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Background: The main occupational hazard of wastewater workers (WWs) is the direct exposure to the variety of infectious agents present in sewage material, with hepatitis A virus (HAV) being the most frequent one. Most epidemiological studies have shown a higher risk of hepatitis A among WWs, although some studies have produced conflicting evidence., Aims: To evaluate the hypothesis of increased risk of HAV infection in WWs., Methods: The prevalence of antibodies to HAV in 869 WWs was compared to 311 other subjects and analysed to detect the main potentially confounding variables., Results: Univariate analysis demonstrated that occupational exposure to sewage was not significantly associated with the prevalence of anti-HAV(+). The anti-HAV(+) prevalence was strongly associated with age and shellfish consumption (P < 0.05) when the subcategories of workers were examined separately (WWs and control group) and jointly. In the logistic regression model, a significant association between anti-HAV(+) prevalence and duration of employment (P < 0.05) was found. The interaction term (age x duration of employment) was significant (P < 0.001) when included in the logistic model., Conclusions: This study shows that working in a wastewater treatment plant does not seem to be related to a greater prevalence of antibodies to hepatitis A. Moreover, the relative risk of HAV infection among WWs seems to be correlated with low anti-HAV(+) prevalence in the general population.

Analysis of epidemiological data on health problems related to international travel helps put into perspective preventive interventions for travelers. To document the epidemiological context of travel health interventions in Québec, we reviewed surveillance data for three infectious diseases. The analysis included data collected in the notifiable diseases surveillance system for hepatitis A, typhoid, and malaria cases reported from 2000 to 2002. Additional data were obtained from the provincial hepatitis risk factor database as well as from regional public health departments. More than 40% of cases of hepatitis A for which risk factor information is available are associated with international travel; 20% of these cases were contracted in Mexico and 22% in the West Indies. The risk of acquiring hepatitis A seems to be higher among travelers under 35 years of age; also, given the number of Quebecers traveling to all regions of the world, this risk is proportionally higher in Africa. Data gathered for typhoid indicate that the risk to travelers from Québec is proportionately higher for Quebecers traveling to the Indian subcontinent and whose purpose is to visit family and friends, and for those who stay abroad for 4 weeks or longer. The risk of malaria is greater in Africa (where contracted cases are mostly caused by Plasmodium falciparum). Over half of malaria cases involve individuals traveling abroad for business (including volunteerism), and almost 75% contracted the disease during a stay of a month or more. Nearly half of the cases had not taken chemoprophylaxis. Available data have limitations for infectious disease surveillance among Québec travelers: imprecise number of cases (underdiagnosis and underreporting), imprecise denominators (number of travelers), and lack of data on the characteristics of trips taken. However, despite its limitations, this profile of infectious diseases among travelers from Québec provides interesting data for preventive intervention.

Immigrants to the United States from developing countries have a higher probability of previous infection with hepatitis A virus (HAV) and/or hepatitis B virus in their countries of origin. Prior knowledge of hepatitis A and B seroprevalence in this population may aid in determining the need for pretravel immunizations when these individuals travel to endemic regions. We conducted a retrospective analysis of hepatitis A and B serologies in a travel clinic population (from March 1999 through September 2002) to determine the seroprevalence in our predominantly highly educated foreign-born subjects. All our patients who had immigrated from China and India and who were older than 60 years (born on or before 1940) were immune to hepatitis A. The Indian and Chinese subjects who were anti-HAV positive were also significantly older than the anti-HAV negative group. In addition, in our Indian study group, the hepatitis A-seropositive individuals first left India at a significantly older age than the hepatitis A-seronegative group (mean age 22.7 years vs 11.4 years, p < 0.05). Our small sample size of Chinese subjects may not have permitted a statistically significant difference to be detected for hepatitis A seroprevalence and age at departure from their country of origin. These results have helped tailor our recommendations for pretravel immunizations for our groups of foreign-born individuals planning to visit endemic areas. Individuals born in China or India on or before 1940 are likely to have preexisting antibody to hepatitis A and probably do not need the vaccine when they travel. Younger individuals may elect to have a hepatitis A antibody titer checked before getting the vaccine.

