors in the African savannas.

title: Feeding habits of anophelines (Diptera: Culicidae) in 1971–78, with reference to the human blood index: a review
abstract: A synoptic view is given of the data amassed by WHO, with technical assistance from the Imperial College of Science and Technology, on the origins of blood-meals in Anopheles samples collected from 1971 to 1978. Attention is focused on the proportion of each sample found to contain human blood and on the problems of interpreting from this the human blood index or degree of biting-contact with man exhibited by vector populations. The difficulties of overcoming bias in sampling, which are formidable in unsprayed areas, are further compounded where the dwellings are treated with a slow-acting residual insecticide which knocks down many engorged mosquitoes before they can be collected from their daytime resting places. There is evidence to suggest that the host-selection patterns of those vectors which are ‘opportunistic’ feeders may be heavily influenced, even from village to village or from month to month, by the changing availability of alternative hosts, particularly cattle. This suggests in turn that the possibilities of manipulating the degree of mosquito-man contact by encouraging deflection to animals (zooprophylaxis) or by measures to afford a degree of personal protection should not be under-estimated by malaria strategists. It may sometimes be found less difficult to reduce the vector’s human blood index than it is to measure it, but in view of the epidemiological importance of this parameter, suggestions are put forward for improving entomological field practice in this area. They include a quantitative survey of the biotopes available to the mosquito population as diurnal shelters, a longitudinal survey of the densities of blood-fed females per biotope, and a survey of the numbers and the respective distribution of people and domestic animals available as hosts. The work-load entailed by such a thorough form of investigation, to be repeated where necessary at different seasons of the year, underlines the necessity to concentrate efforts on a small number of localities, carefully chosen for the malaria situations they represent and the vector populations they support. A large-scale blood-meal sampling programme, confined to these selected localities, is most likely in our estimation to yield information of value for controlling malaria vectors.

title: Odor-mediated host preferences of West African mosquitoes, with particular reference to malaria vectors.
abstract: The role of odors in mosquito host preferences was studied in a village near Ouagadougou, Burkina Faso. Two odor-baited entry-traps were put beside one another and a choice of host odor-laden air was blown out of them. Odors of a human and a calf (of similar mass) were drawn from two tents in which each was separately concealed. Allowances were made for trap position, differences in human-subject attractiveness, CO2 levels, and trap contamination with alternative host odors. Choices for the human-baited trap greater than the 0.5 random expectation were made by Anopheles gambiae s.l. (0.96) and An. pharoensis (0.68). The choices for the human-baited trap of Culex antennatus were significantly lower than 0.5 (0.25), whereas for the Cx. decens species group (0.56), the difference was not significant. Interpretation of the latter result was complicated by the significant effect of CO2 levels on the index. Species caught in low numbers but whose trap distribution showed a bias towards the human-baited trap were An. funestus (total numbers in the human-baited trap to the calf-baited trap = 9:0), Mansonia africana (17: 1), Aedes dalzieli (22:4), and Ae. hirsutus (13:1); species showing bias towards the calf-baited trap were An. rufipes (0:11), Cx. duttoni (0:17), and Cx. nebulosus (2:35). Mansonia uniformis was the only species distributed randomly between the two traps. Molecular identification of the An. gambiae s.l. samples revealed a marked difference in trap distribution: for the human-baited trap the ratio was 52% An. arabiensis to 48% An. gambiae s.s.; for the calf-baited trap, it was 92% An. arabiensis to 8% An. gambiae s.s.

title: No accounting for taste: host preference in malaria vectors.
abstract: The ability of a few Afro-tropical Anopheles species to target humans as a source of blood and shelter, a feature generally defined as anthropophily, represents a key factor in the recent evolutionary success of these species and in their capacity to transmit malaria. Anthropophily presumably results from specific and coordinated behavioural repertoires, but these have been only superficially described and their genetic basis is unknown. A comparative approach exploiting recent molecular and ethological advances promises to shed light on the genetics of anthropophily, thereby presenting novel targets for vector control.

