Complete cure

The story of malaria control is the story of the promise — and peril — of wonder drugs. With hundreds of millions of people infected with malaria around the globe every year, effective treatment may be the difference between ending the disease and humanitarian disaster.

Quinine, the first anti-malarial, was discovered in the bark of the cinchona tree in the foothills of the Andes Mountains in the 1600s. But it was hard to produce and administer, and by World War I, there still was no reliable global supply.

Finding a cheap, reliable alternative to quinine that could be mass-produced became a military imperative during World War II. The United States suffered humiliating defeats “not because the ammunition was gone,” The New York Times reported then, “but because the quinine tablets gave out.”

However, the synthetic drugs that emerged from that furious research and development effort — most notably chloroquine — were little match for the fast-evolving parasite, which developed resistance in under a decade.

Progress threatened

Our current front-line treatments for malaria, called artemisinin-based combination therapies, underscore the arms race between science and parasite. ACTs have been wildly successful in saving lives — a true wonder drug by any definition — but their effectiveness may also be cut short by resistance.

First touted for its curative powers in an ancient Chinese medical book dating back to 168 B.C., artemisinin was finally brought to scale globally by Swiss healthcare company Novartis, which received WHO international approval for its drug in 1999. Global funders threw their weight behind ACTs five years later, and today more than 280 million ACT treatments are distributed every year in Africa alone.

But resistance is once again threatening to rob us of our best tool in the malaria fight. Just as chloroquine resistance emerged along the Thailand-Cambodia border in the 1960s, first signs of artemisinin resistance have now been documented in the region. If it follows the same pattern as past resistance — emerging across Asia, in India, then making the leap to Africa — it could potentially cost millions of lives.

History has shown that containment isn’t an option. Only by eliminating malaria in Asia-Pacific can we staunch the spread of resistance. So the Greater Mekong sub-region will be ground zero for a renewed global eradication effort.

In search of a solution

The race is already on to develop the next generation of wonder drugs — this time tailor-made for eradication. Such a drug would have four key features:

1. Single-dose treatment. The pharmaceutical industry talks about the “pill burden” — the total number of pills someone has to take to complete a full course of treatment. The more pills, over more days, the greater the chance that a patient will stop midway and fail to be fully cured. Malaria treatment currently requires between three and 14 days of treatment, depending on the strain of the parasite. Getting people to take all their pills is complicated by the fact that the drugs are so fast-acting and effective that malaria symptoms may subside after the first or second day, leading people to think they’ve been treated, when in fact trace amounts of the parasite may still be hanging around in their bodies waiting to mount another attack. A single dose treatment would ensure that everyone who is treated is parasite-free.

2. A “complete cure.” Malaria is so challenging in part because the parasite plays hide and seek in the human body: traveling in the bloodstream, lodging in the liver, the brain — even bone marrow, as a recent study highlighted. Before you can hope to eliminate malaria in a community of people, you must be able to effectively eliminate it in a single person. A complete cure treatment would wipe out the parasite at every stage of its life cycle, ensuring zero risk of passing the parasite along to others.

3. Prophylactic effect. Essentially, you want a drug that will remain in the body for a period of time to prevent a person from developing another case of malaria if bitten again by an infected mosquito.

4. High barrier to resistance. Even as you scale up use, it’s able to maintain its effectiveness. This means developing an arsenal of molecules that attack the parasite in novel ways, and then using drugs in combination to stave off resistance. New malaria drugs are a great investment, but they’re expensive to develop, so we must ensure they last.

In the pipeline

The good news is we’re well on our way to making a new slate of wonder drugs (or “one-der” drugs) a reality. Supported by a product development partnership called Medicines for Malaria Venture out of Geneva, the malaria community and pharmaceutical industry leaders including Novartis, Sanofi, and GlaxoSmithKline have started clinical trials for treatments that will make ending malaria a reality.

As one example, Novartis has fast-tracked its first non-artemisinin-based single-dose drug candidate, called KAE609, and recently published results showing that it was able to clear malaria parasites in adults in 12 hours on average. Read more about the quest for a malaria wonder drug here.

This article is part of a new series entitled Solve for M: 5 Key Challenges to Ending Malaria, hosted by Devex in partnership Malaria No More and the Bill & Melinda Gates Foundation.

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