How did a group of villagers living in a remote area of South America develop an antibiotic resistance to a drug they had never been given? Canadian researchers say the answer may lie with a drug widely used around the world to combat malaria. This drug, chloroquine, is chemically similar to a commonly used antibiotic. The team's theory is that, even though the drug is effective at destroying the malaria parasite, it creates a resistance in gut bacteria not only to chloroquine, but to the antibiotics as well. "This means that chloroquine used for malaria may make the fluoroquinolones (a "family" of antibiotics) less effective for many common tropical diseases such as typhoid fever, diarrheal illnesses, and possibly also tuberculosis and pneumonia in the developing world," said Dr Michael Silverman, who led the study.
During humanitarian medical visits between 2002 and 2005, Dr. Silverman, from the Lakeridge Health Centre in Oshawa, Ontario, and 19 other volunteer health care professionals traveled to Bartica and other remote villages just outside the Guyanese rainforest, where they took rectal swabs from 535 villagers. They took the samples home and analyzed them for resistance to ciprofloxacin, one of the most commonly used antibiotics in the world. They found a high degree of resistance; 4.8 percent, which compares to the 4 percent found in U.S. intensive care units where fluoroquinolones are widely used. While these individuals had not been treated with ciprofloxacin or related fluoroquinolone antibiotics, a large number of the villagers said they had been given chloroquine in the preceding two years because of a widespread malaria outbreak a year before the tests.
These findings were confirmed by a team from Dalhousie University in Halifax, Nova Scotia led by Dr. Ross Davidson and Dr. Ian Davis. In the laboratory, E. coli bacteria that were exposed to chloroquine became resistant to fluoroquinolones, including ciprofloxacin. "Together, these data suggest that we must focus our efforts on prevention of malaria using mosquito-control measures such as bed nets and by developing vaccines," concluded Dr. Silverman. "For the short term, however, we still will have no choice but to use these lifesaving anti-malarial drugs."
Some experts say this shouldn't be surprising given the fact that the family of antibiotics involved-fluoroquinolones, which includes Cipro used during the 2001 U.S. anthrax scare, were developed from chloroquine. Because the two kinds are molecularly similar, bacteria exposed to chloroquine develop protective mutations against it, and those also work against fluoroquinolones.
"We need to investigate which of the anti-malarials can be used in the future with the least impact on bacterial drug resistance," Dr. Silverman said. He added that major global health-promotion organizations are considering plans to launch a campaign of widespread use in Africa and South America of a new anti-malarial treatment regimen called Artemesinin combination therapy (ACT). ACT usually includes quinoline drugs similar to chloroquine, which are closely related to both chloroquine and fluoroquinolones. "We plan to carry out further studies to identify whether some quinolines may be less likely to induce quinolone resistance than others, and thus may be safer for malaria control programs," he said.
Malaria is a mosquito-borne disease caused by a parasite. It is thought to have killed more people throughout human history than any other disease, and according to the World Health Organization, it still kills a million people each year, especially in developing countries. For example, in Africa, a child dies from malaria every 30 seconds. About 1,300 cases of malaria are diagnosed in the United States each year, with the vast majority of cases occurring in travelers and immigrants returning from malaria-risk areas.
While people usually get malaria by being bitten by an infected Anopheles mosquito, it can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood. Malaria may also be transmitted from a mother to her unborn infant before or during delivery.