title: A weather-driven model of malaria transmission
abstract: BackgroundClimate is a major driving force behind malaria transmission and climate data are often used to account for the spatial, seasonal and interannual variation in malaria transmission.MethodsThis paper describes a mathematical-biological model of the parasite dynamics, comprising both the weather-dependent within-vector stages and the weather-independent within-host stages.ResultsNumerical evaluations of the model in both time and space show that it qualitatively reconstructs the prevalence of infection. process-based modelling structure has been developed that may be suitable for the simulation of malaria forecasts based on seasonal weather forecasts.

title: Development of a new version of the Liverpool Malaria Model. I. Refining the parameter settings and mathematical formulation of basic processes based on a literature review
abstract: BackgroundA warm and humid climate triggers several water-associated diseases such as malaria. Climate- or weather-driven malaria models, therefore, allow for a better understanding of malaria transmission dynamics. The Liverpool Malaria Model (LMM) is a mathematical-biological model of malaria parasite dynamics using daily temperature and precipitation data. In this study, the parameter settings of the LMM are refined and a new mathematical formulation of key processes related to the growth and size of the vector population are developed.MethodsOne of the most comprehensive studies to date in terms of gathering entomological and parasitological information from the literature was undertaken for the development of a new version of an existing malaria model. The knowledge was needed to allow the justification of new settings of various model parameters and motivated changes of the mathematical formulation of the LMM.ResultsThe first part of the present study developed an improved set of parameter settings and mathematical formulation of the LMM. Important modules of the original LMM version were enhanced in order to achieve a higher biological and physical accuracy. The oviposition as well as the survival of immature mosquitoes were adjusted to field conditions via the application of a fuzzy distribution model. Key model parameters, including the mature age of mosquitoes, the survival probability of adult mosquitoes, the human blood index, the mosquito-to-human (human-to-mosquito) transmission efficiency, the human infectious age, the recovery rate, as well as the gametocyte prevalence, were reassessed by means of entomological and parasitological observations. This paper also revealed that various malaria variables lack information from field studies to be set properly in a malaria modelling approach.ConclusionsDue to the multitude of model parameters and the uncertainty involved in the setting of parameters, an extensive literature survey was carried out, in order to produce a refined set of settings of various model parameters. This approach limits the degrees of freedom of the parameter space of the model, simplifying the final calibration of undetermined parameters (see the second part of this study). In addition, new mathematical formulations of important processes have improved the model in terms of the growth of the vector population.

title: Development of a new version of the Liverpool Malaria Model. II. Calibration and validation for West Africa
abstract: BackgroundIn the first part of this study, an extensive literature survey led to the construction of a new version of the Liverpool Malaria Model (LMM). A new set of parameter settings was provided and a new development of the mathematical formulation of important processes related to the vector population was performed within the LMM. In this part of the study, so far undetermined model parameters are calibrated through the use of data from field studies. The latter are also used to validate the new LMM version, which is furthermore compared against the original LMM version.MethodsFor the calibration and validation of the LMM, numerous entomological and parasitological field observations were gathered for West Africa. Continuous and quality-controlled temperature and precipitation time series were constructed using intermittent raw data from 34 weather stations across West Africa. The meteorological time series served as the LMM data input. The skill of LMM simulations was tested for 830 different sets of parameter settings of the undetermined LMM parameters. The model version with the highest skill score in terms of entomological malaria variables was taken as the final setting of the new LMM version.ResultsValidation of the new LMM version in West Africa revealed that the simulations compare well with entomological field observations. The new version reproduces realistic transmission rates and simulated malaria seasons are comparable to field observations. Overall the new model version performs much better than the original model. The new model version enables the detection of the epidemic malaria potential at fringes of endemic areas and, more importantly, it is now applicable to the vast area of malaria endemicity in the humid African tropics.ConclusionsA review of entomological and parasitological data from West Africa enabled the construction of a new LMM version. This model version represents a significant step forward in the modelling of a weather-driven malaria transmission cycle. The LMM is now more suitable for the use in malaria early warning systems as well as for malaria projections based on climate change scenarios, both in epidemic and endemic malaria areas.

