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The Variable Presentations and Broadening Geographic Distribution of Hepatic Fascioliasis

2012; Elsevier BV; Volume: 10; Issue: 6 Linguagem: Inglês

10.1016/j.cgh.2012.02.013

1542-7714

Sarah E. Rowan, Marilyn E. Levi, Jean Youngwerth, Brian Brauer, Gregory T. Everson, Steven C. Johnson,

Parasites and Host Interactions

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries. We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries. Human fascioliasis is caused by 1 of 2 liver flukes, Fasciola hepatica or Fasciola gigantica. The disease has a broad geographic distribution, with 91.1 million people estimated to be at risk for infection.1Keiser J. Utzinger J. Emerging foodborne trematodiasis.Emerging Infect Dis. 2005; 11: 1507-1514Crossref PubMed Scopus (446) Google Scholar Before infecting definitive hosts, the flukes require fresh water snails as intermediate hosts.2Marcos L.A. Terashima A. Gotuzzo E. Update on hepatobiliary flukes: fascioliasis, opisthorchiasis, and clonorchiasis.Curr Opin Infect Dis. 2008; 21: 523-530Crossref PubMed Scopus (142) Google Scholar Thus, the risk for infection correlates with proximity to fresh water sources, which is continuously changing with global urbanization. Although reported in 5 continents, the majority of known infections occur in only a few discrete regions of the world.3World Health OrganizationReport of the WHO Informal Meeting on Use of Triclabendazole in Fascioliasis Control. WHO, Geneva, Switzerland2007Google Scholar Cases of fascioliasis in the United States occur almost exclusively in immigrants and returned travelers. Hence the diagnosis might be delayed by failure to recognize the clinical features of the disease or underappreciation of an epidemiologic exposure, especially in patients who have not recently traveled to regions associated with a high prevalence of fascioliasis.4Arjona R. Riancho J.A. Aguado J.M. et al.Fascioliasis in developed countries: a review of classic and aberrant forms of the disease.Medicine (Baltimore). 1995; 74: 13-23Crossref PubMed Scopus (213) Google Scholar, 5Norton R.A. Monroe L. Infection by Fasciola hepatica acquired in California.Gastroenterology. 1961; 41: 46-48Abstract Full Text PDF PubMed Google Scholar Clinical presentations of fascioliasis vary depending on the stage of infection. During the acute phase of the infection, patients might present with fever and severe right upper quadrant abdominal pain. Those presenting with chronic infection might complain of mild abdominal pain. The severity of illness in both stages ranges from asymptomatic infection to overwhelming hepatic infection causing death.2Marcos L.A. Terashima A. Gotuzzo E. Update on hepatobiliary flukes: fascioliasis, opisthorchiasis, and clonorchiasis.Curr Opin Infect Dis. 2008; 21: 523-530Crossref PubMed Scopus (142) Google Scholar, 4Arjona R. Riancho J.A. Aguado J.M. et al.Fascioliasis in developed countries: a review of classic and aberrant forms of the disease.Medicine (Baltimore). 1995; 74: 13-23Crossref PubMed Scopus (213) Google Scholar A 70-year-old man with a medical history of coronary artery disease presented with abdominal pain and fatigue. Three weeks before presenting for medical care, he had traveled to South Africa, Zambia, and Zimbabwe for his honeymoon. He had not traveled internationally in the 10 years preceding his honeymoon trip. During his trip, he went on safaris, stayed in lodges, drank bottled water, and ate food prepared by local cooks. He felt well throughout the trip, developing symptoms only after he returned to the United States. His review of systems was significant for weight loss and pain in his right lateral chest with deep inspiration. His vital signs at the time of his initial presentation were normal with a temperature of 37°C. Physical examination was remarkable for a systolic ejection murmur and right upper quadrant abdominal tenderness without guarding. His