Modelling malaria risk in East Africa at high-spatial resolution.

OBJECTIVES: Malaria risk maps have re-emerged as an important tool for appropriately targeting the limited resources available for malaria control. In Sub-Saharan Africa empirically derived maps using standardized criteria are few and this paper considers the development of a model of malaria risk for East Africa. METHODS: Statistical techniques were applied to high spatial resolution remotely sensed, human settlement and land-use data to predict the intensity of malaria transmission as defined according to the childhood parasite ratio (PR) in East Africa. Discriminant analysis was used to train environmental and human settlement predictor variables to distinguish between four classes of PR risk shown to relate to disease outcomes in the region. RESULTS: Independent empirical estimates of the PR were identified from Kenya, Tanzania and Uganda (n = 330). Surrogate markers of climate recorded on-board earth orbiting satellites, population settlement, elevation and water bodies all contributed significantly to the predictive models of malaria transmission intensity in the sub-region. The accuracy of the model was increased by stratifying East Africa into two ecological zones. In addition, the inclusion of urbanization as a predictor of malaria prevalence, whilst reducing formal accuracy statistics, nevertheless improved the consistency of the predictive map with expert opinion malaria maps. The overall accuracy achieved with ecological zone and urban stratification was 62% with surrogates of precipitation and temperature being among the most discriminating predictors of the PR. CONCLUSIONS: It is possible to achieve a high degree of predictive accuracy for Plasmodium falciparum parasite prevalence in East Africa using high-spatial resolution environmental data. However, discrepancies were evident from mapped outputs from the models which were largely due to poor coverage of malaria training data and the comparable spatial resolution of predictor data. These deficiencies will only be addressed by more random, intensive small areas studies of empirical estimates of PR.

The influence of urbanisation on measures of Plasmodium falciparum infection prevalence in East Africa.

There is a growing interest in the effects of urbanisation in Africa on Plasmodium falciparum risks and disease outcomes. We undertook a review of published and unpublished literature to identify parasite survey data from communities in East Africa. Data were selected to represent the most reliable and contemporary estimates of infection prevalence and were categorised by urban or rural status using a number of approaches. We identified 329 spatially distinct surveys undertaken since 1980 in the sub-region of which 37 were undertaken in urban settlements and 292 in rural settlements. Overall rural settlements reported significantly higher parasite prevalence among children aged 0-14 than urban settlements (on average 10% higher infection rates; p<0.05). No urban settlements recorded parasite prevalence in excess of 75%. In areas of East Africa where climatic conditions are likely to support higher parasite transmission, the rural-urban difference was most marked. There was a significant trend towards documenting higher classes of parasite prevalence in rural compared to urban settlements (p<0.05) and the mean difference between rural and urban samples was 18% (p<0.001). These results further highlight the need to better define urban extents in Africa in order to capture the non-climatic determinants of infection and disease risk and provide a more informed approach to describing the burden of disease across the continent.

Plasmodium falciparum parasite prevalence in East Africa: a review.

OBJECTIVES: Empirical data on malaria endemicity are rarely available for public domain use to guide effective malaria control. This paper describes the work carried in East Africa since 1997 as part of a pan-African collaboration to map the risk of malaria, Mapping Malaria Risk in Africa (MARA) aimed at redressing deficiency. DATA EXTRACTION: Studies of cross-sectional community estimates of Plasmodium falciparum prevalence among children aged 0-15 years were identified from a variety of sources including electronic searches of published material, manual review of pre-electronic peer reviewed journals and searches of libraries and archives in Kenya, Tanzania and Uganda. Each survey source, infection prevalence, date, longitude and latitude and survey characteristics were recorded. DATA SYNTHESIS: All data were subjected to a number of selection criteria including minimum sample sizes, samples randomly selected, community-based surveys, age ranges of sampled communities within 0-15 years, and surveys that were spatially unique. Of the 2,003 survey data points identified since 1907 in East Africa, only 503 were eligible for inclusion in the analysis dating from 1927 to 2003. The spatial plots of the data demonstrate the paucity of information on malaria prevalence from a number of densely populated areas and highlight the concentration of empirical data in concert with research centres in the sub-region. CONCLUSIONS: Models are required to define malaria risk in areas of East Africa where no empirical data are available so that limited resources can be better targeted to those in greatest need.

