Hepatitis E virus antibody prevalence among persons who work with swine.

Prevalence of antibody and risk factors to hepatitis E virus (HEV) infection were determined in a cross-sectional study of 2 group-matched populations: swine farmers (n=264) and persons without occupational exposure to swine (n=255) in Moldova, a country without reported cases of hepatitis E. The prevalence of HEV infection was higher among swine farmers than among the comparison group (51.1% vs. 24.7%; prevalence ratio, 2.07; 95% confidence interval [CI], 1.62-2.64). In multivariate analysis, HEV infection was associated with an occupational history of cleaning barns or assisting sows at birth (odds ratio [OR], 2.46; 95% CI, 1.52-4.01), years of occupational exposure (OR, 1.04 per year; 95% CI, 1.01-1.07), and a history of drinking raw milk (OR, 1.61; 95% CI, 1.08-2.40). HEV infection was not associated with civilian travel abroad or having piped water in the household. The increased prevalence of HEV infection among persons with occupational exposure to swine suggests animal-to-human transmission of this infection.

Childhood hepatitis B virus infections in the United States before hepatitis B immunization.

OBJECTIVE: To estimate the number of hepatitis B virus (HBV) infections among US children younger than 10 years before implementation of routine childhood hepatitis B immunization. METHODS: Incidence of HBV infection in children was modeled from existing prevalence data by means of regression analysis. Sources of data for the models included published and unpublished surveys that determined the prevalence of HBV infection in US-born children. The number of nonperinatal HBV infections in children younger than 10 years was estimated by applying these infection rates to 1991 population data according to maternal race, ethnicity, and birthplace. RESULTS: Estimated annual rates of infection ranged from 24 per 100 000 in non-Asian children to 2580 per 100 000 in children of Southeast Asian immigrant mothers. These rates indicate that by the early 1990s, HBV was infecting 16 000 children who were younger than 10 years (8700 non-Asian children and 7300 Asian-American children) annually. The total estimate, not including perinatal infections, ranged from 12 000 (95% confidence interval: 5500-27 700) to 24 900 (95% confidence interval: 16 700-42 300) infections and depended on how the estimated rates were applied to the population data. CONCLUSION: Thousands of US children were infected each year with HBV before routine infant hepatitis B immunization, placing them at high risk of death from cirrhosis or hepatocellular carcinoma later in life.

Hepatitis B vaccination coverage among United States children.

BACKGROUND: In 1991 the Advisory Committee on Immunization Practices recommended vaccination of all infants with three doses of hepatitis B virus vaccine (HepB) by 18 months of age as a key component of a comprehensive strategy to eliminate hepatitis B virus transmission in the United States. The American Academy of Pediatrics and the American Academy of Family Physicians published similar recommendations soon afterward. METHODS: Data were obtained from the National Immunization Survey, a survey that began in 1994 and is conducted quarterly by the Centers for Disease Control and Prevention to estimate vaccination coverage among noninstitutionalized US children 19 to 35 months of age. RESULTS: The 1999 National Immunization Survey data indicate that approximately 88.1% (95% confidence interval, 87.4, 88.8) of children 19 to 35 months of age had received at least three doses of HepB (HepB3). There has been a consistent increase in HepB3 coverage since 1994. However, the rate of increase has slowed in recent years and HepB3 coverage remains lower than coverage attained with three doses of diphtheria-tetanus-pertussis and Haemophilus influenzae vaccines. HepB3 coverage varied slightly by race/ethnicity and was highest among white and Asian children (89%). Coverage also varied by state; 26 states had levels of at least 90%. CONCLUSIONS: Since the 1991 recommendations for universal hepatitis B vaccination, there has been a dramatic increase in coverage levels among children 19 to 35 months of age. However, the Childhood Immunization Initiative goal of 90% coverage has not been reached. Therefore continued efforts are needed to protect US children against this serious but preventable infection.

Preventing transmission of hepatitis B virus from people with chronic infection.