Background: Uncertainty exists about the current risk of hepatitis A virus infection in nonimmune travelers to destinations with high or intermediate risk of transmission. We analyzed recent epidemiological data on imported hepatitis A to determine region-specific attack rates and incidences., Methods: Surveillance data on hepatitis A virus infections diagnosed during 1988-2004 were evaluated on the basis of notification by laboratories, additional reports of physicians, and traveler's statistics. This study focuses on international travelers with hepatitis A virus infection detected after their return to Switzerland., Results: The rate of imported hepatitis A virus infections decreased 75% from 1988 to 2004 and accounted overall for 42% of all hepatitis A cases reported in Switzerland. The actual incidence of hepatitis A in travelers to countries of high or intermediate risk of transmission was 3.0-11.0 per 100,000 person-months abroad for all travelers and 6.0-28.0 per 100,000 for those presumed to be nonimmune. The actual proportion of those visiting friends and relatives among patients with hepatitis A has increased to 28.2%, with children aged 0-14 years predominating. Reductions in the incidence by hepatitis A vaccination were estimated to vary between 35.0% and 61.8% for different destinations., Conclusions: The risk of hepatitis A virus infections has decreased by a factor of 10-50-fold over time, compared with findings from older studies. The risk, however, remains very considerable at many destinations, including frequently visited places, such as Mexico. Children of immigrants are a high-risk population. Strategies are needed to reach those at highest risk.

Background: Molecular epidemiologic investigations can link geographically separate foodborne hepatitis A outbreaks but have not been used while field investigations are in progress. In 2003, outbreaks of foodborne hepatitis A were reported in multiple states., Methods: Case-control studies were conducted in 3 states. Hepatitis A virus was sequenced from serologic specimens from individuals associated with outbreaks and from individuals concurrently ill with hepatitis A in non-outbreak settings in the United States and Mexico., Results: Case-control studies in Tennessee (TN), North Carolina (NC), and Georgia (GA) found green onions to be associated with illness among restaurant patrons (TN: odds ratio [OR], 65.5 [95% confidence interval {CI}, 8.9-482.5; NC: OR, 2.4 [95% CI, 0.3-21.9]; GA: OR, 20.9 [95% CI, 3.9-110.3]). Viral sequences from TN case patients differed by 2 nt, compared with those from case patients in NC and GA. A third sequence, differing from the TN and GA/NC sequences by 1 nt, was identified among case patients in a subsequent outbreak in Pennsylvania. Each outbreak sequence was identical to > or =1 sequence isolated from northern Mexican resident(s) with hepatitis A. The sources of green onions served in restaurants in TN and GA were 3 farms in northern Mexico., Conclusions: Ongoing viral strain surveillance facilitated the rapid implementation of control measures. Incorporation of molecular epidemiologic methods into routine hepatitis A surveillance would improve the detection of hepatitis A outbreaks and increase our understanding of hepatitis A epidemiology in the United States.

Background: There is a paucity of data describing the risk of acquiring hepatitis A while traveling in the developing world. This paper uses available data to calculate the risk to Canadian travelers., Methods: Information was gathered from Canadian and international sources on the following: the yearly incidence of hepatitis A among Canadians; the proportion of cases of hepatitis A associated with travel to developing countries; the number of days of such travel by Canadians per year; and the percentage of travelers immunized before departure. Calculations were performed on these figures to arrive at an estimated risk of infection for unimmunized Canadian travelers., Results: The annual incidence of hepatitis A in Canada over the period 1996-2001, adjusted for underreporting, averaged 6.15 cases/100,000 people. During that time, Canadians traveled approximately 36.5 million days/year in developing countries. The literature shows that 4% to 28% (mean 16%) of cases are estimated to have been acquired abroad. It also shows that 14% to 24% (mean 19%) of such travelers are immunized before departure. Based on these figures, the risk of acquiring hepatitis A during 1 month of travel in the developing world is calculated to be approximately 1 case per 3,000 unimmunized travelers., Conclusion: Hepatitis A is an important travel-related disease, preventable by immunization. However, our calculations indicate that the risk of acquiring hepatitis A while traveling in the developing world is lower than some previously published estimates. The results represent an average for all types of travel to all such countries. The actual risk will vary considerably, depending on the destination and style of travel.

