Peter D. Reuman

Effect of passive maternal antibody on influenza illness in children: a prospective study of influenza A in mother-infant pairs.

To determine the effect of passive antibody on the incidence of influenza in infants, infants born to mothers with serum antibody to influenza A (immune) and those born to mothers without evidence for this serum antibody (non-immune) were followed during the influenza H1N1 epidemic of 1979. Immune mothers had higher H1-specific antibody titers before the epidemic (P less than 0.001), were less frequently culture positive, showed fewer titer rises (P less than 0.001) and were less symptomatic than were nonimmune mothers. Infants of immune mothers had higher H1-specific passive antibody titers that correlated with their mothers antibody titers. Although infants of both groups showed no difference in incidence of influenza infection, infants of immune mothers had influenza symptoms that were delayed in onset (P = 0.02) and were of shorter mean duration compared with infants of nonimmune mothers. These findings suggest that passive maternal antibody delays the onset and decreases the severity of influenza disease in young infants.

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: Results of a phase I/II trial

BACKGROUNDnNeonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates.nnnMETHODSnInfants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months.nnnRESULTSnTwelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study.nnnCONCLUSIONSnAdministration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Lack of effect of Lactobacillus on gastrointestinal bacterial colonization in premature infants.

Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms. Thirty premature infants were matched by birth weight and gestational age, randomized and fed double blind either lactobacilli-containing formula or non-lactobacilli-containing formula within 72 hours of delivery. The two study groups were screened weekly by culture for stool lactobacilli, for gram-negative bacteria and for antibiotic resistance of these bacteria. Lactobacilli were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli (P < 0.001). Gram-negative enteric organisms were isolated during 40 of the 86 weeks (47%) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks (49%) for patients not receiving lactobacilli. There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates (4 of 40 vs. 0 of 28). These results suggest that facultative gram-negative enteric bacterial colonization, with either total or aminoglycoside-resistant strains, is not decreased by oral feedings of Lactobacillus acidophilus in premature infants.

The effect of age and weight on the response to formalin inactivated, alum-adjuvanted hepatitis A vaccine in healthy adults

Formalin-inactivated, alum-adsorbed, hepatitis A vaccine was evaluated in 100 healthy adults who were stratified at enrollment into two age groups: 18-39 years: n = 50; 40-65 years: n = 50. All individuals received vaccine at 25 U of viral antigen. After stratification, both groups were randomized to receive either vaccination at 0 and 24 weeks or vaccination at 0.2 and 24 weeks. Subjects were bled for serology at 0, 2, 4, 24, 28 weeks and 1 year. The seroconversion rate and geometric mean titer (GMT = mIU ml-1) after one dose of vaccine was lower for older subjects [second week: < 40 years: 15/25 (60%) (GMT: 12.9). > 40 years: 5/22 (23%) (GMT: 6.1): fourth week: < 40 years: 20/22 (91%) (GMT: 29.0), > 40 years: 16/23 (70%) (GMT: 14.3)]. After a second dose at 2 weeks the seroresponse improved so that there were no longer differences between age groups [24 weeks: < 40: 21/22 (95%) (GMT: 123.9), > 40: 22/23 (96%) (GMT: 106.1)]. A third dose at 24 weeks resulted in a 20-40-fold increase in GMT in both age groups. As a separate evaluation height, weight, skin fold thickness, and body mass index (BMI) were assessed by logistic regression for their ability to predict serologic response. Serologic response was significantly associated with lower weight (P = 0.032) and BMI (P = 0.024) but not with height or skin fold thickness. Hepatitis A vaccine was well tolerated, with no serious adverse experiences. Adults older than 40 years appear to respond less well than younger adults to a single dose of 25 U of hepatitis A vaccine but equally well after two doses of vaccine. The slower antibody response to hepatitis A vaccine in overweight individuals was not attributable to skin adipose tissue.

Comparative safety and efficacy of clarithromycin and cefadroxil suspensions in the treatment of mild to moderate skin and skin structure infections in children

&NA; A prospective, randomized, single (investigator) blind multicenter study was performed to compare the safety and efficacy of clarithromycin and cefadroxil oral suspensions in the treatment of mild to moderate skin and skin structure infections in children. Male and female patients ages 6 months to 12 years were enrolled at 24 study centers in the United States. Patients had signs and symptoms consistent with mild to moderate skin or skin structure infections judged suitable for oral antimicrobial therapy. Clarithromycin oral suspension was given to 118 children in a dose of 7.5 mg/kg (maximum of 500 mg) twice daily; cefadroxil oral suspension was given to 113 children in a dose of 15 mg/kg (maximum of 1000 mg) twice daily. Among clinically evaluable patients clinical success rates (cure plus improvement) were 96% (71 of 74) for clarithromycin and 98% (83 of 85) for cefadroxil (P = 0.664). Bacteriologic cure rates in evaluable clarithromycin and cefadroxil patients were 96% (72 of 75) and 99% (89 of 90), respectively (P = 0.331). Pathogen eradication rates based on 204 evaluable pathogens were 97% in the clarithromycin group and 99% in the cefadroxil group (P = 0.326). Adverse events were mild or moderate and were reported in 25% of clarithromycin and 35% of cefadroxil patients (P = 0.085). In both groups adverse events involved primarily the digestive tract. No significant laboratory changes were noted. Clarithromycin oral suspension appears to be a safe and effective alternative to cefadroxil for the treatment of pediatric skin and skin structure infections.

Safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen months old. The MMRV Study Group.