BACKGROUND: People with chronic hepatitis B virus (HBV) infection are the major source of HBV transmission in the United States. The Public Health Service recommends prevention counseling for HBV-infected people and vaccination of their household contacts and sexual partners. OBJECTIVES: To describe the implementation of these recommendations by community physicians. METHODS: Telephone survey of 69 people with chronic HBV infection and their healthcare providers, October 1997 through November 1997, in San Diego, California. MAIN OUTCOME MEASURES: Counseling of people with chronic HBV infection and vaccination of their household contacts and sexual partners. RESULTS: Forty-three percent of providers reported providing prevention counseling to their HBV-infected patients to reduce transmission; 16% of patients reported receiving counseling. For the 32 pairs for which both the patient and provider could be reached and the patients were aware of their HBV infection, 20 (63%) providers reported counseling patients, and 10 (50%) of these providers' patients reported receiving counseling. Fifty-five percent of providers recommended vaccination of contacts; 13% of eligible adult household contacts and sexual partners and 20% of eligible child household contacts had begun hepatitis B vaccination. CONCLUSIONS: Prevention counseling of people with chronic HBV infection and vaccination of their contacts occur infrequently despite guidelines and an effective vaccine. Collaborative efforts between providers and people involved in public health are needed to improve delivery of these preventive health services.

The economics of vaccinating restaurant workers against hepatitis A.

The economics of vaccinating restaurant workers against hepatitis A were studied using Monte Carlo simulation models, one with a restaurant-owner perspective, and one with a societal perspective. The restaurant model allowed for a different size, number of employees and employee turnover rate. Benefits were the avoidance of loss of business (including the possibility of bankruptcy) after publicity linking the restaurant to an outbreak associated with a case of hepatitis A in a food handler. Additional benefits in the societal model included reductions in costs of food handler-associated cases of hepatitis A. The outcome used was Net Present Value (NPV), allowing comparison between models. Regardless of the cost of vaccination ($50-140/employee), for a restauranteur to ensure that all employees were vaccinated at all times substantial costs were involved (i.e. negative NPV). Even a 75% probability of bankruptcy still resulted in negative NPVs at the 95th percentiles. For society, vaccination was only cost-saving (i.e. positive NPV) if done only during epidemics and if it cost < $20/employee. Vaccinating restaurant employees is unlikely to be economical from either the restaurant owner or the societal perspective, even during hepatitis A epidemics.

Empty virus-like particle-based enzyme-linked immunosorbent assay for antibodies to hepatitis E virus.

Hepatitis E, an enterically transmitted non-A, non-B hepatitis, is a serious viral infection that occasionally causes large epidemics in developing countries. In developed countries, the disease only appears sporadically due to the transmission routes, and it is considered to be less important. The hepatitis E virus (HEV) cannot grow in cultured cells and no reliable assay system has ever been developed. In addition, the present diagnostic are not perfect, and actual rates of HEV infection may be underestimated. Highly purified empty virus-like particles (VLPs) of HEV have been produced by the use of a recombinant baculovirus vector in insect cells. Using these VLPs as an antigen, an enzyme-linked immunosorbent assay (ELISA) for antibodies to HEV was developed. A panel of 164 sera that were randomized and coded, and sera collected periodically from three patients with hepatitis E were used for the evaluation. The sensitivity of the assay was shown to be equal to or better than that obtained in previous research that used the same serum panel. The ELISA demonstrated that the serum IgM level of the patients was highest at the onset of the clinical illness and then rapidly decreased. In contrast, a high level of circulating IgG antibody titers lasted for more than 4 years. In Japan, a non-endemic country, the prevalence of the IgG class antibody to HEV in healthy individuals was found to range from 1.9% to 14.1%, depending on the geographical area. Only one out of 900 (0.1%) serum samples was IgM-positive. The IgM class antibody to HEV was detected in 10.8% of non-A, non-B, and non-C acute hepatitis patients in northeast China, whereas none of the patients in Korea had the IgM antibody. The ELISA utilizing the VLPs is sensitive and specific in its detection of the IgM and IgG antibodies to HEV. The ELISA is therefore useful for diagnosing HEV infection and for seroepidemiological study of hepatitis E.

Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus.

Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family and is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Owing to shared routes of transmission, HCV and human immunodeficiency virus (HIV) coinfection are common, affecting approximately one-third of all HIV-infected persons in the United States. In addition, HIV coinfection is associated with higher HCV RNA level and a more rapid progression of HCV-related liver disease, which leads to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons, because the incidence of infection is increased and the natural history of HCV infection is accelerated in coinfected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed for HIV-HCV-coinfected individuals.

An outbreak of hospital-acquired hepatitis B virus infection among patients receiving chronic hemodialysis.