title: A dynamic model of some malaria-transmitting anopheline mosquitoes of the Afrotropical region. I. Model description and sensitivity analysis
abstract: BackgroundMost of the current biophysical models designed to address the large-scale distribution of malaria assume that transmission of the disease is independent of the vector involved. Another common assumption in these type of model is that the mortality rate of mosquitoes is constant over their life span and that their dispersion is negligible. Mosquito models are important in the prediction of malaria and hence there is a need for a realistic representation of the vectors involved.ResultsWe construct a biophysical model including two competing species, Anopheles gambiae s.s. and Anopheles arabiensis. Sensitivity analysis highlight the importance of relative humidity and mosquito size, the initial conditions and dispersion, and a rarely used parameter, the probability of finding blood. We also show that the assumption of exponential mortality of adult mosquitoes does not match the observed data, and suggest that an age dimension can overcome this problem.ConclusionsThis study highlights some of the assumptions commonly used when constructing mosquito-malaria models and presents a realistic model of An. gambiae s.s. and An. arabiensis and their interaction. This new mosquito model, OMaWa, can improve our understanding of the dynamics of these vectors, which in turn can be used to understand the dynamics of malaria.

title: A dynamic model of some malaria-transmitting anopheline mosquitoes of the Afrotropical region. II. Validation of species distribution and seasonal variations
abstract: BackgroundThe first part of this study aimed to develop a model for Anopheles gambiae s.l. with separate parametrization schemes for Anopheles gambiae s.s. and Anopheles arabiensis. The characterizations were constructed based on literature from the past decades. This part of the study is focusing on the model’s ability to separate the mean state of the two species of the An. gambiae complex in Africa. The model is also evaluated with respect to capturing the temporal variability of An. arabiensis in Ethiopia. Before conclusions and guidance based on models can be made, models need to be validated.MethodsThe model used in this paper is described in part one (Malaria Journal 2013, 12:28). For the validation of the model, a data base of 5,935 points on the presence of An. gambiae s.s. and An. arabiensis was constructed. An additional 992 points were collected on the presence An. gambiae s.l.. These data were used to assess if the model could recreate the spatial distribution of the two species. The dataset is made available in the public domain. This is followed by a case study from Madagascar where the model’s ability to recreate the relative fraction of each species is investigated. In the last section the model’s ability to reproduce the temporal variability of An. arabiensis in Ethiopia is tested. The model was compared with data from four papers, and one field survey covering two years.ResultsOverall, the model has a realistic representation of seasonal and year to year variability in mosquito densities in Ethiopia. The model is also able to describe the distribution of An. gambiae s.s. and An. arabiensis in sub-Saharan Africa. This implies this model can be used for seasonal and long term predictions of changes in the burden of malaria. Before models can be used to improving human health, or guide which interventions are to be applied where, there is a need to understand the system of interest. Validation is an important part of this process. It is also found that one of the main mechanisms separating An. gambiae s.s. and An. arabiensis is the availability of hosts; humans and cattle. Climate play a secondary, but still important, role.

title: A simulation model of African Anopheles ecology and population dynamics for the analysis of malaria transmission
abstract: BackgroundMalaria is one of the oldest and deadliest infectious diseases in humans. Many mathematical models of malaria have been developed during the past century, and applied to potential interventions. However, malaria remains uncontrolled and is increasing in many areas, as are vector and parasite resistance to insecticides and drugs.MethodsThis study presents a simulation model of African malaria vectors. This individual-based model incorporates current knowledge of the mechanisms underlying Anopheles population dynamics and their relations to the environment. One of its main strengths is that it is based on both biological and environmental variables.ResultsThe model made it possible to structure existing knowledge, assembled in a comprehensive review of the literature, and also pointed out important aspects of basic Anopheles biology about which knowledge is lacking. One simulation showed several patterns similar to those seen in the field, and made it possible to examine different analyses and hypotheses for these patterns; sensitivity analyses on temperature, moisture, predation and preliminary investigations of nutrient competition were also conducted.ConclusionsAlthough based on some mathematical formulae and parameters, this new tool has been developed in order to be as explicit as possible, transparent in use, close to reality and amenable to direct use by field workers. It allows a better understanding of the mechanisms underlying Anopheles population dynamics in general and also a better understanding of the dynamics in specific local geographic environments. It points out many important areas for new investigations that will be critical to effective, efficient, sustainable interventions.

