Sarah H. Sell

Evaluation of a live, attenuated respiratory syncytial virus vaccine in infants

Respiratory syncytial virus ts-1 is a live attenuated experimental vaccine which was administered intranasally to 25 infants 11 to 19 months of age. Clinical evaluation was carried out following a controlled, double-blind protocol which eliminated observer bias, assessed intercurrent illness, and was designed to detect virus transmission. At the low dose of virus of virus used (100 TCID50) 8 of the 25 recipients were successfully infected with RS virus ts-1 as determined by virus shedding or antibody response.

Impact of recurrent otitis media on middle ear function, hearing, and language.

Whether recurrent otitis media in infants and young children is followed by delayed language development was addressed by following 210 normal subjects longitudinally through the first 2 years of life with pneumatic otoscopy and tympanometry performed at every physician encounter. Otitis accounted for 26% of the medical visits. One hundred fifty-six of these children had speech and hearing evaluation at 2 years of age. Thirty percent of the children with recurrent otitis media had a mild or moderate hearing loss. However, after multiple speech and language tests, we could not identify a delay in language acquisition in the otitis-prone children. At 3 to 4 years old, 36 children, including nine with a hearing loss at 2 years of age, were retested; all nine had normal hearing. Recurrent otitis media induced a temporary decrease in hearing sensitivity demonstrable at 2 years of age, which appeared to resolve as the children matured and which was not associated with delay in language acquisition.

Clinical reactions and serologic response following inactivated monovalent influenza type B vaccine in young children and infants

A monovalent, zonally purified, inactivated influenza B vaccine was administered to 29 children, 3 to 6 years of age, and 16 infants, 12 to 28 months of age, as a single dose of 0.25 ml containing 250 chick cell agglutinating units. The vaccine was both antigenic and well tolerated in the older group of preschool children. In the infants the vaccine was also antigenic but poorly tolerated clinically. Febrile reactions to 102 or greater were seen in 9 of the 16 infants, and two of these infants experienced a seizure following vaccination. The clinical reactions observed with the administration of influenza B vaccine in the dose used in this study would suggest significant limitations on its use in children under 3 years of age.

Safety and antigenicity of influenza A/Hong Kong/68-ts-1 [E] (H3N2) vaccine in young seronegative children

Influenza A/Hong Kong/68-ts-1 [E] (H3N2) vaccine was administered intranasally to 18 seronegative children 14 to 32 months of age. Fourteen children, 78%, shed influenza A/Hong Kong virus for a mean of eight days following vaccination. Sixteen children, 89%, experienced a fourfold or greater rise in hemagglutination-inhibition antibody. Some children appeared to experience a febrile reaction to the vaccine although interpretation of this data was complicated by intercurrent illness. These findings demonstrate that influenza A ts-1 [E] replicates more readily in the young seronegative child than in the HAI negative adult. In addition, the temperature-sensitive marker of the vaccine was not genetically stable in four of the vaccinated children. Careful evaluation of any future live respiratory viral vaccines needs to be undertaken in the young seronegative child before the vaccines safety is fully established.

Age-related response to two Haemophilus influenzae type b vaccines.

Two types of Hib vaccines were compared for efficacy and safety in 71 normal children in three age groups: 36 to 72 months, 15 to 18 months, and 6 to 8 months. One vaccine contained the Hib-specific capsular polysaccharide, PRP; the second vaccine contained PRP combined with pertussis vaccine, PRP-P. A third vaccine, DTP, was administered to a control group for each age. Anti-PRP antibody levels were greater after vaccination with PRP-P than after PRP in all three age groups. Immunoresponsiveness to both vaccines increased with age. A lower incidence of side effects was seen with both PRP (15%) and PRP-P (20%) than with DTP (56%). The results suggest that PRP-P is both well tolerated clinically and has greater immunogenicity than PRP.

A longitudinal study of the detection of otitis media in the first two years of life.

A number (210) of children were followed longitudinally through the first two years of life with pneumatic otoscopy and electroacoustic immitance, tympanometry, at every physician encounter. Tympanometry proved to have a high predictive value (86%) for detecting normal ears but relatively poor predictive value (58%) for detecting abnormal ears when utilized as a routine screening procedure with every clinic visit. In part the tympanometrically abnormal ears which appeared normal in otoscopic exam were temporally related to recent episodes of otitis and concurrent upper respiratory congestion, but many were unrelated to detectable middle ear pathology. These observations detract from the utility of tympanometry as a screening tool for middle ear pathology.

