It is a drug that has its roots in ancient Chinese medicine. In the fight against malaria, a disease that over 200 million people are estimated to have caught in 2010, some 655,000 of whom died of it, protecting the effectiveness of artemisinin-based drugs has become vitally important.
A number of Indian pharmaceutical companies have been among those manufacturing and marketing drugs that are likely to foster resistance to artemisinin in the malaria parasite, according to the latest World Malaria Report that was recently released.
However, India's Drugs Controller General initiated action earlier this year to stop the production and export of these drugs.
Artemisin and its derivatives have saved countless lives after the single-celled parasite, Plasmodium falciparum, that causes the most dangerous forms of the disease became resistant to the drug chloroquine. However, strains that are resistant to even artemisinin have emerged in parts of South-East Asia and could potentially spread, as has happened with earlier antimalarial drugs.
“A looming threat to malaria control is the emergence of parasites that are resistant to antimalarial medicines,” pointed out the World Health Organisation (WHO) in its ‘Global Plan for Artemisinin Resistance Containment' published earlier this year. Resistance had developed to every antimalarial medicine used so far. When that happened, the burden of malaria increased. Child mortality in Africa increased, for instance, as P. falciparum strains that were resistant to chloroquine spread in the 1970s and the 1980s.
Although the problem of artemisinin resistance is currently confined to the Mekong river region, there is now “early evidence” of such resistance in Myanmar and Vietnam, warned Margaret Chan, the WHO's Director-General, in a foreword to the World Malaria Report 2011.
“Exposure of malaria parasites to suboptimal doses of artemisinin is a primary cause of the spread of resistance,” the Global Plan noted. Giving artemisinin and its derivatives alone as 'monotherapies,' instead of as a cocktail with another drug, could create opportunities for resistant forms of the parasite to arise and spread.
Although oral artemisinin-based monotherapies could be effective when taken for the full seven-day course, patients often stopped taking them after just a few days when the symptoms generally subsided. Parasites that were sensitive to the drug could get eliminated, allowing drug-resistant strains to proliferate and get transmitted to other people.
To prevent that from happening, the global health agency recommends that artemisinin be given in combination with another drug. Such artemisinin-based combination therapy (ACT) should, it says, be first-line treatment for uncomplicated malaria caused by P. falciparum. The two-drug combination reduced the chances of the parasite developing resistance. Moreover, a three-day course of a recommended ACT generally cleared the parasites from the body.
The use of ACT has grown rapidly. Globally, the number of ACT courses procured by the public sector jumped nearly seven-fold between 2005 and 2006, and then more than doubled, reaching 181 million, in 2010, according to the World Malaria Report. The demand for these drugs was expected to reach 287 million treatments this year and touch 295 million courses in 2012.
In 2006, the WHO called for a halt to using oral artemisinin monotherapies to treat uncomplicated malaria. This was followed a year later by a resolution adopted by the World Health Assembly, the WHO's apex decision-making body, that urged its member states to “cease progressively the provision in both the public and private sectors” of such monotherapies and promote the use of ACTs.
However, according to the latest World Malaria Report, 25 countries were still allowing the marketing of these products and 28 pharmaceutical companies were making these drugs, down from 39 a year ago. “Most of the countries that still allow the marketing of monotherapies are located in the African Region, while most of the manufacturers are located in India.”
Ten of the 28 manufacturers of monotherapies were in India, according to a spokesperson for the WHO Global Malaria Programme.
The WHO has called on all manufacturers to cease the marketing of monotherapies. Besides, “greater collaboration and involvement of national regulatory authorities is required to ensure complete withdrawal of oral artemisinin-based monotherapies from all countries,” noted the World Malaria Report.
“Oral artemisinin monotherapy is banned in India,” according to the ‘Guidelines for Diagnosis and Treatment of Malaria in India' published in 2010 by the National Institute of Malaria Research in Delhi and the Union Health Ministry's National Vector Borne Disease Control Programme.
In April this year, DCGI wrote to all State Drugs Controllers requesting them to cancel licenses to manufacture oral artemisinin-based monotherapies with immediate effect. The manufacturing of such monotherapies for export should also be stopped. “We have been very encouraged by the steps that the Government of India has taken over the past year,” said Robert Newman, director of the Global Malaria Programme at a press conference to mark the release of the World Malaria Report.