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A technician at the Osvaldo Cruz Institute's laboratory in Rio de Janeiro, Brazil works in the preparation of ASMQ antimalaric drug capsules in 2008. AFP
A technician at the Osvaldo Cruz Institute's laboratory in Rio de Janeiro, Brazil works in the preparation of ASMQ antimalarial drug capsules in 2008. AFP

Cautious optimism as malaria drug cocktail makes a comeback

Amid mounting international concern over the emergence of drug-resistant malaria in the Kingdom’s western provinces, a drug cocktail discontinued in 2008 has been reintroduced to stunning success – though how long that success can be sustained is uncertain.

At the end of 2015, failure rates of Dihydroartemisinin-piperaquine (DHA-PIP) surpassed 60 per cent in Siem Reap and 30 to 40 per cent in Oddar Meanchey, Stung Treng and Battambang provinces, according to Dr Luciano Tuseo, the Malaria program director for the World Health Organization in Cambodia.

“Further increase in multi-drug resistance including artemisinin resistance could lead to the resurgence of malaria not only in Cambodia” but in other countries as well, a “dire” threat that was emphasised at the launch of the Ministry of Health’s new malaria elimination plan, which warned that “no alternative” was available with the same efficacy.

Enter Artesunate Mefloquine (ASMQ), a drug combination that was deployed by the National Center for Malaria – with WHO financing and supervision – from December 2015 through January across three “sentinel” sites in Pursat, Siem Reap and Kratie provinces to test its efficacy. Thus far, it’s been incredibly effective.

“Therapeutics Efficacy Studies show 100% efficacy of ASMQ in Cambodia,” Tuseo wrote in an email yesterday.

According to Tuseo, the new therapy will need to be deployed in 10 provinces where resistance has been detected and where proper supervision and oversight is already in place.

“The stock of ASMQ available in the country exceeds 2 years,” he wrote. But with malaria parasites in Cambodia developing resistance in shorter and shorter time frames, just how long it can remain effective remains an open question.

“Cambodia is quite a special case, we don’t know why the most resistant strains are in Cambodia,” said Dr Didier Menard, head of the Molecular Epidemiology Unit at the Institut Pasteur in Phnom Penh during a phone interview yesterday.

“One hypothesis is that Cambodia . . . [is] where we are using the last generation of drugs,” which puts selective pressure for malaria to develop resistance. “The parasites want one thing, to survive,” he said.

What’s more, the closer to eliminating malaria one gets, the harder the parasite fights back.

“The last parasite in Cambodia will be the strongest; it will be the most resistant in the world,” he said.

Menard explained that in the 1990’s, mefloquine was the drug of choice until resistance emerged, so after 2001, ASMQ was used. However, ASMQ began to fail around 2007, so DHA-PIP was introduced in 2008 in Pailin and then nationwide in 2010.

So why go back to ASMQ?

“We have some clues showing that – it’s the good news – if the parasite is able to resist piperaquine [part of DHA-PIP], it becomes sensitive to mefloquine”, and vice-versa, Menard said.

However, “ASMQ is really, really a short-term option, we have to have new combinations, new strategies, new drugs if we want to eliminate malaria in Cambodia.”

Luckily, there are options such as using multiple treatments in one area – a “mosaic” approach – as well as using triple rather than the conventional double combination drug cocktails, according to Menard.

The WHO is also bringing something to the table, according to Tuseo.

“A new [combination] proposed by WHO will be tested this year.”

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