OBJECTIVE: To investigate a cluster of hepatitis B virus (HBV) infections between December 1995 and May 1996 among chronic hemodialysis patients in one county. SETTING: Two dialysis centers (A and B) and a hospital (C) in one county. PATIENTS: Six case-patients who were dialyzed in one of two centers, A and B, and had all been hospitalized between January and February 1996 at hospital C. METHODS: Patient 1, usually dialyzed in center A, sero-converted to hepatitis B surface antigen (HBsAg) in December 1995 and could have been the source of infection for the others, who seroconverted between March and April 1996. Two cohort studies were conducted: one among patients dialyzed in center A, to determine where transmission had occurred, and one among patients dialyzed at hospital C at the time patient 1 was hospitalized, to identify factors associated with infection. RESULTS: Four (15%) of the 26 susceptible patients dialyzed at center A became infected with HBV. Hospitalization at hospital C when patient 1 was hospitalized was associated with infection (P = .002). A cohort study of the 10 susceptible patients dialyzed at hospital C during the time patient 1 was hospitalized did not identify specific risk factors for infection. However, supplies and multidose vials were shared routinely among patients, providing opportunities for transmission. CONCLUSION: When chronic hemodialysis patients require dialysis while hospitalized, their HBsAg status should be reviewed, and no instrument, supplies, or medications should be shared among them.

Strategies to prevent and control hepatitis B and C virus infections: a global perspective.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of acute and chronic liver disease worldwide. Chronic infection with these viruses often leads to chronic liver disease, including cirrhosis or primary hepatocellular carcinoma. Both HBV and HCV are bloodborne viruses; however, HBV is transmitted efficiently by both percutaneous and mucosal exposures, and HCV is transmitted predominantly by percutaneous exposures. Because the relative importance of various modes of transmission of these viruses differs by country, the choice of specific prevention and control strategies depends primarily on the epidemiology of infection in a particular country. Comprehensive hepatitis B prevention strategies should include (1) prevention of perinatal HBV transmission, (2) hepatitis B vaccination at critical ages to interrupt transmission and (3) prevention of nosocomial HBV transmission. The prevention of hepatitis C is problematic because a vaccine to prevent HCV infection is not expected to be developed in the foreseeable future. From a global perspective, the greatest impact on the disease burden associated with HCV infection will most likely be achieved by focusing efforts on primary prevention strategies to reduce or eliminate the risk for transmission from nosocomial exposures (e.g. blood transfusion, unsafe injection practices) and high-risk practices (e.g. injecting drug use).

Hepatitis C: Part II. Prevention counseling and medical evaluation.

An estimated 3.9 million Americans are infected with hepatitis C virus (HCV), and most do not know that they are infected. This group includes persons who are at risk for HCV-associated chronic liver disease and who also serve as reservoirs for transmission of HCV to others. Because there is no vaccine to prevent HCV infection and immune globulin is not effective for postexposure prophylaxis, prevention of HCV infection is paramount. Patients who are at risk of exposure to HCV should be advised on steps they might take to minimize their risk of infection. Patients who are infected with HCV should be counseled on ways to prevent transmission of HCV to others and to avoid hepatotoxins. They should also be examined for liver disease and referred for treatment, if indicated.

Hepatitis C: Part I. Routine serologic testing and diagnosis.

Hepatitis C, which is caused by the hepatitis C virus (HCV), is a major public health problem in the United States. HCV is most efficiently transmitted through large or repeated percutaneous exposures to blood. Most patients with acute HCV infection develop persistent infection, and 70 percent of patients develop chronic hepatitis. HCV-associated chronic liver disease results in 8,000 to 10,000 deaths per year, and the annual costs of acute and chronic hepatitis C exceed $600 million. An estimated 3.9 million Americans are currently infected with HCV, but most of these persons are asymptomatic and do not know they are infected. To identify them, primary health care professionals should obtain a history of high-risk practices associated with the transmission of HCV and other bloodborne pathogens from all patients. Routine testing is currently recommended only in patients who are most likely to be infected with HCV.

Hepatitis E: an overview.