laboratory studies revealed leukocytosis of 12,300 white blood cells/mm3 with 21% eosinophils (absolute eosinophil count 2600 cells/mm3) and elevated liver transaminases (aspartate aminotransferase 229 U/L, alanine aminotransferase 456 U/L, alkaline phosphatase 145 U/L, bilirubin 0.7 mg/dL). A computed tomography scan of the abdomen and pelvis with contrast revealed a complex fluid collection in the right upper lobe of the liver, with hematoma tracking laterally along the right lobe of the liver (Figure 1) . Initial studies, including blood cultures, stool for ova and parasites, Entamoeba serology, and Echinococcus serology, were negative. An angiogram of the liver revealed no evidence of active bleeding. The patient's pain persisted during the next few weeks. He continued to lose weight (about 20 pounds) and experienced intermittent fevers. He was admitted to the University of Colorado Hospital for further evaluation. Magnetic resonance imaging of the liver revealed serpiginous tracts (Figure 2) . Peripheral eosinophilia had increased to 41% of total leukocytes (absolute eosinophil count 3700 cells/mm3). The findings of intermittent fevers, weight loss, eosinophilia, elevated liver transaminases with hypodense liver lesions and a subcapsular hematoma were consistent with acute Fasciola infection. In consultation with the Centers for Disease Control and Prevention, Fasciola serology testing was sent to a reference laboratory in Puerto Rico (Departmento de Patologica y Medicina de Laboratoria, Universidad de Puerto Rico, San Juan, Puerto Rico). While awaiting the results of the serology testing, the patient received a 7-day course of nitazoxanide, without improvement in symptoms or eosinophilia. The Falcon assay screening test–enzyme-linked immunosorbent assay (ELISA) results were in the intermediate range of absorbance at each dilution. A second laboratory (Parasitic Disease Consultants, Atlanta, GA) reported a positive ELISA to Fasciola with a titer of 1:32. The patient received 1 dose of triclabendazole 10 mg/kg, the treatment of choice for fascioliasis.3World Health OrganizationReport of the WHO Informal Meeting on Use of Triclabendazole in Fascioliasis Control. WHO, Geneva, Switzerland2007Google Scholar During the next 3 months his symptoms resolved and his eosinophil count normalized. Repeat imaging of the liver 6 and 12 months after treatment revealed progressive decreases in the size of the subcapsular hematoma and the intraparenchymal hypodensities. The second case occurred in a 60-year-old woman with an extensive travel history who presented with complaints of bilateral upper abdominal pain for 2 months, low-grade fevers, severe fatigue, and a 3-pound weight loss. The patient had no significant medical history, and her only medications were doxycycline or mefloquine, which she took for prophylaxis when she traveled. In the 10 years before she presented with her current symptoms, she had traveled to Colombia, Afghanistan, Pakistan, Malawi, Uganda, Mozambique, Ghana, and Rwanda for work-related duties. She typically stayed in Western-style hotels, drank bottled water, and occasionally ate fresh fruits and vegetables. She was married, had 1 grown son, and lived on a farm in Colorado. Physical examination revealed normal vital signs, and she was afebrile. The only abnormal finding on examination was mild abdominal tenderness without guarding or rebound tenderness. Her white blood cell count was 10,400/mm3. The differential revealed 32% eosinophils (absolute eosinophil count 2654 cells/mm3). Her liver transaminases were moderately elevated (alanine aminotransferase 53 U/L, aspartate aminotransferase 43 U/L, γ-glutamyltransferase 102 U/L, alkaline phosphatase 196 U/L). Her bilirubin level was normal (0.6 mg/dL). An ultrasound of the abdomen revealed a 10-cm hepatic mass, and a computed tomography scan of the abdomen revealed a multilocular cystic mass in the anterior segment of the right hepatic lobe (Figure 3) . Serologic tests for Echinococcus, Schistosoma, Strongyloides, Fasciola, and Entamoeba were negative. Stool cultures and examinations for ova and parasites were also negative. The patient underwent endoscopic retrograde cholangiopancreatography during which a parasite was detected within the biliary tree and retrieved endoscopically via sphincterotomy and balloon sweep, followed by aspiration and collection in a polyp trap (Figure 4, Figure 5) . The parasite was identified as F hepatica (Figure 6) . The patient received a single dose of triclabendazole 10 mg/kg orally, after which her eosinophil count quickly normalized. She subsequently developed ongoing abdominal pain and an elevated alkaline phosphatase of 371 U/L, which was attributed to cholangitis. Her symptoms resolved on oral amoxicillin-clavulanate 875 mg twice daily for 2 weeks. She also took ursodiol 600 mg twice daily for 6 months after normalization of alkaline phosphatase and resolution of abdominal pain.Figure 5Endoscopic image shows the parasite (arrow) as it is removed from the bile duct.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6F hepatica specimen retrieved from common bile duct.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fasciola was the first of the flukes for which the life cycle was fully characterized.6Mas-Coma S. Valero M.A. Bargues M.D. Chapter 2: Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.Adv Parasitol. 2009; 69: 41-146Crossref PubMed Scopus (480) Google Scholar Eggs develop in fresh water and release miracidia, which then enter aquatic snails where they transform into cercariae. The cercariae are then released back into fresh water and attach to aquatic vegetation. Usually while still attached to plants, the encysted metacercariae are then ingested by humans or more commonly domestic ruminants such as cattle or sheep. Inside the mammalian host, the metacercariae excyst, and the larvae penetrate the intestinal wall and migrate through the peritoneal cavity to the liver. They penetrate Glisson capsule and traverse through the liver parenchyma, leading to necrosis and microabscesses, which cause the characteristic track-like lesions seen on liver imaging. Damage to liver vasculature might cause subcapsular and pericapsular hematomas at this stage.2Marcos L.A. Terashima A. Gotuzzo E. Update on hepatobiliary flukes: fascioliasis, opisthorchiasis, and clonorchiasis.Curr Opin Infect Dis. 2008; 21: 523-530Crossref PubMed Scopus (142) Google Scholar, 7Han J.K. Choi B.I. Cho J.M. et al.Radiological findings of human fascioliais.Abdom Imaging. 1993; 18: 261-264Crossref PubMed Scopus (83) Google Scholar When present, symptoms of disease during this acute or “liver” stage might include fever, right upper quadrant abdominal pain, hepatomegaly, anorexia, urticaria, anemia, and elevated eosinophil counts. Most patients are asymptomatic. The flukes eventually migrate to the biliary ducts, where they develop into adults and might live for several years and cause chronic infection. The chronic or “biliary” stage of disease might also be asymptomatic, or patients might present with biliary colic, nonspecific abdominal pain, nausea, vomiting, diarrhea, weight loss, hepatomegaly, or jaundice.2Marcos L.A. Terashima A. Gotuzzo E. Update on hepatobiliary flukes: fascioliasis, opisthorchiasis, and clonorchiasis.Curr Opin Infect Dis. 2008; 21: 523-530Crossref PubMed Scopus (142) Google Scholar, 4Arjona R. Riancho J.A. Aguado J.M. et al.Fascioliasis in developed countries: a review of classic and aberrant forms of the disease.Medicine (Baltimore). 1995; 74: 13-23Crossref PubMed Scopus (213) Google Scholar Obstruction of the common bile duct during the chronic phase has also been reported.8Gulsen M.T. Savas M.C. Koruk M. et al.Fascioliasis: a report of five cases presenting with common bile duct obstruction.Neth J Med. 2006; 64: 17-19PubMed Google Scholar Eosinophilia at this stage is variable. Eggs from the adult flukes pass into the stool, recontaminating the water source.3World Health OrganizationReport of the WHO Informal Meeting on Use of Triclabendazole in Fascioliasis Control. WHO, Geneva, Switzerland2007Google Scholar, 4Arjona R. Riancho J.A. Aguado J.M. et al.Fascioliasis in developed countries: a review of classic and aberrant forms of the disease.Medicine (Baltimore). 