American Academy of Pediatrics. Committee on Infectious Diseases. Recommendations for using pneumococcal vaccine in children.
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Biomedical subjects
Publications and source records attributed to R S Daum.
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In a multicenter study, responses to a combined vaccine containing standard diphtheria-tetanus-pertussis (DTP) and polyribosylribitol phosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b, were evaluated in 107 infants who received single doses at two, four, and six months of age and compared with those in 61 infants given single doses of DTP alone on the same schedule. Reaction rates were comparable in the two treatment groups. At seven months of age 61% of the subjects given the combined DTP-PRP vaccine and 8% and of those given DTP alone showed an antibody response to PRP, as defined as a twofold increase in titer over the lowest previous level. Among those given the DTP-PRP combined vaccine, 92% of the positive antibody responses occurred after the third dose. There was a variation in antibody response, possibly due to a difference in the vaccine lots administered.
Of beta-lactamase-producing strains of Haemophilus influenzae, 65% do not contain extrachromosomal plasmid DNA. These strains, however, conjugally transfer beta-lactamase production to a recipient strain from which a 30-megadalton plasmid can be isolated. Restriction enzyme analysis and Southern transfer of DNA from both donor and recipient strains revealed that chromosomal integration of plasmid sequences occurred in all donor strains examined.
Munchausen syndrome by proxy is a rare form of child abuse that can cause great diagnostic difficulties. We treated an 8-year-old boy who had recurrent polymicrobial sepsis over 6 years. An extensive evaluation to determine the infectious focus and to exclude immunodeficiency was carried out before it was determined that his mother had repeatedly introduced material containing faecal or vaginal bacterial flora into his intravenous lines.
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We compared the effectiveness of rifampin-trimethoprim in fixed combination (3.75:1) to rifampin alone in the eradication of Haemophilus influenzae type b carriage among contacts of patients with invasive infection caused by this organism. The study population was composed of 127 index patients and 620 contacts. Twenty-six percent of contacts were colonized. Rifampin-trimethoprim eradicated carriage in 77.6% of contacts (71.1% in contacts less than 5 years, 84.2% in contacts greater than or equal to 5 years) whereas rifampin eradicated carriage in 69.9% of contacts (56.4% in contacts less than 5 years, 81.8% in contacts greater than or equal to 5 years). A single isolate resistant to rifampin and rifampin-trimethoprim was encountered. The eradication rate achieved with this regimen of rifampin-trimethoprim was too low to recommend its routine use. However, a higher dose or longer course might merit clinical trial.
To determine the protective efficacy of human hyperimmune globulin to Haemophilus influenzae type b disease in an infant rat model, we compared hyperimmune globulin containing 600 mug of anti-polyribophosphate (PRP) antibody per ml to conventional immune globulin containing 66 mug of anti-PRP antibody per ml. The hyperimmune globulin was fractionated from the pooled plasma of 55 adult donors immunized with PRP, the capsular polysaccharide of H. influenzae type b. The disappearance of passively administered antibody was biphasic, with a linear first-order disappearance curve during the first 7 days. The initial half-life for anti-PRP antibody was 2.38 days in rats nasally colonized but not detectably bacteremic with H. influenzae type b and significantly longer (half-life, 10.3 days; P < 0.01) in noncolonized animals. Hyperimmune globulin afforded 10 times the protection of conventional globulin against bacteremia and meningitis. Globulin depleted of anti-PRP antibody offered no protection. The initial serum antibody levels and the levels during the 8-day observation period predicted protection. Rats maintaining serum antibody levels greater or equal to 50 ng/ml to day 8 had a 10% bacteremia and 5% meningitis incidence in contrast with 95% bacteremia (P < 0.001) and 55% meningitis (P < 0.001) in rats with less than 50 ng of anti-PRP antibody per ml. We conclude that studies of the pharmacology and efficacy of hyperimmune globulin are warranted in high-risk children unable to respond to active immunization.
Although oral glucose-electrolyte solutions containing 90 mmol of sodium per liter have been widely used in the treatment of acute diarrhea among under-nourished children in the developing world, they have rarely been studied in well-nourished children. We therefore conducted a controlled randomized study among well-nourished children three months to two years who were hospitalized with acute diarrhea (52 in the United States, and 94 in Panama), to compare the efficacy of this solution with that of one containing 50 mmol of sodium per liter and with standard intravenous therapy. Oral rehydration with both solutions according to protocol was successful in 97 of 98 children (one required unscheduled intravenous therapy), and in 87 (89 per cent) no intravenous therapy was required. All of six children admitted with hypernatremia were successfully treated with oral therapy alone. We conclude that glucose-electrolyte oral solutions containing either 50 or 90 mmol of sodium per liter are effective and safe in the treatment of well-nourished children hospitalized with acute diarrhea, and that they may completely replace the intravenous fluids in the majority of such children.
