Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

Clinical and laboratory evaluation of cytomegalovirus-induced mononucleosis in previously healthy individuals. Report of 82 cases.

The present report describes the clinical and laboratory profile of 82 previously healthy individuals who developed cytomegalovirus (CMV)-induced mononucleosis. Many of these patients posed initial diagnostic problems and were hospitalized with diagnoses such as fever of undetermined origin, active viral hepatitis, acute leukemia, probable systemic lupus erythematosus, autoimmune hemolytic anemia, and severe pancytopenia. These patients underwent a variety of diagnostic biopsies, including liver biopsies (6) and bone marrow aspirations (9). Four patients had exploratory laparotomies, 1 for a ruptured spleen, and another had a splenectomy following an erroneous initial diagnosis of agnogenic myeloid metaplasia. There was no apparent clinical response to a short course of steroid therapy in 3 of 5 cases and acyclovir in another. The vast majority of these patients demonstrated infectious mononucleosis-type reactive blood smears, negative heterophil antibody studies, mildly or moderately elevated aspartate aminotransferase activity, and evidence for subclinical hemolysis on serial specimens. The peak serum bilirubin levels were above 2.0 mg/dl in only 2 of 71 cases tested, both of the latter patients having significant hemolysis (hemoglobin values 8.6-9.3 g/dl). The CMV-IgM test had a high sensitivity for detection of CMV macroglobulins (positive in 81 of 82 cases). In contrast, complement-fixing antibodies to CMV showed diagnostic four-fold titer changes in only 39/82 cases (47.6%). Despite its great sensitivity, the CMV-IgM test is limited by a one-way crossreaction of acute Epstein-Barr virus (EBV)-IM sera and spurious positive reactions in some sera due to the presence of rheumatoid factors. Based on EBV-specific serologic studies, the 82 patients with CMV-IM could be divided into 4 groups: 3 patients without antibodies to EBV; 2) 69 patients with uncomplicated serologic data indicative of long-past EBV infections; (3) 6 patients with unusual antibody profiles, e.g., anti-D responses; and (4) 5 patients, including 1 originally susceptible to EBV, with apparent dual CMV/EBV infections. At the conclusion of our study, final diagnoses and initial hematologic data were correlated in 750 cases in which CMV macroglobulins were searched for. The vast majority of patients with active CMV infections initially demonstrated either markedly or moderately reactive peripheral blood smears. These data support our impression that diagnostic tests for CMV, as well as for EBV, are seldom indicated in symptomatic previously healthy patients whose blood smears during the acute phase (first several weeks) of their illnesses are either nonreactive or minimally reactive.

An outbreak of varicella-zoster virus infection among cancer patients.

An outbreak of varicella-zoster infection occurred among patients of the Medicine Branch, National Cancer Institute, National Institutes of Health. Epidemiologic investigation suggested that the outbreak was due to two distinct types of disease. One type was acquired without previous exposure to other diseased patients and invariably associated with dermatomal lesions. The other, an a typical form, was associated with person-to-person transmission and equivocal initial dermatomal distribution and had an incubation period of approximately 11 to 25 days. Despite the diagnosis of zoster, the latter probably was varicella, occurring in patients who were immunodeficient because of disease, debility, and chemotherapy.

Serum antibody levels as risk factors in the dissemination of herpes zoster.

Serum antibody levels against varicella-zoster virus (VZV) were examined by immune adherence hemagglutination assay (IAHA), indirect fluorescent antibody (IFA) assay, and complement fixation techniques in 67 immunocompromised patients with localized and disseminated herpes zoster. In the serum obtained initially, undetectable IAHA titers were found in 56.5% of the patients with disseminated zoster compared with 18.2% of those with localized zoster. When serum obtained within the first seven days of illness was analyzed, undetectable IAHA titers and IFA titers of less than 32 were noted in 77.8% of those with disseminated zoster but in only 18.5% of those with localized disease. Peak serum antibody titers in patients with disseminated zoster were eventually equal to or greater than those in localized zoster. The patient groups were comparable in age, underlying disease, and therapy, although Hodgkin's disease was more frequent in patients with disseminated zoster. Thus, the absent IAHA or low IFA levels of circulating antibody early in illness were highly significant risk factors in dissemination of virus in herpes zoster.

Herpes zoster at the NIH: a 20 year experience.

