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Objective: To determine whether an outbreak of hepatitis A virus (HAV) infection that occurred in 52 patients with hemophilia in Italy was acquired through infusion of contaminated factor VIII or through environmental enteric transmission.Design: A case-control study and a molecular analysis of HAV sequences from implicated lots of factor VIII and from infected patients.Patients: The first 29 patients with hemophilia and jaundice in whom hepatitis A developed were compared with one to three matched controls with hemophilia but no jaundice.Measurements: Type of concentrate and batches infused, number of doses, contacts with persons who had jaundice or hepatitis A, travel abroad to countries reported to have a high attack rate for hepatitis A, and consumption of raw shellfish. Hepatitis A viral sequences sought by polymerase chain reaction in lots of factor VIII and in serial serum samples from two patients with hemophilia in whom hepatitis A developed. Amplification by polymerase chain reaction of cDNA transcribed with reverse transcriptase from matched sets of factor VIII and recipient serum samples. Determination of nucleotide sequence of amplified hepatitis A virus genome.Main Results: Case patients were neither more nor less likely than controls to have traveled to high-risk countries, consumed raw shellfish, or had contact with persons with jaundice. Case patients were more likely than controls to have received a factor VIII concentrate treated with a solvent-detergent mixture to inactivate viruses (odds ratio, infinity; 95% CI, 4.5 to infinity) and to have had larger infusions of the concentrate during the presumed HAV incubation period (odds ratio, 8.54; CI, 2.78 to 27.5). Hepatitis A viral sequences were found in 5 of 12 tested lots of factor VIII. Genomic sequences of HAV obtained for two matched sets of factor VIII and recipient serum samples were identical within each set but different for the two sets.Conclusion: Hepatitis A was transmitted by a factor VIII concentrate treated by a virucidal method (solvent-detergent) that ineffectively inactivates nonenveloped viruses. [ABSTRACT FROM AUTHOR]

The development of a safe and effective vaccine for infection with human immunodeficiency virus (HIV) is complicated by several unique scientific, logistic, and ethical issues. These issues include a lack of understanding of protective immunity to HIV and disease development, the absence of an adequate and convenient animal model for studying HIV infection, and difficulties in phase III evaluation of candidate vaccines. Because HIV can be transmitted as either a cell-free or cell-associated virus, a protective immune response against HIV infection will likely require both humoral and cell-mediated immunity. A neutralizing antibody against HIV and an antibody involved in antibody-dependent cellular cytotoxicity have been shown in HIV-infected persons, but their precise relation to protection is unclear. Cytotoxic lymphocytes from HIV-infected persons have been shown to lyse target cells expressing HIV or its proteins. Cloned T cells have been developed that manifest HIV-specific, major histocompatibility-complex class I-restricted cytotoxic capabilities that are broadly specific. Thus far, all attempts to protect chimpanzees, currently the only suitable animal model, from HIV infection have failed. Ongoing vaccine studies in humans include phase I trials of recombinant proteins of the HIV envelope in uninfected persons as well as the administration of whole killed virus to persons already infected with HIV. Rapid progress is being made in the development of new animal models for HIV infection. The establishment of alternative animal models, both primate and small animal models, will greatly facilitate the development of a vaccine for HIV infection. [ABSTRACT FROM AUTHOR]

Four hundred sixty patients and staff from 15 U.S. dialysis centers were surveyed by the immune adherence hemagglutination technique for antibody to hepatitis A antigen (anti-HA). The age-standardized anti-HA prevalence was 42.9% in patients and 42.1% in staff. These rates are almost identical to those of socioeconomically comparable urban volunteer blood donors never exposed to dialysis settings. There was no correlation between anti-HA prevalences and duration of dialysis treatment or employment. Among 100 patients and staff followed for 1 year 92% to 94% did not change their anti-HA status. The prevalence of anti-HA was identical in subjects with past histories of multiple blood transfusions or accidental inoculations with blood-contaminated instruments and in those without such histories. We conclude that hepatitis A virus rarely if every spreads by parenteral mechanisms, that there is no epidemiologic evidence confirming the existence of chronic hepatitis A viremic carrier states, and that hemodialysis does not play a significant role in the spread of type A hepatitis. [ABSTRACT FROM AUTHOR]