Updating Historical Maps of Malaria Transmission Intensity in East Africa Using Remote Sensing.

Remotely sensed imagery has been used to update and improve the spatial resolution of malaria transmission intensity maps in Tanzania, Uganda, and Kenya. Discriminant analysis achieved statistically robust agreements between historical maps of the intensity of malaria transmission and predictions based on multitemporal meteorological satellite sensor data processed using temporal Fourier analysis. The study identified land surface temperature as the best predictor of transmission intensity. Rainfall and moisture availability as inferred by cold cloud duration (ccd) and the normalized difference vegetation index (ndvi), respectively, were identified as secondary predictors of transmission intensity. Information on altitude derived from a digital elevation model significantly improved the predictions. "Malaria-free" areas were predicted with an accuracy of 96 percent while areas where transmission occurs only near water, moderate malaria areas, and intense malaria transmission areas were predicted with accuracies of 90 percent, 72 percent, and 87 percent, respectively. The importance of such maps for rationalizing malaria control is discussed, as is the potential contribution of the next generation of satellite sensors to these mapping efforts.

An empirical malaria distribution map for West Africa.

The objective of this study was to produce a malaria distribution map that would constitute a useful tool for development and health planners in West Africa. The recently created continental database of malaria survey results (MARA/ARMA 1998) provides the opportunity for producing empirical models and maps of malaria distribution at a regional and eventually at a continental level. This paper reports on the mapping of malaria distribution for sub-Saharan West Africa based on these data. The strategy was to undertake a spatial statistical analysis of malaria parasite prevalence in relation to those potential bio-physical environmental factors involved in the distribution of malaria transmission intensity which are readily available at any map location. The resulting model was then used to predict parasite prevalence for the whole of West Africa. We also produced estimates of the proportion of population of each country in the region exposed to various categories of risk to show the impact that malaria is having on individual countries. The data represent a very large sample of children in West Africa. It constitutes a first attempt to produce a malaria risk map of the West African region, based entirely on malariometric data. We anticipate that it will provide useful additional guidance to control programme managers, and that it can be refined once sufficient additional data become available.

Using evidence to change antimalarial drug policy in Kenya.

Chloroquine resistance was first detected in Kenya in 1978 and escalated during the 1980s. Chloroquine remained the treatment of choice for uncomplicated malaria infections until revised guidelines were launched in 1998 despite a plethora of scientific evidence on failure. This review analyses the range and quality of the evidence base that was used to change the drug policy in Kenya from chloroquine to SP and examines the process of consensus building and decision making. Our review illustrates the difficulties in translating sensitivity data with gross geographical, temporal and methodological variations into national treatment policy. The process was complicated by limited options, unknown adverse effects of replacement therapies, cost, as well as limited guidance on factors pertinent to changing the drug policy for malaria. Although > 50% of the studies showed parasitological failures by 1995, there was a general lack of consensus on the principles for assessing drug failures, the inclusion criteria for the study subjects and the relative benefits of parasitological and clinical assessments. A change in international recommendations for assessment of drug efficacy in 1996 from parasitological to clinical response further perplexed the decisions. There is an urgent need for international standards and evidence-based guidelines to provide a framework to assist the process by which decision-makers in malaria-endemic countries can make rational choices for antimalarial drug policy change.

Evidence for a mass community effect of insecticide-treated bednets on the incidence of malaria on the Kenyan coast.

The use of insecticide-treated bednets (ITBNs) has been shown to be effective in reducing mortality and morbidity from malaria. However, there is mixed evidence as to whether or not community-wide use of ITBNs engenders a 'mass effect', such that those not sleeping under bednets are offered protection from widespread ITBN use in the area in which they live. We have analysed data collected in Kilifi, Kenya, from a cohort of children followed from birth to investigate how the degree of net usage in the locality of a child affects the risk of developing malaria. This effect was explored using a Cox proportional hazards model. For those not using ITBNs, we found that an increasing level of ITBN usage within the area surrounding each child was associated with a decreasing risk of developing malaria, thus providing evidence in support of a mass community effect. The size and significance of this effect were found to decrease as non-overlapping areas of increasing distance away from a child's home were considered. The effect was significant for areas at distances of up to 1.5 km away from each child.

