CAMBODIA: Malaria becoming deadlier

PAILIN, 13 January 2009 (IRIN) - A deadly strain of malaria along the Thai-Cambodian border is becoming increasingly immune to treatment, threatening the global effort to end malaria, new evidence shows.

Artemisinin combination therapy (ACT), whereby patients take both a fast-acting and slow-acting drug to kill the parasite, is losing its therapeutic effects as treatment is taking longer.

"We are facing a problem that instead of killing the parasite within 24 to 36 hours as before, ACT now needs up to 120 hours to kill the parasites," Pascal Ringwald, a medical officer at the World Health Organization (WHO), in charge of monitoring anti-malarial drug resistance, told IRIN from Geneva.

The parasite's resistance to Artemisinin, one of two drugs in ACT therapy, is the driving factor behind the deterioration of ACT.

Usually, doctors will prescribe Artemisinin with one of many slower-acting drugs.

Yet the problem is not only resistance to Artemisinin, which has existed since the 1970s, but rather tolerance to ACT, the more advanced therapy consisting of two drugs, Ringwald said. Artemisinin monotherapy refers to taking the drug alone and is not recommended by the WHO.

"Artemisinin resistance appears in parts of Southeast Asia where there has been rampant and uncontrolled use of Artemisinin monotherapy," Sir Richard Feachem, director of the Global Health Group at the University of California at San Francisco, told IRIN.

At one-tenth the price of ACT and without its adverse side-effects, such as vomiting, Artemisinin monotherapy continues to remain a popular choice for many.

However, if the threat is not contained, resistant malaria will spread through the region and hit poor communities in particular, Feachem warned.

Duong Socheat, director of the National Centre for Parasitology, Entomology and Malaria Control in Phnom Penh, told IRIN that ACTs, outreach and prevention tools like mosquito nets had seen remarkable progress despite a tolerance threat. A total of 100,000 malaria cases were reported in 2006, falling to 59,000 in 2007 and 54,000 in 2008.

The malaria death rate has been halved in only two years – from 396 in 2006 to 241 in 2007 and 184 in 2008.

Containing the threat

At an emergency meeting in October, the WHO recommended a switch to a new ACT therapy called dihydroartemisinin–piperaquine (DHA-PIP) for 2009, which is virtually 100 percent effective according to new trial results in Cambodia.

The previous ACT treatment since 2001, artesunate mefloquine, is still 90 percent effective, but unpopular among at-risk populations that still use monotherapy despite the ban.

Merchants often sell cheap, counterfeit monotherapies in rural areas.

The WHO also recommended wider distribution of mosquito nets, stricter enforcement of the ban on monotherapies, and the rapid deployment of WHO-endorsed drugs.

Drug-resistant history

Yet malaria has been developing resistance to Artemisinin for decades, and ACT tolerance is only a new phase in the parasite's evolution.

Since the 1970s, factors such as gem-mining migrants from all over Southeast Asia mixing malaria strains at the Thai-Cambodia border, an unregulated drug market, and overuse of Artemisinin monotherapy have all caused plasmodium falciparum, a common malaria parasite in Cambodia, to develop resistance to the drug.

The government and WHO responded by endorsing ACT in 2001 and banning Artemisinin-only therapy. But even ACT, despite being more than 90 percent effective against malaria, will need to be adapted soon, Feachem said.

"Ensuring that Artemisinin is always given with another drug, in the form of ACT, is a clever use of a clever drug," Feachem said. "However, parasite resistance will eventually catch up with this, and for this reason the development of new drugs ... is of the utmost importance to the health of people worldwide."

Fake drugs and patients not complying with their treatment schedules are other factors.

"If people don't take their drugs regularly, then they will have problems with resistance," Hou Nirmita, head of the health department at the Ministry of Women's Affairs, told IRIN.

But Feachem, who thinks malaria could be eradicated worldwide by 2050, sees hope. "The challenge of drug resistance, and the fact that we can never prevent the development of resistance in the long term, provides a strong argument for the acceleration of elimination and control efforts now," he said.

"To delay or to implement programmes in a half-hearted manner is both expensive and dangerous,” he explained.

According to the WHO World Malaria report for 2008, half the world's population is at risk, and an estimated 247 million cases led to nearly one million deaths in 2006. Pregnant women and children in Africa are especially threatened, the WHO says.