Reinvigorating the battle against an old disease

In Zulu, “nagana” means “depressed in spirits.” To many poor farmers in sub-Saharan Africa, however, nagana is more than just an emotion—it’s a disease that plagues their livestock, exacerbating poverty and hunger in the region. But researchers in Belgium may soon have something to raise the temperaments of African farmers: a drug aimed at curing nagana-infected livestock.

Nagana, or African animal trypanosomiasis, is caused by the parasitic microorganism Trypanosoma and spread by the bite of host tsetse flies. The disease, whose symptoms include fever, muscle atrophy and anemia, annually kills more than 30 percent of the approximately ten million cattle in tsetse-infected regions of sub-Saharan Africa, according to the U.N. Food and Agriculture Organization.

“It is a very old disease,” says Peter Van den Bossche, a researcher at the Antwerp-based Institute for Tropical Medicine and a veterinary professor at the University of Pretoria in Onderstepoort, South Africa. With reports of nagana dating back to at least the mid-1800s, Van den Bossche believes the disease played an important role in slowing the development of the African continent.

Researchers developed effective drugs in the 1960s to cure the disease, but as early as the 1970s, certain species of Trypanosoma evolved mechanisms to pump the drugs out of their systems. Since nagana mostly affects poor farmers who cannot afford expensive drugs, pharmaceutical companies have little incentive to invent new medicines, according to Van den Bossche.

So, Van den Bossche and his research team took it upon themselves to find an affordable solution for African farmers. They developed a drug cocktail that combined an existing drug called ISM (isometamidium chloride)—which some strains of Trypanosoma have adapted to—with common antibiotics like oxytetracycline and fluoroquinolone enrofloxacine. Injecting the cocktail into cattle infected with ISM-resistant Trypanosoma congolense, the team was able to cure six of the twelve cows they tested, according to their study published in September in the journal PLoS Neglected Tropical Diseases. The researchers believe this is a promising step towards arming farmers with a new weapon against previously untreatable strains of Trypanosoma.

The antibiotics interfere with Trypanosoma’s ability to expel ISM, explained Vincent Delespaux, another researcher with the Institute of Tropical Medicine and first author of the study. By administering antibiotics alongside ISM, the parasite is forced to pump out both drugs—the more antibiotic Trypanosoma extrudes, the less ISM it can get rid of. Essentially, the team wanted to overload Trypanosoma’s pumping system with antibiotics to give ISM more time to take effect, Delespaux said.

However, the high dosage of antibiotics used in the cure renders cattle meat inedible. If consumed, the meat could kill symbiotic bacteria essential for digestion.  So now the team is researching alternate antibiotics and dosages, as well as different ways to administer the drugs. “We know that it works but it needs fine tuning,” said Van den Bossche, adding that his team requires “at least another year” to develop a solution that yields healthy cattle meat and a higher cure rate.

Because the drug dosage has not yet been optimized, an exact cost for the nagana cure is not known. “We don’t know how much antibiotic is really required,” explained Van den Bossche. However, he is confident that the optimized cure will be affordable for poor farmers, saying, “ISM and antibiotics, such as tetracycline, are fairly cheap drugs.”

Glyn Vale, a leading researcher on tsetse fly behavior and nagana control, cautions that the new drug “should only be regarded as a temporary expedient.” A visiting professor of insect behavior at the University of Greenwich in the U.K., Vale believes that the way to stop nagana in the long run is to deal with the tsetse flies spreading the disease, either by using insecticides, tsetse bait traps or other similar, inexpensive control methods.

Van den Bossche agrees. He said their proposed cure is part of “an integrated approach” to support livestock farming in tsetse-infested areas until researchers can effectively manage the pestilent flies.