Hepatitis E is an enterically transmitted, acute, self-limited, icteric viral disease that occurs in large numbers in countries of the Indian subcontinent, Asia, and Africa. The frequency of epidemics and the high mortality rate among infected pregnant women are strong indicators that hepatitis E is an important cause of morbidity and mortality in humans. Several isolates of hepatitis E virus (HEV) derived from infected humans and experimental animals have recently been cloned and sequenced, allowing investigators to determine the molecular structure of the HEV genome. Laboratory diagnosis of HEV infection is done by detection of HEV antibodies, HEV RNA in stool and serum samples, HEV particles in stool specimens, and HEV antigen in hepatocytes and stool specimens. The detection of anti-HEV by enzyme immunoassay, with the use of several recombinant HEV proteins or synthetic peptides, is the most frequently applied method for the diagnosis of the infection and characterization of its epidemiologic features. Laboratory determination of HEV replication, immune response, and liver pathologic features in patients with hepatitis E and in infected primates has facilitated studies of the disease. Preventive measures against HEV infection include the passive transfer of protective antibodies or active immunization. In efforts to develop HEV vaccines, various recombinant proteins have been used. Although a range of protective immune responses have been induced in primates, further modifications of immunogen, adjuvant, and immunization schedules are necessary to prevent HEV infection. Much remains to be learned about epidemiology of HEV infection, reservoir(s) of the virus, and protective immunity in order to develop effective strategies to prevent hepatitis E.

Hepatitis A through E.

Viral hepatitis is a term commonly used for several clinically similar, yet etiologically and epidemiologically distinct, diseases. Five human hepatitis viruses have been identified. Hepatitis A, B, C, and D are endemic in the United States; hepatitis E is rarely reported in the United States, and most U.S. cases are seen in persons who have traveled to areas where hepatitis E. is endemic. Hepatitis A and E are transmitted by the fecal-oral route; hepatitis B, C, and D are blood-borne diseases. Hepatitis A and B have been recognized as separate entities since the early 1940s and can be diagnosed by serologic tests. Tests are available to detect the antibody to hepatitis C and D virus; no commercial test is available to diagnose hepatitis E. Hepatitis A, B, and D can be prevented by vaccine, but no vaccines are available for hepatitis C or E.

Hepatitis C.

Hepatitis C virus (HCV) has emerged as a major cause of chronic liver disease worldwide. The widespread endemicity of HCV infection is the result of a combination of factors, including those related to the genetic diversity of the virus and the host response and those related to the specific settings and behaviors that have facilitated transmission. Most people who contract HCV infection become persistently infected, and the mechanism by which persistent infection is established seems to be related to the lack of development of an effective neutralizing immune response. The magnitude of the spread of HCV infection primarily is related to specific risk factors for transmission. The most important human behavior related to the transmission of HCV has been injection drug use, which in many developed countries has been the leading source of HCV infection during the past 20 to 30 years. The recognition of the clinical importance of HCV infection has resulted in a substantial amount of attention and resources rapidly directed toward developing new and improved therapies. The perception, however, of the public health importance of HCV infection is still limited. Despite the knowledge that injection drug use is the major source of HCV infection in the United States, this message has not been included in prevention and treatment programs, and the resources needed to support strong public health programs have yet to be identified.

Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group.

Few data are available to evaluate the performance of existing assays for antibody to the hepatitis E virus (anti-HEV). A panel of 164 randomized and coded sera was tested for anti-HEV by 12 different assays. The panel included a dilution series of an early convalescent human serum, known-positive sera (undiluted human sera obtained 2 months to 13 years after acute hepatitis E, and postinoculation chimpanzee sera), known-negative sera (preinoculation chimpanzee sera; sera from chimpanzees with hepatitis A virus, hepatitis B virus, or hepatitis C virus infection; and normal human sera), and sera obtained from previously tested U.S. blood donors without a history of hepatitis. Six tests detected anti-HEV in > or =90% of undiluted known-positive sera. The sensitivity of all of the assays with known-positive sera ranged from 17% to 100%, and the limit of detection by endpoint dilution ranged from 1:5 to 1:160. Ten tests were nonreactive for all of the 22 known-negative sera, one test was reactive for one serum, and one test was reactive for 5 sera. In pairwise comparisons of different tests in blood donor sera, the overall concordance ranged from 49% to 94% (median, 69%) and the concordance among reactive sera ranged from 0% to 89% (median, 32%). Several of these tests performed well in detecting anti-HEV in known positive sera. However, highly discrepant results among U.S. blood donor sera indicate that anti-HEV seroprevalence data in non-HEV-endemic countries may be unreliable and should be interpreted with caution.

Hepatitis B vaccination of adolescent and adult high-risk groups in the United States.

