Academic journal article Bulletin of the World Health Organization

Progress with New Malaria Vaccines

Academic journal article Bulletin of the World Health Organization

Progress with New Malaria Vaccines

Article excerpt

Introduction

Malaria is a parasitic disease of major global health significance caused by one of four species of the Plasmodium genus, i.e.P. falciparum, P. vivax, P. ovale or P. malariae. This review focuses on the development of vaccines against P. falciparum because it is the cause of most of the deaths from malaria. It is estimated that up to 2.7 million people, mainly children, die each year from malaria and more than 2 billion people live in regions where inhabitants are exposed to infection with P. falciparum (1). Infection with P. falciparum leads to a wide spectrum of clinical disease including life-threatening anaemia and coma in children, and a severe disease syndrome during pregnancy in primigravida women (2). However, malaria is more than just a health problem--in regions where the disease flourishes, societies have prospered least. The global distribution of per-capita gross domestic product shows a striking correlation between malaria and poverty. Countries in which malaria is endemic also have lower rates of economic growth as a consequence of numerous factors including effects of the disease on fertility, population growth, saving and investment, worker productivity, absenteeism, premature mortality and medical costs (3).

The burden of malarial disease continues to increase as the countries in which it is endemic face increasing and ever more widespread drug-resistance in the parasite and increasing resistance of the vector to insecticide, together with a lack of the necessary infrastructure to tackle the problems. This increase is occurring despite evidence that certain mechanisms for controlling malaria are proving successful; these include the use of insecticide-treated bednets (4, 5) and the development and availability of new anti-malarial drugs such as dapsone-proguanil (6, 7) and artemisinin derivatives (8). An effective vaccine against this parasitic disease is urgently needed. We outline below the complex life cycle of the malaria parasite before reviewing the evidence that supports the view that a malaria vaccine is feasible. We then review recent developments in vaccinology that may speed up the process of developing a successful vaccine, and finally discuss those vaccines that are currently being tested in clinical trials or are close to being tested.

Life cycle of the Plasmodium falciparum parasite

P. falciparum has a complicated life cycle involving several stages, with different antigens being expressed at each stage. Thus, unlike most currently licensed vaccines, a live attenuated or killed whole organism vaccine is unlikely to be practical because an attenuated parasite from one stage of the life cycle may well confer immunity only to that stage. A vaccine that works at one stage in the life cycle of the parasite was thought until recently to be unlikely to have any effect on any other stage. However, data from the malaria genome project call into question some of the previously held ideas about the stage-specific expression of antigens and several antigens formerly believed to be specific to one stage have been found also at other stages of the life cycle (9). The main stages of the parasite's life cycle can be summarized as follows:

* Pre-erythrocytic stage: P. falciparum is spread by the bite of an infected female anopheline mosquito that ejects an estimated 15 sporozoites (10) into the circulation of the host. These sporozoites migrate to liver cells, which become infected within minutes of biting. Once inside the liver cells these sporozoites mature over 6-7 days into liver-stage trophozoites and then into schizonts before rupturing the infected liver cell and releasing an estimated 20 000-40 000 merozoites into the circulation.

* Blood stage: Once in the systemic circulation, the merozoites follow a cycle of invasion of the erythrocytes and multiplication takes place until either the infection is brought under control by the immune system or death of the host results. …

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