Michael J. Bangs

The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis

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. (Cel.) funestus*, An. (Cel.) gambiae, An. (Cel.) melas, An. (Cel.) merus, An. (Cel.) moucheti and An. (Cel.) nili*, and in the European and Middle Eastern Region: An. (Anopheles) atroparvus, An. (Ano.) labranchiae, An. (Ano.) messeae, An. (Ano.) sacharovi, An. (Cel.) sergentii and An. (Cel.) superpictus*. These maps are presented alongside a bionomics summary for each species relevant to its control.

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

BackgroundThe final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.ResultsExpert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.ConclusionsThis article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.

A global map of dominant malaria vectors

BackgroundGlobal maps, in particular those based on vector distributions, have long been used to help visualise the global extent of malaria. Few, however, have been created with the support of a comprehensive and extensive evidence-based approach.MethodsHere we describe the generation of a global map of the dominant vector species (DVS) of malaria that makes use of predicted distribution maps for individual species or species complexes.ResultsOur global map highlights the spatial variability in the complexity of the vector situation. In Africa, An. gambiae, An. arabiensis and An. funestus are co-dominant across much of the continent, whereas in the Asian-Pacific region there is a highly complex situation with multi-species coexistence and variable species dominance.ConclusionsThe competence of the mapping methodology to accurately portray DVS distributions is discussed. The comprehensive and contemporary database of species-specific spatial occurrence (currently available on request) will be made directly available via the Malaria Atlas Project (MAP) website from early 2012.

Vivax malaria resistant to treatment and prophylaxis with chloroquine

Chloroquine has been the treatment of choice for vivax malaria for more than 40 years. Lately, several case-reports have suggested the emergence of resistance to chloroquine in Plasmodium vivax in Papua New Guinea and Indonesia. We undertook prospective treatment and prophylaxis trials of chloroquine in children and adults with vivax malaria living in Irian Jaya (Indonesia New Guinea). 46 villagers with P vivax parasitaemia were treated with chloroquine by mouth (25 mg base/kg body weight divided over 3 days) and followed up for 14 days. Parasitaemia cleared initially but recurred within 14 days in 10 (22%) subjects. All recurrences were in children younger than 11 years, 7 of whom were younger than 4 years; the failure rate among children under 4 was 70%. 7 of the patients with recurrences were given a second course of chloroquine. In all, the infections initially cleared but recurrent parasitaemia developed in 5 (71%) within 14 days. Whole-blood chloroquine concentrations were consistently above those previously shown to cure P vivax blood infections (90 micrograms/L whole blood). Subjects whose initial infections cleared and who had no parasitaemia on day 14 received weekly prophylaxis with chloroquine. Despite the presence of expected blood chloroquine concentrations, P vivax parasitaemia developed in 9 of 17 subjects receiving prophylaxis during 8 weeks of follow-up (median time to parasitaemia 5.3 weeks). Chloroquine can no longer be relied upon for effective treatment or chemoprophylaxis of P vivax blood infections acquired in this part of New Guinea.

Developing global maps of the dominant anopheles vectors of human malaria.

Simon Hay and colleagues describe how the Malaria Atlas Project has collated anopheline occurrence data to map the geographic distributions of the dominant mosquito vectors of human malaria.

Spatial repellents: from discovery and development to evidence-based validation

International public health workers are challenged by a burden of arthropod-borne disease that remains elevated despite best efforts in control programmes. With this challenge comes the opportunity to develop novel vector control paradigms to guide product development and programme implementation. The role of vector behaviour modification in disease control was first highlighted several decades ago but has received limited attention within the public health community. This paper presents current evidence highlighting the value of sub-lethal agents, specifically spatial repellents, and their use in global health, and identifies the primary challenges towards establishing a clearly defined and recommended role for spatial repellent products in disease control.

Review on global co-transmission of human Plasmodium species and Wuchereria bancrofti by Anopheles mosquitoes

Malaria and lymphatic filariasis are two of the most common mosquito-borne parasitic diseases worldwide which can occur as concomitant human infections while also sharing common mosquito vectors. This review presents the most recent available information on the co-transmission of human Plasmodium species and Wuchereria bancrofti by Anopheles mosquitoes. Important biological and epidemiological aspects are also described including the lifecycle of each parasite species and their specificities, the geographical biodiversity of each pathogen and their vectors where the parasites are co-endemic, and biological, environmental and climatic determinants influencing transmission. The co-transmission of each disease is illustrated from both a global perspective and a country level using Thailand as a study case. Different diagnostic methods are provided for the detection of the parasites in biological samples ranging from traditional to more recent molecular methods, including methodologies employing concomitant detection assays of W. bancrofti and Plasmodium spp. parasites. The relevant issues of combined malaria and Bancroftian filariasis control strategies are reviewed and discussed.

