Malaria cure: The journey so far

Children are more affected by malaria

The cost implication of malaria on health and the economy is tremendous and scientists are bent on getting a cure for it, reports Sade Oguntola.

A baby born in sub Saharan Africa faces a lifetime health risks, but none is more challenging than surviving its first five years. A major reason for this is malaria, a parasitic disease that is being spread by mosquitoes. Of the more than one million malaria deaths worldwide annually, about 90 per cent children under five years of age and as many as 50 per cent of the severe cases occur in babies under 18 months old.

However, hope is rising, as the number of cases of malaria, especially among children would in no distant future become greatly reduced, with success already recorded on the malaria vaccine currently under test in Africa. If this turned out successfully, experts said the vaccine could become available in the next few years to protect infants and young children from the mosquito-borne illness. This is the first time the prototype vaccine previously proved to be safe and effective in adults and children is being tested on babies who are the most vulnerable of all age groups. The clinical trial of the malaria vaccine in Mozambique involved 214 infants, aged 10 to 18 weeks. Though the researchers said the results are still early and that they are cautious about interpreting the data, but the vaccine appears to be safe and also highly protective.

The researchers reported in The Lancet that there were 62 per cent fewer new cases of the disease among 214 infants between 10 and 18 months, who had received the full three-dose course of the RTS, SI AS02A vaccine during this trial. And among infants from a rural area in southern Mozambique who had received at least one injection, there were 35 per cent fewer malaria episodes. The clinical trial is one of many being undertaken to assess the safety of the RTS, S vaccine developed by GlaxoSmithKline (GSK). Researchers said that it caused initial pain at the injection site (the thigh in babies) but that no other serious side effects were reported. A previous study showed the vaccine, created in 1987, reduced young children’s malaria risk by 30 per cent—an inoculation that lasted for at least 18 months. The vaccine also protected 34 per cent of men in a study in Gambia.

The vaccine attacked Plasmodium falciparum—the parasite that causes malaria—at the early infection stage, when it had just been injected into human blood by the bite of a carrier mosquito. Unchallenged, the parasitic sporozoites (the form of the malaria parasite that is injected by mosquitoes) make their way to the liver where they grow and mature into the merozoites. These are potentially deadly when released from the liver into the blood.

The vaccine, named RTS, S/ AS02A carries two short proteins, called RTS and S, mimicking a key surface component of the sporozoite usually recognised by the immune system. Incorporated into the empty shell of a hepatitis B vaccine, the new vaccine is thought to trigger production of antibodies and white blood cells that recognise and neutralise the sporozoites.

Joe Cohen, inventor of the vaccine at GSK said that it “ works by preventing the parasite from emerging from the liver, or at least reduce the load of parasites emerging. The next parasitic stages are controlled and manifestation of the disease is greatly decreased.” A large trial to determine the overall efficacy of the vaccine in children of all ages is expected to begin later this year, assuming results from last year’s safety trials continue to be positive. That trial will enroll at least 16,000 children from as many as 10 areas in seven African countries, according to physician W. Ripley Ballou, Vice- president of global clinical research and development at GSK Biologicals. It would investigate, among other things, whether adding a booster shot later in life provides added protection.

The good news is that the vaccine appears to be effective against all strains of the malaria parasite, Plasmodium falciparum, and those initially protected have not shown any rebound effects later in life. John McNeill, director of research and development for PATH Malaria Vaccine Initiative, which has provided financial support for development of the malaria vaccine expected that the three-shot vaccine regimen would be given to infants and children at the same time they receive other routine vaccinations against childhood illnesses. “These are opportunities for immunising kids that really provide us the chance to get the vaccine to the largest number of kids that need it,” he said. The results of the malaria vaccine trial are published in the British medical journal, The Lancet. There are, however, some challenges ahead as the vaccine does not seem to protect against certain parasites, said molecular biologist Joe Cohen, Vice-president of research and development for emerging diseases, HIV and vaccines at GSK Biologicals.

But “this is a question that we will need to continue to address in further studies and even probably after the vaccine has been implemented,” which could come as soon as year 2011 if all trials go well, he stated, Experts agreed that a vaccine is the best way to fight the disease, but this has proven nearly impossible. The Plasmodium falciparum parasite has a complex lifecycle inside the mosquito and the human body, which helps it to evade the immune system. Lead researcher, Professor Pedro Alonso, said it would have been unrealistic to expect the vaccine to prevent infections totally and that the results were really encouraging. “It’s difficult to imagine that we will have in the near future, a magic bullet that by itself can sort out the problem of malaria. Just like any other malaria control tool that we have, like insecticide treated nets none of them is 100 per cent effective. Control will rely on using a combination of malaria control tools together. We believe a malaria vaccine, even of moderate efficacy, could make a huge impact.”

Allan Shapira, of Roll Back Malaria, said, “the research is very high quality and the findings are very encouraging.” He said there would always be concern about the possible cost and availability of vaccines and treatments for malaria. In the meantime, Dr. Fatai Fehintola, a malaria expert at the University College Hospital (UCH), Ibadan, said the results do not have convincing evidence to really make him share the optimism as to having a vaccine for mass usage in the shortest period of time, not in the next five years. Even the Mozambique vaccine being tested, I am not sure it is a multistage, multivalent vaccine, which is the ideal vaccine for malaria parasite. “We need a multistage vaccine because we have various developmental stages of malaria in humans. Looking at the different stages and targeting these different stages have been the major problem with developing malaria vaccine so far.”

Despite the heavy investments and efforts at developing an “ideal” vaccine, he stated that a challenge to this has being the nature of the parasite and the ecology in which it is usually found. Actually, we have a lot of strains and sub-strains in the wild and the strains of malaria parasite undergoing changes (mutation) continually. These are reasons why getting one ideal vaccine has being unsuccessful, unlike the Mozambique vaccine that protects only against just one strain of the parasite. According to Dr. Fehintola, the ideal vaccine for any disease is however taking as that substance that causes the immune system to develop responses that protect against a specific disease. It should be: safe; easy to manufacture; easy to administer, and, when administered in infancy, confer life-long immunity against all forms of the disease. “This ideal is rarely achieved, however, and some of our best-licensed vaccines, such as tetanus vaccine, must be given repeatedly throughout life to maintain immunity. In practice, most vaccines do not actually prevent infection, but instead enhanced the immune system to limit the pathogen’s ability to cause disease, “ he said.

“An ideal malaria vaccine should prevent that infection by making the immune system destroy all parasites, whether free swimming in the blood, in the liver, or even, theoretically, while in red blood cells. This degree of protection would be extremely difficult to achieve and might not be technically feasible with current vaccinology art and science. Many vaccine developers have therefore focused their efforts on creating a vaccine that limits the ability of the parasite to successfully infect large numbers of red blood cells. This would not prevent infection but would limit the severity of the disease and help prevent malaria deaths. Like the Microsoft, billionaire Bill Gates that gave hundreds of millions of dollars to malaria vaccine and treatment programmes said, “We have a real chance to build the partnerships, generate the political will, and develop the scientific breakthroughs we need to end this disease.” Work must continue until malaria is eradicated.