Age and dose interval as factors in agglutinin formation to pertussis vaccine.

The agglutinin response to pertussis agglutinogens in diphtheria-tetanus-pertussis (DTP) vaccine was determined in human infants inoculated initially at ages four weeks to eight months. The effects of age at the time of initial dose and the interval between subsequent doses were specifically evaluated. Our findings demonstrate that optimum agglutinin production is best achieved with DTP vaccine by beginning immunization at five months of age or later followed by a second dose at eight weeks or more. Variation in the two variables, age and dose interval, decreases the likelihood of an optimum agglutinin response.

Further evaluation of the optimum age for rubella vaccine administration.

The hemagglutination-inhibition (HI) antibody responses of 452 children to HPV-77, DE5 rubella vaccine were studied. Results indicated that seroconversion rates and geometric mean titers in infants inoculated at 12 through 14 months of age are comparable with those achieved in older children. "Vaccine failures" seem to occur randomly in vaccinees after 1 year of age; the infectivity of individual vaccines is questioned. The persistence of HI antibody was evaluated through serial sampling up to three years postinoculation.

Ampicillin dosage in bacterial meningitis with special reference to Haemophilus influenzae.

Ampicillin remains the preferred drug for most cases of bacterial meningitis, including those due to Haemophilus influenzae type b. A prospective study was performed comparing high (400 mg/kg per day)- and low (150 mg/kg per day)-dosage regimens of ampicillin in the treatment of 172 patients with bacterial meningitis. Response to both regimens was equivalent in terms of average hospital stay, duration of ampicillin therapy, microbiological response, and death and residua. Patients with H. influenzae infections treated with low-dosage regimens had slightly prolonged febrile courses. This study suggests that high-dosage regimens of ampicillin offer no benefit over low-dosage regimens in the treatment of bacterial meningitis.

Additional evidence against measles vaccine administration to infants less than 12 months of age: altered immune response following active/passive immunization.

Quantitative serologic responses following the inoculation of infants less than one year of age with live, further-attenuated measles virus vaccine were compared to those of infants and children inoculated after one year of age. Active/passive immunization resulted in reduced antibody formation in some infants especially those less than 9 months of age. Thirty-seven infants identified as "vaccine failures" following their initial inoculation at less than one year of age were revaccinated after one year of age. Fifty-one percent had no detectable HI antibody by eight months postrevaccination, contrasted to 6.8% of the vaccinees with no detectable HI antibody following one inoculation after one year of age; 49% responded optimally to revaccination. In face of an observed altered response in many infants less than one year of age, it would appear prudent to withhold vaccine in this age group until the consequences of such an approach are better defined.

Further characterization of responses of infants and children to meningococcal A polysaccharide vaccine.

The responses to 10 or 50 microgram doses of meningococcal group A polysaccharide vaccine were evaluated in infants and children. Although the 50 microgram dose was shown to be more effective in the induction of detectable anti-A antibody in vaccinees of all ages, only 6.5% (7/108) of infants smaller than or equal to 12 months demonstrated a "protective level" (greater than or equal to 2 mug/ml antibody protein) at 28 or 35 days postinoculation. Unexpected variations in the response to different lots, supplied by three different manufactures, were observed. These findings indicate the need for additional studies before routine immunization of young infants can be recommended.

The role of antibiotics, immunizations, and adenoviruses in pertussis.