1995; 74: 13-23Crossref PubMed Scopus (213) Google Scholar Although a well-known disease of livestock for decades, fascioliasis was only recently declared a human parasitic disease of major global and regional importance by the World Health Organization (WHO) in 2007. Fascioliasis has been recognized as one of the most neglected among neglected tropical diseases.3World Health OrganizationReport of the WHO Informal Meeting on Use of Triclabendazole in Fascioliasis Control. WHO, Geneva, Switzerland2007Google Scholar In 1995, WHO created an initiative to increase awareness of food-borne trematode infections in humans. Their estimate of disease prevalence at the time was 2.4 million.4Arjona R. Riancho J.A. Aguado J.M. et al.Fascioliasis in developed countries: a review of classic and aberrant forms of the disease.Medicine (Baltimore). 1995; 74: 13-23Crossref PubMed Scopus (213) Google Scholar, 9World Health OrganizationControl of foodborne trematode infections: report of a WHO study group. World Health Organization, Geneva, Switzerland1995Google Scholar Other estimates suggest prevalence of infection might be closer to 17 million cases worldwide, although the actual prevalence is unknown.10Hopkins D.R. Homing in on helminthes.Am J Trop Med Hyg. 1992; 46: 626-634Crossref PubMed Scopus (104) Google Scholar, 11Mas-Coma S. Epidemiology of fascioliasis in human endemic areas.J Helminthol. 2005; 79: 207-216Crossref PubMed Scopus (267) Google Scholar WHO estimates that 180 million people worldwide are at risk for the infection.3World Health OrganizationReport of the WHO Informal Meeting on Use of Triclabendazole in Fascioliasis Control. WHO, Geneva, Switzerland2007Google Scholar, 10Hopkins D.R. Homing in on helminthes.Am J Trop Med Hyg. 1992; 46: 626-634Crossref PubMed Scopus (104) Google Scholar The countries with the highest reported rates of fascioliasis are Bolivia, Peru, Puerto Rico, Ecuador, Cuba, Egypt, the Islamic Republic of Iran, Vietnam, Turkey, Spain, France, and Portugal.3World Health OrganizationReport of the WHO Informal Meeting on Use of Triclabendazole in Fascioliasis Control. WHO, Geneva, Switzerland2007Google Scholar, 11Mas-Coma S. Epidemiology of fascioliasis in human endemic areas.J Helminthol. 2005; 79: 207-216Crossref PubMed Scopus (267) Google Scholar Fasciola infections occur on 5 continents and have the widest latitudinal, longitudinal, and altitudinal distribution among diseases requiring a vector or an intermediate host. The infection has been reported in areas from 27 m below sea level up to 4200 m above sea level.11Mas-Coma S. Epidemiology of fascioliasis in human endemic areas.J Helminthol. 2005; 79: 207-216Crossref PubMed Scopus (267) Google Scholar The global distribution of fascioliasis reflects the fluke's ability to adapt to a variety of fresh water habitats and mammalian hosts, as well as the widening ecological niche of Lymnaeid snails, the intermediate hosts.6Mas-Coma S. Valero M.A. Bargues M.D. Chapter 2: Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.Adv Parasitol. 2009; 69: 41-146Crossref PubMed Scopus (480) Google Scholar The plants to which the metacercariae adhere are most commonly reported to be watercress, although alfalfa, khat, and lettuce are also frequently associated with the infection, and the cysts might be ingested from contaminated water alone. The definitive host is commonly a domestic ruminant, although Fasciola flukes have also been recovered from several wild animals.6Mas-Coma S. Valero M.A. Bargues M.D. Chapter 2: Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.Adv Parasitol. 