Hepatitis E Among U.S. Travelers, 1989-1992

Outbreaks of hepatitis E (i.e., enterically transmitted non-A, non-B hepatitis) have occurred in some parts of the world and have generally been related to contaminated water supplies. Until recently, when research-based serologic tests (1,2) were developed to test for antibody to hepatitis E virus (anti-HEV), no serologic test was available to identify HEV infection, and diagnosis depended on a history of exposure in an appropriate epidemiologic setting and the exclusion of other causes of viral hepatitis. During 1989-1992, acute HEV infection was documented among six persons in the United States who had returned from international travel. This report summarizes CDC's serologic documentation of acute HEV infection -- presumed to have been acquired during international travel -- in four of these persons. Patient 1

On February 23, 1991, a woman from Denver traveled to Rosarito Beach, Mexico, for 1 day (3). On March 17, she developed headache and nausea, and on March 23, became jaundiced. A serum specimen obtained on March 23 demonstrated a serum aspartate aminotransferase (AST) level of 2100 U/L (normal: 0-35 U/L), an alkaline phosphatase level of 516 U/L (normal: 110-295 U/L), and a total bilirubin level of 7.5 mg/dL (normal: 0-1 mg/dL). Physical examination was normal except for jaundice. Tests for serologic markers for hepatitis A, B, and C were negative, and an ultrasonogram of the liver was normal. Serum samples obtained on April 18 and May 31 were positive for anti-HEV by fluorescent antibody (FA) blocking assay (titers of 1:512 and 1:128, respectively) and by a Western blot assay.

The patient had no underlying medical problems and denied excessive alcohol consumption, injecting-drug use (IDU), blood transfusions, or contact with anyone known to have hepatitis during the 6 months before onset of her illness. Although the source of infection for this patient was not clearly established, she reported drinking margaritas with crushed ice at two restaurants and eating salsa and chips while in Mexico; she denied drinking water or eating other uncooked food. The patient recovered fully.

Although her three traveling companions also consumed margaritas with ice, they did not become ill, and serum samples from all three were negative for anti-HEV. Patient 2

During June 1991, a high school student, who had been born in India but lived in the United States since the age of 1 year, traveled to Varanasi, India. Before his trip he received prophylactic immune globulin. Approximately 4 weeks after his arrival in India, he developed diarrhea, sore throat, fever, and general malaise and subsequently had weight loss of 20 pounds. On return to the United States, 1 week after onset of his symptoms, physical examination revealed scleral icterus and a mildly tender and enlarged liver. Serum samples included AST of 1262 U/L (normal: 15-37 U/L), total bilirubin of 5.5 mg/dL (normal: 0-1 mg/dL), and an alkaline phosphatase of 245 U/L (normal: 50-136 U/L). Although serologic markers for hepatitis A, B, and C were negative, anti-HEV was detected by FA blocking assay.

The patient denied a history of alcohol abuse, IDU, blood transfusions, or known contact with anyone diagnosed with hepatitis. The patient reported that during his stay in Varanasi, most of the drinking water he consumed was boiled or commercially filtered. However, he reported he occasionally drank unboiled or unfiltered water, and he swam in the Ganges River. The patient recovered fully. Patient 3

From mid-June through the end of July 1989, a male college student traveled to Pakistan, Nepal, and India. Before his trip, he received prophylactic immune globulin. After his return to the United States, he developed nausea, fever, epigastric discomfort, and marked fatigue. Physical examination revealed scleral icterus and a mildly tender and enlarged liver. Serum samples included an AST of 2256 U/L (normal: 9-53 U/L), total bilirubin of 6.4 mg/dL (normal: 0.2-1.4 mg/dL), and an alkaline phosphatase of 258 U/L (normal: 30-125 U/L). Although tests for serologic markers for hepatitis A, B, and C were negative, anti-HEV was detected by FA blocking assay at a titer of 1:1024.

The patient denied a history of alcohol abuse, IDU, blood transfusions, or known contact with anyone diagnosed with hepatitis. The patient reported that during his trip abroad he did not boil his drinking water (he treated the water with iodine), and he swam in the Ganges River. The patient recovered fully. Patient 4.

From June through August 1991, a woman who had lived in India until 1988 (when she moved to the United States) traveled to India. Approximately 1 month following her return to the United States, she developed fever, nausea, intermittent vomiting, anorexia, fatigue, and abdominal discomfort. Serum specimens included an AST of 1717 U/L (normal: 15-47 U/L), total bilirubin of 2.5 mg/dL (normal: 0-1 mg/dL), alanine aminotransferase of 1580 (normal: 30- 65 U/L), and alkaline phosphatase of 172 U/L (normal: 50-136 U/L). Although tests for serologic markers for hepatitis A, B, and C were negative during her acute illness, both IgM and IgG class anti-HEV were detected by Western blot assay. The patient denied a history of alcohol abuse, IDU, blood transfusions, or known contact with anyone diagnosed with hepatitis. Information was not available regarding her risk exposure (e.g., food and water consumed) while in India.

