Hepatitis-A-virus exposure in the Gambia.
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Biomedical subjects
Publications and source records attributed to J W Mosley.
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In the 1975-76 school year, 3 cases of icteric hepatitis occurred almost simultaneously in 2 grades of an Athenian school. An initial survey of the 2 classes approximately one week later found that 88 of 94 children were susceptible to type A hepatitis. No further clinical cases occurred. A second survey at the end of the school year revealed only 2 subclinical hepatitis A virus infections: one coincident with the overt cases in November, and a second from extramural exposure in February. Two carriers of hepatitis B virus in class A were not associated with serologic evidence for communicability of that agent in this setting. Testing of faecal specimens for agents possibly responsible for epidemiological interference with the spread of hepatitis A virus was unsuccessful. Nevertheless, the hypothesis of Band that other agents may interfere with transmission of hepatitis A virus deserves further study.
Experimental transmission of non-A, non-B hepatitis was apparently accomplished in 5 chimpanzees following inoculation with presumably infectious human sera. Administration of sera from implicated donors with normal alanine aminotransferase (ALT) values, as well as from those with abnormal ALT levels, resulted in the development of ALT abnormalities in the inoculated chimpanzees. Transmission from donors with normal ALT values implies that healthy carriers of non-A, non-B virus exist. Evidence is presented which indicates that a period of viremia precedes the clinical illness by at least 12 days.
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The e antigen HBeAg and its antibody anti-HB, have been said to be predictive of chronicity and resolution, respectively, in viral hepatitis. We found, as have others, a specific association with hepatitis B virus-induced disease. In addition, detectability of HBeAg in the acute phase of type B hepatitis was followed by a sixfold higher incidence of chronic hepatitis. Unfortunately, the prediction was erroneous in 65% of positive cases and 6% of negative cases. In chronic hepatitis, HBeAg did not necessarily disappear in advance of resolution, and its disappearance did not necessarily indicate resolution. Two patients with acute hepatitis progressing to chronicity were anti-HBe-positive in both phases, as were seven (5%) with chronic hepatitis. For individual patients, therefore, HBeAg and anti HBe are not prognostically useful indexes.
We evaluated the causes of 30 episodes of acute viral hepatitis in 13 patients who had multiple attacks. Two (seven per cent) of 30 bouts were caused by hepatitis A virus, and 12 (40%) by hepatitis B virus. No patient, however, had more than one attack with the serologic characteristics of Type A or Type B disease. Thus, there were 16 bouts (53 per cent) not attributable to either of the two recognized hepatitis viruses. None of these "non-A, non-B" episodes, evaluated for infectious mononucleosis and cytomegalovirus infection, could be ascribed to either. From this evidence, therefore, it appears that the clinical syndrome of viral hepatitis is produced not only by the two viruses (hepatitis A virus and hepatitis B virus) recognized since the 1940's but also, in all probability, by two non-A, non-B agents.
To define more completely the period of fecal excretion of virus during hepatitis A virus infection, we studied 24 fecal samples from six children with clinical illness during an epidemic of type A hepatitis. As determined by immune electron microscopy, the six patients had detectable viral excretion before or by the time of the first abnormality in serum glutamic-pyruvic transaminase (alanine aminotransferase). Viral excretion reached a peak early and declined to undetectable levels before levels of serum enzyme reached a peak. These data accord with epidemiologic evidence that the person who already has symptoms and signs of type A hepatitis is unlikely to transmit the infection to others. Immune electron microscopy, therefore, may be a better index to the period of communicability than studies of experimental infection in human subjects. This conclusion would imply that precautions against fecal contamination are not usually necessary for patients hospitalized with type A hepatitis.
An epidemic of viral hepatitis beginning in late 1975 in a residence for multiply handicapped children, recognized very early in its course, was investigated prospectively to permit comparison of enzymatic and serologic tests. Thirty-three residents of the institution and 46 full- and part-time employees were studied by the immune adherence hemagglutination procedure for antibody (anti-HAV) to hepatitis A virus (HAV). Of these, 31 residents and 37 staff members were susceptible at the beginning of the epidemic. Nineteen and six, respectively, had anti-HAV seroconversion indicating HAV infection. Thus, 12 children (39%) and 31 staff members (81%) of presumed susceptibles did not have serologic evidence of infection. The subclinical/clinical ratio for the children was 1.1:1; for personnel, it was 1:1. Serum alanine aminotransferase (ALT) levels compatible with viral hepatitis occurred in 21 persons (84%) who had anti-HAV seroconversion; conversely, there were 10 persons who had ALT abnormality without detectable anti-HAV in late specimens among the total of 68 susceptibles. There was no evidence the latter could be attributed to hepatitis B virus infection; therefore, they may represent the endemic occurrence of non-A, non-B agent(s).
Antibody to hepatitis A virus demonstrable by immune electron microscopy appeared early but remained at low levels for several weeks. Antibody detectable by immune adherence hemagglutination was delayed.
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.
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In outbreaks of type A hepatitis in Los Angeles, USA, and Rosario, Argentina, virus particles were isolated from faeces. The geographically diverse strains were identical in appearance and serological reactivity. They differed only in buoyant density, but other workers have also obtained inconsistent results in estimating this. We conclude that the virus strains in the two epidemics were identical.
Because the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one--identified as HBIG--that had a high concentration (442 mug per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient. Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk.
Plasma from persons with high titers of hepatitis B antibody (anti-HBs) was used to manufacture one lot of hepatitis B "immune" globulin sufficient for four interlocking clinical trials of prevention or modification of hepatitis B infections. The trials were carried out in renal dialysis units, in medical personnel with accidental exposures to hepatitis B, in transfused patients, and in patients with fulminant hepatitis. A single policy board developed protocols that allowed comparisons among the four studies while respecting the unique requirements of each.
To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.
Two episodes of acute viral hepatitis occurred in each of 34 patients. One episode in each patient was serologically diagnosable as type B hepatitis on the basis of tests for hepatitis B surface antigen or antibody. The other episode was classified as "non-B" on the basis of seronegativity, reinforced by seropositivity in an alternate bout. An epidemiologic background appropriate to "serum" hepatitis, either transfusion (one bout) or illicit self-injection (46 bouts), was associated just as frequently with serologically non-B episodes as with identified type B disease. The diagnosis of type B hepatitis, therefore, should be made only on the basis of serologic tests specific for hepatitis B virus infection. Other cases of sporadic diseases in adults must be labeled "viral hepatitis, type unspecifiable."