2009; 69: 41-146Crossref PubMed Scopus (480) Google Scholar, 11Mas-Coma S. Epidemiology of fascioliasis in human endemic areas.J Helminthol. 2005; 79: 207-216Crossref PubMed Scopus (267) Google Scholar, 12Hammond J.A. Infections with Fasciola spp in wildlife in Africa.Trop Anim Health Prod. 1972; 4: 1-13Crossref PubMed Scopus (12) Google Scholar Although the definitive host is crucial for the reproduction of the fluke, areas with high prevalence of infection in animals and humans are only loosely correlated.11Mas-Coma S. Epidemiology of fascioliasis in human endemic areas.J Helminthol. 2005; 79: 207-216Crossref PubMed Scopus (267) Google Scholar, 13Mas-Coma M.S. Esteban J.G. Bargues M.D. Epidemiology of human fascioliasis: a review and proposed new classification.Bull World Health Organ. 1999; 77: 340-346PubMed Google Scholar Because snails play an integral role in the life cycle of the fluke, Fasciola infection is associated with proximity to fresh water. The relative risk for trematode infection in villages near fresh water bodies is 2.15. As aquaculture for fish production has increased, bringing fresh water bodies closer to human residences, rates of trematodiasis have concurrently increased.1Keiser J. Utzinger J. Emerging foodborne trematodiasis.Emerging Infect Dis. 2005; 11: 1507-1514Crossref PubMed Scopus (446) Google Scholar With the exception of Egypt where up to 830,000 people might be infected,6Mas-Coma S. Valero M.A. Bargues M.D. Chapter 2: Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.Adv Parasitol. 2009; 69: 41-146Crossref PubMed Scopus (480) Google Scholar, 14Soliman M.F. Epidemiological review of human and animal fascioliasis in Egypt.J Infect Dev Ctries. 2008; 2: 182-189Crossref PubMed Scopus (57) Google Scholar human fascioliasis is not considered prevalent in African countries. The first known case of human fascioliasis in Africa was reported in 1895, followed by isolated case reports from Malawi, Cameroon, Burundi, Rwanda, Uganda, and Rhodesia during the next half century.15Fanthom H.B. Braun M.G. Stephens J.W. et al.The animal parasites of man.in: J Bale, Sons & Danielsson Ltd, New York, Wood1916: 244-245Google Scholar, 16Hammond J.A. Human infection with the liver fluke Fasciola gigantica.Trans R Soc Trop Med Hyg. 1974; 68: 253-254Abstract Full Text PDF PubMed Scopus (19) Google Scholar In a 1946 study of human stool specimens in Zimbabwe, Fasciola eggs were detected in 2 samples (0.04%), suggesting that the parasite was present but not prevalent in the area.17Goldsmith J.M. Studies on intestinal helminthes in African patients at Harari Central Hospital, Rhodesia.Trans R Soc Trop Med Hyg. 1968; 62: 619-629Abstract Full Text PDF PubMed Scopus (21) Google Scholar More recent reports of human fascioliasis acquired in Africa have been associated with travel, immigration, or imported vegetables. During the last 2 decades in the United States, 3 cases of human fascioliasis thought to have been acquired in Cape Verde have been reported.18Graham C.S. Brodie S.B. Weller P.F. Imported Fasciola hepatica infection in the United States and treatment with triclabendazole.Clin Infect Dis. 2001; 33: 1-6Crossref PubMed Scopus (70) Google Scholar, 19Price T.A. Tuazon C.U. Simon G.L. Fascioliasis: case reports and review.Clin Infect Dis. 1993; 17: 426-430Crossref PubMed Scopus (78) Google Scholar In the United Kingdom, 11 cases were confirmed at the national reference laboratory in 2008 and 2009. Two of the cases occurred in British citizens after travel to Uganda and Kenya. The other cases occurred in immigrants from Somalia, Ethiopia, and Yemen who were thought to have acquired the infection while in the United Kingdom from imported khat.20Chand M.E. Herman J.A. Partridge D.G. et al.Imported human fascioliasis, United Kingdom.Emerging Infect Dis. 2009; 15: 1876-1877Crossref PubMed Scopus (16) Google Scholar During the last few decades reports of human fascioliasis in southern Africa have been absent from the medical literature, although a recent snail study revealed the presence of Lymnaea truncatula, the intermediate host for F hepatica, in several loci throughout South Africa, suggesting suitable conditions for F hepatica existing there despite a lack of reported cases.21De Kock K.N. Wolmarans C.T. Bornman M. Distribution and habitats of the snail Lymnaea truncatula, intermediate host of the liver fluke Fasciola hepatica, in South Africa.J S Afr Vet Assoc. 