Scientists report major breakthrough in malaria vaccine development (1)

THERE is hardly anyone born in Nigeria or sub-Saharan Africa who has not had an encounter with malaria at least once in their lifetime. Indeed, besides HIV/AIDS and tuberculosis, malaria is now said to be one of the topmost killer diseases across the globe.

Worst hit by the disease are African countries, where it ravages communities, thus enforcing multiplication of efforts by governments at different levels to save their countries' populations. Each African country has designed its own malaria control and roll back programmes for implementation with global partners.

No fewer than half a billion cases of malaria occur each year say scientists, who have warned that the World Health Organization's estimates are off by nearly 50 per cent. Figures compiled by a team of tropical medicine specialists add up to 515 million clinical attacks of the deadliest form of malaria worldwide

The disease, which accounts for over 90 per cent of deaths in Africa, remains a heavy burden in the continent with devastating effects on her socio-economic welfare. According to the World Health Organization's (WHO) weekly epidemiological records, the burden of malaria is weighing too heavily on the continent, especially within the poor.

Latest statistics hold that malaria kills between one to two million children each year in sub-Saharan Africa, while some 15 to 40 per cent of children with cerebral malaria, as well as malaria associated acidosis and anaemia die, half of the deaths occurring within 12 hours after arrival at the hospital.

Malaria is a parasitic infection transmitted to humans through the bites of infected female Anopheles mosquitoes. The resulting disease in humans can be devastating. After spreading rapidly through the blood stream to the liver, the parasite emerges again into the blood stream, finally to settle in the red blood cells, where it multiplies and emerges in bursts of new organisms. These parasites, because of their large numbers, can cause particular damage to the nervous system, liver, and kidney.

In young children and adults who have not recently been infected - and therefore have not developed natural immunity - this cycle can result in death within hours from cerebral malaria. Others also die at a later stage in the infection from overwhelming anaemia or liver and kidney failure. Untreated, up to 20 per cent of persons infected with falciparum malaria die.

Four species of malaria infect humans, though only two, falciparum and vivax cause the vast majority of clinical cases and nearly all of the deaths and serious incidence of the disease. The disease is particularly prevalent in sub-Saharan Africa, and is common throughout tropical regions of China, India, Southeast Asia, and South and Central America.

Almost all of the serious morbidity caused by falciparum malaria occurs in children under the age of 10, and the impact is especially severe in those under the age of five. Protecting these children from malaria therefore, is a major goal of current malaria vaccine development efforts.

Malaria has a complex life cycle. Infected female mosquitoes inject malaria sporozoites, or parasitic cells that infect new hosts, when they bite, and they are carried to the liver where they rapidly infect liver cells. Without causing symptoms, these sporozoites undergo a radical change and multiply furiously over the next four to five days.

Tens of thousands of asexual stage merozoites, or daughter cells of the parasite, are released from each infected liver cell, each of which rapidly target and invade a red blood cell. Every few days, the merozoites multiply ten-fold and burst out to infect other red blood cells. This cyclic and massive increase in parasite burden gives rise to the clinical disease we recognize as malaria.

In the absence of immunity or drug treatment, death can occur within hours of noticeable symptoms. If death does not occur and infection continues, some of the parasites further differentiate into a form that is infectious for mosquitoes, thus permitting the life cycle to continue.

Strategies for developing malaria vaccines have been targeted at specific points in the parasite life cycle during which the organism appears particularly susceptible to the host's immune system

Children of less than five and pregnant women are population groups at highest risk for malaria morbidity and mortality. It is recorded that over 90 per cent of all malaria deaths in Africa occur in young children. Most often, they experience their first malaria infections during the first one or two years after birth, in forms of cerebral malaria, anaemia, diarrhoea, respiratory infections and other delicate diseases.

An estimated two per cent of children who recover from cerebral malaria infections suffer from learning impairment, disabilities, epilepsy and spasticity, according to WHO's Africa malaria report, 2003.

Much of the morbidity and mortality associated with malaria is caused by the rupture of iRBCs (infected red blood cells) during the stages of reproduction of the parasite by cell division. Intense fever, occurring in 24-72 hour intervals, is accompanied by nausea, headaches, and muscular pain among other symptoms.

The characteristic fever spike has been correlated with incremental rises in blood levels of cytokines or immune system proteins - associated with the release of parasite proteins during the rupture of red blood cells. Furthermore, a variety of potentially fatal symptoms, including liver failure, renal failure, and cerebral disease are associated with untreated P. falciparum

The immune system is the human body's natural defence apparatus for all infections including those of the malaria parasites. However, the immune response to malaria is not well understood. The presence of blood serum antibodies - the immune system's foot soldiers in the form of proteins - in individuals living in regions where malaria is endemic indicates that the immune system mounts a blood fluid response against the parasite.

This immunity is parasite strain-specific and can be lost if the individual migrates to a region where malaria is not endemic. Furthermore, the efficacy of the humoral or blood fluid response is limited by the intracellular behaviour of the parasite as well as its ability to alter its surface molecules through various stages of maturity

Since ninety percent of all malaria cases are in sub-Saharan Africa, preventing infection is especially important because resistance to anti-malarial drugs is a growing problem. This means that immunisation must come into the frame of medical assault on malaria. However the vast majority of vaccine candidates fail during development, making vaccine development an expensive and financially risky endeavour.

Nonetheless the need for a malaria vaccine is urgent, but unfortunately traditional market forces are not strong enough to prompt substantial investment in vaccines that protect against a disease that primarily affects people in developing countries.

To be continued.

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