Fasciola hepatica Infection in the United States
Transcription
Fasciola hepatica Infection in the United States
CE Update Fasciola hepatica Infection in the United States Adnan Alatoom, MD, PhD, Dominick Cavuoti, DO, Paul Southern, MD, Rita Gander, PhD (Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX) DOI: 10.1309/MLFFXA77UBBFH4GP Abstract Enzyme-linked immunosorbent assay (ELISA) testing is sensitive for both stages while stool exams for F. hepatica eggs are positive only in the biliary stage. Radiographic findings using computed tomography and ultrasonography are not specific but support the diagnosis. Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly used to diagnose F. hepatica and After reading this article, readers should be able to discuss Fasciola hepatica and its epidemiology, life cycle, clinical features, diagnosis, and treatment. to remove the adult fluke from the biliary tree. Triclabendazole is currently the recommended drug for treating F. hepatica infection. The rarity of the disease in the United States can result in a delayed diagnosis and sometimes in mismanagement. Physicians should consider this infection in patients with abnormal liver function and peripheral eosinophilia, especially in the immigrant population. Microbiology 70802 questions and corresponding answer form are located after this CE Update on page 429. Epidemiology Life Cycle Fascioliasis is a worldwide disease caused by Fasciola hepatica. The genus name is derived from the Latin word fasciola, meaning fascia or band. Fasciola hepatica is a liver fluke, a term that refers to the flat or rhomboid shape of the adult form of the parasite. Fasciola hepatica infects herbivores (such as sheep, goats, and cattle) as well as humans, who become infected by ingesting contaminated water or plants, including watercress, lettuce, and spinach.1 Up to 2.4 million people are infected with F. hepatica worldwide.2 In 1998, Esteban and colleagues compiled 7,071 human cases in 51 countries in 5 geographic regions during the preceding 25 years, distributed as follows: Africa (487), America (3,267), Asia (354), Europe (2,951), and Oceania (12).2,3 Countries with high and intermediate prevalence include Peru, Bolivia, Egypt, Iran, Puerto Rico, and Portugal.2 Because fascioliasis is a rare disease in the United States, there is no reported prevalence of the disease in this country. Although most reported cases were related to travel outside the United States, native cases have also been reported since the conditions that allow completion of the life cycle, including snail host, climate conditions (soil and sufficient moisture that is suitable for the snail population primarily in the Gulf Coast and western states), and raising animals, are present in the United States.2,4,5 Bovine fascioliasis is a significant problem in the southern, central, and western regions of the United States. For example, El Bahy and colleagues reported that approximately 5% of the cattle in the United States are infected4; however, MacLean and Graeme-Cook reported that the infection rate in beef cattle in California and Florida is 53% and 68%, respectively.6 The eggs of F. hepatica are excreted in the feces of infected animals and hatch into ciliated miracidia in water after 9 to 15 days (Figure 1).7-9 The eggs measure 130 to 150 μm by 63 to 90 μm and have an indistinct operculum (Figure 2). They are usually ellipsoidal and light yellow-brown in color. The miracidia find the intermediate host (freshwater Lymnaea snail) where they grow into the cercarial form. The cercariae leave the snail, encyst on aquatic vegetation, and develop into the metacercarial stage.10 When sheep, cattle, or humans ingest metacercariae, these infective forms excyst in the intestine, perforate the intestinal wall, and pass through the peritoneum to the liver and biliary tree. The mature fluke releases eggs into feces and ultimately to the environment, where another life cycle begins.7 The adult form measures up to 30 mm by 13 mm, has a cone-shaped anterior end, and the internal organs are extensively branched (Figure 3). labmedicine.com Clinical Features Infection with F. hepatica has 2 clinical phases with different signs and symptoms.11 One to 3 months after ingestion of