title: Modelling the spatial spread of a homing endonuclease gene in a mosquito population
abstract: Homing endonuclease genes (HEGs) exist naturally in many single‐celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean‐field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail. Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.

title: Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics
abstract: Gene drive mosquitoes have tremendous potential to help eliminate malaria, and multiple gene drive approaches have recently shown promise in laboratory settings. These approaches include population suppression through fertility disruption, driving-Y chromosomes, and population replacement with genes that limit malaria transmission. Mathematical modeling is used to evaluate these approaches by simulating realistic field settings with seasonality to determine constraints on construct parameters and release strategies. Parameter variation from simulation baselines captures much of sub-Saharan African epidemiology and shows high potential for gene drive constructs to provide transformational tools to facilitate elimination of malaria, even in the most challenging settings. This analysis provides insights into performance characteristics necessary for each approach to succeed that can inform their further development. The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings.

title: The ERA-Interim reanalysis: configuration and performance of the data assimilation system
abstract: ERA-Interim is the latest global atmospheric reanalysis produced by the European Centre for Medium-Range Weather Forecasts (ECMWF). The ERA-Interim project was conducted in part to prepare for a new atmospheric reanalysis to replace ERA-40, which will extend back to the early part of the twentieth century. This article describes the forecast model, data assimilation method, and input datasets used to produce ERA-Interim, and discusses the performance of the system. Special emphasis is placed on various difficulties encountered in the production of ERA-40, including the representation of the hydrological cycle, the quality of the stratospheric circulation, and the consistency in time of the reanalysed fields. We provide evidence for substantial improvements in each of these aspects. We also identify areas where further work is needed and describe opportunities and objectives for future reanalysis projects at ECMWF.

title: The West African Sahel: A Review of Recent Studies on the Rainfall Regime and Its Interannual Variability
abstract: The West African Sahel is well known for the severe droughts that ravaged the region in the 1970s and 1980s. Meteorological research on the region has flourished during the last decade as a result of several major field experiments. This paper provides an overview of the results that have ensued. A major focus has been on the West African monsoon, a phenomenon that links all of West Africa. The characteristics and revised picture of the West African monsoon are emphasized. Other topics include the interannual variability of rainfall, the atmospheric circulation systems that govern interannual variability, characteristics of precipitation and convection, wave activity, large-scale factors in variability (including sea-surface temperatures), and land-atmosphere relationships. New paradigms for the monsoon and associated ITCZ and for interannual variability have emerged. These emphasize features in the upper atmosphere, as well as the Saharan Heat Low. Feedback mechanisms have also been emphasized, especially the coupling of convection with atmospheric dynamics and with land surface characteristics. New results also include the contrast between the premonsoon and peak monsoon seasons, two preferred modes of interannual variability (a latitudinal displacement of the tropical rainbelt versus changes in its intensity), and the critical importance of the Tropical Easterly Jet.

title: Effects of Available Sugar on the Reproductive Fitness and Vectorial Capacity of the Malaria Vector Anopheles gambiae (Diptera: Culicidae)
abstract: Although females of most mosquito species are known to use sugar as a necessary source of energy, female Anopheles gambiae Giles sensu stricto are thought to use it facultatively or not at all. However, field evidence of sugar-free living is inconclusive, and the implications for reproductive fitness and vectorial capacity are unknown. To evaluate the role that sugar may play in the ecology of these mosquitoes, mated female An. gambiae in the laboratory were given access to either no food (water only), 10% sucrose, human blood, or human blood + 10% sucrose, and comparisons of daily mortality, fecundity, and biting frequency were made. The effect of sugar availability on vectorial capacity and the intrinsic rate of increase, a measure of fitness, then were determined. Females (pooled and individual) given blood + sugar lived significantly longer than did those on the other diets. Daily fecundity was higher for females given blood alone than for those fed blood + sugar (13 versus 9 eggs per female daily). However, total fecundity and intrinsic rate of increase were not affected by sugar availability. Biting frequency was significantly higher (0.41 versus 0.26 bites per female per day) for females given blood alone. Despite the reduced survivorship, exclusive blood-feeding led to a theoretically higher vectorial capacity for Plasmodium falciparum at 27°C. These data indicate that female An. gambiae could replace sugar with increased blood feeding without suppressing reproductive fitness. Increased blood feeding could, in turn, increase the rate of malaria transmission and may explain the unusual efficiency of this vector.

