Disease burden and geography
Malaria is a tropical disease of major global health significance. There are approximately 300 to 500 million cases each year and around 2 to 3 million deaths. Most of these deaths are in children aged 1 to 5 in sub-Saharan Africa, making it the biggest single infectious killer of children in the world. For detailed maps of the malaria endemic areas, follow this link.
Different types of Malaria
Malaria is caused by several species of the parasite Plasmodium - these are P. falciparum, P.vivax (these first two cause most of the vast number of clinical cases of malaria), P. malariae and P. ovale. The research work of our group concentrates on P. falciparum as this is the type that leads to the majority of malaria deaths. The Plasmodium parasite is spread to humans by the bite of an infected female Anopheles mosquito.
These mosquitoes breed in areas where there is stagnant water such as swamps and during the rainy seasons of African countries. Unfortunately, the problem of malaria is getting worse as the mosquitoes that transmit the disease are becoming resistant to insecticides and the parasites themselves are becoming increasingly resistant to the drugs used to treat the disease.
The parasite life cycle
The life cycle of the falciparum malaria parasite is complex. When an infectious mosquito feeds on someone, parasites (called sporozoites) are injected into the blood stream. From here they travel directly to the liver where they mature for about 6 days. At this stage there are no symptoms of disease in the person who has been infected. The sporozoites divide rapidly with each producing 20000 merozoites which burst from the liver cells and go on to invade red blood cells. Here they develop further before bursting from red blood cells to go on to infect other red blood cells.
Once the parasites have begun to accumulate in numbers in the blood stream the infected individual starts to experience the symptoms of malaria, the most devastating consequences of which are cerebral malaria and severe malarial anaemia. The life cycle is completed when another mosquito feeds on an infected person and the parasites further develop within the mosquito before being injected into another unsuspecting victim.
Vaccines against Malaria
It may be possible to intervene at any or a combination of the stages in the parasite's life cycle to produce an effective vaccine.
For many infectious diseases it is possible to produce an attenuated (harmless) version of the pathogen or a pathogen subunit that will lead to protective immunity without causing disease. Although this is technically possible (irradiated malaria sporozoites given by infected mosquito bite can lead to protective immunity), it is impractical to do this on a large scale.
Most currently used vaccines work by getting the body to produce antibodies against the disease. Antibodies are unable to attack the malaria parasite once it has invaded liver cells and thus the approach of the Jenner Institute's Malaria Vaccines Programme has been to design vaccines that will induce potent T-cell responses against the liver stage of malaria infection.
T-cells are a type of white blood cell called lymphocytes that circulate in the blood. This approach could prevent both blood-stage infection (and thus disease) and also prevent malaria transmission in endemic areas. The vaccines stimulate populations of T-cells that will destroy liver cells that are harbouring the malaria parasite and thus prevent parasite development. The T-cells recognise the infected liver cells as they express small peptides (protein fragments) from malaria on their surface.
An alternative, novel approach is to attack the transmission capacities of the parasite, a research direction which is also being followed by the Institute's Transmission-blocking Vaccine Group.