SCIENTISTS FIND CONSEQUENCES FOR DISEASE REMEDIES

FROM:  THE NATIONAL SCIENCE FOUNDATION 
Treatment for parasitic worms helps animals survive infectious diseases--and spread them

Scientists discover unanticipated consequences of some disease remedies
Parasitic worms, which infect millions of people and other animals around the world, influence how the immune system responds to diseases like HIV and tuberculosis.

In a new study of African buffalo, University of Georgia (UGA) ecologist Vanessa Ezenwa has found that de-worming drastically improves an animal's chances of surviving bovine tuberculosis--but with the consequence of increasing the spread of TB in the population.

"Health interventions can sometimes have unexpected and unwelcome outcomes," said Sam Scheiner, National Science Foundation (NSF) director for the Ecology and Evolution of Infectious Diseases (EEID) program, which funded the research. NSF, the National Institutes of Health and the U.S. Department of Agriculture support the EEID program.

"By examining such outcomes, we can design better intervention strategies for infectious diseases."

The findings, published this week in the journal Science, have implications for human health.

"If you think about humans in this context, this is what we'd like to do--to figure out how to help people who get infected by something live longer and be less sick," Ezenwa said. "But here we found that doing exactly that can have unanticipated consequences."

Testing buffalo for parasitic worms

Ezenwa and co-author Anna Jolles of Oregon State University conducted the research in South Africa's Kruger National Park.

In 2008, with the assistance of the park's Veterinary Wildlife Services Department, they captured 216 African buffalo and tested them for parasitic worms, known as helminths, and for bovine TB.

Half the buffalo received treatment for helminths; the rest were left untreated as a control group.

For the next four years, the scientists recaptured and retested each buffalo approximately once every six months.

They found that animals treated for worms were nine times more likely to survive TB infections than untreated animals; with the worms gone, their immune systems were able to mount a stronger defense against TB.

According to Ezenwa, this finding confirmed predictions about the effects of worms on the immune system based on an earlier study of TB and helminth infections in African buffalo.

"We'd done a one-off, short-term experiment to see if we could replicate, in this wild animal, the immunological results seen in laboratory experiments treating helminths in mice," she said. "That led to this larger experiment in a much bigger population over a longer time."

Treatment not always a plus

Ezenwa said that the previous work also suggested that treatment would reduce the rate at which individuals acquire TB infection and therefore the TB transmission rate.

"We expected it would be a net positive for the individual and for the population," she said. "But in fact when you carry out an experiment at this larger scale, in a real population, you see it's not all positive outcomes."

The improved survival rate allows infected buffalo to continue to spread TB within the herd, Ezenwa said.

Since they still get infected at the same rate there is an unexpected negative result for the population as a whole.

"Because coinfection is such a complicated area, laboratory studies are really essential in telling us about the detailed mechanisms of how immunological interactions work," she said.

"But we will never understand the real implications if all the work concentrates in the lab."

Need to look at similar animals to humans

Ezenwa said that in order to address human infectious disease problems, researchers need to also look at coinfection in populations that bear more similarity to humans.

"African buffalo are long-lived, they're in the wild in social groups, they're genetically variable--that's a little bit closer to people than laboratory mice, which have the same genetic background and live under artificial conditions," she said.

And understanding bovine TB-helminth coinfection in African buffalo is particularly relevant for human health because helminths are known to influence human immune responses to TB.

"The number of human cases of bovine TB worldwide is unknown, but where it's studied, it appears to be a substantial fraction of the total," said Frederick Quinn, head of the UGA Department of Infectious Diseases in the College of Veterinary Medicine.

"It's also unknown if bovine TB bacteria transmit more efficiently than other TB bacteria, what traits this pathogen possesses that allow infection of so many different species of mammals, and what happens when the host is co-infected with parasites or HIV.

"This work is a tremendous start in answering some of the fundamental questions about this disease and how best to control it in humans and other animals."

-NSF-


Media Contacts
Cheryl Dybas, NSF

SNAILS AND HUMAN DISEASE

Countries worldwide where people are at risk for the snail-borne disease schistosomiasis.