Background: Older individuals and those born overseas are thought at increased risk of prior exposure and thus have naturally acquired immunity to hepatitis A. Whether these individuals or other groups of international travelers should be screened for acquired immunity or empirically immunized is not clear. Hepatitis A serology and risk factor data was obtained prospectively in patients presenting for hepatitis A immunization and used to develop a cost-effective strategy for the use of serologic screening and empiric immunization in our traveler population., Method: Candidates for hepatitis A immunization were routinely screened for total hepatitis A serum antibody. Risk factor data including country of birth, travel history, and history of jaundice was collected. Cost-effectiveness was assessed by comparing the cost of serology to screen all patients plus cost to immunize those found to be seronegative with, the cost of empirically immunizing all patients., Results: Analyses were conducted comparing age, travel history, country of birth, and history of jaundice for significance in predicting seropositivity in a group of 115 subjects. Country of birth was statistically a significant predictor of positive results with 80.0% of foreign-born patients positive for total antibody against hepatitis A compared with 35.6% of patients born in the United States. Living outside of the United States (defined as greater than 30 days) was also correlated with a higher prevalence of hepatitis A positive serology. Age was not predictive for the group as a whole. A lower prevalence (24.3%) was noted in the group of US born individuals aged 30 to 60. Travel and prior history of jaundice failed to demonstrate significance., Conclusions: Employing a simple cost-effectiveness equation using cost of serological testing, cost of vaccine, and prevalence of acquired immunity in the community, a strategy was developed. In our population it was cost-effective to screen all foreign-born individuals and those who had lived outside the United States.

To assess the possible influence of human immunodeficiency virus type 1 (HIV-1) infection on the clinical course of acute hepatitis A virus (HAV) infection, 15 HIV-1-infected homosexual men and 15 non-HIV-infected age-matched subjects were compared. HAV load was higher in HIV-1-infected than in non-HIV-infected patients (P<.001). Duration of viremia in HIV-1-infected patients (median, 53 days) was significantly (P<.05) longer than in non-HIV-infected patients (median, 22 days). HIV-1-infected patients had lower elevations in alanine aminotransferase levels than did non-HIV-infected patients (P<.01) but had higher elevations in alkaline phosphatase levels than did non-HIV-infected patients (P<.001). Some HIV-1-infected patients still had HAV viremia when clinical symptoms had disappeared and alanine aminotransferase levels had returned to normal (60-90 days after the onset of symptoms). HIV-1 infection was associated with prolongation of HAV viremia, which might cause a long-lasting outbreak of HAV infection in HIV-1-infected homosexual men.

We reviewed 232 consecutive patients admitted to a tertiary-care hospital under the care of an infectious diseases unit for management of febrile illness acquired overseas. A total of 53% presented to hospital within 1 week of return and 96% within 6 months. Malaria was the most common diagnosis (27% of patients), followed by respiratory tract infection (24%), gastroenteritis (14%), dengue fever (8%), and bacterial pneumonia (6%). Pretravel vaccination may have prevented a number of admissions, including influenza (n=11), typhoid fever (n=8) and hepatitis A (n=6). Compared to those who had not traveled to Africa, those who had were 6 times more likely to present with falciparum than nonfalciparum malaria. An itinerary that included Asia was associated with a 13-fold increased risk of dengue, but a lower risk of malaria. Palpable splenomegaly was associated with an 8-fold risk of malaria and hepatomegaly with a 4-fold risk of malaria. As a cause of fever, bacterial pneumonia was > or =5 times more likely in those who were aged >40 years.

