Malaria gets its own barcode

Scientists have developed a genetic barcode that could help to track the emergence of drug-resistant malaria strains.

Malaria is one of the most prevalent infectious diseases in the world. There are at least 225-million cases and 781?000 deaths a year, most involving Plasmodium falciparum parasite infections in children in sub-Saharan Africa.

In 2007, Bill and Melinda Gates challenged the world to eradicate malaria in their lifetimes, and thanks to subsequent investment there have been significant gains: 19 of the 97 countries with ongoing malaria transmission are on track towards elimination.

But a major obstacle to the successful elimination of malaria in any given area is the reintroduction of parasites through imported infections. In the 1950s, programmes for the control and eradication of malaria in Africa were undermined by failure to take population mobility into account, and by the difficulties of providing access to adequate healthcare to mobile sectors of the population.

Further risks
Today, greater mobility with international travel carries further risks of reintroducing parasites to elimination areas, as well as dispersing drug-resistant parasites to new regions.

The international transit of people with malaria played a significant role in the global dispersal of resistance to both chloroquine and sulphadoxine-pyrimethamine (also known as SP or Fansidar), two drugs that were the mainstay of malaria treatment in Africa for 30 years.

With both drugs, resistance mutations that first arose in Southeast Asia were imported to Africa. Today, there is emerging resistance to the drug artemisinin in Southeast Asia, which could pose a threat to the successful artemisinin-based antimalarial treatments used in Africa, if introduced to the continent by human migration.

But a simple genetic marker that quickly and accurately identifies the geographic origin of malaria infections would be a valuable tool for locating the source of outbreaks, and could potentially contribute to national planning and regional co-ordination of malaria control measures directed at elimination. In the past, genetic markers have proved extremely valuable in tracking and eradicating other diseases such as polio.

Early malaria genetic barcodes relied on DNA markers found in the parasite cell’s nucleus. These are subject to a process known as recombination, which shuffles DNA-producing new combinations with every parasite, changing every generation. Alternatively, our study looked at DNA outside the nucleus – in the mitochondria and theapicoplast – which, crucially, does not undergo recombination.

Accurate ‘barcode’
In new research published in Nature Communications, we analysed the DNA of more than 700 P?falciparum malaria parasites. We identified short sequences in the DNA of the parasite’s mitochondria and apicoplasts that were distinct for parasites from certain geographic locations.

This enabled us to design a genetic “barcode” that is highly accurate in predicting where a malaria parasite has come from, and is also stable to changes in the parasite’s genome over time.

By taking just a finger-prick blood sample from a malaria patient, rapid DNA sequencing technologies can identify genetic “barcode” markers from very small amounts of parasite material. This means local agencies could use this new barcode to identify the source of new malaria infections quickly and accurately. Such a tool will be valuable to malaria elimination programmes, and will also help to spot and contain the spread of drug-resistant parasites from Asia.

With resistance to the latest artemisinin combination treatments confirmed in Southeast Asia, the identification of parasites imported from that continent could assist with future management of the problem. By including other genetic markers of drug resistance, the barcode could also be used for routine drug resistance surveillance.

With this breakthrough in the genetic barcoding of P?falciparum we are refining the barcode to cover additional populations, such as India, Central America, Southern Africa and the Caribbean, and plan to include genetic markers for other malaria species in the future. – © Guardian News & Media 2014

Taane Clark is a reader of genetic epidemiology and statistical genomics and Cally Roper is a senior lecturer at the London School of Hygiene and Tropical Medicine

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