Malaria drug breakthrough

About 200 000 deaths from malaria each year could be averted if African governments follow new World Health Organisation (WHO) guidelines, soon to be released, and switch from the far less effective medication quinine to artesunate, according to Médecins sans Frontières (MSF).

MSF, in a new report, “Making the Switch”, also called on the WHO and donors to support governments to make this change quickly.

Severe malaria kills more than 600 000 African children under the age of five annually and each year eight million simple malaria cases progress to severe malaria, in which patients show clinical signs of organ damage that may involve the brain, lungs, kidneys or blood vessels. All malaria deaths are the result of severe malaria.

Uncomplicated malaria is most likely to progress to severe malaria in patients who have not been exposed repeatedly to malaria in the past and have not had a chance to develop an immune response to the parasite. For this reason, children are the most vulnerable.

Quinine has to be given three times a day with a slow intravenous drip that takes four hours at a time, which is a burden on both patients and health staff. But artesunate can be given in just four minutes by intravenous or intramuscular injection.

Dr Martins Dada, the MSF’s medical coordinator in the Democratic Republic of Congo, said: “Staff in clinics based in very remote areas run by the ministry of health often have great difficulties setting up the thrice daily infusions with quinine. Sometimes this is because they lack basic medical supplies such as glucose solutions, infusion lines and intravenous catheters.

Treating malaria
“Other times, placing the infusion in a child can be tricky because they cannot find a good enough vein, or because the infusion needs to remain in place for four hours at a time, multiple times and movement can disturb this.

“Also, treatment isn’t standardised and each treatment has to be adapted specifically to each child and this makes things complex for medical staff too.”

Besides the challenge of administering the correct dosage of quinine, it has a wide range of side effects, including short-term dizziness, hearing loss or ringing in the ears, which can progress into far more serious, life-threatening ones, such as irregular heartbeat and even falling into a coma.

Artesunate is three times more expensive than quinine but, according to MSF, “the difference in cost of $31-million each year for a global switch is very little for the nearly 200 000 lives that researchers say could be saved. African governments must urgently change their treatment protocols and donors must send a clear signal to countries that they will support the additional cost where needed.”

To meet the millennium development goal of halting and beginning to reverse the incidence of malaria by 2015, more than $1-billion is needed.

A landmark clinical trial concluded that the use of artesunate to treat children with severe malaria reduces the risk of death by nearly a quarter. The study, carried out in nine African countries, found that for every 41 children given artesunate instead of quinine, one extra life was saved. But because of the complexities of administering quinine, children in the trial who were assigned to receive quinine were almost four times more likely to die before even receiving treatment.

Artesunate has been recommended to be given to adults since 2005. Despite this, many African countries still use quinine. Research on its efficacy in children has lagged because of the difficulties of obtaining ethical approval for clinical trials on children and because of less interest globally in issues relating to children’s health.

MSF provided malaria treatment to about one million people in 2010. “When children arrive at the clinic with severe malaria, they often are having convulsions, vomiting or are at risk of going into shock and you just want to be able to give them effective treatment quickly,” said Veronique de Clerck, the medical coordinator for MSF in Uganda. “For decades quinine has been used in severe malaria but it can be both difficult to use and dangerous, so it’s time to bid it farewell.”

But, according to Dr Tom Ellman, the director of MSF South Africa’s medical unit, there are issues beyond the need to finance the switch that could delay the implementation of the switch from quinine to artesunate.

First, although doctors know the dangers of quinine when used incorrectly, such as hyperarithmia, quinine-induced comas and fatally low bloodsugar levels, physicians often mask these dangers by ascribing the cause of death to severe malaria.

Ellman said policymakers and health planners could also be reluctant to stop using quinine because there are large stockpiles of the drug owing to its long shelf-life. Quinine is also often produced locally in African countries where it is most used, whereas artesunate is produced mainly in China and South America. But Ellman said this should not be an obstacle to switching drugs because African countries can be involved in the production of artesunate.

MSF has changed its guidelines for the malaria projects where it works and has found that the greatest barrier to implementing the switch is if artesunate is not in the national protocols or registered in the country.

Dr Martin De Smet, who coordinates MSF’s malaria work, said: “We’ve been here before – when WHO changed its treatment recommendations for simple malaria in 2001 it took years for countries to make the switch and, shockingly, in some countries the far inferior drugs are still being used 10 years on,” he said. “With severe malaria, WHO needs to make sure that the change is much less sluggish, so lives can be saved immediately. There’s simply no excuse not to make the switch now.”

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