metacercariae, the hepatic (acute) phase occurs when the worm enters the liver and begins to migrate through the parenchyma.8,12 The clinical features and laboratory findings of this stage include fever, right-upper-quadrant pain, nausea, anorexia, vomiting, eosinophilia, urticaria, hepatomegaly, jaundice, pruritis, weight loss, elevated liver enzymes, and hypergammaglobulinemia.11 This stage can be complicated by mild hepatitis, hepatic necrosis, and subcapsular hemorrhage. The biliary (chronic) stage can remain asymptomatic July 2008 j Volume 39 Number 7 j LABMEDICINE 425 Downloaded from http://labmed.oxfordjournals.org/ by guest on October 12, 2016 Fascioliasis is a worldwide infection caused by the liver fluke, Fasciola hepatica. In the United States, fascioliasis is an uncommon infection and is mainly reported among the immigrant population. Fasciola hepatica infection comprises 2 distinct stages (hepatic and biliary) and manifests mainly as abdominal pain, elevated liver enzymes, and eosinophilia. CE Update Diagnosis and Treatment Figure 2_Saline preparation of Fasciola hepatica egg in the stool (40x). The arrow indicates the operculum of the egg. 426 LABMEDICINE j Volume 39 Number 7 j July 2008 Figure 3_Gross appearance of the adult flukes of Fasciola hepatica. The adult fluke is flat, brownish, and measures approximately 2.5 to 3 x 1 cm. labmedicine.com Downloaded from http://labmed.oxfordjournals.org/ by guest on October 12, 2016 Diagnosis of fascioliasis is difficult without high clinical suspicion. Testing the stool for the presence of F. hepatica eggs is useful to establish the diagnosis; however, these eggs are absent in the stool in the acute stage of fascioliasis. Antibody detection using the enzymelinked immunosorbent assay (ELISA) has a high sensitivity (98%) in both acute and chronic infections but lacks optimal specificity due to cross reactivity with other parasitic infections such as echinococcosis and schistosomiasis.5,13 In animal models, antibodies are detected within 4 weeks of infection and can persist for years. With effective treatment, titers return to baseline after 18 to 21 weeks.5 Imaging techniques, such as computed tomography (CT) and ultrasonography (US), are not specific but can support the diagnosis of fascioliasis and assess the response to treatment. Computed tomography may demonstrate different types of lesions, such as single or multiple hypodense nodular areas due to deposition of the parasite, tunnel-like branching due to the migration of the parasite in the liver, frequent subcapsular location of lesions, and dilatation of bile ducts.5,8,13 Ultrasonography has variable sensitivities for detecting hepatic lesions and might be more useful in biliary fascioliasis since it may show gallbladder wall thickening, duct dilatation, and the adult fluke in the gallbladder or bile duct.3,5,14 In biliary fascioliasis, endoscopic retrograde cholangiopancreFigure 1_Life cycle of Fasciola hepatica. Reprinted from the Institute of Tropical Medicine atography (ERCP) and sphincterotomy (ITM), Antwerp, Belgium. have been used for diagnosis and therapy to extract the parasites from the biliary tree by balloon or basket.1,8,10,15,16 In for many years or present with intermittent right-upperfact, the infection is sometimes diagnosed unexpectedly by quadrant pain, cholangitis, cholestasis, pancreatitis, bile duct ERCP in patients suspected of having choledocholithiasis. stones, and biliary obstruction due to duct-wall thickening or Triclabendazole is currently the recommended treatment mechanical obstruction.11 of choice. Bithionol may also be used but is less effective CE Update than triclabendazole. Mebendazole, albendazole, and praziquantel have been used with variable success.8 Fascioliasis in the United States To examine the status of fascioliasis in the United States, we searched the literature available on the Internet for cases that have been reported in this country. We were able to find 9 cases reported in different states during the period from 1993 to 2006. We summarized the details of these cases for the following: age and sex of the patient, state where the case was reported, tests ordered to reach the final diagnosis, history of watercress ingestion and travel, time of