Malaria has long been an entrenched and debilitating feature of the tropical landscape. Efforts to develop a vaccine have a winding and rather chequered history, but during the past decade a concerted international effort is now finally coming to fruition. Increased funding by private and governmental organisations has resulted in accelerated clinical development of malaria vaccines targeting various stages of the malaria parasite life cycle.
Malaria is caused by four species of the single-celled parasite plasmodium. This has a complex life cycle in humans, passing initially through the liver but causing all its clinical effects when it enters the bloodstream and destroys red blood cells.
Transmission of Plasmodium is by a vector female Anopheles mosquito feeding on the blood from an uninfected human after having previously fed on the blood of a human infected with malaria parasites.
The impact of malaria in sub-Saharan Africa, the worst affected continent, is mainly on children and pregnant women, particularly in poor rural areas. Young children suffer fever, headache, anaemia and vomiting.
In its rarer severe form, malaria can cause coma, respiratory distress, metabolic disorders and severe anaemia. Up to 30% of children with severe malaria will die. For those who survive, impaired learning or neurological deficits are common although natural immunity is also gradually built up.
Pregnant women and their unborn children suffer from maternal anaemia, low birth weight, prematurity and neonatal deaths.
Under less intense transmission (as in much of Asia and South America), P. falciparummalaria affects adults as well as children, causing fever and the potentially fatal severe form. The burden of P. vivax malaria, particularly in Asia, is also becoming increasingly apparent.
Malaria impacts individuals, communities and the economy. There are an estimated 350-500 million malaria episodes every year, in more than 100 countries covering more than 40% of the world population (Robert W. Snow, Carlos A. Guerra, Abdisalan M. Noor, Hla Y. Myint & Simon I. Hay. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434, 214-217 10 March 2005).
Most malaria is caused by P. falciparum. Around 90% of cases worldwide are in children aged under five in Africa. Africa has a virulent form of the P. falciparum parasite, efficient mosquito vector and a climate conducive to the spread of malaria. African children also suffer 80% of the 1 million deaths each year, an equivalent of one child every 30 seconds.
Malaria is estimated to cost sub-Saharan Africa US$ 12 billion in Gross Domestic Product every year and to restrict economic growth by 1.3% per year (ref?). Malaria is thus both a cause and a consequence of poverty (Jeffrey Sachs & Pia Malaney. The economic and social burden of malaria. Nature 415, 680-685 7 February 2002).
Current malaria control methods, notably new Artemisinin Combination Drug Therapies (ACTs), insecticide-treated nets and residual spraying, have led to reduced disease burdens in some countries. However, P. falciparum is already showing signs of resistance to ACTs and the mosquito has historically always developed resistance to insecticides. A partially effective vaccine could reduce the global disease burden, but only a highly effective vaccine would offer the prospect of malaria elimination.
Approaches to malaria vaccine development target various stages in the parasite life cycle:
- Pre-erythrocytic vaccines - these target the early stage when the parasite is entering the liver
- Asexual blood-stage vaccines - these aim to reduce infection of red blood cells and consequently, prevents clinical disease
- Transmission-blocking vaccines - these prevent the parasite from maturing in the mosquito. They would need to be combined with another type of vaccine to protect the vaccinated individual.
Recent advances in the understanding of malaria in pregnancy also give hope that a vaccine targeted specifically against malaria infection of the placenta is feasible.
Information on Vaccines has been selected from Stephen M. Todryk & Adrian V. S. Hill . Malaria vaccines: the stage we are at. Nature Reviews Microbiology 5, 487–489 1 July 2007.