Robert W. Snow

The global distribution of clinical episodes of Plasmodium falciparum malaria

Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300–660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHOs reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.

A world malaria map: Plasmodium falciparum endemicity in 2007

Background Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. Methods and Findings A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2−10 ≤ 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2−10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2−10 ≥ 40%) areas. High endemicity was widespread in the Africa+ region, where 0.35 billion people are at this level of risk. Most of the rest live at intermediate risk (0.20 billion), with a smaller number (0.11 billion) at low stable risk. Conclusions High levels of P. falciparum malaria endemicity are common in Africa. Uniformly low endemic levels are found in the Americas. Low endemicity is also widespread in CSE Asia, but pockets of intermediate and very rarely high transmission remain. There are therefore significant opportunities for malaria control in Africa and for malaria elimination elsewhere. This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process.

The global distribution and population at risk of malaria: past, present, and future

The aim of this review was to use geographic information systems in combination with historical maps to quantify the anthropogenic impact on the distribution of malaria in the 20th century. The nature of the cartographic record enabled global and regional patterns in the spatial limits of malaria to be investigated at six intervals between 1900 and 2002. Contemporaneous population surfaces also allowed changes in the numbers of people living in areas of malaria risk to be quantified. These data showed that during the past century, despite human activities reducing by half the land area supporting malaria, demographic changes resulted in a 2 billion increase in the total population exposed to malaria risk. Furthermore, stratifying the present day malaria extent by endemicity class and examining regional differences highlighted that nearly 1 billion people are exposed to hypoendemic and mesoendemic malaria in southeast Asia. We further concluded that some distortion in estimates of the regional distribution of malaria burden could have resulted from different methods used to calculate burden in Africa. Crude estimates of the national prevalence of Plasmodium falciparum infection based on endemicity maps corroborate these assertions. Finally, population projections for 2010 were used to investigate the potential effect of future demographic changes. These indicated that although population growth will not substantially change the regional distribution of people at malaria risk, around 400 million births will occur within the boundary of current distribution of malaria by 2010: the date by which the Roll Back Malaria initiative is challenged to halve the worlds malaria burden.

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.

Averting a malaria disaster

Estimates for the annual mortality from malaria range from 0·5 to 2·5 million deaths. The burden of this enormous toll, and the concomitant morbidity, is borne by the world’s poorest countries. Malaria morbidity and mortality have been held in check by the widespread availability of cheap and effective antimalarial drugs. The loss of these drugs to resistance may represent the single most important threat to the health of people in tropical countries. Chloroquine has been the mainstay of antimalarial drug treatment for the past 40 years, but resistance is now widespread and few countries are u n a f f e c t e d . 1 Pyrimethamine-sulphadoxine (PSD) is usually deployed as a successor to chloroquine. Both these antimalarials cost less than US

Insecticide‐treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast

0.20 per adult treatment course, but the drugs required to treat multidrug-resistant falciparum malaria (quinine, mefloquine, halofantrine) are over ten times more expensive and cannot be afforded by most tropical countries— especially those in Africa, where it is estimated that more than 90% of the world’s malaria deaths occur. Resistance to chloroquine is widespread across Africa and resistance to PSD is increasing. 2 A health calamity looms within the next few years. 3 As treatments lose their effectiveness, morbidity and mortality from malaria will inevitably continue to rise. Can this disaster be prevented? Can we really “roll back malaria”, as the new Director-General of WHO has demanded? 4

Climate change and the resurgence of malaria in the East African highlands.

New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub‐Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast.

Satellite imagery in the study and forecast of malaria.

The public health and economic consequences of Plasmodium falciparum malaria are once again regarded as priorities for global development. There has been much speculation on whether anthropogenic climate change is exacerbating the malaria problem, especially in areas of high altitude where P. falciparum transmission is limited by low temperature. The International Panel on Climate Change has concluded that there is likely to be a net extension in the distribution of malaria and an increase in incidence within this range. We investigated long-term meteorological trends in four high-altitude sites in East Africa, where increases in malaria have been reported in the past two decades. Here we show that temperature, rainfall, vapour pressure and the number of months suitable for P. falciparum transmission have not changed significantly during the past century or during the period of reported malaria resurgence. A high degree of temporal and spatial variation in the climate of East Africa suggests further that claimed associations between local malaria resurgences and regional changes in climate are overly simplistic.

The Limits and Intensity of Plasmodium falciparum Transmission: Implications for Malaria Control and Elimination Worldwide

More than 30 years ago, human beings looked back from the Moon to see the magnificent spectacle of Earth-rise. The technology that put us into space has since been used to assess the damage we are doing to our natural environment and is now being harnessed to monitor and predict diseases through space and time. Satellite sensor data promise the development of early-warning systems for diseases such as malaria, which kills between 1 and 2 million people each year.

The international limits and population at risk of Plasmodium vivax transmission in 2009.

Background The efficient allocation of financial resources for malaria control using appropriate combinations of interventions requires accurate information on the geographic distribution of malaria risk. An evidence-based description of the global range of Plasmodium falciparum malaria and its endemicity has not been assembled in almost 40 y. This paper aims to define the global geographic distribution of P. falciparum malaria in 2007 and to provide a preliminary description of its transmission intensity within this range. Methods and Findings The global spatial distribution of P. falciparum malaria was generated using nationally reported case-incidence data, medical intelligence, and biological rules of transmission exclusion, using temperature and aridity limits informed by the bionomics of dominant Anopheles vector species. A total of 4,278 spatially unique cross-sectional survey estimates of P. falciparum parasite rates were assembled. Extractions from a population surface showed that 2.37 billion people lived in areas at any risk of P. falciparum transmission in 2007. Globally, almost 1 billion people lived under unstable, or extremely low, malaria risk. Almost all P. falciparum parasite rates above 50% were reported in Africa in a latitude band consistent with the distribution of Anopheles gambiae s.s. Conditions of low parasite prevalence were also common in Africa, however. Outside of Africa, P. falciparum malaria prevalence is largely hypoendemic (less than 10%), with the median below 5% in the areas surveyed. Conclusions This new map is a plausible representation of the current extent of P. falciparum risk and the most contemporary summary of the population at risk of P. falciparum malaria within these limits. For 1 billion people at risk of unstable malaria transmission, elimination is epidemiologically feasible, and large areas of Africa are more amenable to control than appreciated previously. The release of this information in the public domain will help focus future resources for P. falciparum malaria control and elimination.