Credit-CDC

FROM: NATIONAL SCIENCE FOUNDATION
Snails in the Waters, Disease in the Villages
November 19, 2012

Watch where you jump in for a swim or where your bath water comes from, especially if you live in Africa, Asia or South America. Snails that live in tropical freshwater in these locations are intermediaries between disease-causing parasitic worms and humans.

People in developing countries who don't have access to clean water and good sanitation facilities are often exposed to the infected snails. Then they're left open to the parasitic worms.

The worms' infectious larvae emerge from the snails, cruise in shallow water, easily penetrate human skin and mature in internal organs.

The result is schistosomiasis, the second most socioeconomically devastating disease after malaria. As of 2009, 74 developing nations had identified significant rates of schistosomiasis in human populations.

There has been much debate about how best to prevent the disease, says Charles King, a physician and researcher at Case Western Reserve University in Cleveland, Ohio. "Beyond that," he asks, "how long should treatment last once someone has schistosomiasis?"

"Current guidelines focus on suppressing the disease's effects by limiting the infection during childhood," says King. "But that may not be enough to cure it or to prevent re-infection, leaving children still at risk for stunted growth and anemia."

King and colleagues recently published results of a study of long-term treatment of schistosomiasis in the journal PLOS Neglected Tropical Diseases.

The team's work is funded by the National Science Foundation (NSF)-National Institutes of Health (NIH) Evolution and Ecology of Infectious Diseases (EEID) program.

At NSF, the EEID program is supported by the Directorate for Biological Sciences and Directorate for Geosciences. At NIH, it's supported through the Fogarty International Center.

Schistosomiasis is usually treated with a single dose of the oral drug praziquantel.

World Health Organization (WHO) guidelines set forth in 2006 recommend that when a village reports that more than 50 percent of its children have parasite eggs in their urine or stool--a clear sign of schistosomiasis--everyone in the village should receive treatment.

When 10 to 50 percent of children are affected, say the guidelines, only school-age children should be treated--every two years. With less than 10 percent, mass treatment is not suggested.

But because of the long-term health effects of schistosomiasis, says King, "we now think it's better to provide regular yearly treatment."

He and scientists Xiaoxia Wang, David Gurarie and Peter Mungai of Case Western Reserve University; Eric Muchiri of the Ministry of Public Health and Sanitation in Nairobi, Kenya; and Uriel Kitron of Emory University in Atlanta, Georgia, used data collected in 10 villages in southeastern Kenya to run advanced models of village-level schistosomiasis transmission.

They scored the number of years each of the 10 villages would be projected to remain below a 10 percent infection level during a simulated 10-to-20-year treatment program.

All strategies that included an initial four annual treatments reduced community prevalence of the disease to less than 10 percent. Programs with gaps in treatment, however, didn't reach this objective in half the villages.

At typical levels of treatment, the researchers found, current WHO recommendations likely could not achieve full suppression of schistosomiasis.

"With more aggressive annual intervention that lasts at least four years," says King, "some communities might be able to continue without further treatment for 8 to 10 years.

"But in higher-risk villages, repeated annual treatment may be necessary for an indefinite period--until the eco-social factors that foster the disease [such as poor wastewater treatment] are removed."

In high-risk places, ongoing surveillance for the disease and annual drug treatment, the scientists say, need to become the mainstays of control.

In short, these villages require what they call "re-worming after de-worming."

But what happens if townspeople move to a more arid location, one with less freshwater and fewer snails?

In drier landscapes, schistosomiasis is a rare event that happens only during floods. Response to treatment therefore may be much better. Unless or until another flood occurs.

Although drier locales carry less risk for the disease, they're by no means free and clear. Even in arid locations, people would likely need to be treated more than once to get rid of the parasites.

"This research demonstrates the value of understanding where disease-causing organisms are in the environment," says Sam Scheiner, NSF program officer for EEID.

"Such knowledge can reduce human diseases much more effectively and at a lower cost than simply focusing on treatment."

The best goal, says King, is complete eradication of schistosomiasis.

To achieve that, scientists need to determine what makes a "wormy village," how often therapy is needed to prevent disease in such locations--and what can be done to change the environment such that a high-risk village becomes a low-risk one.