Mosquitoes Have Developed Resistance to Every One of Our Malaria-Fighting Tools

Malaria's Last Stand is an expository look at the ongoing burden of one of humanity's oldest diseases. Staff writer Kaleigh Rogers travelled to Tanzania to capture the scope of malaria's impact on the road to elimination. Read more here.

Arusha, Tanzania

Over the last decade and a half, malaria rates globally have plummeted. In 2000, 839,000 people around the world died from malaria, according to the World Health Organization. In 2015, 438,000 did.

This reduction was achieved for the most part through a concerted global aid effort that focused on simple solutions with widespread distribution. Insecticide-treated bednets (ITNs) were handed out to expectant mothers and school kids to protect families from hungry mosquitoes while they slept. Homes were sprayed with long-lasting insecticide to kill the insects after a blood feed, before they can spread the parasite. Artemisinin combination therapy—the gold standard in antimalarial drugs—was made more widely available, subsidized to be more affordable or free.

Studies tracking these efforts have shown a direct link between interventions like distributing ITNs and the drop in malaria rates. At first glance, it all seems remarkably hopeful: this is working. If we just keep doing what we're doing, we should be able to wipe out malaria completely, right?

Unfortunately, for every study showing the efficacy of these interventions, there's another study showing something much less optimistic: All of our best strategies for fighting malaria are at risk of failing. The malaria parasite and mosquitoes have started to develop resistance to ITNs, indoor insecticides, and Artemisinin combination therapy. Though not widespread yet, this developing resistance threatens to render each of our most effective malaria-stopping technologies useless.

"There's an ethical issue there," said Sonia Shah, a science journalist and author of The Fever: How Malaria Has Ruled Humankind for 500,000 Years. "You have a disease and you have some means of controlling it to some degree, so what do you do? You have to do something. But all of the short term interventions are highly problematic."

With no major contenders in the pipeline to replace these standbys, we're teetering on a very real precipice. What's worse, history has taught us that forcing malaria rates down and then losing the tools to fight it mean the disease will surge back and be stronger than ever. If new solutions aren't found in time and current efforts aren't rolled out very strategically, we risk losing all the ground we've made toward eliminating malaria.

For the past few decades, ITNs have proven to be cost-effective, safe, and efficacious, but one of the major design flaws has remained consistent: there's only one kind of insecticide that can be used to make ITNs. Pyrethroids are approved for ITNs because they're both non-toxic to humans and they last long without breaking down. Unfortunately, the uniformity of insecticide distribution increases the risk of resistance.

Mosquito resistance to pyrethroids has been confirmed across sub-Saharan Africa, in India, and in parts of South America. In every malaria-endemic area, at least some pyrethroid resistance has been detected, and in some areas certain pyrethroids are barely effective at all. One study in Burkina Faso found that two commonly used pyrethroids were only 1 percent to 6 percent effective against local mosquitoes. What's more alarming, this study also showed the resistance significantly reduced the efficacy of the ITNs.

"As far as pyrethroid resistance in the nets, we are having bad news on that," said Dr. Sigsbert Mkude, the team leader for the Tanzanian Ministry of Health's National Malaria Control Program. "We are seeing this much faster than we expected."

At the Ministry of Health Office in Dar es Salaam, Mkude told me that other interventions like indoor spraying have helped mitigate some of the resistance to the nets. Unlike ITNs, there are a few different insecticides that are suitable to spray indoors, so when resistance starts to emerge to one type of insecticide in a particular area, a different one is swapped in. Unfortunately, making these swaps is slow, and costly, and doesn't guarantee it will solve the problem.

Like ITNs, resistance to indoor residual spraying (IRS) is spreading, too, and though there are a few options, the list of different pesticides that can be used is pretty short, and it's not growing. Only 2 percent of the world's pesticides are developed for public health and only a quarter of those are used for IRS, according to Tanzania's National Institute for Medical Research. New products can take up to 15 years to get to market and since the need for new products is resistance, it's an additional challenge when looking for new products.

As the technology we've invested in to prevent people from getting malaria in the first place starts to fail, so too is the best cure we have for the disease. In the 1800s, we discovered quinine, and for a long time we used the harsh drug to knock out a malaria infection. In the 1930s, another antimalarial was discovered: chloroquine, and it quickly became the preferred medication. But by the 1950s, resistance had already started to develop to both drugs, and an alternative was sought. Thanks to ancient Chinese texts, a top secret assignment from Mao Zedong, and a team of tenacious scientists, a new antimalarial was found: artemisinin. It was a last-minute hail Mary that wound up becoming the gold standard in malaria cures: artemisinin control therapy, a cocktail of artemisinin-based drugs and other antimalarials, is used around the world. But the malaria parasites have started to develop a resistance to artemisinin, now, too.

Artemisinin resistance has been confirmed in five countries as of 2015, according to the WHO, all in Southeast Asia. And these mutations have been detected in Africa too, in small numbers.

To make matters worse, the very efforts used to try to prevent the spread of malaria have helped contribute to the risk of resistance. In many parts of sub-Saharan Africa, where malaria is common and considered a normal part of life, education campaigns were needed to convince locals to take preventative measures against the disease. But in some areas, these efforts were too successful. Public information campaigns now warn parents that "not every fever is malaria."

"A lot of the time, when people have a fever, they assume it's malaria," said Apolinary Mushi, a lab technician at the Ithna-Asheri Charitable Hospital in Arusha, Tanzania, while demonstrating how to do a rapid malaria blood test. Sometimes, even after a negative test, patients will argue with him, he said, convinced of their self-diagnosis. Mushi called it "psychological malaria."

Rather than going for a test at a distant health clinic, many people simply assume when their child has a fever that it's malaria, and go grab ACT from the local duka la dawa—unaccredited drug stores that sell prescriptions without tests and sometimes dole out counterfeit medication. The problem is that overuse of antimalarials, especially when they're not needed or you don't finish the prescription, increases the risk of resistance developing. Of all the threats, experts take this one the most seriously, because there are no alternative antimalarials in the pipeline. Most sub-Saharan African nations have surveillance programs to watch for signs of artemisinin resistance, and programs are in place to stop the resistant pathogens in Southeast Asia from quickly spreading around the globe.

The threat of resistance is serious, but it doesn't necessarily spell disaster. Close monitoring and strategic roll-out can make a huge difference in staving off resistance, and new technologies are being developed, like insecticide-treated wallpaper. There are also dozens of malaria vaccine candidates in development, and a focus on socio-economic development will go a long way toward eliminating the disease.

Mosquito and parasite resistance was always a known risk with each of these interventions. We've known since the beginning that these strategies would inevitably one day fail. But in the meantime, they've saved a lot of lives.

"Resistance must be regarded as an unavoidable threat whenever an insecticide is used widely, intensely, and for extended periods," the WHO predicted in a report back in 1996, when pyrethroid resistance was just beginning to emerge. "Some argue that, as a public-health tool, pyrethroid ITNs are doomed from the start. The same can be said of any antibiotic or anti-malarial drug, but no one would suggest that eventual resistance is a good reason not to use new drugs."

Travel expenses while reporting this series were funded through a fellowship provided by the International Center for Journalists and Malaria No More.