We conducted a descriptive study in 9 cases of acute hepatitis A diagnosed in patients with human immunodeficiency virus (HIV). Despite the small number of cases studied, the results indicate that moderate HIV infection does not impair the natural history of acute hepatitis A.

Objective: To determine whether Behçet's disease (BD), being a systemic vasculitis of unknown aetiology, is associated with hepatitis viruses (HAV, HBV, HCV and HEV)., Methods: In addition to 124 patients [male:female (M/F): 73/51], all fulfilling the diagnostic criteria of the International Study Group for BD (1991), 14 patients with systemic necrotizing vasculitis (M/F: 7/7), 47 patients with ankylosing spondylitis (M/F: 36/11) and 51 healthy controls (M/F: 22/29) were also included in this study. Serological markers of four different types of hepatitis (anti-HAV IgM, total anti-HAV, HBsAg, anti-HBs, total anti-HBc, anti-HBc IgM, anti-HCV and anti-HEV) were studied in all cases., Results: There was no difference between the groups with respect to HAV, HCV and HEV serologies. Anti-HBs positivity was observed less frequently in BD compared with healthy controls and systemic vasculitis (P<0.05)., Conclusion: Serological evidence of previous HAV, HCV and HEV infections was not significantly different between Behçet's patients and other groups. However, previous HBV infection was found in a significantly lower number of BD patients as compared with healthy controls and systemic vasculitic patients.

Hepatitis A virus (HAV) circulation in a given area is closely related to socioeconomic standards. Following the improvement of living conditions, HAV seroprevalence rates in the population have decreased steadily during the last decades in many Western European countries, including Italy, thereby leading to a shift of risk of disease towards older age groups. Since the severity of the disease closely parallels age, a higher incidence of symptomatic cases in adults is now reported in Europe and the United States, being travel-related to a large extent. Intrafamilial person-to-person spread is also an important source of infection and transmission from children to parents may occur due to the lack of immunity in the general population. In the last two decades, Italy has been the destination of an increasing number of migrants from developing countries, where HAV is highly endemic. Furthermore, international adoption programmes cause pediatric populations from HAV endemic countries to increase in low endemic areas, possibly leading to secondary cases in close contacts.7 The aim of this paper is to report the epidemic HAV outbreak which occurred among the voluntary nursing staff of a pediatric Rwandan refugee community hosted in a village of the Brescia Province, in northern Italy.

Background: In The People's Republic of China in 1990, the age-specific seroprevalence of hepatitis A was investigated in eight large cities., Methods: A stochastic model, the two-state Markov chain, was applied to hepatitis A virus seroprevalence data by age group. An age-specific risk rate, Markov Risk Rate (MRR), and its weighted sum, Total MRR, are defined and used as novel measure indices to prioritize age groups for allocating vaccine or to decide in which cities vaccine should be used to prevent hepatitis A., Results: In 1990, the MRR1- in Xi'an, Jinan, Ha'erbin and Huhehaote, and the MRR10- in Chongqing were over 40. The MRR10- in Xi'an, Nanjing, Jinan and Ha'erbin and the MRR20- in Chongqing and Nanjing were over 20. The Total MRR in Chongqing and Ha'erbin were over 160, which was higher than the warning value., Conclusions: All age groups whose MRR was over 20 are strongly recommended to be vaccinated first. Chongqing and Ha'erbin are cities at high risk of a hepatitis A virus epidemic in the 1990s and therefore should be under close surveillance.