One hundred and seven cases of herpes zoster in a hospitalized population with a variety of illnesses during a 20 year period were reviewed. Zoster occurred throughout the year, without seasonal predominance, and was most frequent in lymphoproliferative malignancy. In the majority, lesions were confined to the skin in one or more adjacent dermatomes (localized zoster) and were most frequent in the thoracic region. In 15 per cent of the cases, cutaneous dissemination of the lesions developed; this occurred four to 11 days after the onset of dermatomal lesions, and in one-third of these there was central nervous system involvement. Dissemination of zoster, however, directly resulted in only one death. Predisposing factors for zoster included local irradiation and, occasionally, surgery in subsequently involved areas. There were trends for more frequent splenectomies in patients with Hodgkin's disease in whom zoster subsequently developed, and for more frequent corticosteroid therapy in patiens with disseminated zoster. Advanced stage of Hodgkin's disease, in itself, was not associated with development of zoster, and the onset of zoster did not herald a poor prognosis for the underlying disease. Herpes zoster was, thus, largely a source of increased morbidity rather than mortality in the population studied, and multiple factors appeared to predispose to the development of zoster in this group of patients.

Immunogenicity and reactogenicity of influenza A/New Jersey/76 virus vaccines in normal adults.

Inactivated influenza A/New Jersey/76 virus vaccines were administered intramuscularly to 199 normal adults, aged 19-59, in doses of 200, 400, or 800 chick cell-agglutinating units in a double-blind, placebo-controlled trial. Systemic reactions (including fever) were uncommon, were mild, lasted less than 24 hr, and were more frequently associated with the largest dose. Local reactions were common but mild. A single, rapidly reversible, allergic reaction was noted in a volunteer 2 hr after vaccination. There was a trend toward fewer systemic reactions in vaccines who had preexisting hemagglutination-inhibiting (HAI) antibodies to the vaccine virus in their sera as compared with seronegative vaccines. All vaccine preparations at all three dosages evoked serum HAI titers of greater than or equal to 20 to greater than or equal to 40 in a high proportion of seronegative recipients, with significantly greater geometric mean titers at the highest dosage. Vaccines between the ages of 19 and 23 years manifested significantly lower serologic responses than did vaccinees over the age of 23. Thus, normal adults over the age of 23 can be immunized with a single, well-tolerated dose of A/New Jersey/76 vaccines.

Serologic responses and systemic reactions in adults after vaccination with bivalent A/Victoria/75-A/New Jersey/76 and monovalent B/Hong Kong/72 influenza vaccines.

Bivalent A/Victoria/75-A/New Jersey/76 and monovalent B/Hong Kong/72 influenza vaccines were given alone or together to adutls, and systemic reactions and antibody responses were determined. The rates of systemic reactivity observed varied among vaccine groups. Disrupted vaccines and whole-virus vaccines containing type B antigen only did not cause significant reactivity. Systemic reactions were observed after administration of the bivalent A whole-virus vaccines, and this reactivity was increased if the B vaccine was also administered. Reactions to the more reactive vaccines were less frequent in older subjects or in younger individuals with evidence of previous exposure to influenza antigens in the vaccine. Antibody responses in this study indicated that individuals older than 25 years responded better to A/New Jersey antigens than did younger subjects. The A/Victoria antigen produced lower antibody levels in older individuals than in younger subjects. The B/Hong Kong antibody responses were similar in all vaccine groups.

Serologic responses after two sequential doses of influenza A/New Jersey/76 virus vaccine in normal young adults.

The serologic responses after two sequential nonreactive doses of either chemically disrupted or whole-virus influenza A/New Jersey/76 virus vaccine were evaluated in 112 normal young adults. In general, levels of hemagglutination-inhibiting (HAI) antibody were low after the first dose of vaccine and increased significantly (P less than 0.05) in response to a second dose. Whereas one dose of the preparation from Merck Sharp and Dohme (West Point, Pa.) effectively vaccinated this population, two doses of the vaccines prepared by Parke, Davis and Company (Detroit, Mich.) and Merrell-National Laboratories (Cincinnati, Ohio) were required to produce a similar serologic response. The preparation from Wyeth Laboratories (Philadelphia, Pa.) produced low levels of HAI antibodies even after two doses. These different serologic responses correlated with the viral hemagglutinin content of each vaccine.