In an effort to define the value of computed tomographic (CT) scanning in assessment of cerebral involvement in children with severe Haemophilus influenzae meningitis, we studied 12 children who had focal neurologic deficits on admission or within the early days of illness. The CT scan reliably excluded abscess and cerebritis and suggested ischemic cerebrovascular lesions in 11 of 12 children. Scans performed early in the hospital course generally showed low-density lesions occurring in a vascular distribution without detectable mass effect or enhancement. Later in the clinical course there was consistent enhancement of gray matter or diffuse enhancement in the area of the vascular lesion. The duration of symptoms of meningitis ranged from five to 21 days (mean, 13 days) and appeared to predispose to these vascular lesions. A CT scan consistent with infarction of brain parenchyma occurred predictably in patients with persistent focal neurologic deficits and was correlated with poor outcome.
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H. influenzae can cause not only meningitis in children but epiglottitis, cellulitis, pneumonia, pericarditis, and bacteremia. It is possible to radically reduce, if not abolish, the spread of this pathogen. But effective prophylaxis requires answers to questions of practicability relative to the availability, cost, and logistics of administering rifampin to contacts, as has been recommended.
The effectiveness of a commercially available latex particle agglutination test (Bactogen) in the diagnosis of invasive Haemophilus influenzae type b infection was evaluated. Bactogen correctly diagnosed all 27 patients with bacteriologically proven H influenzae type b infection (sensitivity 100%). Two of 39 patients with proven, non-H influenzae type b infections had false-positive tests (specificity 95%). One of 103 sera and 0 of 55 urine specimens from hospitalized adults contained detectable H influenzae type b antigen. Bactogen is a sensitive, specific, commercially available test for rapid diagnosis of H influenzae type b infection.
We examined the events associated with phagocytosis, lysis and digestion of Haemophilus influenzae type b (Hib) by subarachnoid leukocytes in infant rats with experimental Hib meningitis. In early stages of infection, large numbers of bacteria were attached to the surfaces of neutrophils and macrophages invaded the subarachnoid space and actively ingested Hib. The bacteria, coccobacillary in shape with an approximate length of 1.0 micrometers and 0.3 micrometer in width, were interiorized after fusion of leukocyte microplicae which had arisen around them. Ingested Hib were sequestered within large, membrane-bound vacuoles containing five or more microbes. Following the fusion of primary lysosomes with the membrane of the phagocytic vacuole, bacteria were lysed and degraded. In later stages of infection, macrophages possessed large numbers of inclusions containing extensively digested Hib and myelin figures. Histochemical analysis of subarachnoid leukocytes revealed that macrophages actively synthesized acid phosphatase and that this enzyme aided in the digestion of phagocytosed bacteria. Peroxidase was also demonstrated within phagocytic vacuoles of neutrophils. Our results suggest that subarachnoid macrophages and neutrophils actively lyse and digest ingested Hib through the direct action of their hydrolytic enzymes.
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.
Apparent R factor-negative segregation was documented during infection of infant monkeys with two of three strains of ampicillin-resistant Haemophilus influenzae type b. In vitro the bacterial population of one strain (A-Sm) uniformly produced beta-lactamase. All bacteria isolated from blood or cerebrospinal fluid from both animals inoculated with strain A-Sm produced the enzyme. In contrast, 98% and 96% of bacteria from two other strains produced beta-lactamase in vitro. After intranasal inoculation of infant Macacca mulatta with these two strains, bacteria isolated from blood and cerebrospinal fluid uniformly did not produce beta-lactamase. Loss of the beta-lactamase-producing phenotype was associated with loss of plasmid DNA. Strains containing a mixed population of bacteria may undergo spontaneous loss of plasmid DNA during experimental infection. It is suggested that in these strains the bacteria carrying plasmids are less virulent.
We examined the origin, nature and role of cellular defense mechanisms in experimental Haemophilus influenzae type b (Hib) meningitis in the infant rat using ultrastructural techniques. An extensive inflammatory exudate composed of granulocytes, lymphocytes and macrophages was observed on the leptomeninges of all animals with meningitis. At 1-3 days following Hib-inoculation, neutrophils were the major leukocytic element within the exudate while at 7-9 days the leukocyte population was dominated by macrophages. Irrespective of day of inoculation, leukocytes were observed undergoing diapedesis through the thin-walled blood vessels of the subarachnoid space and pial connective tissue, a phenomenon which suggested that the cellular elements composing the inflammatory exudate originated directly from the systemic circulation. Only neutrophils and macrophages demonstrated phagocytosis of free bacteria in the cerebrospinal fluid. The presence of plasma cells suggests that antibody to Hib may be synthesized locally within the subarachnoid space. Furthermore, cell-to-cell contacts among leukocytes may also contribute to the initiation and maintenance of the humoral immune response to Hib.
The families of 126 consecutive patients with Haemophilus influenzae type B meningitis were surveyed for secondary invasive H influenzae disease among household contacts. A total of 120 of the families were contacted. In six cases no contact was possible and the medical record was reviewed. Some 555 household contacts were found; 31% (171) were under 5 years of age. A secondary case was defined as a household contact with H influenzae type B isolated from blood or cerebrospinal fluid more than 24 hours, but less than 30 days, after admission to hospital of the index case. Four secondary cases were identified, all in children aged under 5 years. The secondary attack rate in children under 5 years or less in the month after exposure to an index case was thus 2.3%, 800 times the endemic attack rate for H influenzae meningitis. This is a conservative estimate since five additional contact cases were documented, but not included in the secondary attack rate. Young contacts of a child with H influenzae meningitis are thus at significant risk of life-threatening secondary disease.