Two genetic markers that predict malaria treatment failure found

November 3, 2016
Credit: CDC

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, this research will allow health officials to monitor the spread of resistance, and help doctors and public health officers decide where the treatment is most likely to be effective.

Resistance to this key anti-malarial drug has recently emerged in Cambodia, leading to complete treatment failure there, threatening global efforts to treat and eliminate malaria.

Malaria is caused by Plasmodium parasites and in 2015, the World Health Organisation estimated that more than 200 million people were infected and nearly half a million people died worldwide from the disease. Children under the age of five made up 70 percent of these deaths. Malaria is a treatable disease when caught early enough, but is a huge problem in many areas due to drug .

Piperaquine is a powerful drug, which is used in combination with another anti-malarial, artemisinin, as a first-line treatment in many areas of the world. Resistance to artemisinin emerged more than seven years ago in South East Asia, but until recently the combination of the drugs still successfully killed the malaria parasites there. Now, the development of piperaquine resistance has led to complete failure of treatment in Cambodia.

Researchers carried out a genome-wide association study on approximately 300 Plasmodium falciparum samples from Cambodia to study the genetic basis behind piperaquine resistance. They looked at thousands of variations in the DNA sequence of the parasites, comparing these across samples with different levels of resistance to piperaquine.

Dr Roberto Amato, lead author from the Sanger Institute, said: "By studying the genomes of these parasites we found two that are linked with piperaquine resistance. Not only can we now use these markers to monitor the spread of the drug resistant malaria, they will also help towards understanding as much as possible about the biology and evolution of the parasite."

The scientists found that extra copies of the genes encoding two proteins of a family called plasmepsin, were linked with piperaquine resistance. Plasmepsins are part of a biological pathway that is targeted by other anti-malarial drugs, so this marker could also help the researchers understand the mechanism of the . In addition to this, a mutation on chromosome 13 was found to be a second genetic marker linked with the resistance. Both markers were observed in parasites infecting patients who were not responding to treatment.

Dr Amato added: "The emergence of piperaquine resistance in these Cambodian parasites has led to complete treatment failure there. These malaria parasites are now resistant to both drugs, and since they are no longer being killed, resistance to both drugs will spread. This will threaten global attempts to eliminate malaria."

Professor Dominic Kwiatkowski, from the Sanger Institute said: "These findings provide the tools needed to map how far this resistance has spread, looking for these molecular markers in parasites in Cambodia and neighbouring countries. This will allow national malaria control programmes to rapidly recommend alternative therapies where possible and where needed, enhancing treatment for patients, and helping towards the ultimate goal of eliminating malaria."

Explore further: Current malaria treatment fails in Cambodia due to drug-resistant parasites

More information: R Amato et al. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study, Lancet Infectious Diseases DOI: 10.1016/S1473-3099(16)30409-1 (2016).

Related Stories

Current malaria treatment fails in Cambodia due to drug-resistant parasites

January 7, 2016
New findings from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), confirm dihydroartemisinin-piperaquine, the first-line treatment for Plasmodium falciparum ...

Drug-resistant malaria strain contained in Asia: scientists

June 23, 2016
A parasite resistant to the top anti-malaria drug is confined to Southeast Asia and has not yet spread to sub-Saharan Africa as feared, said researchers Wednesday.

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 ...

Malaria—a mapping of artemisinin resistance confirms that resistance is confined to Asia

June 23, 2016
The first global mapping of artemisinin resistance (the KARMA study) has definitively confirmed that resistance to the main drug currently used in the treatment of Plasmodium falciparum malaria is for the moment confined ...

Increasing malarial drug resistance a growing threat

July 31, 2014
(HealthDay)—The parasite that causes malaria is growing increasingly resistant to the drugs commonly used to fight it, according to new surveillance reports. But several new drugs are in development, and at least one in ...

New hope for malaria treatment as drug resistance found unable to spread for the first time

April 14, 2016
New hope for malaria treatment as drug resistance found unable to spread for the first time

Recommended for you

Four simple tests could help GPs spot pneumonia and reduce unnecessary antibiotics

November 23, 2017
Testing for fever, high pulse rate, crackly breath sounds, and low oxygen levels could be key to helping GPs distinguish pneumonia from less serious infections, according to a large study published in the European Respiratory ...

New approach to tracking how deadly 'superbugs' travel could slow their spread

November 22, 2017
Killer bacteria - ones that have out-evolved our best antibiotics—may not go away anytime soon. But a new approach to tracking their spread could eventually give us a fighting chance to keep their death toll down.

Research points to diagnostic test for top cause of liver transplant in kids

November 22, 2017
Biliary atresia is the most common cause of liver transplants for children in the United States. Now researchers report in Science Translational Medicine finding a strong biomarker candidate that could be used for earlier ...

Metabolites altered in chronic kidney disease

November 22, 2017
Chronic kidney disease (CKD) affects 1 in 7 people in the United States, according to the U.S. National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK). These individuals have a very high risk of cardiovascular ...

Rainfall can indicate that mosquito-borne epidemics will occur weeks later

November 22, 2017
A new study demonstrates that outbreaks of mosquito-borne viruses Zika and Chikungunya generally occur about three weeks after heavy rainfall.Researchers also found that Chikungunya will predominate over Zika when both circulate ...

Alcohol consumption and metabolic factors act together to increase the risk of severe liver disease

November 22, 2017
A new study provides insights into the interaction between alcohol consumption and metabolic factors in predicting severe liver disease in the general population. The findings, which are published in Hepatology, indicate ...

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.