An important and cheap malaria drug compromised by parasitic resistance over the years has made a strong comeback in Malawi. A new study shows that the drug chloroquine is effective after being out of use for more than a decade in the southern African country. But, the researchers are not yet recommending that it become a treatment mainstay again.
Public health experts consider chloroquine, introduced widely in the 1950s, to be the most important modern anti-malarial drug. It is inexpensive at about 10 cents per treatment, simple to administer, and in the beginning was highly effective in only a few doses. It helped control malaria and even eradicate the disease in some places during the global campaign of that decade.
But by the end of the 1950s, resistance had begun to emerge in the deadly form of malaria. Resistant forms of the parasite spread around the world and reached eastern Africa by the late 1970s.
University of Maryland physician Miriam Laufer says in many places, chloroquine's effectiveness dropped below 50 percent.
"By the 1980s, the resistance was so bad that people noticed that there were increased cases of malaria and increased deaths due to malaria," she said. "That was attributed to the failure of chloroquine to treat the disease."
In 1993, Malawi become the first African country to shift from chloroquine therapy to a combination of sulfadoxine and pyrimethamine. But these drugs fell to parasite resistance even faster than chloroquine, so nations are switching to the new, but more expensive combination treatments based on the Chinese herb artemisinin.
Now, a team led by Dr. Laufer has shown that the layoff in use has been good for chloroquine, making it a potential candidate for re-introduction. In a trial of 210 Malawian children, chloroquine was 99 percent effective, compared to only 21 percent effectiveness in the group that got sulfadoxine-pyrimethamine.
"Chloroquine worked remarkably well," she said. "There was only one case of chloroquine treatment failure."
The study, published in the New England Journal of Medicine, attributes chloroquine's renewed success to the disappearance of a genetic mutation in the parasite as a result of the drug's disuse. The mutation had developed to protect the parasite against the compound.
Is this good news for public health?
"It is good news, but I do not think we can go back to our reliable old chloroquine as it once was," said Dr. Nicholas White, a physician and infectious diseases expert at Mahidol University in Bangkok, Thailand.
He, like Miriam Laufer's group, points out that chloroquine should not be re-introduced as a single therapy against malaria in places like Malawi where parasite resistance to it has faded.
"The problem is that although resistance can go away, the reality is that Malawi is surrounded by a sea of resistance in other countries and it would come back rapidly in people," he said.
White says that, instead, chloroquine should be completely removed from use to allow resistance to it to die everywhere before the drug makes a comeback, and then it should be only as part of a combination of compounds.
Miriam Laufer puts it this way.
"What we have learned over time is that it is better for anti-malarial drugs to use combinations," she said. "So the idea is that if you brought back chloroquine, you would bring it back in a smarter way, which would be in combination with another drug."
The currently recommended combinations use artemisinin and, presumably, chloroquine could join it. But Nicholas White says that if these new mixtures are to have an impact on malaria, they must be made more affordable and available, requiring an international funding and distribution plan to help countries acquire them.