New strategies in the mosquito war

Bryan Pearson

The battle against malaria has to involve a wide range of weaponry – vaccines may work in the future but people still need better protection, diagnosis and treatment on a day-to-day basis Bryan Pearson

For centuries, the mosquito has taunted mankind with its ability to develop resistance to medicines, and its refusal to raise the white flag to a preventive vaccine. But the hugely scaled-up campaign against it over recent years is close to bearing fruit: a vaccine is maybe three years away, new medicines are coming through the research process, rapid diagnostics tests are now available, and the insecticide-treated bednet campaign is reporting progress. It has been an epic struggle against one of the cleverest and most complex vectors of deadly human parasites.

Malaria affects about 40 percent of the world population and is thought to infect around 250 million people every year, resulting in around 1 million or so deaths. In Africa, approximately 20 percent of childhood mortality is due to malaria with children on average experiencing between 1.6 and 5.4 episodes of malarial fever each year. Each episode weakens their immune system and can cause serious damage to their nervous systems, kidneys and liver. Malaria related-illnesses and mortality are estimated to cost Africa’s economy $12 billion a year.

Although its impact is still low, the most exciting development is a candidate vaccine called RTS,S from the GlaxoSmith- Kline Biologicals stable. Phase III trials of Mosquirix (as it is also known) indicate that, whilst it is not yet the complete magic bullet of prevention, when administered to children between five and 17 months it reduces infection by 53 percent and is well tolerated. Larger trials are now underway in Tanzania, Malawi, Kenya, Mozambique and Gabon, and researchers are confident that they will soon be able to start entering the complex process of filing data for clinical regulatory approval and it could be ready for use by 2015. With the understanding gained from this vaccine, the first to target a complex human parasite rather than a bacterium or virus, an improved vaccine might provide around 80 percent protection by 2025, with full protection sometime beyond that.

The vaccine is formulated to attack a single strain of the most serious form of the parasite – plasmodium falciparum – and targets malaria in the blood stage. This is the period after the mosquito has bitten its victim, when the parasite multiplies in the blood, causing disease and death. Other blood stage vaccines have been tested but none has advanced this far.

While the vaccine story is exciting, significant work and attention needs to continue to be spent on better treatments, and appropriate forms of prevention. The sheer cost – and process – of rolling out any future vaccine also has to be carefully planned for. By using a framework to guide decision-making, countries could ensure that an informed decision is made as soon after licensing as possible and thus speed up the delivery in developing country health systems.

Led by the Malaria Vaccine Initiative (MVI), set up by PATH, a health NGO, work began in January 2006 on a generic decision-making framework that could be adapted to a specific country’s needs. MVI and WHO then consulted with stakeholders from six African countries – Gabon, Ghana, Kenya, Mali, Mozambique, and Tanzania – to adapt the framework to reflect the distinct circumstances of respective health systems. So, when the vaccine becomes available, Africa should be ready, in practical terms at least. Where the money will come from will be another matter.

On the prophylaxis and treatment front, there have been other advances too. Most revolve around the artemisinin-derived medicines with different combination therapies. However an interesting new piece of research conducted through the KEMRI-Well- come Trust Research Programme in Kenya in association with Dr Steffen Borrman of the Heidelberg University School of Medicine, showed that the antibiotics clindamycin and azithromycin damaged malaria parasites when they entered the liver. The damaged malaria parasites were then prevented from becoming the disease-causing form of malaria that enters into the bloodstream. The research could help vaccine researchers and those working on prophylaxis and treatment.

Diagnosing malaria is another area where huge strides are being made. New rapid diagnostic tests do not require laboratories and microscopes and can produce results in a matter of minutes. This is crucial as without reliable laboratory services many doctors (and parents) adopt malaria routinely as the diagnosis of convenience for any fever. Unnecessary treatments only increase the pace of resistance.

Perhaps the most high profile mainline treatment at the moment is Coartem. It is an artemisinin-based combination therapy produced by Novartis and now priced at around 80 US cents for an adult treatment pack, and about half this for a child’s pack. But already reports are starting to be heard of malaria not responding to this treatment, and doctors need to remain alert to other combinations for certain cases. Two new treatments are expected from the Medicines for Malaria Venture in 2011. It is currently a very fertile ground.

And finally, there is a huge industry surrounding bednets and vector spraying. This year is targeted as the year for universal coverage in the supply of treated nets or, as are now being used, special long-lasting insecticide-treated nets. To meet a target of two nets per household, a huge programme has been launched, with companies such as Sumitomo Chemical’s Olyset factory in Arusha, Tanzania, now employing over 600 workers. Distribution has been good but the jury is still out on the level of take-up. Evidence suggests that many nets still remain in their packets, or have been used for fishing or even as a part of bridal headwear. In many communities, mothers and under-five children are using them, but over five-year-olds and adult males are not doing so. Educating people on why they should sleep under a net is not a simple process.


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