Ciro V. Sumaya

Predictors of Morbidity and Mortality in Neonates with Herpes Simplex Virus Infections

BACKGROUND In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Tuberculous meningitis in children during the isoniazid era.

Fifty-nine cases of tuberculous meningitis in children seen at the Charity Hospital at New Orleans since the addition of isoniazid to the therapy in 1952 are reviewed. Fourteen of the children died during hopsitalization. At discharge 21 children had complete or nearly complete clinical recovery. Follow-up of 21 available long-term survivors revealed a significant number with neurologic and social disabilities. The endemicity of tuberculous infections in the households of the children and factors responsible for transmission of tubercle bacilli from an adult source are reported. The importance of chemoprophylaxis and public health measures in eliminating this disease are stressed.

Antibody responses following rubella immunization analyzed by HLA and ABO types

HLA typing was performed on 232 rubella seronegative (HAI antibody titer <8) children immunized with RA 27/3 vaccine. High convalescentphase geometric mean antibody titers were noted in children one to five years of age, in girls one to 12 years of age, in subjects with AB blood type and in vaccinees with HLA types B14 and BW22. Of nine children with rubella titers≧512, 44 percent had HLA type A28; in contrast, only eight percent of the total group had A28 HLA type. HLA-A2 was present in four, and HLA types B12 and BW17 were present in three of the six children in whom seroconversion did not occur. Fifteen of 37 sibling pairs had identical antibody responses; in contrast, only 18 percent of randomly paired children had titers identical to each other. Vaccine-related symptomatology could not be associated with any HLA type. The results of this study suggest that infection with and antibody response to RA 27/3 rubella vaccine is influenced by genetic factors, which include cellular membrane determinants.

Changes in T-Lymphocyte Subsets During Childhood Epstein-Barr Virus Infectious Mononucleosis

Lymphocyte subsets were measured using monoclonal antibodies in 11 children with Epstein-Barr virus-induced infectious mononucleosis and compared with those of 10 normal children. In acute infectious mononucleosis the percentage of T8+ lymphocytes was greater while the percentage of T4+ lymphocytes and the T4+ to T8+ ratio were less than those measured in normal children. The percentage and absolute number of T lymphocytes, as enumerated by E rosetting, did not differ from the values for normal children. The children with acute infectious mononucleosis had a somewhat lower T8+ response than that observed in four adult infectious mononucleosis patients. With clinical recovery, the T lymphocyte-subset values returned toward normal. T8+ lymphocytes, a phenotype subset with predominantly suppressor activity, presumably reduce normal cellular immune functions transiently and may limit the continued proliferation of Epstein-Barr virus-infected B lymphocytes.

Enteroviral meningitis in early infancy: significance in community outbreaks

Sixty-eight episodes of aseptic meningitis were diagnosed in 67 children during summer-fall 1979. Enteroviruses were isolated from 38 (79%) of 48 cases (47 children) with viral isolation studies performed. In 27 cases the enterovirus was isolated from the cerebrospinal fluid. Except for one Coxsackie B-4 and one Coxsackie B-5 virus infection, all of the enteroviruses isolated were echoviruses; no single echovirus type predominated. The ages of the children with aseptic meningitis associated with an enteroviral infection ranged from 3 weeks to 14 years, with 79% of patients being under 1 year old. Forty-seven percent were infants less than 4 months old. Mild hypoglycorrhachia defined as a cerebrospinal fluid: blood sugar ratio of less than 0.50 may be a common finding in enteroviral meningitis in very young children.

Genital Infections with Herpes Simplex Virus in a University Student Population

The frequency of clinically evident genital infections with herpes simplex virus among students attending a large urban public university was studied. One-hundred ninety-eight students experienced 222 episodes of this disease over a one-year period. The mean age of the students, both undergraduate and graduate, with the diagnosis of genital herpes ranged from 23.6 years for those with a single initial episode to 24.9 years for those with recurrent episodes. The male-to-female ratio and socioeconomic class of students with genital herpes were not significantly different from those of the general university population. The incidences of both initial and recurrent episodes of genital herpes were statistically significantly higher during the months of July through October (with the exception of September). Genital herpes was a frequently diagnosed sexually transmitted disease among this student population.