title: Density-Dependent Development of Anopheles gambiae (Diptera: Culicidae) Larvae in Artificial Habitats
abstract: The growth and development of Anopheles gambiae Giles larvae were studied in artificial habitats in western Kenya. Larvae responded to increasing densities by extending their development time and by emerging as smaller adults, although survival was not significantly affected. Addition of nutrients in the form of cow dung collected near the study site had no impact on larval growth and development. Regression analysis showed that female development time increased by 0.020 d and female dry mass decreased by 0.74 μg with each additional larva. By fitting the data to the pupation window model, the estimated minimum dry mass to achieve pupation was 0.130 mg and the estimated minimum time to pupation was 5 d. The most likely food source for An. gambiae larvae was algal growth, which was significantly reduced by the presence of larvae. Bacterial densities were not significantly affected by the presence of larvae although total bacteria counts were lower at the higher densities indicating they may provide a secondary food source when algal resources are depleted. Similarly, the levels of nitrogen and phosphorus in the habitats were not significantly affected by the presence of larvae although there was evidence of decreasing nitrogen levels occurring with increasing larval densities suggesting that nitrogen may be a limiting resource in the larval environment. The data indicate that competition within the larval environment may indirectly regulate An. gambiae populations by reducing adult body size, which may in turn reduce adult survivorship and fecundity. The potential impact of density-dependent interactions among An. gambiae larvae on the transmission of Plasmodium falciparum is discussed.

title: Ecology: A Prerequisite for Malaria Elimination and Eradication
abstract: 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.

title: Larval density dependence in Anopheles gambiae s.s., the major African vector of malaria.
abstract: Anopheles gambiae sensu stricto is the most important vector of malaria in Africa although relatively little is known about the density-dependent processes determining its population size. Mosquito larval density was manipulated under semi-natural conditions using artificial larval breeding sites placed in the field in coastal Kenya; two experiments were conducted: one manipulating the density of a single cohort of larvae across a range of densities and the other employing fewer densities but with the treatments crossed with four treatments manipulating predator access. In the first experiment, larval survival, development rate and the size of the adult mosquito all decreased with larval density (controlling for block effects between 23% and 31% of the variance in the data could be explained by density). In the second experiment, the effects of predator manipulation were not significant, but again we observed strong density dependence in larval survival (explaining 30% of the variance). The results are compared with laboratory studies of A. gambiae larval competition and the few other studies conducted in the field, and the consequences for malaria control are discussed.

title: Movement of Anopheles gambiae s.l. malaria vectors between villages in The Gambia
abstract: ovement of mosquitoes belonging to the Anopheles gambiae complex (mixed wild populations of An.arabiensis, An.gambiae and An.melas) between three neighbouring rural villages in The Gambia was investigated by mark‐release‐recapture. A total of 12,872 mosquitoes were collected in bednets, marked with a magenta fluorescent powder and released over a 15‐day period in one of the villages. A further 15,507 mosquitoes were collected in exit traps, marked with a yellow powder and released over the same period. Mosquitoes were captured daily in all three villages using pyrethrum spray catches, as well as bednet and exit trap catches. The catching period extended for 6 days after the last day of release.

title: Density, survival and dispersal of Anopheles gambiae complex mosquitoes in a West African Sudan savanna village
abstract: To obtain information on adult populations of Afrotropical malaria vector mosquitoes, mark‐release‐recapture experiments were performed with Anopheles females collected from indoor resting‐sites in a savanna area near Ouagadougou, Burkina Faso, during September 1991 and 1992. Results were used to estimate the absolute population densities, daily survival rates, and dispersal parameters of malaria vectors in that area.

