During the early days of the outbreak ― back in 2013 ― physicians in the Canadian province of Alberta were flummoxed: for several patients with liver masses suggestive of cancer, biopsy results were inconclusive, and the patients were cancer free.
"The first individual required three biopsies before the diagnosis was made," said Stan Houston, MD, professor of medicine and public health at the University of Alberta in Edmonton.
"For our second patient, we even sent the biopsy to the CDC [Centers for Disease Control and Prevention] in Atlanta, where it was misdiagnosed," he said.
Now, 7 years later, the outbreak of alveolar echinococcosis (AE), a rare, potentially fatal parasitic liver disease, has expanded to 15 patients in the province. Last year, Houston and colleagues reported in the New England Journal of Medicine on a cluster of seven cases.
AE is spread by wildlife infected with the Echinococcus multilocularis tapeworm. The parasite is found in coyotes and foxes but can spread to rats and then to domestic dogs and cats that eat infected rodents.
Humans can pick up the infection by accidentally ingesting the organisms or after handling items contaminated by feces from infected animals. In humans, the tapeworm larvae form cysts, typically in the liver. These cysts are slow growing and may not cause any symptoms for many years, notes the CDC.
Eventually, pain or discomfort in the upper abdominal region, weakness, and weight loss may occur. These symptoms may mimic those of liver cancer and cirrhosis of the liver, the CDC states.
Diagnosis Remains a Challenge
Despite the growing number of cases in Alberta, the diagnosis of AE remains a challenge, as evidenced by a recent report in which a patient with a 10-cm growth on her liver ― shown in the CT scan depicted below ― was initially suspected of having terminal fibrolamellar carcinoma.
"It's a very new infection in the Western Hemisphere," said Houston, who wants physicians to keep AE in mind when considering the differential diagnosis. "Indications are that we're just seeing the early phase of this wave."
"Although it is a rare disease and hopefully will remain so in North America, AE should be at least thought of when an abnormal image is found in the liver," advised Dominique Vuitton, MD, PhD, author of a Medscape article on the condition.
"For decades, the scientific community was amazed at the discrepancy between the infection in foxes and coyotes in Canada and the USA and the near absence of human cases," said Vuitton. He is part of the World Health Organization's Collaborating Center for Prevention and Treatment of Echinococcosis and is professor emeritus of clinical immunology at the University of Franche-Comté, in Besançon, France.
"After being well recognized but silently present in the wildlife of North America, this parasite should now be taken more seriously by health professionals because of the emergence of this new cluster of human cases," he said.
Indeed, evidence suggests that more virulent European strains of the parasite are likely invading wildlife in the central United States and Canada, reported Alessandro Massolo, PhD, a zoologist from Alberta's University of Calgary.
He is first author of an article in Parasite that reports that E multilocularis has been identified in wildlife in three other Canadian provinces (Saskatchewan, Manitoba, and British Columbia) as well as in 13 US states (North Dakota, South Dakota, Iowa, Minnesota, Montana, Wyoming, Nebraska, Illinois, Wisconsin, Indiana, Ohio, Missouri, and, more recently, central and southwestern Michigan).
"It seems to be doing very well in the wild here, so that has implications for human exposure," agreed Houston, who noted that Albertan coyotes are quite urbanized and can spread the eggs via feces to domestic pets and humans.
"There are thought to be maybe 500 coyotes in the city of Edmonton ― in the park and river valley and ravines ― and the proportion that are carrying this parasite is very high: in one Edmonton park, it was 80%, which is much higher than in foxes, which are the reservoir host in Europe."
Cancer Is Initially Suspected
AE is believed to have a long incubation period ― up to 15 years – during which time patients may be asymptomatic, despite the growth of tumor-like cysts. "MR imaging and molecular identification of the parasite are keys to the proper diagnosis," said Vuitton.
In every Alberta case except one, "the starting point was an abnormality on liver imaging," said Houston. About half of the cases were found incidentally. "Cancer was the initial suspicion in all, whether incidentally found or symptomatic," he said.
Images of AE lesions, which are "very typical at late stages of the disease," might be misleading in cases in which AE is found incidentally, especially in immunosuppressed patients, "since the lesions at an early stage may mimic any liver tumor, including hemangiomas, metastases, and liver abscesses," said Vuitton.
"T2-weighted MRI usually shows the pathognomonic picture of E multilocularis microcysts," she added. "Serology in such cases may be negative, which adds to delayed diagnosis.
"Confirmation of E multilocularis infection by molecular biology on a biopsy may be the ultimate recourse," she commented. This also "allows genotyping of the parasite, which is particularly important to ascertain the geographical origin of the parasite and help scientists to track the source of infection."
Patients who are immunosuppressed are also at increased risk for infection, according to research by Vuitton and colleagues.
"The most recent data from our French registry of AE cases confirm this trend," she added. "On average, 20% of our incident patients now (ie, for the last 10 years) are immunosuppressed patients.
"We began to see such cases at the beginning of the 2000s," she said. This spike could be driven by the use of more powerful immunosuppressive agents and immunomodulating biotherapies, she added.
Physicians should be aware of the potential to overlook an AE diagnosis in patients who have a history of cancer, added Houston.
"If a liver mass is seen in someone with a preexisting cancer, you can pretty easily see how a very reasonable doctor might make the assumption that this is a metastatic lesion without doing a biopsy. In many circumstances, it might be a very reasonable decision that subjecting the patient to more investigation isn't warranted, but with this new possibility emerging, it complicates that ― a treatable diagnosis might be missed."
His group is now reexamining any inconclusive liver biopsy results from the past 5 years to make sure AE cases were not missed.
Without treatment, AE infection is eventually fatal, but through a combination of hepatic resection and long-term albendazole therapy, the prognosis "is currently very good in countries with high level of healthcare," said Vuitton.
"It's always treatable and sometimes curable," agreed Houston. "What you'd like is to find it at a stage when it can be totally resected, and then it's cured. Patients would still have to take antiparasitic drugs for a time, but not forever. But sometimes the parasite mass is too big or involves vital structures, and therefore surgery may not be technically possible."
Vuitton says that her references center, which now has experience with more than 500 cases, is available for physicians at email@example.com.
Her team would be happy to discuss with physicians any cases in which there is doubt over the diagnosis, or any "difficult cases ― especially for care management, decisions about surgery, follow-up with albendazole treatment (which must be given to all patients and has a narrow therapeutic range...).
"For the past 25 years, we have also worked in close cooperation with Chinese teams of the highest endemic areas in the world, which have developed new surgical approaches for patients with very advanced lesions, a situation which is less and less often found in European cases," she added.
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Cite this: Looks Like Liver Cancer, but Large Cysts Contain Tapeworm Larvae - Medscape - Feb 26, 2020.