Epidemic dengue transmission in southern Sumatra, Indonesia

An outbreak of dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) in the city of Palembang, south Sumatra, Indonesia was investigated to (i) validate epidemic occurrence, (ii) confirm dengue virus aetiology and associated serotype(s), (iii) provide a demonstrable measure of community impact, and (iv) identify causative relationship (if any) with climatic El Niño Southern Oscillation (ENSO) influences. Trend analysis based on a 6-year retrospective review of hospital records demonstrates a 3-fold increase in clinical cases for the outbreak period (January-April 1998), relative to historical records. In the 2 hospitals surveyed, the monthly mean number of outbreak-related dengue cases over 4 months was 833 (range 650-995 cases/month); the mean monthly value for the previous 72 months was 107 (range 14-779 cases/month). An apparent trend in epidemic transmission was observed, evolving from a 5-year cyclic phenomenon to an annual occurrence, often indistinguishable from one year to the next. The proportional distribution of clinical outbreak cases into DF, DHF and DSS diagnostic categories was 24%, 66%, and 10%, respectively. The population aged 10-19 years accounted for the largest (35%) proportion of hospitalized DHF cases, followed by children aged 5-9 years (25%) and children aged 4 years (16%). Serum samples obtained during acute illness from 221 hospitalized patients were examined using serology, RT-PCR, and virus isolation in cell culture: 59% of samples had laboratory evidence of a dengue infection. All 4 dengue virus serotypes (DEN 1-4) were identified in epidemic circulation, with DEN 3 predominating (43%). DEN 1 was the principal serotype associated with less severe dengue illness, suggesting that virulence may be, in part, a function of infecting serotype. The climatic influence of ENSO on rainfall and temperature in the months leading up to and during the outbreak was dramatic, and is likely to contribute to favourable outbreak conditions.

Randomized, Parallel Placebo-Controlled Trial of Primaquine for Malaria Prophylaxis in Papua, Indonesia

Malaria causes illness or death in unprotected travelers. Primaquine prevents malaria by attacking liver-stage parasites, a property distinguishing it from most chemoprophylactics and obviating 4-week postexposure dosing. A daily adult regimen of 30 mg primaquine prevented malaria caused by Plasmodium falciparum and P. vivax for 20 weeks in 95 of 97 glucose-6-phosphate dehydrogenase (G6PD)-normal Javanese transmigrants in Papua, Indonesia. In comparison, 37 of 149 subjects taking placebo in a parallel trial became parasitemic. The protective efficacy of primaquine against malaria was 93% (95% confidence interval [CI] 71%-98%); against P. falciparum it was 88% (95% CI 48%-97%), and >92% for P. vivax (95% CI >37%-99%). Primaquine was as well tolerated as placebo. Mild methemoglobinemia (mean of 3.4%) returned to normal within 2 weeks. Blood chemistry and hematological parameters revealed no evidence of toxicity. Good safety, tolerance, and efficacy, along with key advantages in dosing requirements, make primaquine an excellent drug for preventing malaria in nonpregnant, G6PD-normal travelers.

Dihydrofolate Reductase Mutations in Plasmodium vivax from Indonesia and Therapeutic Response to Sulfadoxine plus Pyrimethamine

BACKGROUND The target enzyme of pyrimethamine is dihydrofolate reductase (DHFR), but little is known about allelic variants of dhfr in Plasmodium vivax populations. Still less is known about associations between specific alleles and the failure of sulfadoxine/pyrimethamine (S/P) to clear the erythrocytic stages of P. vivax in vivo. METHODS We studied P. vivax dhfr mutations in 24 patients who received S/P therapy in Papua or Central Java, Indonesia, and we measured the resistance of the alleles in vitro in a dhfr yeast expression assay. RESULTS Fourteen (58%) of 24 patients had an inadequate therapeutic response. Two of 6 alleles that were identified were novel. One allele that expressed 4 point mutations (57L+58R+61M+117T) correlated with a high risk of therapeutic failure. The 9 patients infected by P. vivax carrying this allele proved 23 times more likely to experience early therapeutic failure, compared with patients infected by P. vivax carrying other alleles (P=.003; 95% confidence interval, 2-450). This allele also conferred high levels of pyrimethamine resistance in vitro. The experimental antifolate WR99210 inhibited the allele in this system. CONCLUSIONS The present study identified a strong correlation between specific mutations in P. vivax dhfr and S/P treatment failure. Our results suggest that WR99210 could provide effective therapy for S/P-resistant P. vivax.