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Although immunization programs with Haemophilus influenzae type b (Hib) conjugate vaccines have dramatically reduced disease incidence, few data are available regarding the duration of protection after vaccination. We measured serum anti-polyribosylribitol phosphate (PRP) levels in healthy 4- to 5- year-old children previously given 4 doses of PRP-T vaccine (at 2, 4, 6, and 18 months) or 1 dose of PRP-D vaccine (at 19 months) during clinical trials to assess antibody persistence. Concurrent with other preschool immunizations, half of the children were randomly assigned to receive a PRP-T booster immunization to assess responsiveness. Among 136 subjects who were primed with PRP-D, the baseline geometric mean concentration of antibody was 0.7 microg/mL (95% CI 0.5 to 0.9). Concentrations were <0.15 microg/mL in 24 (17.6%) subjects. Among 212 children who were primed with PRP-T, the geometric mean concentration was 2.2 microg/mL (95% CI 1.9 to 2.5) (P <.001). Only 2 (0.9%) had concentrations <0.15 microg/mL. Four weeks after PRP-T immunization, geometric mean concentrations had increased to 98.4 and 102.0 microg/mL, respectively. Responses were strong even in those with low or undetectable preimmunization antibody levels. Spontaneous increases in antibody levels were seen in 9 (5.2%) of 172 subjects not given additional PRP-T. We concluded that among 4- to 5-year-olds, anti-PRP levels remained above 0.15 microg/mL in nearly all children after PRP-T priming and in most after PRP-D priming, and that both groups were able to respond vigorously to restimulation, consistent with persistent immune memory.

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A simplified test for endotoxemia was evaluated in parallel with 198 blood cultures from 115 neonates requiring transitional or intensive care. The Limulus assay disclosed endotoxemia in seven of eight patients with gram-negative bacteremia tested on one or two occasions. It was not specific for bacteremia, especially during the first week of life, when 37 of 112 tests from nonbacteremic infants (33%) were positive. In older infants, positive tests were obtained in only ten of 55 without bacteremia (18%) (P less than 0.07), six of whom had necrotizing enterocolitis as the likely source of endotoxemia. Gram-negative bacteremia existed in 5% of infants (two of 39) less than or equal to 7 days with positive tests and in 37% of older infants (six of 16) (P less than 0.01). Endotoxemia appears to be frequent among infants appearing to have sepsis and may contribute to neonatal morbidity. The Limulus assay may be a useful diagnostic test for coliform bacteremia and necrotizing enterocolitis beyond the first week of life.

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We determined the frequency of ventricular involvement during Hemophilus influenzae type b meningitis in ten bacteremic infant rhesus monkeys. Meningitis was defined as cerebrospinal fluid obtained from the lumbar subarachnoid space or cisterna magna containing bacteria and ten or more leukocytes per mm3. HIB were cultured from 22 of 22 ventricular CSF samples. In 17 of 18 comparisons of bacterial density in ventricular and cisternal CSF, the values were within one log10: similarly, 5 of 8 quantitative ventricular-lumbar comparisons were within one log10. This concordance was present at bacterial densities of 2 x 10(1) to 1 x 10(9) CFU/ml. When discordance was present, the ventricular CSF contained more bacteria. In 15 of 20 comparisons of leukocyte density in ventricular and cisternal CSF, the ventricular pleocytosis was lower (mean ventricular/cisternal ratio 0.08). We conclude that infection of the lateral cerebral ventricle is a uniform feature of HIB meningitis in infant monkeys, but the cellular inflammatory component is less.

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Latex particle agglutination and counterimmunoelectrophoresis techniques were compared in a clinical trial to demonstrate their sensitivity, specificity, and usefulness in the rapid diagnosis of invasive Hemophilus influenzae type b disease. LPA, a simplified LPA performed by house officers, and CIE used in this study detected 0.2, 0.5, and 1 to 10 ng/ml of Hib capsular antigen, respectively. One hundred-six illnesses suspected of being caused by Hib were evaluated prospectively by these assays. A total of 39 of these were confirmed by culture or detection of antigen or both. LPA and simplified LPA were more sensitive and specific than CIE in the diagnosis of Hib disease (P less than 0.01), especially in invasive disease other than meningitis. LPA is inexpensive, can be performed quickly, and detects all invasive Hib infections. The results emphasize the usefulness of antigen detection in the rapid diagnosis of Hib infections, demonstrate that LPA is more sensitive and specific than CIE, and can be conveniently performed by physicians.

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