Earth observation, geographic information systems and Plasmodium falciparum malaria in sub-Saharan Africa.

This review highlights the progress and current status of remote sensing (RS) and geographical information systems (GIS) as currently applied to the problem of Plasmodium falciparum malaria in sub-Saharan Africa (SSA). The burden of P. falciparum malaria in SSA is first summarized and then contrasted with the paucity of accurate and recent information on the nature and extent of the disease. This provides perspective on both the global importance of the pathogen and the potential for contribution of RS and GIS techniques. The ecology of P. falciparum malaria and its major anopheline vectors in SSA in then outlined, to provide the epidemiological background for considering disease transmission processes and their environmental correlates. Because RS and GIS are recent techniques in epidemiology, all mosquito-borne diseases are considered in this review in order to convey the range of ideas, insights and innovation provided. To conclude, the impact of these initial studies is assessed and suggestions provided on how these advances could be best used for malaria control in an appropriate and sustainable manner, with key areas for future research highlighted.

Mapping malaria transmission intensity using geographical information systems (GIS): an example from Kenya.

That there are so few examples of the use of epidemiological maps in malaria control may be explained by the lack of suitable, spatially defined data and of an understanding of how epidemiological variables relate to disease outcome. However, recent evidence suggests that the clinical outcomes of infection are determined by the intensity of parasite exposure, and developments in geographical information systems (GIS) provide new ways to represent epidemiological data spatially. In the present study, parasitological data from 682 cross-sectional surveys conducted in Kenya were abstracted and spatially defined. Risks of infection with Plasmodium falciparum among Kenyan children, estimated from combinations of parasitological, geographical, demographic and climatic data in a GIS platform, appear to be low for 2.9 million, stable but low for another 1.3 million, moderate for 3.0 million and high for 0.8 million. (Estimates were not available for 1.4 million children.) Whilst the parasitological data were obtained from a variety of sources across different age-groups and times, these markers of endemicity remained relatively stable within the broad definitions of high, moderate and low transmission intensity. Models relating ecological and climatic features to malaria intensity and improvements in our understanding of the relationships between parasite exposure and disease outcome will hopefully provide a more rational basis for malaria control in the near future.

Models to predict the intensity of Plasmodium falciparum transmission: applications to the burden of disease in Kenya.

There is an increasing need to provide spatial distribution maps of the clinical burden of Plasmodium falciparum malaria in Africa. Recent evidence suggests that risk groups and the clinical spectrum of severe malaria are related to the intensity of P. falciparum transmission. Climate operates to affect the vectorial capacity of P. falciparum transmission and this is particularly important in the Horn of Africa and parts of East Africa. We have used a fuzzy logic climate suitability model to define areas of Kenya unsuitable for stable transmission. Kenya's unstable transmission areas can be divided into areas where transmission potential is limited by low rainfall or low temperature and, combined, encompass over 8 million people. Among areas of stable transmission we have used empirical data on P. falciparum infection rates among 124 childhood populations in Kenya to develop a climate-based statistical model of transmission intensity. This model correctly identified 75% (95% confidence interval CI 70-85) of 3 endemicity classes (low, < 20%; high, > or = 70%; and intermediate parasite prevalences). The model was applied to meteorological and remote sensed data using a geographical information system to provide estimates of endemicity for all of the 1080 populated fourth level administrative regions in Kenya. National census data for 1989 on the childhood populations within each administrative region were projected to provide 1997 estimates. Endemicity-specific estimates of morbidity and mortality were derived from published and unpublished sources and applied to their corresponding exposed-to-risk childhood populations. This combined transmission, population and disease-risk model suggested that every day in Kenya approximately 72 and 400 children below the age of 5 years either die or develop clinical malaria warranting in-patient care, respectively. Despite several limitations, such an approach goes beyond 'best guesses' to provide informed estimates of the geographical burden of malaria and its fatal consequences in Kenya.

