Closing the net

Screen Shot 2014-04-11 at 1.44.43 PMThe deadliest creature in the world can be squashed with a casual slap. Yet the tiny mosquito still manages to kill hundreds of thousands of people a year with the diseases it carries: malaria, dengue, Japanese encephalitis and yellow fever. Now it seems science is getting closer to controlling some of the mosquito’s cargo of deadly maladies. It’s far too soon to say the days of dengue and malaria are numbered, but after decades of stymied research and frustrating failure, it appears that well-funded science is finally beginning to make progress.

Large-scale phase III trials, with 30,000 participants, are underway in South America and south-east Asia (the Philippines, Vietnam, Malaysia, Indonesia and Thailand) to gauge the efficacy of a potential dengue vaccine from Sanofi-Pasteur. Although phase II results were ultimately disappointing, the big pharma company pushed ahead and has even built a new factory and begun manufacture in order to maintain its competitive edge. In development for more than 20 years, the vaccine is the first to offer some partial protection against the four viruses that make up dengue.

In Africa, phase III trials of the malaria vaccine RTS,S/AS0, developed by GlaxoSmithKline Biologicals and non-profit PATH (with a grant from the Bill and Melinda Gates Foundation) began in 2009. The World Health Organisation (WHO) expects to begin evaluating the trial data soon, but notes that early reports suggest that if and when it is rolled out, the vaccine won’t be a magic bullet. It will have to be used along with long-lasting insecticidal nets, rapid diagnostic tests and frontline drug therapies.

Meanwhile, on another front, trials are underway in Australia, Indonesia and Vietnam to gauge the ability of certain strains of ‘wolbachia’ bacteria to render aedes aegypti mosquito populations incapable of transmitting dengue. The ‘Eliminate Dengue’ program’s interim results have been encouraging and a city-wide trial is planned for later this year in Townsville, Australia and another in Yogyakarta, Indonesia in 2017. Also assisted by the Gates Foundation, the program has inspired other researchers to consider whether wolbachia might be used to neutralise the malaria-carrying anopheles mosquito and its load of malaria parasites.

Yet as fast as science makes strides, the diseases evolve. Over the years, malaria parasites have become increasingly resistant to chloroquine and sulphadoxine-pyrimethamine, once the drugs of choice to battle the disease. Resistance to these drugs first emerged on the Thai-Cambodian border before spreading across Asia and Africa.

Echoing this pattern, malaria parasites resistant to the frontline drug artemisinin were first encountered in 2008 on the Thai-Cambodian border and the diaspora of these resistant parasites has already begun. Now, despite great efforts to limit the spread, there are pockets of resistance in Myanmar and Vietnam as well.

Dr Eva-Maria Christophel, a malaria expert with the WHO, says the emergence of artemisinin resistance prompted a concerted international effort to contain the evolving parasite. “These efforts are ongoing and they are an unprecedented response to malaria drug resistance,” she says, adding there were no real alternatives to artemisinin. “There are very few other malaria medicines in the pipeline”.

Artemisinin-based combination therapies have been credited with much of the malaria reduction in Asia today and it is feared the spread of resistant parasites could trigger a major health emergency. According to United Nations figures, the annual numbers of malaria deaths in the Asia-Pacific region fell progressively between 2000 and 2011, from 7,848 to 2,481, and the pervasive fear is that artemisinin resistance could reverse that trend.

Originating from the sweet wormwood (Artemisia annua) plant, long used in Chinese traditional medicine, artemisinin can now be produced using genetically-engineered yeast. Artemisin has been used in western Cambodia for more than 30 years, and often in short and inadequate courses, which might have prompted the emergence of resistant parasites on the Thai-Cambodian border.

Mosquitos are enjoying the warmer and wetter conditions imposed by climate change. WHO entomologist Dr Rabindra Abeyasinghe says increasing temperatures have already created a more conducive environment for the insects, even at higher altitudes.

“It has now already been shown that increases in temperatures result in a geographical expansion of disease-affected areas, including the reporting of diseases such as malaria from higher elevations,” he explains.

“Additionally, higher temperatures result in shorter development times for disease-causing agents within mosquitoes and longer life spans for mosquitoes, thus resulting in more efficient transmission. This also makes control of these diseases more difficult.”