Multidrug-resistant malaria spread under the radar for years in Cambodia

February 2, 2018, Wellcome Trust Sanger Institute
Credit: CC0 Public Domain

The most comprehensive genetic study of malaria parasites in Southeast Asia has shown that resistance to antimalarial drugs was under-reported for years in Cambodia. Researchers from the Wellcome Sanger Institute and their collaborators have shown that the parasites developed multidrug resistance to first-line treatments extremely rapidly. They found that one main resistant strain had spread aggressively in the five years before clinical resistance was reported. Delays in detecting the spread of resistance could threaten global efforts to eliminate malaria.

Reported in The Lancet Infectious Diseases, the study suggests that ongoing genomic surveillance is vital to monitor the spread of resistance, to inform public health control strategies.

Malaria is caused by Plasmodium and the World Health Organisation estimated that more than 200 million people were infected and nearly half a million people died worldwide from the disease in 2016*. Children under the age of five are most at risk. Malaria is a treatable disease when caught early enough, but is a huge problem in many areas due to .

The first-line for malaria in many areas of the world is a combination of two powerful antimalarial drugs - dihydroartemisinin and piperaquine - otherwise known as DHA-PPQ treatment. Introduced into Cambodia in 2008, this treatment was initially effective, but in 2013, clinical trials showed that the malaria parasites were resistant to both drugs. Subsequent studies have reported that resistance has since spread to Thailand, Laos and Vietnam.

To help understand future consequences and risks, an accurate picture of the initial emergence and spread of the malaria resistance was needed. Researchers analysed DNA sequence data from nearly 1500 Plasmodium falciparum parasites from Southeast Asia, including more than 450 collected in Cambodia between 2007 and 2013. This allowed them to look back in time to see how the malaria parasites treated with DHA-PPQ evolved resistance.

The genetic study revealed that in the very same year that DHA-PPQ became the official first-line antimalarial treatment in Cambodia, a single multidrug resistant strain of Plasmodium parasite emerged. The researchers found this strain then spread aggressively, outcompeting all the other resistant malaria parasites and leading to complete failure of treatment in Cambodia. Other drugs may be effective at the moment but the situation is extremely fragile.

These findings have significant implications for management of the global health risk associated with the current malaria outbreak.

Dr Roberto Amato, first author on the paper from the Wellcome Sanger Institute, said: "Our study has provided the most comprehensive analysis by far of the parasites responsible for the outbreak of drug resistant malaria in Cambodia. It reveals that resistance to the combination therapy appeared almost as soon as that treatment was introduced as the official first line therapy and that it spread steadily and aggressively after that. Various factors allowed the extent of this outbreak to stay under the radar for years, but we show it is now possible to use modern genomic technologies to get a full picture of an outbreak."

Drug resistance is spreading across parts of Southeast Asia and experts are unclear how the malaria parasites will respond to current malaria treatments.

Professor Mike Turner, Head of Infections and Immunobiology at Wellcome, said: "This study confirms earlier observations that a strain of malaria, resistant to our most effective drugs, has emerged in the Greater Mekong Subregion. If this parasite strain keeps spreading and becomes dominant further afield it could devastate vulnerable populations globally.

"It is surprising to see that the parasites developed resistance so rapidly. Coordinated actions by governments and organisations to control and eliminate this parasite population are urgently needed. Real-time genetic sequencing would allow regional malaria control programmes to respond immediately to evolutionary changes in the parasite population."

Dominic Kwiatkowski, a corresponding author on the paper from the Wellcome Sanger Institute and the University of Oxford, said: "Our study shows that modern genomic surveillance can detect patterns of resistance much sooner than was possible in the past, providing vital information and allowing public health officials to respond as soon as possible. There is now an urgent need to provide national malaria control programmes with the tools for active genomic surveillance that will help to detect new emergences of as soon as they arise and thereby reduce the risk of a major global outbreak."

Explore further: Two genetic markers that predict malaria treatment failure found

More information: Roberto Amato et al, Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study, The Lancet Infectious Diseases (2018). DOI: 10.1016/S1473-3099(18)30068-9

*Figures from the 2017 World Health Organisation report www.who.int/malaria/publicatio … aria-report-2017/en/

Related Stories

Two genetic markers that predict malaria treatment failure found

November 3, 2016
Scientists at the Wellcome Trust Sanger Institute and their collaborators have discovered genetic markers in malaria parasites linked with resistance to the anti-malarial drug piperaquine. Reported in Lancet Infectious Diseases, ...

Superbug's spread to Vietnam threatens malaria control

September 21, 2017
A highly drug resistant malaria 'superbug' from western Cambodia is now present in southern Vietnam, leading to alarming failure rates for dihydroartemisinin (DHA)-piperaquine—Vietnam's national first-line malaria treatment, ...

Experts discover ways to tackle drug resistant parasites that cause the killer disease malaria

December 11, 2017
A new analysis of all relevant previously published clinical data shows how parasites causing malaria become resistant to a commonly used treatment for malaria in travelers.

Malaria superbugs threaten global malaria control

February 1, 2017
A lineage of multidrug resistant P. falciparum malaria superbugs has widely spread and is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for the main falciparum malaria medicines, ...

Researchers identify genetic marker of resistance to key malaria drug

December 18, 2013
An international team of researchers has discovered a way to identify, at a molecular level, malaria-causing Plasmodium falciparum parasites that are resistant to artemisinin, the key drug for treating this disease. The research ...

Recommended for you

Dengue: Investigating antibodies to identify at-risk individuals

May 23, 2018
Using an original mathematical and statistical analysis method, a team of scientists from the Institut Pasteur partnered with researchers from the United States and Thailand to analyze a Thai cohort that has long been a focus ...

Fatty liver disease research set to benefit from stem cell advance

May 23, 2018
Scientists have developed a lab-based system for studying the most common type of liver disease, paving the way for research into new therapies.

More frequent checks control MRSA in newborns, but can hospitals afford them?

May 22, 2018
The more often a hospital can check its newborns for deadly MRSA germs, the more likely it will be that they are contained, according to a new study.

Could we predict the next Ebola outbreak by tracking the migratory patterns of bats?

May 22, 2018
Javier Buceta, associate professor of bioengineering, Paolo Bocchini, associate professor of civil and environmental engineering, and postdoctoral student Graziano Fiorillo of Lehigh University have created a modeling framework ...

Helping preterm infants grow bigger kidneys would prevent kidney disease later in life

May 21, 2018
Nephrons are the microscopic blood-filtering units inside our kidneys that convert waste products into urine, regulate our electrolyte levels and our blood pressure.

Kidney docs worry over no dialysis for undocumented immigrants

May 21, 2018
(HealthDay)—Undocumented immigrants in the United States are often denied treatment for kidney failure until they have a life-threatening emergency. Now a new study finds that the doctors and nurses who treat them are frustrated ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.