China’s first Nobel Prize for physiology or medicine was 419 years in the making. Tu Youyou, an 85 year-old chemist, won last year’s prize for her work in the 1970s developing artemisinin as a malaria treatment.

She had been alerted to the potential of artemisinin — an extract from the sweet wormwood plant — after scouring Chinese literature in search of traditional herbal remedies for the disease.

Records of sweet wormwood, or Artemisia annua, being used against malaria date back to at least 1596, when Li Shizhen, a Chinese medical scholar, suggested that it be given to patients as a tea.

It is still one of the main weapons in the world’s armoury against the disease. Treatment courses of artemisinin-based combination therapies increased from 11m in 2005 to 392m in 2013 as global health authorities put the drug at the centre of their fight against the mosquito-borne scourge.

Concern is growing, however, that four centuries after artemisinin’s first use, the parasites responsible for malaria may be starting to get the better of its ancient powers. Artemisinin-resistant strains were first detected eight years ago in western Cambodia. Cases have since been detected in Myanmar, Thailand, Vietnam and Laos.

For global health leaders, the pattern is alarmingly similar to the way resistance to chloroquine, another malaria treatment, emerged in Southeast Asia in the 1950s and spread to Africa — where the large majority of cases occur.

“We see a little bit of history repeating itself,” says Thierry Diagana, head of the Novartis Institute for Tropical Diseases. “Artemisinin resistance has spread as far as the western border of Thailand and Cambodia. If it crosses into India it will become a much bigger challenge.”

Novartis, the Swiss pharmaceuticals group, commercialised artemisinin combination therapy in the 1990s. The group is among the leaders in the hunt for new drugs to replace artemisinin as its efficacy fades.

In 2014, the Novartis unit led by Dr Diagana demonstrated the first clinical proof-of-concept — a clinical trial showing that a drug works — for a new malaria treatment. The compound, codenamed KAE 609, works by interfering with the sodium concentration in both of the two parasites that cause the majority of cases. Plasmodium vivax is common in Asia and South America, while the more virulent Plasmodium falciparum is most prevalent in Africa. Importantly, KAE 609 also worked in people with artemisinin-resistant strains in Southeast Asia.

Proof-of-concept data are expected soon on a second Novartis compound, known as KAF 156. It has shown promise against drug-resistant strains of both parasites as well as a further unique advantage. Unlike artemisinin-based therapies, KAF 156 acts against the parasites while still in the asymptomatic “liver stage” of the disease, before it has spread into the blood stream.

This would enable it not only to treat sufferers at malaria’s earliest stage — the disease can remain dormant in the liver for months after infection — but also prevent them passing on the parasite to mosquitoes for further transmission.

The positive early data must be replicated in larger studies if KAE 609 and KAF 156 are to satisfy regulators. Dr Diagana says Novartis aims to have at least one of them on the market by 2021.

The Novartis compounds are among the most promising of over 50 antimalarial products being developed in partnership with the Medicines for Malaria Venture (MMV). Donors including the Bill & Melinda Gates Foundation, the UK Department for International Development and the Wellcome Trust have pledged $865m to the non-profit organisation since it was set up in 1999.

However, that is small compared with the billions of dollars invested by the pharmaceuticals industry in more commercially attractive disease areas such as cancer, and progress is slow. It typically takes about 10 years to get a new drug from early stage development to market and less than 10 per cent of candidates make it all the way.

The MMV is not relying solely on big pharmaceuticals groups. It has also awarded research grants for academics to pursue assets from its so-called Malaria Box of compounds that have shown potential against the disease but have lacked funding for development.

Back in China, last year’s Nobel Prize for Ms Tu — she is neither a doctor nor professor — has stirred pride but also surprise that she received little previous recognition in her own country. The official Xinhua news agency said that the four-decade gap between her discovery and the award showed that “science is never about instant success.”

The spread of artemisinin-resistant malaria is adding urgency to the search for a fresh generation of drugs. In her Nobel lecture in Stockholm in December, Ms Tu issued a “severe warning” over the looming threat to the drug she helped discover.

Dr Diagana says that Novartis and its partners are moving as fast as possible. “It’s a good time for malaria drug discovery,” he says. “But we need to make progress quickly so we can avoid another global failure like we had with chloroquine.”