The School Adjustment of Post-Meningitic Children

To explore relationships between success in school and infectious childhood diseases, 25 children who had survived laboratory confirmed acute bacterial meningitis without observable sequelae were matched with 25 non-meningitic controls and subjected to intensive multidisciplinary examinations. The postmeningitic children differed significantly from their controls on measures of instructional receptivity, student image, motor coordination, and visual orientation.

1091 AGE RELATED RESPONSE TO HEMOPHILUS INFLUENZAE TYPE B VACCINES

Safety and age related immunogenicity of 2 HIB vaccines, prepared by Lederle Laboratories, polyribosylribitol phosphate (PRP) and PRP-pertussis (PRP-p) were compared in 3 groups of normal children aged 6-7 months,15-18 months and 3-6 years. Children in the older age groups received a single dose of 1 of the HIB vaccines or DPT. Children aged 6-7 months received either: 1) 2 monthly doses of an HIB vaccine, 2) DPT followed 1 month later by PRP or 3) PRP-p followed by DPT. Reactions were evaluated at 24 hours and RIA antibody (method of Anderson) determined at 1 month after injections. In the 2 older age groups,mild-moderate local and/or systemic reactions were similar for PRP-p (4/10 injections) and DPT (5/10 injections). PRP was without reactions. 6-7 month old children tolerated PRP-p and PRP equally well with 3/31 and 4/31 injections causing reactions. In contrast, 12/22 DPT injections caused reactions. Serologic responses to both HIB vaccines were age dependent. The ratio of post-pre geometric mean titers:The addition of pertussis to PRP enhanced antibody response to the HIB polysaccharide antigen and holds promise as an approach to immunization.

1092 INFLUENCE OF ACUTE AND SEROUS OTITIS IN INFANCY ON HEARING TESTING AT 2 YEARS OF AGE

Despite the high level of interest, there is little definitive data concerning hearing outcome in prospectively followed infants with recurrent acute otitis media (AOM). 149 normal children were followed closely during the 1st 24 months of life with special emphasis on middle ear status as judged by pneumatic otoscopy and impedance tympanometry. The incidence of AOM peaked at 7-9 months with 46 visits/100 children with a decrease to 7 visits/100 children by 21-24 months. Type “A” tympanograms correlated with normal ears at each 3 month block between 86-99% of the time. However, type “B” tympanograms were seen 29-59% of the time with ears also judged to be normal by pneumatic otoscopy. At 2 years of age children were tested utilizing sound field audiometry, impedance tympanometry and acoustic reflex thresholds. Sound field testing at 5 frequencies between 250-4000 Hz. showed a hearing loss ≥30 decibels at one or more frequencies in 5-10% of children with no AOM, 11-14% with 1-2 episodes of AOM and 15-29% with ≥3 episodes of AOM. Acoustic reflex thresholds were ≥115 decibels at one or more of 4 frequencies between 500-4000 Hzs. in 3-13% of ears with no AOM, 32-34% with 1-2 episodes of AOM and 44-50% with ≥3 episodes of AOM. In children carefully followed and optimally treated for recurrent AOM abnormal middle ear status and hearing loss were frequent sequelae of AOM in infancy.

1067 CLINICAL STUDIES IN INFANTS OF TWO PNEUMOCOCCAL VACCINES

As a step towards prevention of diseases due to Streptococcus pneumoniae, separate studies of 2 polyvalent polysaccharide vaccines [8-valent Eli Lilly (L) and 14-valent Merck,Sharp and Dohme (MSD)] were undertaken involving 210 normal infants. At age 6 months children were assigned to groups receiving 5 to 50 mcg per vaccine component doses at 6 and/or 12 months or to serve as unvaccinated controls (C). Clinical reactions were monitored by a home visit at 24 hours after vaccination. Antigenicity was determined by radioimmunoassay (RIA) of type specific antibody at ages 6,7,12,13 and 24 months.RESULTS: Clinical reactions to both vaccines were mild. The 8-valent L vaccine stimulated significant antibody to type 3 at 6 months and types 3,7,18 and 23 at 12 months when compared to controls. The 14-valent MSD vaccine stimulated significant antibody at 12 months to types 6,7,8 and 14 when compared to controls. Vaccination at 6 months depressed antibody responses at 12 month revaccination. RIA antibody rose in control groups ≥1.8 fold for all types between the ages of 6 to 13 months indicating some natural acquisition of antibody. By age 24 months, GMTs of all vaccinated groups were similar to C. No influence of vaccination on pneumococcal nasopharyngeal carriage or otitis could be demonstrated. It is concluded that the present pneumococcal polysaccharide vaccines are poor immunogens in infants in all dosage schedules tested.