title: Health impacts of small reservoirs in Burkina Faso.
abstract: I n t e r n a t i o n a l Water Management I n s t i t u t e Working Papers The publications in this series record the work and thinking of IWMI researchers, and knowledge that the Institute's scientific management feels is worthy of documenting. This series will ensure that scientific data and other information gathered or prepared as a part of the research work of the Institute are recorded and referenced. Working Papers could include project reports, case studies, conference or workshop proceedings, discussion papers or reports on progress of research, country-specific research reports, monographs, etc. Working Papers may be copublished, by IWMI and partner organizations. Although most of the reports are published by IWMI staff and their collaborators, we welcome contributions from others. Each report is reviewed internally by IWMI staff. The reports are published and distributed both in hard copy and electronically (www.iwmi.org) and where possible all data and analyses will be available as separate downloadable files. Reports may be copied freely and cited with due acknowledgment. About IWMI IWMI's mission is to improve the management of land and water resources for food, livelihoods and the environment. In serving this mission, IWMI concentrates on the integration of policies, technologies and management systems to achieve workable solutions to real problems—practical, relevant results in the field of irrigation and water and land resources. / reservoirs / health hazards / river basins / water resources development / environmental effects / waterborne diseases / malaria / schistosomiasis / control methods / water policy / Burkina Faso / West Africa / Acknowledgements This study has benefited from the facilities and support provided by Research Unit 167 of the Institut de Recherche pour le Développement (IRD) and by their Delegation in Ouagadougou, Burkina Faso. The authors wish to personally thank Matthew McCartney, for writing the first version of the summary of the paper, and Hugh Turral, Marc Andreini, Pay Drechsel, and the late Felix Amerasinghe, all at the International Water Management Institute, for providing valuable comments on earlier versions of this paper. Project This research study was part of the collaborative program on " Investments in Agricultural Water Management in Sub-Saharan Africa: Diagnosis of Trends and Opportunities " and of the research project " Planning and Evaluating Ensembles of Small, Multipurpose Reservoirs for the Improvement of Smallholder Livelihoods and Food Security: Tools and Procedures " (Small Reservoirs …

title: Habitat characterization and spatial distribution of Anopheles sp. mosquito larvae in Dar es Salaam (Tanzania) during an extended dry period
abstract: IntroductionBy 2030, more than 50% of the African population will live in urban areas. Controlling malaria reduces the disease burden and further improves economic development. As a complement to treated nets and prompt access to treatment, measures targeted against the larval stage of Anopheles sp. mosquitoes are a promising strategy for urban areas. However, a precise knowledge of the geographic location and potentially of ecological characteristics of breeding sites is of major importance for such interventions.MethodsIn total 151 km2 of central Dar es Salaam, the biggest city of Tanzania, were systematically searched for open mosquito breeding sites. Ecologic parameters, mosquito larvae density and geographic location were recorded for each site. Logistic regression analysis was used to determine the key ecological factors explaining the different densities of mosquito larvae. total of 405 potential open breeding sites were examined. Large drains, swamps and puddles were associated with no or low Anopheles sp. larvae density. The probability of Anopheles sp. larvae to be present was reduced when water was identified as "turbid". Small breeding sites were more commonly colonized by Anopheles sp. larvae. Further, Anopheles gambiae s.l. larvae were found in highly organically polluted habitats.ConclusionsClear ecological characteristics of the breeding requirements of Anopheles sp. larvae could not be identified in this setting. Hence, every stagnant open water body, including very polluted ones, have to be considered as potential malaria vector breeding sites.