Background: An outbreak of hepatitis A (HAV) occurred in 1992 in Irish haemophilia A patients treated with high purity solvent-detergent (SD) treated factor VIII. Similar outbreaks were reported in Italy, Germany and Belgium. The aim of this study was to investigate the outbreak, and to test the hypothesis that it was caused by exposure to SD-treated factor VIII., Methods: A case-control study was started in early 1993. Haemophilia A cases with acute HAV (n = 29) were compared with haemophilia A controls for exposure to SD-treated factor VIII and other environmental factors. Details of factor VIII usage were obtained from the National Haemophilia Register and environmental data were obtained by a telephone-administered questionnaire. The response rate was approximately 90%., Results: The incidence of acute HAV infection among haemophilia A patients exceeded the notified national incidence of HAV by a factor of approximately 300. The incidence was higher in younger patients and those with more severe bleeding disorders. Contact with hepatitis, with children, and exposure to factor VIII were associated with increased risk. The association with factor VIII was the strongest risk factor after controlling for other factors (odds ratio = 27.6, 95% confidence interval [CI] 6.5-117.3). A dose-response effect was demonstrated., Conclusions: Although person-to-person transmission is likely to have caused a few of the cases, the results of our investigation suggest that the major contributing factor was exposure to certain batches of SD-treated factor VIII.

Vertical transmission of hepatitis A virus (HAV) has not been reported. From 25 October to 15 November 1989, 10 cases of symptomatic HAV infection occurred among neonatal intensive care unit (NICU) staff. Testing of other NICU staff and patients identified 4 infected infants. Hepatitis A among staff was associated with caring for 1 of these infants, infant A (relative risk [RR], undefined; P = .05). Risk of illness was greater for staff who did not routinely wash their hands after treating infant A for apnea and bradycardia (RR = 4.9; P = .02). Staff, infants, visitors, and transfused blood products could not be implicated as a source of infant A's infection. Infant A's mother, however, was diagnosed with hepatitis A 10 days after premature labor and delivery. Evidence suggests that infant A was infected by his mother before or during birth. HAV then spread within the NICU because of breaks in infection control precautions. To prevent future outbreaks, NICU staff should adhere rigorously to body substance isolation measures.

A seroepidemiological survey of a group of drug abusers has been carried out to determine the prevalence of hepatitis C virus and hepatitis B virus, hepatitis D virus, hepatitis A virus infection markers in sera, as well as to evaluate the role of potential risk factors. A total of 645 symptomless subjects with a history of injecting heroin were recruited as volunteers from methadone maintenance centres in Rome. For all hepatitis viruses the total figures showed high prevalence rates giving considerable viral circulation in this group. Among heroin addicts the prevalence was 63.4% for HCV, 65% for HBV, 13.3% for HDV and 50.9% for HAV. Anti-HCV prevalence correlated with serological evidence of HBV infection. A significant correlation was also found between presence of HCV antibodies and exposure time to drug addiction > 5 years earlier. The data reveal the important role played by needle sharing in the spreading of multiple infections among intravenous drug abusers (IVDA).

A multistate outbreak of hepatitis A was traced to frozen strawberries processed at a single plant. Among 827 students and 60 teachers at an elementary school in Georgia during a 2-week period, 15 developed hepatitis A. Three months later, among 174 residents and 467 staff in an institution for the developmentally disabled in Montana during a 3-week period, 13 developed hepatitis A. Primary attack rates were 10% in the school and 8% in the institution. Cohort analysis in the school implicated consumption of strawberry shortcake in hepatitis A virus (HAV) infection (relative risk, 7.6; 95% confidence interval, 1.04-55.6). In the institution, such analysis implicated desserts and uncooked strawberries as the most biologically plausible vehicle of HAV transmission. Molecular analysis of HAV from patients in the two outbreaks revealed that the viral genomes were genetically identical and distinct from other known US strains. Contamination of food products before retail distribution is rare but should be considered in investigating common-source outbreaks of hepatitis A.

