Intestinal hitchhikers may render people more vulnerable to the microbe and might lessen vaccines’ effectiveness
Harboring intestinal parasites seems to limit a person’s ability to fend off cholera, a study conducted in Bangladesh shows. The finding might explain why vaccines against cholera have shown only spotty effectiveness and also suggests that vaccination campaigns should be preceded by programs to wipe out parasites, particularly intestinal worms. The study appears in the March PLoS Neglected Tropical Diseases.
The bacterium Vibrio cholerae causes cholera and is spread in unsanitary food or drinking water. In the past, scientists had been puzzled when experimental cholera vaccines that induced a strong response in Western volunteers failed to generate consistent immunity when given to people in the tropics. Researchers initially suspected poor nutrition or genetic differences, says pediatrician Jason Harris of Harvard Medical School and Massachusetts General Hospital in Boston. But in recent years, some came to wonder whether other infections, including those caused by parasites that are prevalent in poor tropical countries, might be hindering the immune response and therefore a vaccine’s effect.
Harris and his U.S. colleagues teamed with researchers at the International Centre for Diarrhoeal Disease Research in Dhaka to collect and analyze blood and feces samples from 361 people who were brought to hospitals with severe cholera from 2001 to 2006. The scientists found that 53 of the patients also had parasitic infections.
Those with intestinal worms had markedly poorer antibody production against the toxin made by the cholera microbe than did those without worms, the researchers report. These responses against the actual microbe would suggest a similar effect in people getting vaccinated.
The Vibrio cholerae toxin causes severe diarrhea when it comes into contact with the intestinal lining, and hospitalized cholera patients receive fluids to prevent life-threatening dehydration. People naturally develop antibodies against the toxin and against the microbe itself to the point that adults in endemic countries such as Bangladesh become largely immune to cholera after repeated exposures. Children initially exposed are most vulnerable.
The precise mode of action by which intestinal worms lessen antibody production against the toxin is poorly understood, the researchers say.
“Intestinal parasites do seem to have influences beyond their own little niche,” says Thomas Nutman, an immunologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “This is among a growing list of studies that have addressed the bystander effect — a spillover effect, if you will – of these [worm] parasites,” he says.
Medication can clear intestinal worms from the body, including roundworms, the parasites most frequently detected in this study. Campaigns using drugs to de-worm large numbers of people are under way in many parts of the tropics as health officials seek to improve school-age children’s growth and cognitive development, Nutman says.
The new findings suggest that these de-worming programs could have “an unexpected benefit” in communities with endemic cholera by improving the effectiveness of cholera vaccination, Harris says.
Cholera infects roughly 5 million people worldwide each year and causes about 100,000 deaths.
Harris JB et al. Immunologic Responses to Vibrio cholerae in Patients Co-Infected with Intestinal Parasites in Bangladesh. 2009. PLoS Neglected Tropical Diseases, March, Vol. 3, p. e403. doi:10.1371/journal.pntd.0000403
Cooper PJ et al. Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. 2001. Infection and Immunity, March, Vol. 69, p. 1574–1580.
Chowdhury F et al. A comparison of clinical and immunologic features in children and older patients hospitalized with severe cholera in Bangladesh. 2008. Pediatric Infectious Disease Journal, Vol. 27, p. 986–992.