Malaria genome sequencing brings hope

Genetic variability has been revealed in malaria genomes newly sequenced by two international research teams, including a group from India. This, scientists hope, will provide a roadmap for development of vaccines and drugs to combat malaria, reports Kalyan Ray

The search for a vaccine against malaria remains high on the global research agenda for many years. The parasites being tricky customers, there is not much of a success. But genetic variability revealed in malaria genomes newly sequenced by two multi-national research teams including a group from India offers a clearer and more detailed picture of its genetic composition, providing an initial roadmap in the development of pharmaceuticals and vaccines to combat malaria. Needless to say the studies also point out the challenges in efforts to eradicate the parasite.

The genetic analysis focuses on two lesser studied types of parasites – plasmodium vivax that afflicts humans and the most prevalent human malaria parasite outside Africa, and plasmodium cynomolgi, a close relative that infects Asian old world monkeys.

Even though it infects about 100 million people each year, plasmodium vivax has is generally known as the neglected plasmodium, due to limited studies as compared to the p falciparum parasite. The other species p cynomolgi, provides an important model system for characterising p vivax and human malaria. 

Falciparum and vivax

In general, plasmodium falciparum is considered deadly and responsible for most of the deaths, amounting to less than a million. It dominates in Africa. On the other hand, p vivax infection has been mistakenly considered to be benign and comparatively less well studied. India has significant vivax malaria (used to be 75 per cent, but perhaps it is now 50 per cent, since drug-resistant p falciparum has spread). But malaria caused by p vivax is more treacherous, since it can immobilise patients for months and can relapse after several months. 

Recent studies have shown that vivax strain can also cause severe malaria, including cerebral malaria and would need greater emphasis in research. 

While, the genome sequences of several strains of p falciparum are known, only two strains of p vivax have so far been sequenced. In one of the papers published in the August 5 issue of Nature Genetics, scientists reported sequence of four more vivax strains, including one from India, which was sequenced at National Institute of Malaria Research in New Delhi. 

The sequences indicate as much diversity as can be seen in p falciparum and are also suggestive of an older association with humans than p falciparum.

“Variability in the vivax genome is almost double compared to falciparum. The diversity is important to study resistance, virulence as well as developing a vaccine against malaria,” NIMR scientist Anup Kumar Anvikar, who along with former NIMR director A P Dash did the genetic analysis of the Indian strain told Deccan Herald.

“The bad news is there is significantly more genetic variation in p vivax than we’d thought, which could make it quite adept at evading whatever arsenal of drugs and vaccines we throw at it,” said Jane Carlton, senior author of both studies and part of New York University’s Center for Genomics and Systems Biology. 

“However, now that we have a better understanding of the challenges we face, we can move forward with a deeper analysis of its genomic variation in pursuing more effective remedies.” The researchers examined p vivax strains from different geographic locations in West Africa, South America and Asia, providing the researchers with the first genome-wide perspective of global variability within this species. 

Their analysis showed that p vivax has twice as much genetic diversity as the world-wide p falciparum strains, revealing an unexpected ability to evolve and, therefore, presenting new challenges in the search for treatments.

Other studies

The second study performed jointly with Kazuyuki Tanabe at Osaka University, Japan, sequenced three genomes of p  cynomolgi. The researchers compared its genetic make-up to p vivax and to plasmodium knowlesi, a previously sequenced malaria parasite that affects both monkeys and humans in parts of Southeast Asia.

Their work marked the first time p cynomolgi genomes have been sequenced, allowing researchers to identify genetic diversity in this parasite. Its similarity to p vivax means that their results will also benefit future efforts to understand and fight against forms of malaria that afflict humans.

“We have generated a genetic map of p cynomolgi, the sister species to p vivax, so we can now push forward in creating a robust model system to study p vivax,” explained Tanabe. “This is important because we can’t grow p vivax in the lab, and researchers desperately need a model system to circumvent this.”

“This would suggest that drug or vaccine development against p vivax would pose challenges in view of sequence variations. There was a great expectation that drugs and vaccines would role out with the availability of p falciparum sequences. But, this has not happened,” G Padmanabhan, former director of Indian Institute of Research, Bangalore and one of India’s leading researchers on malaria told Deccan Herald. 

Padmanabhan said knowledge of genome sequence had given a spurt to extensive research and identification of drug targets had become easier.

“But, target identification is only the first step and there are several other challenges to be faced. Thus, while more information on p vivax variability would lead to newer diagnostic options and identification of newer drug and vaccine targets, it would still be a long way to come up with effective therapeutic options,” he said.