Endophthalmitis due to Salmonella enteritidis.

The clinical characteristic serving as the first clue to the etiologic diagnosis was the lack of response to the various antibiotic regimens utilized. The diagnosis of Mycoplasma gneumoniae infection in these children was made on the basis of elevated mycoplasma complement fixation titers, exclusion of other known respiratory pathogens, and on epidemiologic grounds. The father, who had been symptomatic with respiratory complaints the week before the first childs illness, was found to have a stable, high mycoplasma complement fixation titer. Serious mycoplasmal infections manifested by respiratory distress, mult i lobular pneumonitis, pleural effusion, prolonged fever, and leukocytosis have been described previously in patients with hemoglobinopathies ~~ or dysgammagl0bulinemias.~ There have been no reports of mycoplasmal pulmonary disease of comparable severity in otherwise healthy children. Though severe mycoplasmal disease has been uncommon in children, our experience with these three siblings suggests that the disease spectrum is wider than previously thought, and that severe pulmonary involvement can occur in otherwise healthy children. R E F E R E N C E S

A clinical trial with Alice/R-75 strain, live attenuated serum inhibitor-resistant intranasal bivalent influenza A/B vaccine.

A clinical trial was conducted with Alice/R-75 strain live attenuated intranasal influenza A/B vaccine. With double blind control 88 adult volunteers were administered 2 doses of Alice/R-75 vaccine, 93 volunteers received one dose of Alice/R-75 vaccine and one dose placebo solution and 94 subjects were administered 2 doses of placebo solution. Twenty-three other subjects received Alice strain monovalent influenza A vaccine. For comparison, data from 21 subjects who received monovalent intranasal R-75 strain influenza B in two doses is included. The vaccine was generally well tolerated. Four-fold serum hemagglutination-inhibiting (HAI) antibody titer rises to A/England/42/72 occurred in 39% of the monovalent Alice strain vaccinees; in contrast 18% of those given 2 doses of bivalent Alice/R-75 vaccine and 11% of those given 1 dose of bivalent vaccine had similar four-fold HAI antibody titer rises. HAI antibody titer rises to influenza B/Hong Kong/72 occurred in 38% of R-75 strain monovalent vaccinees, 14% of Alice/R-75 2-dose vaccinees and 11% of Alice/R-75 one dose vaccinees. An epidemic of influenza at the onset of the study made evaluation of the efficacy of the vaccine impossible.

Predictors of morbidity and mortality in neonates with herpes simplex virus infections

Abstract Background. In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. Methods. Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. Results and Conclusions. There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) t...

The rapid diagnosis of infectious mononucleosis using an ELISA that detects IgM antibody to a peptide component of Epstein-Barr virus nuclear antigen.

An enzyme-linked immunosorbent assay (ELISA) that detects IgM antibody to a peptide component of the Epstein-Barr virus (EBV) nuclear antigen (EBNA-1) was compared with a conventional rapid heterophil antibody method for the rapid diagnosis of infectious mononucleosis. Discrepancies between the two methods were further analyzed using an indirect immunofluorescence assay to detect antibodies to EBV antigens. We evaluated 298 cases of suspected infectious mononucleosis. The ELISA was very sensitive (98.7%) and able to detect some cases (seven (9%) of 75 confirmed positives) that were negative by the rapid heterophil antibody test, but confirmed by immunofluorescence. However, approximately 17% of all positive tests could not be confirmed by EBV-specific immunofluorescence; thus, the overall positive predictive value was 83%; negative predictive value was 99.5%; and specificity was 93%. The high rate of false-positive tests makes this rapid ELISA unsuitable for the diagnosis of infectious mononucleosis.