A multistate outbreak of hepatitis A was traced to a campground in Louisiana. Among 822 campers during one weekend, 20 developed hepatitis A. Case-patients ranged in age from 4 to 36 years; the highest attack rate (6.4%) was for children aged 5-9 years. A case-control study revealed that case-patients were more likely than controls to have swum in a public swimming pool on Saturday afternoon (19/19 vs. 26/38; odds ratio [OR], undefined; lower 95% confidence limit, 1.7). Case-patients were more likely than controls to have swum in the jacuzzi pool (16/19 vs. 10/26; OR, 8.0; 95% confidence interval, 1.5-47.1) or adult pool A (19/19 vs. 15/26; OR, undefined; lower 95% confidence limit, 2.6). Case-patients were also more likely to have swum for greater than 1 h and to have put their heads under the water. Because of the design of the filtering system of adult pool A, a cross-connection between a sewage line and the pool water intake line was possible. This outbreak may have been caused by transmission of hepatitis A through swimming; thus, swimming may serve as a mode of transmission of hepatitis A virus, especially among small children.

An epidemic of hepatitis A in 1988 in Shanghai had an overall attack rate of 4083/100,000 population (292,301 cases). The epidemic curve showed three peaks in January and February. A case-control study of 1208 matched pairs supported that clams were the vehicle for the virus (summary odds ratio, 9.47; P less than .001). Analysis of subsets who had eaten clams indicated that only 3.5% with hepatitis A had cooked their clams compared with 18.1% without hepatitis A, and those with the disease consumed more clams. A historical cohort study indicated that approximately 31.7% of the population had eaten clams one or more times between 9 December 1987 and 3 January 1988. The estimated attack rates in those who had and had not eaten clams were 11.93% and 0.52%, respectively (relative risk, 22.94; attributable risk, 11.41%). The three peaks in the consumption curve correlated with those in the epidemic curve. Hepatitis A virus was demonstrated in clams taken from the Shanghai markets and from the catching area.

The association between hepatitis A and domestic or international travel from Italy was investigated. Data from a nationwide surveillance system (SEIEVA) for type-specific acute viral hepatitis were used to compare 1102 hepatitis A cases with 3671 hepatitis B cases. An association between hepatitis A and travel was found in northern Italy, where most young and adult people are susceptible. Estimates of odds ratios vary dramatically according to geographical area of travel. Travellers to Mediterranean countries, Eastern Europe, Africa, Asia, and South and Central America had the highest education and age-adjusted odds ratios for hepatitis A, ranging from 6 to 25. Prophylaxis against hepatitis A for such travellers is recommended.

An outbreak of hepatitis A virus (HAV) infection occurred among cancer patients treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells between July and September 1986 at six different clinical centers. Among 85 patients tested serologically for recent HAV infection, 22 (39%) of 56 susceptible patients developed acute HAV infection. Only exposure to LAK cells cultured in medium containing human serum from two specific manufactured pools was associated with HAV infection. Attack rates were 85% among patients exposed to pool X, 62% in patients exposed to pool Y, and 50% in those exposed to both pools, compared with none among the 24 susceptible persons exposed to other serum pools (P less than .001). The serum used in production of LAK cell medium was obtained from multiple paid donors. Twenty persons donated plasma to both serum pools X and Y. Although none of 12 donors tested had evidence of recent HAV infection, it is likely that an asymptomatic plasma donor viremic for HAV contaminated both serum pools and the LAK cell medium made from it.

A cluster of cases of hepatitis A that occurred among 46 participants in a family reunion in Utah in August 1980 was investigated with epidemiologic and serologic techniques. No index patient with clinical illness had been present at the reunion. Twenty-three cases of hepatitis A were ultimately identified; 14 developed clinical hepatitis. Immunoglobulin M-specific hepatitis A virus antibody testing identified nine recently infected asymptomatic subjects. Eight additional individuals had serologic evidence of prior infection. Detection of these asymptomatically infected and nonsusceptible subjects among presumably well individuals led to the alteration of the food questionnaire analysis, ultimately implicating the green salad. The green-salad maker was identified as an asymptomatically infected individual and was thought to be the probable index case. Determination of hepatitis A virus antibody status of study subjects revealed age-related differences in clinical manifestations and disease susceptibility between individuals exposed to foodborne hepatitis A.