Relationship Between Severe malaria Morbidity in Children and Level of Plasmodium Transmission in Africa

Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity. So; the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted. Methods: We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community; the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory - tract ifnections (ARI) as a comparison. Findings: 3556 malaria admissions were recorded for the five sites. Marked differences were observed in age; clinical spectrum and rates of severe malaria between the five sites. Paradoxically; the risks of severe malaria; for example; admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3.9; 25.8;25.9; 16.7; and 18.0 in the five communities; the forces of infection estimated for those communities (new infections per infant per infant per month) were 0.001; 0.034; 0.050; 0.093; and 0.176; respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing intensity. Interpretation: We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective meachanisms may operate. In highy endemic areas measures which reduce parasite transmission; and thus immunity; may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity. Source: Lancet. 1997 Jun 7; 349(9066):1650-4

Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa.

BACKGROUND: Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted. METHODS: We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory-tract infections (ARI) as a comparison. FINDINGS: 3556 malaria admissions were recorded for the five sites. Marked differences were observed in age, clinical spectrum and rates of severe malaria between the five sites. Paradoxically, the risks of severe disease in childhood were lowest among populations with the highest transmission intensities, and the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. For severe malaria, for example, admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3.9, 25.8, 25.9, 16.7, and 18.0 in the five communities; the forces of infection estimated for those communities (new infections per infant per month) were 0.001, 0.034, 0.050, 0.093, and 0.176, respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing transmission intensity. INTERPRETATION: We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate. In highly endemic areas measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.

PIP: 3556 pediatric admissions with severe malaria over 3-5 years from five discrete communities in the Gambia and Kenya were recorded prospectively in a study of the relationship between parasite exposure and the development of effective clinical immunity against malaria. The exposure to Plasmodium falciparum infection in each community was determined through repeated parasitological and serological surveys among children and infants, while acute respiratory tract infections (ARI) were used as a comparison. Clear differences were observed in age, clinical spectrum, and rates of severe malaria between the five sites. The risks of severe disease in childhood were lowest in populations with the highest transmission intensities, while the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. Similar trends were observed for cerebral malaria and severe malaria anemia, but not for ARI. The mean age of disease decreased with increasing transmission intensity.

The effects of malaria control on nutritional status in infancy.

Both malaria and undernutrition are major causes of paediatric mortality and morbidity in sub-Saharan Africa. The introduction of insecticide-treated bed nets (ITBN) during a randomized controlled trial on the Kenyan coast significantly reduced severe, life-threatening malaria and all-cause childhood mortality. This paper describes the effects of the intervention upon the nutritional status of infants aged between 1 and 11 months of age. Seven hundred and eighty seven infants who slept under ITBN and 692 contemporaneous control infants, were seen during one of three cross-sectional surveys conducted during a one year period. Standardized weight-for-age and mid-upper arm circumference measures were significantly higher among infants who used ITBN compared with control infants. Whether these improvements in markers of nutritional status were a direct result of concomitant reductions in clinical malaria episodes remains uncertain. Never-the-less evidence suggests that even moderate increases in weight-for-age scores can significantly reduce the probability of mortality in childhood and ITBN may provide additional gains to child survival beyond their impressive effects upon malaria-specific events.

Infant parasite rates and immunoglobulin M seroprevalence as a measure of exposure to Plasmodium falciparum during a randomized controlled trial of insecticide-treated bed nets on the Kenyan coast.

Repeated cross-sectional surveys among infants sleeping under insecticide-treated bed nets (ITBN) and contemporary control infants were used to estimate changes in Plasmodium falciparum exposure due to ITBN use on the Kenyan coast. Presence of P. falciparum parasites or total P. falciparum Immunoglobulin M (IgM) seropositivity were used independently and in combination in a constant risk catalytic conversion model to estimate the force of infection in ITBN and control communities. Such studies during infancy avoid problems of early saturation of prevalence due to high forces of infection and persistence of infection, minimize problems of self-treatment, and can be conducted among large populations covering a wide geographic area. These contrast previous parasitologic studies of ITBN among older children and the traditional entomologic studies of transmission that are logistically demanding. Our investigations demonstrated that parasite prevalence, IgM seropositivity, and the force of transmission were all significantly reduced by 50%. In addition, more infants under ITBN entered their second year of life without previous exposure to P. falciparum than control infants. These effects upon delayed acquisition of effective immunity require careful monitoring during future vector control programs using ITBN.