2003; 74: 117-122Crossref PubMed Scopus (23) Google Scholar Although the actual global prevalence of human fascioliasis is unknown, increased estimates of the prevalence of the infection in the last decade likely reflect many factors. Increased surveillance, global urbanization and expansion of aquaculture, and the parasite's ability to adapt to a variety of fresh water environments, snail hosts, and mammalian hosts are all likely contributors to the expanding epidemiology of the infection. In addition, diagnosis of fascioliasis in individuals without known geographic exposures might represent prior underestimates of disease prevalence in certain countries. Fascioliasis might be diagnosed by detection of ova in stool or biliary aspirates during the chronic phase of the disease, although this method lacks sensitivity because egg production by adult flukes might be low and intermittent.2Marcos L.A. Terashima A. Gotuzzo E. Update on hepatobiliary flukes: fascioliasis, opisthorchiasis, and clonorchiasis.Curr Opin Infect Dis. 2008; 21: 523-530Crossref PubMed Scopus (142) Google Scholar, 6Mas-Coma S. Valero M.A. Bargues M.D. Chapter 2: Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.Adv Parasitol. 2009; 69: 41-146Crossref PubMed Scopus (480) Google Scholar In the acute phase, the immature flukes have not migrated to the biliary tract yet and are not producing eggs. Diagnosis during the acute phase might be through clinical features such as peripheral eosinophilia and characteristic findings on liver imaging, or serologic tests. ELISAs are the most commonly used serologic tests, with sensitivities ranging from 92% to 100% and specificities ranging from 84% to 98%.22Hillyer G.V. Soler de Galanes M. Rodriguez-Perez J. et al.Use of the Falcon assay screening test–enzyme-linked immunosorbent assay (FAST-ELISA) and the enzyme-linked immunoelectrotransfer blot (EITB) to determine the prevalence of human fascioliasis in the Bolivian Altiplano.Am J Trop Med Hyg. 1992; 46: 603-609Crossref PubMed Scopus (155) Google Scholar, 23Apt W. Aguilera X. Vega F. et al.Treatment of human chronic fascioliasis with triclabendazole: drug efficacy and serologic response.Am J Trop Med Hyg. 1995; 52: 532-535Crossref PubMed Scopus (107) Google Scholar, 24Espinoza J.R. Maco V. Marcos L. et al.Evaluation of Fas2-ELISA for the serological detection of Fasciola hepatica infection in humans.Am J Trop Med Hyg. 2007; 76: 977-982Crossref PubMed Scopus (92) Google Scholar The gold standard for diagnosis of infection with an adult fluke is retrieval of the organism from the gastrointestinal tract, as occurred in the second case that we reported. Interestingly, the ELISA in this case was negative despite a high reported sensitivity for this test. Our cases of Fasciolia infection occurred in travelers returning from countries in which human fascioliasis is not endemic. It is likely that fascioliasis might be more common in Africa than previously reported. The diagnosis of fascioliasis is frequently delayed because of the low incidence of the infection in the United States, an underappreciation of the changing epidemiology, and the variability in clinical features. Because of the broadening epidemiologic distribution associated with global urbanization and the fluke's adaptability to a variety of habitats and intermediate and definitive hosts, fascioliasis should be considered in all patients with an international travel history who present with eosinophilia, upper abdominal pain, or liver lesions.