Joan P. Giles

The natural history of infectious hepatitis

Abstract Since 1956 approximately 700 cases of infectious hepatitis with jaundice were observed at Willowbrook State School, an institution for mentally defective children. This endemic situation provided an ideal setting for the study of the natural history of the disease. The incubation period of infectious hepatitis acquired either parenterally or orally ranged between thirty-five and fifty days. Virus was detected in stools and blood during the incubation period and early in the course of the disease. Stools collected at the following intervals were shown to be infective: on the twenty-fifth day of the incubation period (two weeks before onset of jaundice) and on the first to eighth day after onset of jaundice. Stools collected on the eleventh day of the incubation period and on the nineteenth to thirty-third day after onset of jaundice were not shown to be infective. Viremia was detected on the twenty-fifth day of the incubation period, three to seven days before and three days after onset of jaundice. Viremia was not detected on the eighteenth day of the incubation period. A parenteral inoculation of 0.025 ml. of a serum pool was highly infective, inducing hepatitis with jaundice in six of nine subjects. The demonstration of viremia in a case of inapparent infectious hepatitis provided proof that infection can occur without overt signs or symptoms of disease. Second attacks were observed in 4.6 per cent of 697 cases of infectious hepatitis with jaundice. In an institution in which infectious hepatitis was endemic, the administration of gamma globulin, 0.06 ml. per pound of body weight, suppressed jaundice for a five-month period but it did not prevent an icteric infection.

Studies on immunity to measles

Studies on immunity to measles have been in progress since 1960. Primary infection with measles virus was followed by evidence of detectable antibody by the twelfth day; peak antibody titers were observed by the twenty-first to the twenty-eighth day. Subsequently, in most instances antibody persisted for at least four years at levels capable of completely inhibiting measles infection. However, when antibody declined to minimal or undetectable levels, exposure to measles virus was usually followed by an asymptomatic infection and a booster response; under these circumstances antibody was detectable by the seventh day and peak antibody levels were observed by the twelfth day. These studies confirm the observation that one attack of measles is followed by lifelong immunity. They also provide strong support for the prediction that one inoculation of live measles-virus vaccine will confer permanent immunity.

Viral hepatitis, type B (MS-2 strain). Detection of antibody after primary infection.

Abstract Further observations of the natural history and prevention of viral hepatitis Type B revealed that all 25 unimmunized susceptible children who had a parenteral exposure to MS-2 serum had evidence of hepatitis B infection; 25 had hepatitis B antigen, and 24 had an abnormal SGOT. Of 15 children who received standard immune serum globulin after a parenteral exposure to MS-2 serum, 13 had detectable hepatitis B antigen, and 12 had an abnormal SGOT. Of 10 children who received hepatitis B immune serum globulin after a parenteral exposure to MS-2 serum, four had detectable hepatitis B antigen and abnormal SGOT; of 29 children who received one to three inoculations of heat-inactivated MS-2 serum before a parenteral exposure to unheated MS-2 serum, 12 had detectable hepatitis B antigen and abnormal SGOT. The use of these active and passive immunizing procedures was associated with a protective effect, a more attenuated hepatitis B infection, and a decreased chronic carrier rate of hepatitis B antigen.

The rubella syndrome

Summary 1. A retrospective survey of 20 children with the rubella syndrome was conducted in an institution for mentally retarded children. Rubella infection was acquired during the first trimester of pregnancy. 2. Among the 20 children, a high incidence of prematurity was observed. The average birth weight was low, even in fullterm infants. 3. Among the 20 children, cataracts were observed in 15, deafness in 11, congenital heart disease in 13, microcephaly in 10 and mental retardation in 20. 4. Although 69 anomalies were observed in the 20 children by 5 years of age only 17 anomalies were detected at birth.

Correlation of measles and subacute sclerosing panencephalitis.

THE SUGGESTIVE association of measles with subacute sclerosing panencephalitis ( SSPE) has recently been documented.13 The evidence to support such an association has included: 1) the presence of “measles-like” intracellular virus bodies on electronmicroscopic study of brain tissue from patients with SSPE; 2) the presence of “measles-like” antigen in the brain, as indicated by fluorescent antibody tests; and 3) the presence of abnormally high measles antibody titers in the serum of patients with the disease. During the past year we have had an opportunity to study the measles antibody pattern in an 8 year old girl with subacute sclerosing panencephalitis which occurred 7 years after an attack of measles. These observations have been correlated with the results of a 7 year follow-up of 46 children who had natural measles in 1960. All measles antibody studies were performed by the highly sensitive hemagglutination-inhibition (HI) test described by Norrby.4

Experimental studies with rubella: Evaluation of gamma globulin for prophylaxis

The studies to be described in this report were undertaken for the purpose of attempting to determine whether pooled human gamma globulin is of value in preventing rubella both when susceptible subjects are inoculated with virus and when they are exposed to the disease under conditions simulating natural contact. In some experiments, efforts were made to provide favorable conditions for the demonstration of a prophylactic effect, i.e., giving a large dose of gamma globulin before inoculation of a small dose of virus; in others, particular emphasis was put on efforts to simulate the conditions under which the pregnant woman is likely to be exposed. Such conditions are thought to comprise two general types: first, the pregnant mother whose child or children contract rubella; in such circumstances, the exposure is likely to be more or less continuous or, at least, intermittent, over a period of severM days or longer; our studies have shown that, in some instances, virus may be isolated from nasopharyngeal secretions for as long as one week before, and up to two weeks after the day of onset of rash; second, the pregnant woman who has a single, perhaps, brief and casual exposure, such as the woman who chats briefly with a friend who shortly thereafter discovers that she has rubella. In both instances gamma globulin is likely to be administered to the woman exposed 24 to 72 hours after the appearance of rash in the person to whom she was exposed.

Protective effect of antiribella human immunoglobulin

Previous experience with immune serum globulin (ISG) indicated 1) that it did not prevent viremia in children with rubella infection, and 2) that it did not prevent congenital rubella. This report describes the protective effect of an experimental lot of high titer antirubella human immunoglobulin (RIG) in 33 children exposed to the Brown strain of rubella virus (RV).RIG was given to 22 of the susceptible children 24 or 96 hours after intranasal exposure to RV. Six other children received ISG. The dose of RV was either 104TCInD50 or 101TCInD50, and the dose of immunoglobulin was 0.3 ml/kg of body weight. In the group that received RIG: 1) passively acquired rubella antibody was detected transiently after inoculation in 15 children; 2) no detectable viremia was observed; 3) pharyngeal shedding of RV was decreased and 4) the rubella specific IgM response was depressed. RIG was more effective when given at 24 hours against low dose virus challenge, preventing or delaying seroconversion; it was less effective in modifying infection when given at 96 hours after high dose challenge. These data suggest that RIG may be useful for the prevention of congenital rubella.