Saul Krugman

Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure.

A serologic study was made in 34 children immunized against measles at the age of 12 months. Using a sensitive virus neutralization test, it was found that many of the children had pre-existing maternal antibody to measles virus. Children with high pre-existing antibody titers failed to seroconvert. Children with lower pre-existing antibody titers seroconverted, but the resulting antibody titer was significantly lower than in children without pre-existing antibody titer. The results of this study demonstrate a probably mechanism for measles vaccine failure in 12-month-old children and support the recommendation of the Public Health Service Advisory Committee on Immunization Practices to postpone measles vaccination to 15 months of age.

Viral hepatitis, type B. Studies on natural history and prevention re-examined.

Frozen serial serum specimens obtained from past studies on the natural history and prevention of Type B hepatitis in children were retested by radioimmunoassay for the following markers of hepatitis B infection: hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), and antibody to hepatitis B core antigen (anti-HBc). The interval between exposure and evidence of viremia (HBsAg) was as short as six days. HBsAg and HBeAg persisted for two to five months and occasionally for more than one year after recovery. After the disappearance of their respective antigens, anti-HBc and anti-HBs persisted for more than seven years and anti-HBe for one to two years. Treatment with hepatitis B immune globulin after exposure induced complete or partial protection or prolongation of the incubation period. Administration of heat-inactivated hepatitis B virus, MS-2 strain, to 29 children induced an inapparent infection in three, characterized by a transient appearance of HBsAg and HBeAg, and the persistence of anti-HBc, anti-HBe and anti-HBs for more than two years.

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.

Viral hepatitis, type A. Identification by specific complement fixation and immune adherence tests.

: Hepatitis A antibody was detected by specific immune adherence and complement-fixation tests in a study involving 473 serum specimens from 20 patients who had viral hepatitis, Type A. In all 20 patients who had no detectable immune adherence antibody (less than 1:5) before onset of hepatitis high levels (greater than or equal to 1:1024) developed one to four weeks later, occasionally reaching peak levels exceeding greater than or equal to 1:81,920 several months thereafter. Five to 10 years later the immune adherence antibody levels ranged between 1:640 and 1:20,480. In general, the complement-fixation test was not as sensitive or as specific as the immune adherence test. These findings indicate that the immune adherence test should be a valuable tool for diagnosis, for epidemiologic surveys, for identification of susceptible and immune persons, for quantitative assays of gamma globulin and for identification of hepatitis A virus in attempts to propagate the virus in cell culture.

Recombinant yeast hepatitis B vaccine compared with plasma-derived vaccine: Immunogenicity and effect of a booster dose

The immunogenic effect of recombinant yeast and plasma-derived hepatitis B vaccines administered at 0, 1 and 6 months was evaluated in 334 seronegative health professionals. The seroconversion rates following 10 micrograms, 5 micrograms and 2.5 micrograms doses of recombinant vaccine were similar to those observed after 20 micrograms doses of plasma-derived vaccine. The geometric mean antibody titres (G.M.T.) induced by 10 micrograms and 5 micrograms doses of recombinant vaccine were similar to those observed after 20 micrograms doses of plasma-derived vaccine. The G.M.T. values were lowest after 2.5 micrograms doses of recombinant vaccine. However, the recipients of the 2.5 micrograms had a significant anti-HBs response after a fourth (booster) dose of recombinant vaccine was given at 12 months. A booster dose of recombinant hepatitis B vaccine was given to 31 health professionals who had been successfully immunised with plasma-derived vaccine 5-7 years previously. A significant anamnestic response was observed in 30 (97%) of these individuals in spite of the fact that 16 (52%) had low or undetectable levels of anti-HBs before the booster dose was given.

Viral Hepatitis, Type B

: Hepatitis A antibody was detected by specific immune adherence and complement-fixation tests in a study involving 473 serum specimens from 20 patients who had viral hepatitis, Type A. In all 20 patients who had no detectable immune adherence antibody (less than 1:5) before onset of hepatitis high levels (greater than or equal to 1:1024) developed one to four weeks later, occasionally reaching peak levels exceeding greater than or equal to 1:81,920 several months thereafter. Five to 10 years later the immune adherence antibody levels ranged between 1:640 and 1:20,480. In general, the complement-fixation test was not as sensitive or as specific as the immune adherence test. These findings indicate that the immune adherence test should be a valuable tool for diagnosis, for epidemiologic surveys, for identification of susceptible and immune persons, for quantitative assays of gamma globulin and for identification of hepatitis A virus in attempts to propagate the virus in cell culture.

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