Scientists sound warning note over malaria drug resistance in Africa

Rwanda study raises fears erosion of efficacy may have begun, with children at greatest risk

Resistance to malaria drugs in Africa may be starting to take hold, according to a study that maps changes similar to those seen a decade ago when drug resistance spread in south-east Asia.

In Cambodia and neighbouring countries, the artemisinin drug compounds widely used against malaria are no longer always effective. The falciparum malaria parasites have developed genetic mutations that allow them to evade the drugs. There has been great concern that drug resistance could spread to Africa, which has the highest burden of cases of this type of malaria – and the highest toll of child deaths from it.

A study in Rwanda, published in the Lancet Infectious Diseases journal on Wednesday, shows that the feared erosion of efficacy of the malaria drugs may have begun. As happened in south-east Asia, researchers have found that giving a child a course of artemisinin compound drugs does not always clear the malaria parasites from their blood in three days, as it should.

Artemisinins, introduced in the early 2000s from China, are given in combination with a different type of malaria drug to ensure all parasites are cleared and the efficacy of the drugs is not compromised. The most common combination is artemether-lumefantrine, which Rwanda began to use in 2006.

If the artemisinin drug does not clear the parasites promptly within three days, the partner drug comes under pressure and resistance to it may develop in turn. At that point, the treatment may fail, as has happened in south-east Asia.

“Mutations can emerge spontaneously, and previous studies have pointed to isolated cases of resistance. However, our new study shows that resistant isolates are starting to become more common and most importantly, are associated with clinical implications [delayed parasite clearance],” said lead author Dr Aline Uwimana, from the Rwanda Biomedical Centre, in Kigali.

The experts called for more intensive surveillance of drug resistance in Rwanda and other African countries. “Our study showed that the treatment for malaria in Rwanda is still 94% effective, but new studies and ongoing monitoring are urgently needed,” said co-author Dr Naomi Lucchi, CDC resident adviser for the US President’s Malaria Initiative.

The researchers monitored the treatment of 224 children with malaria aged six months to five years in three areas of Rwanda – Masaka, Rukara and Bugarama. In two of the sites, about 15% of children still had detectable parasites after three days, fitting the World Health Organization (WHO) criteria for partial resistance.

The researchers also found certain mutations in the parasites, which are implicated by the WHO in delayed clearance.

Experts believe the warning signs are there. This study, and other data, suggest we are “on the verge of clinically meaningful artemisinin-resistance in Africa, as emerged in south-east Asia over a decade ago”, writes Prof Philip Rosenthal, of the University of California, San Francisco, in a commentary in the journal.

“Loss of efficacy of key ACTs [artemisinin-based combination therapies], particularly artemether-lumefantrine, the most widely used antimalarial, could have dire consequences, as occurred when chloroquine resistance led to enormous increases in malaria deaths in the late 20th century.”

It was impossible to predict the pace of progression in Africa, but close surveillance of the development of resistance in the parasite – with prompt replacement of failing regimens – “could save many lives”, he said.

Contributor

Sarah Boseley, health correspondent

The GuardianTramp

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