Reported by: JL Herrera, MD, Univ of South Alabama, Mobile; S Hill, J Shaw, M Fleenor, MD, Jefferson County Health Dept, Birmingham, Alabama. T Bader, MD, Denver. MS Wolfe, MD, Traveler's Medical Svc, Washington, DC. Hepatitis Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The first documented outbreak of hepatitis E (diagnosed retrospectively) occurred in New Delhi, India, in 1955, when 29,000 cases occurred following fecal contamination of the city water supply (4). Outbreaks also have been confirmed in Africa and in the central Asian republics of the former Soviet Union, Afghanistan, Bangladesh, Borneo, Burma, China, India, Mexico, Mongolia, Nepal, Pakistan, and several countries in the Middle East (4,5). The estimated numbers of persons affected in these outbreaks have ranged from fewer than 100 to 29,000. Recent reports from Sudan, Ethiopia, and Egypt have suggested that HEV infection may account for a substantial proportion of acute sporadic hepatitis in adults and children in these countries (6-8). The confirmation of HEV infection in persons in Mexico suggests that HEV infection may be more widespread, particularly along the United States-Mexico border.

Endemic HEV transmission has not yet been documented in the United States. Although the sources of infection could not be established for the four persons described in this report, these persons represent the first serologically documented cases of HEV infection among U.S. residents who have returned from travel abroad.

Transmission of HEV occurs by the fecal-oral route; fecally contaminated drinking water has been the most commonly implicated vehicle of transmission. The incubation period ranges from 2 to 9 weeks with a mean of approximately 45 days (4). Attack rates during outbreaks have been highest in persons aged 15-40 years. The average case-fatality rate among pregnant women is 15%-20%.

Hepatitis A is the most common cause of viral hepatitis among U.S. residents who travel abroad -- particularly among persons who have traveled to countries with endemic hepatitis A and who have not received prophylactic immune globulin. Immune globulin prophylaxis for prevention of hepatitis A is recommended for U.S. residents who travel to developing countries (9). However, prophylaxis with immune globulin prepared from plasma collected in the United States is unlikely to prevent HEV infection, and travelers must diligently avoid food and water that is potentially contaminated with human feces.

HEV infection should be considered in any person who has traveled abroad but is negative for serologic markers for hepatitis A, B, or C--even though seroconversion to anti-HCV may not be detected until 6 months after onset of symptoms. Health-care professionals should obtain a detailed history regarding sources of drinking water, uncooked food, and contact with persons with hepatitis from all international travelers returning to the United States who have signs and symptoms of viral hepatitis. All cases of acute viral hepatitis should be reported to state health departments. Health-care professionals who require additional information concerning serologic testing of travelers returning to the United States with evidence of non-A, non-B, or non-C hepatitis should contact CDC's Hepatitis Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, telephone (404) 639-3048.

References

1. Krawczynski K, Bradley DW. Enterically transmitted non-A, non-B hepatitis: identification of virus-associated antigen in experimentally infected cynomolgus macaques. J Infect Dis 1989;159:1042-9.

2. Favorov MO, Fields HA, Purdy MA, et al. Serologic identification of hepatitis E virus infections in epidemic and endemic settings. J Med Virol 1992;36:246-50.

3. Bader T, Krawczynski K, Polish L, Favorov M. Hepatitis E in a U.S. traveler to Mexico {Letter}. N Engl J Med 1991;325:1659.

4. Bradley DW. Hepatitis E: epidemiology, aetiology and molecular biology. Reviews in Medical Virology 1992;2:19-28.

5. Velazquez O, Stetler HC, Avila C, et al. Epidemic transmission of enterically transmitted non-A, non-B hepatitis in Mexico, 1986- 1987. JAMA 1990;263:3281-5.

6. Tsega E, Hansson BG, Krawczynski K, Nordenfelt E. Acute sporadic viral hepatitis in Ethiopia: causes, risk factors, and effects on pregnancy. Clin Infect Dis 1992;14:961-5.

7. Hyams KC, Purdy MA, Kaur M, et al. Acute sporadic hepatitis E in Sudanese children: analysis based on a new Western blot assay. J Infect Dis 1992;165:1001-5.

8. Hyams KC, McCarthy MC, Kaur M, et al. Acute sporadic hepatitis E in children living in Cairo, Egypt. J Med Virol 1992;37:274-7.

9. ACIP. Protection against viral hepatitis: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1990;39(no. RR-2).

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