OBJECTIVEnTo determine the safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine (MMRV) and PedvaxHIB (Haemophilus influenzae type b conjugate vaccine) vs. M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later.nnnDESIGNnHealthy children, 12 to 18 months of age, were randomly assigned to two groups to receive (1) MMRV and PedvaxHIB given concurrently or (2) M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later.nnnSUBJECTSnThe study group included 294 healthy children, ages 12 to 18 months, with a negative history of measles, mumps, rubella and varicella.nnnMAIN OUTCOME MEASURESnThe seroconversion rate and magnitude of antibody responses when MMRV was given concurrently with PedvaxHIB compared with the antibody responses when VARIVAX was given 6 weeks after M-M-R II and PedvaxHIB.nnnRESULTSnHealthy children, 12 to 18 months of age, who received MMRV and PedvaxHIB concurrently showed immune responses similar to those in the control group who received M-M-RII vaccine with PedvaxHIB followed by VARIVAX 6 weeks later. Antibody titers for varicella were significantly lower when MMRV was administered than when varicella vaccine was given separately (0.712-fold difference, P = 0.028). No vaccine-related serious adverse reactions were reported, and no clinically significant differences were seen in the safety profiles of the two treatment groups.nnnCONCLUSIONSnThere were no statistically significant differences in the seroconversion rates between the two treatment groups for any of the antigens tested at 6 weeks and 1 year. Significantly lower geometric mean titers for varicella were noted in the group who received MMRV compared to VARIVAX given alone. Six-week seroconversion rates, persistence of immune responses at 1 year and the frequency of local and systemic reactions were comparable when MMRV was administered with PedvaxHIB compared with M-M-R II and PedvaxHIB followed by VARIVAX 6 weeks later.

The Importance of Nosocomial Transmission of Measles in the Propagation of a Community Outbreak

In late January 1985, a measles outbreak occurred at a community hospital in Columbia county, Florida. The outbreak spread throughout the county and to two neighboring counties (Alachua and Marion), resulting in 79 cases with a 29% hospitalization rate. Hospitals represented the site with the highest frequency of transmission. At the Alachua county hospitals, where strict respiratory isolation measures were taken, no secondary cases occurred among hospitalized patients. Two independent risk factors existed for hospitalization: measles exposure in a hospital setting (P less than 0.05) and nonvaccination (P less than 0.001). Of the total measles cases, 24% were under the age of 16 months and 47% of those aged 16 months or older had a history of appropriate vaccination. Columbia county, which experienced 86% of the cases, had a 5% frequency of unvaccinated students compared to 0.6% frequency at Alachua (P less than 0.001) where only 10% of the cases occurred. This outbreak demonstrates the role of uncontrolled nosocomial transmission of measles in the propagation of a community outbreak.

Uncontrolled nosocomial rotavirus transmission during a community outbreak

Between Jan. 11 and March 31, 1983, 60 pediatric patients were diagnosed with rotavirus gastroenteritis. Of these cases 24 were community acquired, 29 were nosocomial, and 7 were of undetermined origin. Despite intensive infection control efforts, nosocomial transmission continued as long as patients with community-acquired cases were admitted. The use of disinfectants and germicides that were ineffective against rotavirus may have contributed to the continued nosocomial spread during a community outbreak.

Influenza Infection in the Infant Mouse

Summary: A nonlethal influenza infection [A/PC/1/73 (H3N2)] was given to infant mice to determine (1) the pathology of tracheal epithelium and lung, (2) the time course of viral shedding from the nose and lung, and (3) the subsequent development of protective immunity during adulthood.Both desquamation of the tracheal epithelium and lung pathology similar to that described in adults after influenza infection were observed in the infant. Animals infected at 3 days of age show virus shedding in 12 of 13 infant mice that persists for at least 2 days longer than in the adult. This longer duration of influenza infection did not result from either malnutrition or from intralitter transmission of virus. Recovery from virus shedding in both the upper and lower airway occurred in the absence of detectable serum antibody in six of seven mice. Infants that recover from infection, when rechallenged during adulthood, manifest complete protection in 11 of 13 mice after nonlethal challenge and no mortality after lethal challenge.

1355 CHLAMYDIA TRACHOMATIS (Ct) PNEUMONITIS IN PREMATURE INFANTS

Although Ct is recognized as a common etiologic agent in infant pneumonia, its role in pulmonary infection of premature infants has received little attention. Eight premature high risk babies hospitalized in our intensive care nursery over a 9 month period were documented to have Ct pneumonitis by standard McCoy cell tissue culture of endotracheal tube aspirates (7 patients) or nasopbaryngeal swab (1 patient). All patients had negative CMV urine cultures. Birthweights ranged from 610-2200 g. and gestational ages from 26-34 weeks. Six patients were born vaginally and 2 by Caesarean section. Age ranges at time of Ct isolation was 8-83 days (mean 29 days). All patients were cultured during an acute worsening of their respiratory status; 7 showed acute changes on chest X-ray.Seven patients were treated with erythromycin for 3 weeks; the remaining patient died prior to Ct identification. Five patients died of respiratory failure, 1 patient is at home on oxygen therapy for chronic lung disease and 2 patients have no residual lung disease. During this same time period, there were 8 infants of similar gestational age, birthweight, chronological age and mode of delivery whose endotracheal aspirate culture was negative for Ct. All these infants have survived.Chlamydia trachomatis appears to be associated with severe pulmonary disease in premature infants. Ct pneumonitis should be considered in a premature high risk infant with worsening respiratory status.