Tuesday, May 5, 2015

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Malaria: The Ongoing Fight Against an Old, Adaptive Foe

Why has malaria proven so hard to beat?
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Bed nets and hospital beds in Malawi. Photograph by Gates Foundation.

As the global public health community solemnly marks World Malaria Day, attention turns to the human toll enacted by this deadly disease and the measures needed to eradicate it. According to the World Health Organisation, approximately 219 million people are infected with malaria, and the disease kills 600,000 people every year. One out of every two people that ever lived have been felled by the parasite according to one report. Mortality rates are highest among the youngest, and malaria kills a child in Africa every minute.

Scientists give grudging respect to their highly adaptive foe. “This is a very clever, shifty parasite which cloaks what it is doing”, says David Kaslow, director of the PATH Malaria Vaccines Initiative. It can even camouflage itself, attacking the placentas of expectant mothers and hiding from the body’s immune system. Little wonder Robert Gwadz, a US researcher who spent decades studying the disease, described malaria as “genius", adding "it’s smarter than we are".

Finding a fix

Artemisinin-based treatments have been an effective cure for those who can afford it – but worryingly, there is evidence of the parasite’s resistance to the drug in Cambodia and Thailand. That is a mere hop from African shores in a globalised world. Chloroquine resistance in Africa – which led to an increase in hospital admissions – was the result of the slow spread of chloroquine-resistant parasites from South-East Asia, which arrived in East Africa in 1978. Growing resistance of mosquitoes to insecticides is also a threat.

Constant innovation is needed to find new ways of stopping this perennial enemy. International financial support for the battle against the malaria parasite has increased almost 20-fold since the start of the century, from $100 million in 2000 to $1.8 billion last year. Vaccines in particular are receiving considerable attention and funding from donors. British pharmaceuticals company GlaxoSmithKline is currently working on a vaccine based on “RTS,S”, a protein first discovered in the 1980s. Results from a Phase 3 trial across seven African countries (Kenya, Tanzania, Mozambique, Malawi, Gabon, Ghana and Burkina Faso) show a promising reduction in cases by about half in children aged 5-17 months, with a third fewer cases in those children aged 6-12 weeks of age.

Researchers are now trying to understand why RTS,S was less effective in this youngest age group – who are also the most in need of such a vaccine due to their susceptibility to malaria-induced fatalities. Three possible explanations stand out. One might be the less developed immune system at such a young age; while the very young normally respond positively to vaccinations, the RTS,S compound may not elicit the same response. A second reason could be the interaction of RTS,S with some of the other vaccines typically administered during this period. Lastly, a mother's antibodies pass from her bloodstream to her foetus, and they remain in the child’s system during the early weeks of life – this might interfere with the immune response.

While the results for the youngest group were disappointing, the response in Africa was different to that in the West, says Allan Pemba, GlaxoSmithKline’s director of public engagement and access initiatives. “Even a third reduction in risk has a very different meaning to a population who live with the disease than a population that doesn’t”.

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