The risks of developing hepatitis A and B virus infections were studied in 233 French volunteers working for 18 to 35 months in the field in West and Central Africa. During their stay in Africa, the seroconversion rates to antibody to hepatitis A virus of the immunoglobulin G (IgG) class and hepatitis B marker(s) were 48.1% and 10.5%, respectively; 21.5% of the volunteers developed jaundice, and 78.0% of the jaundice cases were associated with hepatitis A seroconversion, 14.0% with hepatitis B seroconversion, 4.0% with seroconversion to both, and 4.0% without seroconversion. Male health workers were at lower risk than other male occupations for hepatitis A infection. Female health workers were at higher risk than other female occupations for hepatitis A infection. Health workers were at a lower risk of hepatitis B infection, but the significance was borderline. Populations such as these volunteers should receive immunoprophylaxis against hepatitis A and B infections.

From the end of October to the end of December 1973, an epidemic of hepatitis A affected 40 students at a state university, 11 employees of two restaurants, and 11 other residents in a southwestern metropolitan community. Two distinct epidemic waves of illness occurred, and investigation implicated two local restaurants as sources of infection, one for each epidemic wave. An index patient who prepared food was identified at each restaurant, and the two restaurants were linked by the fact that the index patient who worked at the second restaurant had patronized the first restaurant. Foods implicated as vehicles of transmission included 'guacamole,' green salad, spaghetti, and hamburger. The findings represent a rare example of a 'double' common-source outbreak with two distinct epidemic waves related to two separate eating establishments.

An outbreak of oyster-associated hepatitis occurring in Louisiana during the months of October and November 1973 has been shown to be related directly to two similar outbreaks occurring at the same time in Houston, Texas and Calhoun, Georgia. Oysters incriminated in all three outbreaks were traced to approved oyster growing areas along the east Louisiana coast. Although no entirely satisfactory explanation could be found for the mode of contamination of these oysters, the epidemiologic and enviornmental data are most consistent with the conclusion that Mississippi River flooding provided the necessary source of fecal pollution into the oyster growing areas. These data also support recent experimental evidence indicating the under natural conditions shellfish eliminate bacteria and viruses differently and may retain certain enteroviruses for as long as two months after these organisms have disappeared from surrounding waters.

Between April 1984 and January 1985, in the Italian seaport of Livorno, the annual incidence of serologically confirmed acute hepatitis A doubled to 46 per 100,000 population. The exposure histories of each of 75 jaundiced subjects with serologically confirmed hepatitis A were compared with up to four, randomly chosen-, age-, sex-, and neighborhood-matched controls. Illness was strongly associated with consumption of raw mussels and clams within six weeks of onset of illness. When the two thirds of the subjects who had been exposed were classified according to the frequency with which they had recently consumed any type of raw shellfish, there was a clear dose-response relation. In February 1985, comprehensive control measures were introduced and the annual incidence of hepatitis A fell to 2.3 per 100,000 population, a 10-fold decrease from the preepidemic period.

The heterogeneity of the clinical responses to hepatitis A and B infection is well known, and may in part relate to different etiologic agents (hepatitis A, B, "C", etc.) as well as to the individual hosts' immune responses. The spectrum of disease ranges from anicteric asymptomatic infections to fulminant hepatic necrosis with hepatic failure and death. Although the clinical presentation is varied, there are essentially two patterns of necrosis that can be seen histologically during the first few weeks of clinical symptoms. The more common pattern is focal, and necrosis is scattered throughout the hepatic lobule. Less commonly, zones of necrosis that bridge between the portal--portal or portal--central areas of the lobule develop. When the latter process (bridging necrosis) is extensive, confluent lobules may be destroyed. Patients with focal patterns of necrosis eventually recover without sequelae, whereas a sizable proportion (30-60%) of patients who have bridging or multilobular necrosis progress to chronic active hepatitis, postnecrotic cirrhosis, or progressive hepatocellular failure. There is increasing evidence that these widely differing clinical and histologic responses to hepatitis infection may be related to differences in the immune response.

