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Hepatitis E in Developed Countries
  A study published in Clinical Infectious Diseases this month reports on a cluster of 3 individuals in The Netherlands over 80 years of age who contracted hepatitis E. The researchers suggest hepatitis E may occur more often than suspected in developing countries and may occur as acute hepatitis. They suggest the source may be pigs/swine. They also suggest that there should be routine hepatitis E testing in patients with acute hepatitis before a diagnosis of autoimmune hepatitis is reached and steroid therapy started. Here is a summary of the study followed by information from the CDC on hepatitis E symptoms, epidemiology, prevention for travelers,
Cluster of Cases of Acute Hepatitis Associated with Hepatitis E Virus Infection Acquired in The Netherlands
Hepatitis E virus (HEV) is a major cause of enterically transmitted non-A, non-B hepatitis in poor countries, often presenting as large outbreaks of hepatitis in which fecally contaminated water is usually implicated. HEV infection is also considered to be a major cause of sporadic viral hepatitis in these countries, but the source of infection is rarely found. Clinical cases of HEV infection in developed countries have generally been associated with travel to tropical or subtropical countries. Serosurveys with recently developed assays for HEV antibody, however, have consistently indicated a low seroprevalence of antibodies to HEV (1%-%) in countries where HEV infection is not thought to be endemic. There have also been an increasing number of reports from Europe and the United States of sporadic hepatitis attributable to HEV but not associated with travel, leading to suggestions that HEV may be endemic at low levels in developed countries. As yet, however, no outbreak of HEV infection has been reported from developed countries. Strains of HEV related to those that infect humans have been found in swine in The Netherlands and in the United States, which raises the possibility that swine may act a reservoir of infection for humans. Previous reports of HEV infection in developed countries have involved single, epidemiologically unrelated cases
On 2 July 2001, a regional microbiological laboratory in the north of The Netherlands notified the National Institute for Public Health of 3 elderly people who presented to the same local hospital with acute hepatitis in the previous 6 months and who were subsequently shown to be seropositive (IgG) for HEV infection. We describe the investigation of this cluster of 3 cases of hepatitis.
Summary of study findings: Increasing evidence suggests that hepatitis E virus (HEV) infection may occur in developed countries and that swine may act as a reservoir. We report a cluster of 2 confirmed cases and 1 presumptive case of hepatitis associated with HEV. The typed strain from 1 case was related to HEV strains found in North America and Europe, and it was also related to a cluster of swine HEV strains found in The Netherlands. Our findings indicate that locally acquired HEV infections in industrialized countries may be overlooked. Routine testing for HEV infection in patients with acute hepatitis in The Netherlands should be considered before a diagnosis of autoimmune hepatitis is reached and steroid therapy is initiated.
Clinical Infectious Diseases 2003;36:29-33
More On Hepatitis E
Notes from Jules Levin: Usually, hepatitis E is not chronic. In pregnant women HEV can cause fulminant hepatitis (severe & acute hepatitis). In this sense HEV is similar to Hepatitis A.
CDC on Hepatitis E
Hepatitis E virus (HEV), the major etiologic agent of enterically transmitted non-A, non-B hepatitis worldwide, is a spherical, non-enveloped, single stranded RNA virus that is approximately 32 to 34 nm in diameter. Based on similar physicochemical and biologic properties, HEV has been provisionally classified in the Caliciviridae family; however, the organization of the HEV genome is substantially different from that of other caliciviruses and HEV may eventually be classified in a separate family.
Hepatitis E - Clinical Features
Incubation period:
Average: 40 days
Range: 15-60 days
Case-fatality rate: Overall, 1%-3%; Pregnant women, 15%-25%
Illness severity: Increased with age
Chronic sequelae: None identified
The incubation period following exposure to HEV ranges from 15 to 60 days (mean, 40 days). Typical clinical signs and symptoms of acute hepatitis E are similar to those of other types of viral hepatitis and include abdominal pain anorexia, dark urine, fever, hepatomegaly, jaundice, malaise, nausea, and vomiting. Other less common symptoms include arthralgia, diarrhea, pruritus, and urticarial rash. The period of infectivity following acute infection has not been determined but virus excretion in stools has been demonstrated up to 14 days after illness onset. In most hepatitis E outbreaks, the highest rates of clinically evident disease have been in young to middle-age adults; lower disease rates in younger age groups may be the result of an icteric and/or subclinical HEV infection. No evidence of chronic infection has been detected in long-term follow-up of patients with hepatitis E.
The typical serologic course following HEV infection has been characterized using experimental models of infection in nonhuman primates and human volunteer studies. In two human volunteer studies, liver enzyme elevations occurred 4-5 weeks after oral ingestion and persisted for 20-90 days. Virus excretion in stools occurred approximately 4 weeks after oral ingestion and persisted for about 2 weeks. Both IgM and IgG antibody to HEV (anti-HEV) are elicited following HEV infection. The titer of IgM anti-HEV declines rapidly during early convalescence; IgG anti-HEV persists and appears to provide at least short-term protection against disease. No serologic tests to diagnose HEV infection are commercially available in the United States. However, several diagnostic tests are available in research laboratories, including enzyme immunoassays and Western blot assays to detect IgM and IgG anti-HEV in serum, polymerase chain reaction tests to detect HEV RNA in serum and stool, and immunofluorescent antibody blocking assays to detect antibody to HEV antigen in serum and liver.
Hepatitis E - Epidemiologic Features
--Most outbreaks associated with fecally contaminated drinking water
--Minimal person-to-person transmission
--U.S. cases usually have history of travel to HEV-endemic areas
HEV is transmitted primarily by the fecal-oral route and fecally contaminated drinking water is the most commonly documented vehicle of transmission. Although hepatitis E is most commonly recognized to occur in large outbreaks, HEV infection accounts for >50% of acute sporadic hepatitis in both children and adults in some high endemic areas. Risk factors for infection among persons with sporadic cases of hepatitis E have not been defined. Unlike hepatitis A virus, which is also transmitted by the fecal-oral route, person-to-person transmission of HEV appears to be uncommon. However, nosocomial transmission, presumably by person-to-person contact, has been reported to occur. Virtually all cases of acute hepatitis E in the United States have been reported among travelers returning from high HEV-endemic areas.
Outbreaks of hepatitis E have occurred over a wide geographic area (Mexico, Africa, Asia), primarily in developing countries with inadequate environmental sanitation. The reservoir of HEV in these areas is unknown. The occurrence of sporadic HEV infections in humans may maintain transmission during inter-epidemic periods, but a nonhuman reservoir for HEV is also possible. In the United States and other non-endemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) has been found in healthy populations. The source of infection for these persons is unknown.
Prevention and Control Measures for Travelers to HEV-Endemic Regions
--Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler
--IG prepared from donors in Western countries does not prevent infection
--Unknown efficacy of IG prepared from donors in endemic areas
Prevention of hepatitis E relies primarily on the provision of clean water supplies. Prudent hygienic practices that may prevent hepatitis E and other enterically transmitted diseases among travelers to developing countries include avoiding drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruits or vegetables that are not peeled or prepared by the traveler. No products are available to prevent hepatitis E. IG prepared from plasma collected in non-HEV-endemic areas is not effective in preventing clinical disease during hepatitis E outbreaks and the efficacy of IG prepared from plasma collected in HEV-endemic areas is unclear. In studies conducted to date with prototype vaccines in animals, vaccine-induced antibody attenuated HEV infection, but did not prevent virus excretion in stools. If a vaccine is developed, the epidemiology of hepatitis E needs to be further defined in order to determine whether vaccination strategies could be effectively used to prevent this disease.
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