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Malaria refuses to disappear

The number of cases has declined worldwide, but now resistance to drugs threatens to reverse these gains. We visited Southeast Asia to understand its magnitude.
25 Abr 2016 – 02:03 PM EDT
Malaria is transmitted by the female Anopheles mosquito (which bite at dusk and at night). Crédito: Eulimar Núñez

It is not Ebola or Zika and today does not generate as much alarm. Even so, malaria is a serious infectious disease that is both preventable and treatable, and caused 438,000 deaths in 2015 alone, according to estimates by the World Health Organization. Of these, 395,000 occurred in sub-Saharan Africa. The majority of those victims were children under 5 year old.

The global incidence of malaria, which is transmitted by the female Anopheles mosquito, has shrunk since 2000 from 262,000 cases to an estimated 214,000 last year.

The reduction is attributed to the distribution of free mosquito nets, the development of rapid diagnostic tests and the use of effective drugs, in this case the Artemisinin-based Combination Therapy (ACT, for its acronym in English), who have spent years being the more effective.

But now the problem of drug resistance has returned. Reports indicate that in recent years artemisinin has ceased to be effective in several locations in the Greater Mekong, a region spanning six countries: Cambodia (place with more resistance), Laos, Burma, Thailand, Vietnam and Yunnan Province in China. Parasites with genes that challenge anti-malaria drugs have shown up in this area of Southeast Asia: not once, not twice, but three times.

This is where the resistance problems began, limiting global efforts to control the disease: from one day to the next drugs stopped working. When patients are not cured completely, the disease returns and increases transmission (a mosquito bites an infected person and restarts the chain of contagion). Resistance is measured by blood tests to check for the presence of the parasite. Death occurs if the parasite reaches the brain.

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" The resistance of the malaria parasite to existing treatments is probably the largest public health threat over the next 10 years," said Professor Francois Nosten, founder and president of SMRU ( Shoklo Malaria Research Unit) a recognized expert with more than 30 years of experience in the fight against the disease.

Nosten recalls that on his arrival in Thailand quinine was being used (it is not easy to digest, nor easy to use); then came metoquina, developed by the U.S. military during the Vietnam War. "We started using it and saw how after five years we saw resistance beginning to develop. It was not until 1991 that we started using artemisinin. Our concern is that history is repeating itself."

Professor Arjen Dondorp, deputy director of the Unit Mahidol-Oxford Research (MORU) who heads the studies conducted in Bangkok, the Thai capital, understands the urgency: " If we want to eliminate malaria, we must do it now and aggressively," he said.

The goal: to beat resistance

"Resistance always arises in areas of low transmission (such as the Greater Mekong)" Dondorp explains. There are several theories that explain this phenomenon, he says, although none is definitive: fake or poor quality drugs, and lack of acquired immunity. Many patients discontinue treatment due to cost and lack of time.

Although malaria is also present in other regions like Latin America - the WHO reports that there are 112 million people in 21 countries and territories at risk of contracting malaria and 20 million of them at high risk - resistance has been observed only in Asia.

" We're not seeing resistance elsewhere in the world," says Dondorp. "In Africa, transmission is much higher, it is primarily a disease of children, as adults develop immunity. But we know that resistance usually starts in areas of low transmission."

A major concern for Nosten is that resistance could spread to Burma and Bangladesh, then possibly reaching Africa. " We know what the consequences would be: millions of people dying. My main goal right now is to get it right before it is too late. We have failed to communicate this to the world. The message has not reached those responsible for making decisions."

"If you show people dying of Ebola that generates alarm; but malaria is different. Currently few people are dying in this area, only a few cases are being registered. So people think why should we care? Well, the disease is progressing even though we cannot see it. If we do not act cases will emerge, and when that happens the consequences will be catastrophic in places like Africa."

"We do not have time. This is a race against the parasite. If not overcome, there is a possibility that it will become resistant to all the drugs we have. We must do until this window is closed and before resistance reaches Africa," said the renowned professor Francois Nosten.

So, the only way to attack the resistance is to eliminate malaria altogether. That's another challenge: win the trust of the people to accept taking a treatment that eliminates the parasite even though they have no symptoms of the disease. SMRU, for example, sends special teams to inaccessible areas to take and analyze blood samples.

However, giving drugs to a whole community is a much debated measure, as it can help to develop resistance.

Currently Thailand is able to measure and identify the communities that still have malaria: almost all are located on the borders, so officials from different governments have chosen to dismiss the threat. If they see cases down, they stop investing, rather than continuing eradication efforts.

In Dondorp’s view, this attitude is replicated in the rest of the pharmaceutical community. "Novartis has a philanthropic unit in Singapore working on new drugs to treat the disease, but generally the big pharmaceutical companies are not interested in malaria.”

There are five types of parasites that infect humans: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. Of these, P. falciparum and P. vivax (which predominates in Latin America and Southeast Asia, and is more difficult to eradicate) are the most common. However, falciparum is the most dangerous as it is lethal.

To Nosten, the World Health Organization should understand that it is a problem that cannot be resolved through meetings and reports. "We are now in a race against the parasite and despite all the disappointments, we think we know what we need to do. We believe that it must be eradicated as quickly as we can, before it returns. It is difficult and is not cheap, but we know it is possible."

The example of Southeast Asia

When Nosten began working in the Thai town of Mae Sot over 20 years ago, malaria was the leading cause of death and disease in the area. "It’s not any longer and that is the result of a powerful combining of investigation with the provision of health services, while learning about the early symptoms and applying the solution as soon as possible," he explains.

The SMRU clinic, located a few steps from a river that divides Thailand from Burma, is proof that the number of malaria patients in Southeast Asia has been reduced significantly, as cases of the disease are now rare, and most patients who arrive are either pregnant women or seeking some other treatment for fever, aches and pains, but not malaria.

In the same clinic in 2004, 90% of cases were malaria. Now only 1 or 2% are malaria, according to Aung Pyae Phiu: a Burmese doctor working in the health center for five years who specializes in tropical diseases.

"We know that in the area (on the border between Thailand and Burma) there is drug resistance. More than 85% of malaria cases in 2013 and 2014 were resistant to artemisinin. Although still used, it is known that the response is slower," explains Dr. Aung Pyae Phiu.

At this center they have also been monitoring resistance. In 2004 less than 10% of patients tested positive for the parasite on the third day of treatment. By 2013, 45% of cases showed the parasite was still present three days later, confirming that the problem is increasing and posing a challenge to plans to eradication the disease by 2040.

"There has been no death from malaria since 2010, yet it used to be the number one cause of death. We have fewer cases of malaria than ever. And we know that those left are very difficult to treat," said Dr Aung Pyae Phiu.

This report, conducted from Thailand and Cambodia, is the result of a press fellowship from the International Center for Journalists (ICFJ) and Malaria No More.