title: Topographic models for predicting malaria vector breeding habitats: potential tools for vector control managers
abstract: BackgroundIdentification of malaria vector breeding sites can enhance control activities. Although associations between malaria vector breeding sites and topography are well recognized, practical models that predict breeding sites from topographic information are lacking. We used topographic variables derived from remotely sensed Digital Elevation Models (DEMs) to model the breeding sites of malaria vectors. We further compared the predictive strength of two different DEMs and evaluated the predictability of various habitat types inhabited by Anopheles larvae.MethodsUsing GIS techniques, topographic variables were extracted from two DEMs: 1) Shuttle Radar Topography Mission 3 (SRTM3, 90-m resolution) and 2) the Advanced Spaceborne Thermal Emission Reflection Radiometer Global DEM (ASTER, 30-m resolution). We used data on breeding sites from an extensive field survey conducted on an island in western Kenya in 2006. Topographic variables were extracted for 826 breeding sites and for 4520 negative points that were randomly assigned. Logistic regression modelling was applied to characterize topographic features of the malaria vector breeding sites and predict their locations. Model accuracy was evaluated using the area under the receiver operating characteristics curve (AUC).ResultsAll topographic variables derived from both DEMs were significantly correlated with breeding habitats except for the aspect of SRTM. The magnitude and direction of correlation for each variable were similar in the two DEMs. Multivariate models for SRTM and ASTER showed similar levels of fit indicated by Akaike information criterion (3959.3 and 3972.7, respectively), though the former was slightly better than the latter. The accuracy of prediction indicated by AUC was also similar in SRTM (0.758) and ASTER (0.755) in the training site. In the testing site, both SRTM and ASTER models showed higher AUC in the testing sites than in the training site (0.829 and 0.799, respectively). The predictability of habitat types varied. Drains, foot-prints, puddles and swamp habitat types were most predictable.ConclusionsBoth SRTM and ASTER models had similar predictive potentials, which were sufficiently accurate to predict vector habitats. The free availability of these DEMs suggests that topographic predictive models could be widely used by vector control managers in Africa to complement malaria control strategies.

title: The practical importance of permanent and semipermanent habitats for controlling aquatic stages of Anopheles gambiae sensu lato mosquitoes: operational observations from a rural town in western Kenya
abstract: Control of aquatic‐stage Anopheles is one of the oldest and most historically successful interventions to prevent malaria, but it has seen little application in Africa. Consequently, the ecology of immature afrotropical Anopheles has received insufficient attention. We therefore examined the population dynamics of African anopheline and culicine mosquitoes using operationally practicable techniques to examine the relative importance and availability of different larval habitats in an area of perennial malaria transmission in preparation for a pilot‐scale larval control programme. The study was conducted in Mbita, a rural town on the shores of Lake Victoria in Western Kenya, over 20 months. Weekly larval surveys were conducted to identify the availability of stagnant water, habitat characteristics and larval densities. Adult mosquitoes were collected indoors at fortnightly intervals. Availability of aquatic habitats and abundance of mosquito larvae were directly correlated with rainfall. Adult mosquito densities followed similar patterns but with a time‐lag of approximately 1 month. About 70% of all available habitats were man‐made, half of them representing cement‐lined pits. On average, 67% of all aquatic habitats on a given sampling date were colonized by Anopheles larvae, of which all identified morphologically were A. gambiae sensu lato. Natural and artificial habitats were equally productive over the study period and larval densities were positively correlated with presence of tufts of low vegetation and negatively with non‐matted algal content. The permanence of a habitat had no significant influence on larval productivity. We conclude that A. gambiae is broadly distributed across a variety of habitat types, regardless of permanence. All potential breeding sites need to be considered as sources of malaria risk at any time of the year and exhaustively targeted in any larval control intervention.

