Scientists in India are closer to developing a vaccine for infections from a non-lethal but more common variant of the malarial parasite.
The results of the study on primates, to be published in the peer-reviewed journal Vaccine, report encouraging results for a potential vaccine to prevent malarial infections triggered by the plasmodium vivax (p. vivax) parasite, the organism responsible for nearly a million of the approximately 1.86 million cases of malaria annually registered in India. The so-called benign tertian (non-fatal and recurring) parasite is implicated in nearly 70-80 million annual cases of the infections around the world.
Set to enter human trials later this year, the proposed vaccine builds on successful tests on mice in 2004 and is being developed at the International Centre for Genetic Engineering and Biotechnology (ICGEB), a research institute with its India headquarters in New Delhi. It is also a pivotal part of a major vaccine development project involving Hyderabad-based Bharat Biotech India Ltd (BBIL), the PATH Malaria Vaccine Initiative—a global programme initially funded by the Bill and Melinda Gates Foundation, the World Health Organization and India’s department of biotechnology.
Krishna Ella, chairman and managing director of BBIL and Chetan Chitnis, an ICGEB scientist involved with the vaccine, declined specific comments on the vaccine citing non-disclosure agreements.
Though good results on primate tests are at best a green signal for many more years of clinical trial studies, the need for a vaccine has suddenly become stronger because strains of p. vivax, considered to be a relatively harmless version of malaria, are beginning to be associated with other complications such as severe anaemia, acute kidney failure, and worst of all, brain fever, typically associated with plasmodium falciparum (p. falciparum) infection, the more lethal version of malaria.
Highly prevalent: A file photo of a malaria patient being provided treatment at a temporary health camp in Assam. Every year, India registers approximately 1.86 million cases of malaria. (Utpal Baruah / AP)
This implies that strains of p. vivax may be much more diverse and possibly more virulent, than previously assumed. A study in Indonesia, where malaria is endemic and has multi-drug resistance, suggests that irrespective of the cause of malarial infection—p. vivax, p. falciparum or mixed (a combination of both) infections—the number of deaths due to severe malaria was roughly the same.
A related but separate study there said that there was no evidence to show mixed infections reduced the severity of a malarial attack, contrary to current belief that p. vivax tempered the more virulent p. falciparum in the event of simultaneous infection.
Both of these reports appeared last month in PLoS Medicine, a peer-reviewed journal. India too has occasionally reported cases of drug resistance, as well as p. vivax-triggering severe malaria.
In 2005, Dhanpat Kochar, a neurologist at the Sardar Patel Medical College in Bikaner, Rajasthan, reported 11 malarial patients, with p. vivax infections exhibiting a host of complications from jaundice to cerebral fever.
Ira Shah, a paediatrician from Mumbai’s BJ Wadia Children’s Hospital, reported the first case of resistance to chloroquine—the standard drug for treating p. vivax, malarial infection—in an infant last month.
“Cases of chloroquine resistance as well as severe complications in p. vivax malaria have been reported since 1995,” said A.P. Dash, director of the government-run National Institute of Malaria Research. “But these are sporadic. There is cause for concern, but not worry yet,” he added.
The worry is still falciparum malaria—which in 1970 constituted 20% of the total malarial cases and as of 2005 estimates has risen to 48% of the cases—officially the only cause of malarial fatality in India.
“P. falciparum is still the central point of concern, but we have recently initiated studies to better understand the p. vivax,” Dash added.
The ICGEB vaccine approach involves targeting the Duffy protein, which due to a genetic mutation is naturally present in the Asian and European population, and is absolutely essential for the p. vivax to infect human blood cells and trigger malaria. Africans are rarely affected by p. vivax malaria, because they lack the requisite gene.
The protein binds to the blood cells and the potential vaccine hopes to somehow prevent this binding, according to research papers on the subject.
A separate group of researchers in Australia have already begun human trials on another p. vivax vaccine that uses a different approach. “Of the nine major vaccine candidates for malaria only two target p. vivax infections, so that’s about as much importance p. vivax got. But there is hope now,” Chitnis added.
Gennova Biopharmaceuticals Ltd last month announced a dedicated facility for manufacturing vaccine candidates for use in clinical trials, according to a press statement. Because p. vivax didn’t garner enough research attention, the parasite has evolved over time and is still a “pretty harmless thing,” as described by C.R. Pillai, emeritus scientist with the Indian Council of Medical Research.
“P. vivax is much older than p. falciparum and has figured out a way to exist in the body, without attracting too much attention. But lifestyle changes, climate change, threats from newer parasites exert an evolutionary pressure on it and it’s reaction is at times virulent, and thus more noticeable,”said the scientist, who’s studied malarial parasites for over 40 years.
But that’s no reason for complacence. “Malarial parasites are extremely diverse and smart. They quickly evolve drug resistance so any vaccine approach runs the risk of losing its efficacy. We need a lot more research to better understand how these parasites infect, their weakness to combat the disease,” said Pillai.