Sixty-five patients with pertussis were identified by a clinical criterion, and Bordetella pertussis was isolated from 75% of these patients or their symptomatic household contacts. Negative nasopharyngeal cultures were usually associated with either a history of antibiotic therapy with erythromycin or tetracycline (two of three patients), two or more diphtheria and tetanus toxoids with pertussis (DTP) vaccines (six of eight patients), or both (two of three patients). Erythromycin therapy resulted in the elimination of B. pertussis from the nasopharynx in 2 to 7 days (mean, 3.6 days) compared with 7 to 17 or more days (mean, greater than 12 days) in patients treated with no antibiotics, but had no effect on the duration or severity of illness as judged by length of hospitalization. Adenoviruses were recovered from five of 44 patients cultured. Four of these isolates were from throat swabs obtained early in the illness and the remaining isolate was from one of 33 repeated viral cultures obtained two to three weeks later; B. pertussis was also isolated from these five patients. Paired serum samples were obtained from only two of these patients. Neither demonstrated a fourfold rise in adenoviral complement-fixing antibodies. Therefore, in these patients, adenoviral isolation may have been secondary to reactivation of a latent viral infection by infection with B. pertussis.

Evidence for reinstatement of infants 12 to 14 months of age into routine measles immunization programs.

The hemagglutination inhibition (HI) serologic responses of 851 measles-susceptible infants and children to the live, further-attenuated measles virus vaccine were evaluated over a ten-year period. The response by age at 23-day intervals was determined. Infants inoculated at 12 through 14 months of age demonstrated seroconversion rates by HI assay comparable to those in infants and children inoculated at 15 months of age or older. This finding does not support the recent recommendation that routine active immunization with measles vaccine should be postponed until 15 months of age. We emphasize the possible consequence of electively leaving infants 12 throught 14 months of age vulnerable to measles because of the current endemicity of this disease in the United States. We also present evidence for the reinstatement of infants 12 through 14 months of age into routine measles immunization programs and for the need to further evaluate the causes for vaccine failure in vaccines after the loss of maternal antibody.

Antibody of polyribophate of Haemophilus influenzae type b in infants and children: effect of immunization with polyribophosphate.

Antibody to polyribophosphate, the capsular polysaccharide of Haemophilus influenzae type b, was measured in healthy ambulatory children by a radioactive antigen-binding assay. Titers fell from birth through nine months of age, then increased until six years, when they plateaued. Antibody activity was not correlated with the child's sex, ethnic status, or area of residence. Doses of 0.2-50 microgram of polyribophosphate given as single or booster doses had similar effects on antibody activity. Of 368 doses given to infants two to six months of age, 7% produced a significant antibody response; of 95 doses given to infants seven to 12 months old, 17% produced a response. The geometric mean titers of antibody resulting from immunization with polyribophosphate given at various times in relation to diphtheria-pertussistetanus vaccine did not differ significantly from one another or from titers observed in infants given only the latter vaccine. These data indicate that purified polyribophosphate will not provoke humoral immunity in young infants against H. influenzae type b and that it should no longer be considered as a candidate vaccine for this purpose.

Maternal-fetal pharmacological activity of amikacin.

Thirty healthy gravid patients of six to 20 weeks' gestation each received a single dose of 7.5 mg of amikacin/kg within 24 hr prior to elective hysterectomy. The half-life (t1/2) of amikacin in maternal serum was 2.07 hr. The mean peak concentration of amikacin in the sera of these patients was slightly lower than that in nonpregnant adults. Two-thirds of the placental samples had amikacin concentrations of greater than or equal to 8 microng/g during the 20-hr interval between drug injection and delivery time. In fetal kidney the concentration of amikacin peaked at a level of 22.4 microng/g at 12 hr after administration. The peak concentration of amikacin in fetal urine was 24 microng/ml, and the t1/2 was 3.2 hr. High levels of the drug in fetal urine and low levels in fetal serum (less than 4 microng/ml) and amniotic fluid (less than 3 microng/ml) were unrelated to high levels found in fetal kidney. Levels of amikacin in fetal lung were 1.4-8.0 microng/g during intervals of 1-16 hr between administration of the drug and time of delivery. With the increasing number of drugs available for use, both potential benefits and risks for the fetus must be considered when prescribing an antibiotic to treat the infected gravid patient, and it should be kept in mind that low levels in body fluid may not be equated with safety.

Tobramycin: maternal-fetal pharmacology.

To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration of TBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 mug/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 mug/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 mug/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation of the fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 mug/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharmacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.