Sixty-one clinical cases of hepatitis occurred in Ogemaw County, Michigan, in late April and May 1968. The clustering of cases in time and the high attack rate for persons 10-19 years of age suggested a common source of exposure. Investigation implicated a local bakery, where one of the employees directly involved in the baking had had an icteric illness one month before the outbreak. Comparison of exposure histories of patients versus healthy family members established pastries covered with glaze or icing as the vehicle of infection. The glaze and icing were applied to the pastries after all baking had been completed. During the epidemic, immune serum globulin was given on a community-wide basis. No secondary cases of hepatitis were identified.

Experimental hepatitis A virus (HAV) infection was studied in marmosets after enteral (intragastric) inoculation with special reference to the primary sites of HAV replication and immunopathology of the disease. The experiment was carried out using 28 Saguinus mystax negative for antibody to HAV (anti-HAV) and with statistically uniform baseline values of serum isocitrate dehydrogenase (SICD) activity. Each animal was infected with 1 ml of a 15% w/v stool suspension that was derived from marmosets infected with the third or fourth passage of the MS-1 strain of HAV. The incubation period measured by the first significant SICD elevation was 32 days in 11 of 13 marmosets. The animals were sacrificed 2, 4, 7, 11, 14, 18, 23, 28, and 32 days after inoculation and 1, 4, 8, 14, 21, 28, and 35 days after SICD elevation. HAV antigen, immunoglobulins, complement, and fibrin were identified in the liver, eight segments of the gastrointestinal tract, lymphoid system, and kidneys. HAV antigen was found only in the cytoplasm of hepatocytes and in gallbladder bile. These findings indicated that the liver was the sole and primary site of virus replication. Combined immunomorphologic and histopathologic observations also revealed that HAV antigen localization was associated with the sites of hepatocellular damage. There was no immunomorphologic evidence for humoral immune clearance of HAV antigen in the liver, lymphoid system, or kidneys.

During investigation of a food-borne outbreak of hepatitis A among university students in a southwestern metropolitan community, immune electron microscopic examination of a concentrated stool suspension pooled from seven acutely ill individuals revealed viruslike particles 17-nm in diameter. These particles were initially coated by antibody contained in the convalescent-phase serum of one of the ill students as well ad by antibody in convalescent plasma of a prison volunteer originally infected with the MS-1 strain of hepatitis A virus. Rises in titer of antibody to this particle were demonstrated by immune electron microscopy in acute and convalescent sera from student patients as well as in pre-inoculation and convalescent sera from the prison volunteer. Two chimpanzees inoculated intravenously with the concentrated preparation of pooled human stools developed viral hepatitis. During acute illness their feces contained particles morphologically identical to those in the inoculum. These findings represent the first reported recovery of the presumed etiologic agent of hepatitis A from a naturally occurring community outbreak of disease in the United States.

A study of eight cases of herpes simplex hepatitis in apparently immunocompetent adults is presented. The clinical features were nonspecific and were usually those of a severe systemic infection, mimicking septic shock. However, the histologic features were distinctive, with randomly distributed patchy areas of coagulative necrosis surrounded by hepatocytes containing viral inclusions. Viral particles could be identified by electron microscopy and Herpes simplex antigens by immunohistochemistry, but these were not necessary for diagnosis. The light microscopic morphologic features are so distinctive that if these are recognized in a biopsy, the diagnosis of herpetic hepatitis can be made and anti-viral therapy may be instituted.