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      Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007


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          Simon Hay and colleagues derive contemporary estimates of the global clinical burden of Plasmodium falciparum malaria (the deadliest form of malaria) using cartography-based techniques.



          The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches.

          Methods and Findings

          In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales.

          Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349–552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk.

          Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.

          Conclusions and Significance

          Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.

          Please see later in the article for the Editors' Summary

          Editors' Summary


          Malaria is a major global public-health problem. Nearly half the world's population is at risk of malaria, and Plasmodium falciparum malaria—the deadliest form of the disease—causes about one million deaths each year. Malaria is a parasitic disease that is transmitted to people through the bite of an infected mosquito. These insects inject a parasitic form known as sporozoites into people, where they replicate briefly inside liver cells. The liver cells then release merozoites (another parasitic form), which invade red blood cells. Here, the merozoites replicate rapidly before bursting out and infecting more red blood cells. This increase in the parasitic burden causes malaria's characteristic symptoms—debilitating and recurring fevers and chills. Infected red blood cells also release gametocytes, which infect mosquitoes when they take a blood meal. In the mosquito, the gametocytes multiply and develop into sporozoites, thus completing the parasite's life cycle. Malaria can be prevented by controlling the mosquitoes that spread the parasite and by avoiding mosquito bites. Effective treatment with antimalarial drugs also helps to reduce malaria transmission.

          Why Was This Study Done?

          In 1998, the World Health Organization (WHO) and several other international agencies launched Roll Back Malaria, a global partnership that aims to provide a coordinated, global approach to fighting malaria. For this or any other malaria control initiative to be effective, however, an accurate picture of the global clinical burden of malaria (how many people become ill because of malaria and where they live) is needed so that resources can be concentrated where they will have the most impact. Estimates of the global burden of many infectious diseases are obtained using data collected by national surveillance systems. Unfortunately, this approach does not work very well for malaria because in places where malaria is endemic (always present), diagnosis is often inaccurate and national reporting is incomplete. In this study, therefore, the researchers use an alternative, “cartographic” method for estimating the global clinical burden of P. falciparum malaria.

          What Did the Researchers Do and Find?

          The researchers identified seven P. falciparum malaria-endemic countries that had sufficiently reliable health information systems to determine the national clinical malaria burden in 2007 directly. They divided the other 80 malaria endemic countries into countries with a low risk of transmission (unstable transmission) and countries with a moderate or high risk of transmission (stable transmission). In countries with unstable transmission, the researchers assumed a uniform annual clinical incidence rate of 0.1 cases per 1,000 people and multiplied this by population sizes to get disease burden estimates. In countries with stable transmission, they used a modeled relationship between clinical incidence (number of new cases in a population per year) and prevalence (the proportion of a population infected with malaria parasites) and a global malaria endemicity map (a map that indicates the risk of malaria infection in different countries) to estimate malaria incidences. Finally, they used a technique called “joint simulation” to quantify the uncertainty in these estimates. Together, these disease burden estimates gave an estimated global burden of 451 million clinical cases of P. falciparum in 2007. Most of these cases occurred in areas of stable transmission and more than half occurred in India, Nigeria, the Democratic Republic of the Congo, and Myanmar. Importantly, these four nations alone contributed nearly half of the uncertainty in the global incidence estimates.

          What Do These Findings Mean?

          These findings are extremely valuable because they provide a global map of malaria cases that should facilitate the implementation and evaluation of malaria control programs. However, the estimate of the global clinical burden of P. falciparum malaria reported here is higher than the WHO estimate of 247 million cases each year that was obtained using surveillance-based methods. The discrepancy between the estimates obtained using the cartographic and the surveillance-based approach is particularly marked for India. The researchers discuss possible reasons for these discrepancies and suggest improvements that could be made to both methods to increase the validity and precision of estimates. Finally, they note that improvements in the national prevalence surveys in India, Nigeria, the Democratic Republic of the Congo, and Myanmar would greatly reduce the uncertainty associated with their estimate of the global clinical burden of malaria, an observation that should encourage efforts to improve malaria surveillance in these countries.

          Additional Information

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000261.

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          Most cited references74

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          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 WHO's 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.
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            Vivax malaria: neglected and not benign.

            Plasmodium vivax threatens almost 40% of the world's population, resulting in 132-391 million clinical infections each year. Most of these cases originate from Southeast Asia and the Western Pacific, although a significant number also occurs in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact, and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates, the parasite's ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies.
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              Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite.

              Plasmodium vivax is geographically the most widely distributed cause of malaria in people, with up to 2.5 billion people at risk and an estimated 80 million to 300 million clinical cases every year--including severe disease and death. Despite this large burden of disease, P vivax is overlooked and left in the shadow of the enormous problem caused by Plasmodium falciparum in sub-Saharan Africa. The technological advances enabling the sequencing of the P vivax genome and a recent call for worldwide malaria eradication have together placed new emphasis on the importance of addressing P vivax as a major public health problem. However, because of this parasite's biology, it is especially difficult to interrupt the transmission of P vivax, and experts agree that the available methods for preventing and treating infections with P vivax are inadequate. It is thus imperative that the development of new methods and strategies become a priority. Advancing the development of such methods needs renewed emphasis on understanding the biology, pathogenesis, and epidemiology of P vivax. This Review critically examines what is known about P vivax, focusing on identifying the crucial gaps that create obstacles to the elimination of this parasite in human populations.

                Author and article information

                Role: Academic Editor
                PLoS Med
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                June 2010
                June 2010
                15 June 2010
                : 7
                : 6
                : e1000290
                [1 ]Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom
                [2 ]Malaria Public Health and Epidemiology Group, Centre for Geographic Medicine, KEMRI–University of Oxford–Wellcome Trust Research Programme, Nairobi, Kenya
                [3 ]Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
                [4 ]Department of Geography, University of Florida, Gainesville, Florida, United States of America
                [5 ]Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America
                Papua New Guinea Institute of Medical Research, Papua New Guinea
                Author notes

                ICMJE criteria for authorship read and met: SIH EAO PWG APP AJT CAG RWS. Agree with the manuscript's results and conclusions: SIH EAO PWG APP AJT CAG RWS. Designed the experiments/the study: SIH RWS. Analyzed the data: SIH PWG APP AJT RWS. Collected data/did experiments for the study: SIH EAO PWG AJT CAG RWS. Wrote the first draft of the paper: SIH RWS. Contributed to the writing of the paper: EAO PWG APP AJT CAG RWS.

                Hay et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                : 15 February 2010
                : 5 May 2010
                Page count
                Pages: 14
                Research Article
                Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Public Health and Epidemiology/Infectious Diseases



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