[Show abstract][Hide abstract] ABSTRACT: The infant rat model for Haemophilus influenzae type b (Hib) disease was modified to test the protective efficacy of candidate vaccines. The administration of 0.4 micrograms of polyribosylribitol phosphate (PRP) combined with pertussis vaccine or with diphtheria toxoid-tetanus toxoid-pertussis vaccine (DTP) to infant rats at 5, 10, and 15 days of age resulted in significant (P less than 0.001) protection against Hib bacteremia after challenge at 20 days of age. A dose-response effect was demonstrated, and suppression of the protective effect was noted with high doses of PRP. The administration of pertussis vaccine alone or DTP alone did not protect against Hib bacteremia. The degree of protection against Hib bacteremia correlated (P less than 0.005) with the serum anti-PRP antibody response measured before bacterial challenge. High-molecular-weight PRP preparations administered alone or in combination with pertussis vaccine were less effective than standard PRP combined with pertussis vaccine. These data compare favorably with the antibody response in human infants receiving the same vaccines. The observations in this animal model should facilitate the development and testing of other vaccine preparations for human infants.
Infection and Immunity 04/1983; 39(3):1196-200. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An 11 month-old infant had meningitis caused by a strain of Streptococcus pneumoniae, serotype 6b, resistant to penicillin, chloramphenicol, and several other antimicrobials. The minimum inhibitory concentrations (MIC) by agar dilution were 1.0 microgram/ml for penicillin and 16 microgram/ml for chloramphenicol. The infant did not respond to high-dose intravenous penicillin G but was cured by a combination of ampicillin, chloramphenicol, and rifampicin. At the infant's day-care centre this multiply resistant strain was isolated from throat cultures of 27% of the children (age less than or equal to 26 months) assigned to the same room as the index case, and from 11% of older children and staff. There was a 33% carriage rate in family contacts of colonised children. Antibiotic use during the previous 2 months was more frequent among the carriers than among non-carriers. No resistant pneumococci were found in on hundred and twenty-five children and staff in six other Denver day-care centres, in 300 consecutive routine throat cultures processed by our clinical microbiology laboratory, or among 150 pneumococcal isolates collected from Denver area hospitals. The carriers were not treated, and there have been no other cases of infection due to this strain. The emergence of multiply resistant pneumococci in the United States indicates the need to screen important pneumococcal isolates for resistance to both penicillin and chloramphenicol, especially in cases of meningitis.
The Lancet 11/1981; 2(8250):771-3. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the efficacy of rifampin chemoprophylaxis in eradication of oropharyngeal carriage of Haemophilus influenzae type b, we conducted a multicenter, double-blind, placebo-controlled trial among household contacts of patients hospitalized for invasive HIB infection. Seventy-nine index patients and 400 close contacts were studied; 26.5% of contacts were colonized. The efficacy of rifampin (10 mg/kg/dose, 600 mg/dose maximum, twice daily for two days) in eradicating carriage was 52% and varied with age (75.6% in persons greater than or equal to 5 and 27% in those less than 5 years). Eradication rates in those less than 5 years were not significantly better than for placebo. No resistant isolates were encountered in sensitivity testing. The low efficacy of this rifampin regimen in young children precludes its routine use as a chemoprophylactic agent for family contacts. The occurrence of three cases of invasive HIB infection in individuals outside the defined contact group raises concern regarding the efficacy of any chemoprophylactic regimen.
Journal of Pediatrics 04/1981; 98(3):485-91. · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The dynamics of nasopharyngeal colonization, bacteremia, and transmission of infection due to Haemophilus influenzae type b in infant rats were studied. Intranasal inoculation resulted in nasal colonization in 99% and bacteremia in 88% of infant rats. H. influenzae type b was transmitted to 93% of exposed, uninoculated littermates. Pretreatment with burro antibody to H. influenzae type b prevented bacteremia but not nasal colonization. Rifampin, in a dose of 20 mg/kg twice daily for two days, was 97% and 100% effective in eradicating two strains of H. influenzae type b from the nasopharynx. Efficacies of 10 mg/kg twice daily and 5 mg/kg twice daily for two days were 86% and 6%, respectively. No rifampin-resistant isolates were encountered in animals still colonized after rifampin therapy. This model for haemophilus colonization and intralitter transmission could be used to evaluate other chemoprophylactic agents and may provide additional insight into the epidemiology and immunology of haemophilus infections.
The Journal of Infectious Diseases 12/1980; 142(5):739-43. · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of rifampin in eradicating Haemophilus influenzae type b from the pharynx of colonized individuals was assessed for 1,467 close contacts of 291 children hospitalized with invasive infections due to H. influenzae type b. Twenty-six percent of all contacts were carrying H. influenzae type b in the pharynx, and 52% of contacts younger than age five had throat cultures positive for this organism. Four different regimens of rifampin were studied and compared with placebo for efficacy in eradication of carriage of H. influenzae type b. The most effective dosage was 20 mg of rifampin/kg given once daily for four days. This schedule was associated with eradication of carriage in 96.2% of 52 colonized, compliant contacts. Carriage of H. influenzae type b was eradicated in 90.9% of the 22 colonized contacts who were younger than age five. Significantly lower rates of carriage eradication were seen with other regimens of rifampin. Potential problems associated with widespread rifampin usage are reviewed.