Substantial progress has been made in implementing routine infant hepatitis B vaccination in the United States. However, in 1996, an estimated 65,000 acute hepatitis B cases occurred, the majority of which were among young adults in high-risk groups. Recent surveys have found very low vaccination coverage among several high-risk groups, including men who have sex with men and patients with sexually transmitted diseases (STDs). Targeted vaccination of persons with risk factors for hepatitis B virus (HBV) infection can be provided in a variety of settings including family planning clinics, STD clinics, drug treatment centres, detention centres, jails and prisons. However, vaccination programmes have been infrequently implemented in these settings and the majority of persons with acute hepatitis B cases have had a missed opportunity for vaccination in the past. Thus, in order to accelerate elimination of HBV transmission in the United States, increased efforts are needed to implement effective hepatitis B vaccination programmes targeted to adolescents and adults in high-risk groups.

Progress toward elimination of hepatitis B virus transmission in the United States.

The strategy to eliminate hepatitis B virus (HBV) transmission in the United States is comprised of the following components: (1) preventing perinatal transmission, (2) routine infant vaccination, (3) catch-up vaccination of children in high-risk groups at any age, (4) catch-up vaccination of all children at 11-12 years of age and (5) vaccination of adolescents and adults in high-risk groups. According to recent surveys, > 85% of pregnant women are screened for hepatitis B surface antigen (HBsAg). Of infants born to HBsAg-positive women identified in 1995, 93% received appropriate immunoprophylaxis at birth; however, only 69% were fully vaccinated by 6-8 months of age. From 1991 (when routine infant hepatitis B vaccination was first recommended) to 1996, the proportion of 19-35-month-old children who have received three doses of hepatitis B vaccine has increased from < 10 to 83%. During this time, rates of acute hepatitis B in children 7-10 years of age have declined by 27% and rates among children 3-6 years of age have declined by 62%. Implementation of programmes for catch-up vaccination of all adolescents at 11-12 years of age and for vaccination of adolescents and adults in high-risk groups have only recently begun and no data are available to assess the progress of these programmes. However, 26% (13/50) of states now have laws requiring adolescents to be vaccinated in order to enter school. Current data indicate that substantial progress has been made in implementing a strategy to eliminate HBV transmission in the United States. Future efforts need to be focused on improving complete immunoprophylaxis of infants of HBsAg-positive mothers, increasing vaccine coverage among 11-12 year old children and implementing programmes to vaccine adolescents and adults in high-risk groups.

Acute hepatitis E by a new isolate acquired in the United States.

OBJECTIVE: To report the first case of acute hepatitis E by a novel isolate acquired in the United States and confirmed by nucleotide sequencing. MATERIAL AND METHODS: We describe the clinical manifestations and the results of associated laboratory studies in a man who was found to have acute hepatitis E infection. RESULTS: A 62-year-old man was hospitalized because of fever, abdominal pain, and jaundice. After an initial evaluation did not provide a cause, his serum was found to be positive for IgG anti-hepatitis E virus (HEV) by three antibody assays. Serum was also positive for HEV RNA by reverse transcriptase polymerase chain reaction (PCR). Sequencing results from the PCR products demonstrated substantial differences at the nucleotide level between this strain and the known Mexican and Burmese strains. CONCLUSION: On the basis of this initial report, HEV should be considered an etiologic agent in patients with acute non-ABC hepatitis in the United States.

Prevalence of and risk factors for antibody to hepatitis E virus seroreactivity among blood donors in Northern California.

To evaluate antibody to hepatitis E virus (anti-HEV) seroreactivity, 5000 US blood donors were tested for anti-HEV by two EIAs: a mosaic protein assay (MPr-EIA) and a recombinant protein assay (RPr-EIA). Overall, 59 (1.2%) were seroreactive by MPr-EIA and 70 (1.4%) were seroreactive by RPr-EIA. The overall concordance between tests was 98.5% (4925/5000); the concordance among reactive sera by either test was only 27% (27/102). In a case-control study, seroreactive persons were more likely than seronegative persons to have traveled to countries in which HEV is endemic (odds ratio [OR] for MPr-EIA = 4.3, P < .001; OR for RPr-EIA = 2.5, P = .005), but 31% of MPr-EIA anti-HEV-reactive persons and 38% of RPr-EIA anti-HEV-reactive persons had no history of international travel. These findings suggest that travelers to regions in which HEV is endemic can acquire subclinical HEV infection. The significance of anti-HEV seroreactivity among persons without an international travel history needs to be determined.