title: Blood‐feeding behaviour of the malarial mosquito Anopheles arabiensis: implications for vector control
abstract: Feeding behaviour of the malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) was monitored for 12 months (March 2003−February 2004) in the Konso District of southern Ethiopia (5°15′N, 37°28′E). More than 45 000 An. arabiensis females were collected by host‐baited sampling methods (light‐traps, human landing catches, cattle‐baited traps) and from resting sites (huts and pit shelters). In the village of Fuchucha, where the ratio of cattle : humans was 0.6 : 1, 51% of outdoor‐resting mosquitoes and 66% of those collected indoors had fed on humans, human baits outdoors caught > 2.5 times more mosquitoes than those indoors and the mean catch of mosquitoes from pit shelters was about five times that from huts. Overall, the vast majority of feeding and resting occurred outdoors. In the cattle camps of Konso, where humans slept outdoors close to their cattle, ∼ 46% of resting mosquitoes collected outdoors had fed on humans despite the high cattle : human ratio (17 : 1). In both places, relatively high proportions of bloodmeals were mixed cow + human: 22–25% at Fuchucha and 37% in the cattle camps. Anthropophily was also gauged experimentally by comparing the numbers of mosquitoes caught in odour‐baited entry traps baited with either human or cattle odour. The human‐baited trap caught about five times as many mosquitoes as the cattle‐baited one. Notwithstanding the potential pitfalls of using standard sampling devices to analyse mosquito behaviour, the results suggest that the An. arabiensis population is inherently anthropophagic, but this is counterbalanced by exophagic and postprandial exophilic tendencies. Consequently, the population feeds sufficiently on humans to transmit malaria (sporozoite rates: 0.3% for Plasmodium falciparum and 0.5% for P. vivax, by detection of circumsporozoite antigen) but also takes a high proportion of meals from non‐human hosts, with 59–91% of resting mosquitoes containing blood from cattle. Hence, classical zooprophylaxis is unlikely to have a significant impact on the malaria vectorial capacity of An. arabiensis in Konso, whereas treating cattle with insecticide might do.

title: Unexpected High Losses of Anopheles gambiae Larvae Due to Rainfall
abstract: Immature stages of the malaria mosquito Anopheles gambiae experience high mortality, but its cause is poorly understood. Here we study the impact of rainfall, one of the abiotic factors to which the immatures are frequently exposed, on their mortality.  We show that rainfall significantly affected larval mosquitoes by flushing them out of their aquatic habitat and killing them. Outdoor experiments under natural conditions in Kenya revealed that the additional nightly loss of larvae caused by rainfall was on average 17.5% for the youngest (L1) larvae and 4.8% for the oldest (L4) larvae; an additional 10.5% (increase from 0.9 to 11.4%) of the L1 larvae and 3.3% (from 0.1 to 3.4%) of the L4 larvae were flushed away and larval mortality increased by 6.9% (from 4.6 to 11.5%) and 1.5% (from 4.1 to 5.6%) for L1 and L4 larvae, respectively, compared to nights without rain. On rainy nights, 1.3% and 0.7% of L1 and L4 larvae, respectively, were lost due to ejection from the breeding site.  This study demonstrates that immature populations of malaria mosquitoes suffer high losses during rainfall events. As these populations are likely to experience several rain showers during their lifespan, rainfall will have a profound effect on the productivity of mosquito breeding sites and, as a result, on the transmission of malaria. These findings are discussed in the light of malaria risk and changing rainfall patterns in response to climate change.

title: Malaria and climate: sensitivity of malaria potential transmission to climate
abstract: Malaria, according to the World Health Organization, is one of the most serious and complex health problems facing humanity in the 20th century. In the past, climatic changes have greatly affected its geography. Its seriousness and complexity are therefore likely to be compounded by an anthropogenic greenhouse effect. The Malaria Potential Occurrence Zone (MOZ) model was designed to calculate first-order estimates of climate change impacts on malaria. MOZ focuses on the climatic determinants of the life cycles of malaria parasites and vectors. It does not take epidemiology into account. MOZ predicts receptivity, or potential transmission, rather than actual occurrence. MOZ indicates that the intensity and the extent of malaria potential transmission significantly change under the climate change scenarios generated by five atmospheric general circulation models. All five simulations reveal an increase in seasonal malaria at the expense of perennial malaria. This is cause for great concern. Indeed, seasonal malaria is most likely to lead to epidemics among unprepared or nonimmune populations. Moreover, climate change may trigger massive migrations of environmental refugees. Such population movements would likely put national and international health infrastructures under severe stress. Today, malaria is a developing country issue but could spread to higher latitudes. The results obtained with MOZ suggest that malaria could become a publichealth problem for developed countries within decades.