Potomac Breakthrough: A Fluke Larva

Potomac horse fever was an equine disease shrouded in mystery. Scientists knew what caused the illness--the bacterium Ehrlichia risticii--but its source in nature could not be found. No one knew how horses became infected. Until now.

An article that appears in the June issue of the Journal of Clinical Microbiology offers strong evidence that freshwater snails and the larvae of flukes (parasitic flatworms) play key roles in Potomac horse fever's transmission. Based on research conducted at the University of California at Davis, the groundbreaking information shatters the popular theory that the disease is spread by biting arthropods such as ticks. It also suggests that Potomac horse fever can be prevented by keeping horses away from the streams, ponds, and other aquatic habitats in which snails and flukes live.

"This really changes the whole concept of Potomac horse fever," said Dr. John E. Madigan, one of the article's authors. "A lot of good entomologists had looked for the organism (that causes the disease) in flies, mosquitoes, and ticks, but nobody had ever come up with it."

Potomac horse fever is most prevalent in the Eastern United States, but it also occurs in California and other areas of the country as well as in Canada and Europe. Its symptoms include loss of appetite, fever, depression, diarrhea, colic, and dehydration. Laminitis is a complication in a significant number of cases, and the disease is potentially fatal.

Potomac horse fever is seasonal, with cases occurring between late spring and early autumn in temperate areas. It was first observed in 1979 among horses grazing in pastures along the Potomac River in Maryland, and the presence of a large waterway seemed significant.

Madigan said he and his fellow researchers became more interested in the link between Potomac horse fever and water because of work done by Dr. Yasuko Rikihisa of Ohio State University. Through genetic analysis, she showed that the Ehrlichia risticii bacterium was closely related to another organism associated with an aquatic habitat, Neorickettsia helminthoeca, which causes a frequently fatal disease in dogs that eat salmon. A similar bacterium is Ehrlichia sennetsu, an agent of human illness in Japan and Malaysia that also is associated with water exposure.

The UC–Davis project involved the collection of snails from sites where there was a history of Potomac horse fever. At first, the results were not very promising. "Out of a thousand snails," Madigan said, "only four were infected (with Ehrlichia risticii)."

The scientists, however, continued to pursue the snail angle. Collecting more of the animals, they transported them in chilled water to a laboratory at UC–Davis. The snails were placed in tanks and allowed to grow.

When the water that contained the snails was warmed, the researchers discovered that the animals released a substance that Madigan described as "a slimeball or whitish material." The secretion contained cercariae, the tiny tadpole-shaped larvae of flukes. And those larvae contained bacteria that the scientists determined were genetically identical to certain strains of the Ehrlichia risticii organisms obtained from horses with Potomac horse fever.

Madigan and his colleagues do not know exactly how the cercariae containing the Ehrlichia risticii get into a horse's body, and they plan to explore that question further. Cercariae are free swimmers that can penetrate skin, creating one possible route of infection. Horses also might ingest the cercariae when they drink water. In addition, there could be an intermediate host for the cercariae, such as an insect, that horses ingest while drinking or grazing.

"If there is an intermediate host that's along the edge of a creek and it goes out into the pasture, then that might make this disease harder to manage," Madigan said. "But in every instance where we have confirmed Potomac horse fever, the horses either have been in an irrigated pasture where they have been walking in water or they have been drinking the water. This suggests that you should find a different water source for your horses and that you should keep horses out of irrigated pastures until they have had a chance to dry out. More than likely, eradication of the snails would help, but that could be hard to do."

The study's results also indicate that vaccines against Potomac horse fever might have to be redesigned. Based on recent research, the protection they offer is "marginal," according to Madigan, and that probably is because they were developed with the idea that the horses were bitten by a tick or other arthropod, which released disease-causing bacteria in the blood.

"They (the vaccines) were designed to produce circulating antibodies in the bloodstream," Madigan said. "But, if it (the infection) is through the oral route (drinking water, eating an infected insect, etc.) instead of the blood route, then these vaccines may not work at all because they aren't producing immunity at the site where the infection takes place."

There also is another reason why available vaccines are not working well. Studies conducted at UC–Davis and elsewhere have revealed that there is widespread genetic diversity among Ehrlichia risticii bacteria, Madigan said, and the vaccines were not designed to offer immunity against all of the different strains.

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