presentation after the patient returned to the United States in cases which were associated with travel, and medication administered to the patients for the suspected diagnosis. Table 1 shows that the patients included 7 males and 2 females from different states and with a mean age of 44.7 years. Some of these patients required multiple tests and a prolonged period (a few days to 4 months) to reach a final diagnosis of fascioliasis. Stool exams for F. hepatica eggs was positive in only 2 of the 9 cases, possibly due to the absence of eggs in the stool in the acute phase of the disease, sporadic release of eggs, and the wide variation in the number of eggs excreted.5,11,17 Due to the presence of eosinophilia in some of these patients, serology for other parasites including Entamoeba histolytica, Echinococcus granulosus, and Toxocara canis were ordered and appeared to be negative. Six cases were diagnosed by serology using ELISA, indirect immunofluorescence (IIF), indirect hemagglutination, and immunoelectrophoresis. In all of these cases, CT and US were used to show the abnormalities in the liver and bile duct, exclude other abnormalities, and support the final diagnosis. Endoscopic retrograde cholangiopancreatography and sphincterotomy were necessary to diagnose and treat the infection in 2 cases. This scenario usually occurs in patients with extrahepatic bile dilatation, evidence of cholestasis, and a suspicion of choledocholithiasis. Roig explored the importance of ERCP and reported the increase in using ERCP in the diagnosis and Conclusion The long time required to reach a final diagnosis, extensive tests ordered for the patients, unexpected diagnosis of fascioliasis by ERCP, and the inappropriate medication administered to some patients reflect the rarity of the disease and the low index of suspicion in the United States. Physicians should consider fascioliasis in the differential diagnosis of abdominal pain, abnormal liver function, and eosinophilia, especially in the immigrant population. LM Table 1_Review of 9 Cases of Fascioliasis Reported in the United States Age/Sex/ State Tests Required for Final Dx 25/M/KY O/P, US, CT, serology, ERCP 28/M/TX O/P, CT, US, ERCP 26/F/NY O/P, STOP, CT, RBC scan, MRI, serology (IIF, IEP) 51/M/FL O/P, STOP, CT, liver bx, US, laparoscopy, ERCP, serology (IIF, IH, IEP) 67/M/MA US, CT, MRI, paracentesis, duodenal/liver bx, O/P, ELISA 65/M/NY O/P, STOP, CT, liver bx, MRI, serology (IIF, IEP) 56/M/WA CT, liver bx, STOP, O/P 33/M/MA O/P, US, ELISA 52/F/WA O/P, CT, HIDA scan, STOP, ELISA History of Watercress Ingestion/Travel Time of Presentation After Return to USA Medication or Management Reference N/Y (Mexico) Y/Y (Peru) Y/Y (Dominican Republic) 2.5 yr NA 1 mo Antibiotics, mebendazole, cholecystectomy Antibiotics, TCB, cholecystectomy TCB 8 16 9 Y/N NA Antibiotics, albendazole, TCB 13 N/Y (Cape Verde) 3 wk * TCB 5 Y/Y (Ireland) 1 mo Prednisone, TCB 19 Praziquantel TCB Praziquantel, bithionol 20 5 20 N/Y (Puerto Rico, East Africa) 1 and 2 mo† Y/Y (Cape Verde) 2 wk ‡ Y/Y (Cape Verde) NA Dx, diagnosis; NA, not available; O/P, stool for ova and parasite; STOP, serology to other parasites; IIF, indirect immunofluorescence; IH, indirect hemagglutination; IEP, immunoelectrophoresis; CT, computed tomography; bx, biopsy; US, ultrasonography; ERCP, endoscopic retrograde cholangiopancreatography; TCB, triclabendazole; RBC, red blood cell; MRI, magnetic resonance imaging; HIDA, hepatobiliary iminodiacetic acid; Y, present; N, not present. Bold words represent the test that revealed the presence of fascioliasis. * Symptoms started 3 mo before returning to U.S.A. † Symptoms started 1 and 2 mo after returning from Puerto Rico and East Africa respectively. ‡ Symptoms started 10 mo before returning to the U.S.A. labmedicine.com July 2008 j Volume 39 Number 7 j LABMEDICINE 427 Downloaded from http://labmed.oxfordjournals.org/ by guest on October 12, 2016 treatment of fascioliasis during the period from 1980 to 2000 even in a hyperendemic area (Bolivia).18 Liver biopsy was used in 4 cases and showed eosinophilic infiltration, loss of liver parenchyma, necrosis, and fibrosis. In 1 case, a red blood cell scan was performed to rule out hepatic hemangioma or adenoma suspected by magnetic resonance