Researchers hunt malaria vaccines for people and mosquitoes

For years, researchers have been hunting for a vaccine to protect people against malaria. But what about a vaccine that could stop mosquitoes from transmitting the disease?

That is one of the approaches being worked on by the Malaria Vaccine Initiative, an offshoot of the Seattle-based Path health charity and backed by the Bill & Melinda Gates Foundation.

Ashley Birkett, director of the initiative, says such "transmission-blocking" vaccines could become a powerful weapon against malaria by disabling the parasites that cause the disease.

This approach would not prevent a vaccinated person from contracting malaria. But it would trigger antibodies in the parasite that would stop it being passed on to other people by mosquitoes.

This would be especially useful in reducing the many instances of asymptomatic malaria carriers, who spread the disease without knowing they have it. "Many people do not feel sick but are infecting mosquitoes all day long," Mr Birkett says. "Transmission-blocking vaccines would break that cycle."

Vaccines of this kind have shown promise in early trials but remain years away from production for sale. The fact that Mr Birkett and other leading malaria researchers are placing so much hope in them reflects the limitations of other approaches tried so far.

This assessment may sound unduly negative considering that the world's first malaria vaccine is on the cusp of approval. GlaxoSmithKline, the UK-based drugmaker, is hoping for a green light this year from the European Medicines Agency for the vaccine, known as RTS,S.

Mr Birkett, whose organisation helped GSK develop the product, says RTS,S is an "important first milestone" but it "was never going to be a magic bullet".

In clinical trials, the vaccine cut infections by almost half in children aged between five months and 17 months and by about a quarter in younger babies.

Some in the global health community have expressed disappointment that these prevention rates were not higher after 30 years of work on the vaccine. Mr Birkett says such sentiments are misplaced.

"We all want 99 per cent efficacy but we have to be realistic. These are going to be incremental steps. If we can reduce incidence by 50 per during the first five years of life when children are most vulnerable that would be a big step forward."

If approved by European regulators, the next step would be a recommendation from the World Health Organisation for its use. It would then be up to countries in Africa and other malaria-prone regions to decide whether to adopt the vaccine.

GSK has made clear that it sees RTS,S as a primarily humanitarian rather than commercial product. It says the price will cover the cost of manufacturing plus a profit of about 5 per cent to be reinvested in research and development for further vaccines against malaria and other neglected tropical diseases.

Mr Birkett says RTS,S must be the beginning not the end of the story. "We're taking a portfolio approach rather than putting all our eggs in one basket," he adds.

Other organisations are also entering the race. One of the most promising and advanced alternatives to RTS,S is being developed by a Maryland-based biotech company called Sanaria. Its vaccine, known as PfSPZ, successfully completed early-stage clinical trials last year.

Only three of 15 participants who received a high dose of the vaccine developed malaria after being exposed to infected mosquitoes.

Mr Birkett says the speed with which potential Ebola vaccines have been rushed into clinical trials from a standing start shows what can be achieved when the global community commits funding and attention to a health challenge.

He would like to see a similar push against malaria - a disease that kills more people around the world in a week than Ebola has killed in the past year.

"We need to build a whole suite of innovations including better diagnostics and better vector control, but the key missing ingredient has been a vaccine," says Mr Birkett. "We can battle the parasite with drugs and bed nets but eventually the parasite catches up. We believe the long-term solution has to be vaccination and eradication."

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Drugs: New treatment could be ready by 2018

Artemisinin has been used to treat malaria since at least 1596, when Li Shizhen, a Chinese medical scholar, recommended that the plant extract should be given to infected patients in the form of a tea.

Four centuries later, artemisinin, derived from the sweet wormwood plant, remains the key ingredient in one of the most commonly used malaria treatments.

Modern artemisinin-based medicines were developed by the Chinese military in the 1960s to help protect North Vietnamese soldiers from the disease during their jungle battles with US-backed South Vietnam. The drug was commercialised by Novartis of Switzerland in the 1990s and artemisinin-based combination therapies (ACTs) have since become a main line of defence against malaria. About 260m courses are distributed each year.

However, like other treatments before it, ACTs are being gradually blunted as drug-resistant strains of malaria spread through parts of Southeast Asia. If these were to reach Africa, where the bulk of global cases are concentrated, the big gains made against the disease in recent decades could be quickly lost.

This explains the mounting urgency behind efforts to develop a new generation of malaria medicines. "New treatments must be developed that attack the malaria parasites in novel ways in case resistance against current treatments spreads," says Roger Waltzman, who is leading the development of an experimental Novartis drug called KAE609.

In a study among 21 patients in Thailand published last year, researchers saw "rapid parasite clearance" after the medicine was taken. This included some people with the ACT-resistant strain.

Nick White, professor of tropical medicine at Mahidol University in Thailand and lead author of the study findings, said KAE609 was "the first new antimalarial drug candidate with a completely novel mechanism of action to reach phase II clinical development in 20 years".

Novartis has predicted that, if further trials prove successful, KAE609 could be ready for market by 2018.

The drug is one of two experimental antimalarials under development by Novartis in collaboration with the Medicines for Malaria Venture (MMV), a Swiss non-profit group. Sanofi of France, GlaxoSmithKline of the UK and Takeda of Japan are among others working with the public-private partnership. They were joined this month by Merck Serono, the pharmaceuticals arm of Germany's Merck group, when it agreed to work with MMV on an experimental drug discovered at the University of Dundee in Scotland. Timothy Wells, chief scientific officer at MMV, said the compound "holds great promise".

While new drugs may be on the way, artemisinin-based treatments will continue to play an important role for years to come. Sanofi last year launched an ACT using semi-synthetic artemisinin to reduce dependence on volatile supplies of the sweet wormwood plant. The French company said it had capacity to produce 50-60 tonnes a year of the ingredient using genetically modified yeast, enough to meet a third of annual global need.

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