In studies conducted in the early 1950s, sera from six asymptomatic blood donors, implicated in the transmission of viral hepatitis, were inoculated into 10 to 20 volunteers each. Five of these "implicated" donor sera transmitted clinically apparent hepatitis to the recipients. The stored serum samples from these studies have been reanalyzed using serologic markers for hepatitis B virus and hepatitis A virus infection. Two of the donor sera were hepatitis B surface antigen (HBsAg)-positive, and both transmitted hepatitis B virus infection to all susceptible recipients, half of whom showing clinical symptoms. The remaining three infectious donors were HBs-Ag-negative, yet were icterogenic to 10% to 47% of recipients. Testing of serum samples from these recipients with hepatitis showed no evidence of hepatitis B virus or hepatitis A virus infection. This study and other recent evidence suggest that there is a third type of human viral hepatitis--non-A, non-B hepatitis--which is due to a transmissible agent and may well be associated with a chronic carrier state. [ABSTRACT FROM AUTHOR]

We studied serologically 45 adults who had sporadic acute viral hepatitis that was hepatitis B surface antigen (HBsAg) negative. Two cases were due to hepatitis B virus, as demonstrated by the appearance of antibody to hepatitis B core antigen. In three other patients, the serologic pattern was inconclusive. Of 40 non-B cases, 20 were type A hepatitis and 20 were non-A, non-B hepatitis. Clinically, type A and non-A, non-B hepatitis were indistinguishable; one case of fulminant disease occurred in each group. The type A cases were more frequent in young adults; non-A, non-B disease predominated in women 35 years or older. Epidemiologic backgrounds were generally similar, including illicit self-injection; but four transfusion-associated cases were limited to the non-A, non-B group. We conclude that relatively few HBsG-negative cases are due to hepatitis B virus, and that hepatitis A virus and non-A, non-B viruses are both important in acute non-B disease. [ABSTRACT FROM AUTHOR]

Presents information on a study that investigated the effect of the combined exclusion of commercial and hepatitis-B antigen-positive donors on the frequency and severity of post-transfusion hepatitis patients. Methodology of the study; Results and discussion on the study.

Presents information on a study that examined hepatitis C virus infection among hospital employees with needlestick injuries. Research methods; Results and discussion.

In 1972 a nonsocomial outbreak of parenterally transmitted hepatitis affected both marrow transplant patients and normal platelet donors in an oncology unit. Because of the characteristics of the clinical illness, the incubation period of 27 days, and the effect of immune serum globulin on the clinical illness, the outbreak was attributed to hepatitis A; there was no serologic evidence of either hepatitis B virus or cytomegalovirus infection. Stored serums from this outbreak were re-examined by more recently developed serologic techniques for evidence of hepatitis A (HA) virus infection. Ten patients and donors had undetectable anti-HA titers before illness and none seroconverted; five persons had pre-existent anti-HA titers and showed no further rise in convalescent serums. The serum of one patient was inevaluable. With the availability of serologic techniques for the diagnosis of both hepatitis A and hepatitis B virus infections, it is clear that most cases of post-transfusion hepatitis are not due to either of these agents, and short-incubation-period hepatitis can not be assumed to be hepatitis A without further investigation. [ABSTRACT FROM AUTHOR]

The relationship between the presence of antibody to hepatitis B core antigen (anti-HBc) in donor blood and the development of hepatitis in recipients of that blood was studied in 6293 blood donors and 481 recipients who were followed for 6 to 9 months after transfusion. Of 193 recipients of at least 1 unit of blood positive for anti-HBc, 23 (11.9%) developed non-A, non-B hepatitis compared with 12 (4.2%) of 288 recipients of only anti-HBc-negative blood (p less than 0.001). Donor anti-HBc status was not significantly associated with the development of hepatitis B in the recipient and was negatively associated with the development of cytomegalovirus hepatitis. The relationship of donor anti-HBc status and the development of non-A, non-B hepatitis in the recipient was independent of transfusion volume and elevated donor transaminase level. Although 88% of anti-HBc-positive blood units were not associated with recipient non-A, non-B hepatitis, calculation of maximal corrected efficacy predicted that exclusion of anti-HBc-positive donors might have prevented 43% of the cases of non-A, non-B hepatitis with a donor loss of 4%. Because of the serious chronic consequences of non-A, non-B hepatitis, surrogate tests for non-A, non-B virus carriers must be seriously considered.

Immune electron microscopy, which can detect hepatitis A antigen and antibody (anti-HA), was used to study a foodhandler-associated outbreak of hepatitis among 136 naval recruits. In stool specimens collected during the acute phase of illness, 27-nm viruslike hapatitis A antigen particles were shown, but only in patients with icteric hepatitis. Detection was possible in stools collected as early as 10 days before peak serum aminotransferase activity and up to the time of peak enzyme activity, but not thereafter. The immunologic similarity of these viruslike particles to those found in acute phase stools of volunteers inoculated with the MS-1 strain of hepatitis A virus was determined, and an increase in anti-HA was shown between acute and convalescent serums from 25 of the recruits. These data support the view that the MS-1 strain of hepatitis A virus is serologically related to naturally acquired type A hepatitis.