imaging (MRI). The patients were treated with different regimens of medication that targeted the wrong diagnosis in 2 cases. The first patient received steroids for the suspicion of drug reaction and vasculitis, and the authors reported that steroids could have allowed the flukes to develop more quickly and caused more hepatic damage.19 The second patient received albendazole for the suspicion of visceral larva migrans without improvement of symptoms until the patient received triclabendazole.13 Two patients underwent cholecystectomy to exclude the presence of F. hepatica or stones in the gallbladder. Table 1 also shows that 8 of the 9 cases were associated with travel outside the United States, and 6 of the 9 cases were associated with watercress ingestion. The only native case that was reported in Florida was associated with watercress ingestion. The patient stated that he did so after watching a television news report about the health benefits of watercress.13 The short time (up to 2 months) before presentation of these patients after their return to the United States further supports that these infections were acquired outside the United States. Only 1 patient had symptoms after 2.5 years, probably due to an asymptomatic infection. CE Update 1. Gulsen MT, Savas MC, Koruk M, et al. Fascioliasis: A report of five cases presenting with common bile duct obstruction. Neth J Med. 2006;64:17–19. 2. Mas-Coma MS, Esteban JG, Bargues MD. Epidemiology of human fascioliasis: A review and proposed new classification. Bull WHO. 1999;77:340–346. 3. Esteban JG, Bragues MD, Mas-Coma S. Geographical distribution, diagnosis, and treatment of human fascioliasis: A review. Res Rev Parasitology. 1998;58:13–48. 4. El Bahy MM, Malone Jr JB, Todd WJ, et al. Diagnosis of Fasciola infections by detection of antigens in feces or intestinal content. 1994. Available at: www.freepatentsonline.com/5338660.html. 5. Graham CS, Brodie SB, Weller PF. Imported Fasciola hepatica infection in the United States and treatment with triclabendazole. Clin Infect Dis. 2001;33:1–5. 6. MacLean JD, Graeme-Cook FM. Case records of the Massachusetts General Hospital: Weekly clinicopathological exercises. Case 12-2002: A 50-yearold man with eosinophilia and fluctuating hepatic lesions. N Engl J Med. 2002;346:1232–1239. 11. Aksoy DY, Kerimoglu U, Oto A, et al. Fasciola hepatica infection: Clinical and computerized tomographic findings of ten patients. Turk J Gastroenterol. 2006;17:40–45. 12. Saba R, Korkmanz M, Inan D, et al. Human fascioliasis. Clin Microbiol Infect. 2004;10:385–387. 13. Neff GW, Dinavahi RV, Chase V, et al. Laparoscopic appearance of Fasciola hepatica infection. Gastrointest Endosc. 2001;53:668–671. 14. Van Beers B, Pringot J, Geubel A, et al. Hepatobiliary fascioliasis: Noninvasive imaging findings. Radiology. 1990;174:809–810. 15. Cheung J, Enns R, Romney M, et al. Biliary fascioliasis. Gastrointest Endosc. 2005;61:596–597. 16. Clark BM, Lloyd BA, Christopher GW, et al. A young man from Peru with fever and abdominal pain. Clin Infect Dis. 2005;40:879–880. 17. Adachi S, Kotani K, Shimizu T, et al. Asymptomatic fascioliasis. Intern Med. 2005;44:1013–1015. 18. Roig GV. Hepatic fascioliasis in the Americas: A new challenge for therapeutic endoscopy. Gastrointest Endosc. 2002;56:315–317. 19. LaPook JD, Magun AM, Nickerson KG, et al. Sheep, watercress, and the Internet. Lancet. 2000;356:218. 8. Fullerton JK, Vitale M, Vitale GC. Therapeutic endoscopic retrograde cholangiopancreatography for the treatment of Fasciola hepatica presenting as biliary obstruction. Surg Innov. 2006;13:179–182. 20. Price TA, Tuazon CU, Simon GL. Fascioliasis: Case reports and review. Clin Infect Dis. 1993;17:426–430. Downloaded from http://labmed.oxfordjournals.org/ by guest on October 12, 2016 7. Aksoy DY, Kerimoglu U, Oto A, et al. Infection with Fasciola hepatica. Clin Microbiol Infect. 2005;11:859–861. 9. Noyer CM, Coyle CM, Werner C, et al. Hypereosinophilia and liver mass in an immigrant. Am J Trop Med Hyg. 2002;66:774–776. 10. Ozer B, Serin E, Gumurdulu Y, et al. Endoscopic extraction of living Fasciola hepatica: Case report and literature review. Turk J Gastroenterol. 2003;14:74–77. 428 LABMEDICINE j Volume 39 Number 7 j July 2008 labmedicine.com