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D M Granoff

Publications and source records attributed to D M Granoff.

151 records · Page 9Linked to original sources
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Epidemiology and prospects for prevention of disease due to Haemophilus influenzae in developing countries.

Haemophilus influenzae is an important cause of meningitis and severe cases of lower respiratory infection (LRI) in children in developing countries. In children with meningitis, H. influenzae type b organisms are the most frequently encountered serotype, but in some countries type a strains are also implicated. In children with LRI, type b organisms are also important, but the proportion of organisms with other serotypes and non-typable strains is greater than that associated with cases of meningitis. In developing countries, nearly all cases of H. influenzae meningitis and a substantial fraction of cases of LRI occur in children younger than one year of age. This age distribution is younger than that seen in the continental United States, where more than one-half of the cases of invasive H. influenzae disease are in children older than one year of age. New type b polysaccharide-protein conjugate vaccines are immunogenic in infants as young as two months of age and offer the promise of preventing H. influenzae type b disease in infants younger than one year of age. However, for developing countries, more complete data defining the populations at risk, the immunogenicity of candidate vaccines in children in different geographic regions, and the serotypes of the infecting organisms will be needed before successful cost-effective vaccination strategies can be devised and implemented.

Adolescent↗
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Global genetic structure and molecular epidemiology of encapsulated Haemophilus influenzae.

A collection of 2,209 isolates of six polysaccharide capsule types of Haemophilus influenzae, including 1,975 serotype b isolates recovered in 30 countries was characterized for electrophoretically demonstrable allele profiles at 17 metabolic enzyme loci. Two hundred eighty distinct multilocus genotypes were distinguished, and cluster analysis revealed two primary phylogenetic divisions. The population structure of encapsulated H. influenzae is clonal. Currently, most of the invasive disease worldwide is caused by serotype b strains of nine clones. Strains producing serotype c, e, and f capsules belong to single divisions and have no close genetic relationships to strains of other serotypes. Serotype a and b strains occur in both primary phylogenetic divisions, probably as a result of transfer and recombination of serotype-specific sequences of the cap region between clonal lineages. A close genetic relatedness between serotype d isolates and some strains of serotypes a and b was identified. There are strong patterns of geographic variation, on an intercontinental scale, in both the extent of genetic diversity and the clonal composition of populations of encapsulated strains. The analysis suggests that the present distribution of clones is, in part, related to patterns of racial or ethnic differentiation and historical demographic movements of the human host populations.

Alleles↗
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Diversity of outer membrane protein profiles of nontypable Haemophilus influenzae from children from Papua New Guinea and the Philippines.

We determined capsular serotypes and, with use of SDS-PAGE, patterns of outer membrane proteins (OMP) of Haemophilus influenzae isolates from specimens of blood, lung, or CSF from children with acute respiratory tract infections or meningitis who were hospitalized in Papua New Guinea or the Philippines. Among 72 isolates from Papua New Guinea, 72% were type b, 14% were other encapsulated serotypes, and 14% were nontypable. The respective frequencies among 43 isolates from the Philippines were 56%, 7%, and 37%. The type b isolates could be subdivided into at least eight outer membrane subtypes, most of which have been described previously. In contrast, OMP profiles of the nontypable H. influenzae isolates from children in both countries were highly heterogeneous. These results differ markedly from those previously found for isolates from children with acute respiratory tract infections in Pakistan, for which encapsulated H. influenzae strains other than serotype b were not observed; 95% of type b isolates were of a single OMP subtype; and nontypable isolates showed evidence of clonal restriction. Candidate vaccines for use in developing countries as protection against disease caused by H. influenzae will need to include both capsular and noncapsular antigens and investigators must take into consideration regional differences among strains.

Acute Disease↗
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Rifampin alone and in combination with trimethoprim in chemoprophylaxis for infections due to Haemophilus influenzae type b.

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.

Carrier State↗
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Haemophilus influenzae type b infections in day care attendees: implications for management.

Haemophilus influenzae type b is a major cause of several infectious syndromes in young children, the most important of which is meningitis. The mortality rate for H. influenzae meningitis in the United States is less than 10%; 10%-15% of survivors are left with neurologic sequelae. Children in day care may be at increased risk for acquiring primary invasive H. influenzae infection, although the mechanism of increased risk and the age of increased susceptibility are not known. Three prospective studies estimated the risk of subsequent or secondary infections as significantly lower than that observed in age-susceptible household contacts; a retrospective analysis suggested a different conclusion. Asymptomatic carriage rates of H. influenzae type b in day care centers vary widely. A retrospective analysis suggested that the administration of rifampin might have prevented subsequent infections in day care contacts; prospective studies are necessary to convincingly demonstrate the efficacy of rifampin prophylaxis among day care contacts. Acquisition of H. influenzae type b carriage has occurred even among those previously treated with rifampin. Until further data are available, rifampin prophylaxis is usually reserved for use in those facilities in which two or more cases of invasive disease have occurred within 60 days. The impact of the H. influenzae type b capsular polysaccharide vaccine on the epidemiology of disease in day care facilities is not known. However, because the immunogenicity and protective efficacy of the H. influenzae capsular polysaccharide vaccine are strikingly age-related, we recommend immunizing children in day care at 24 months.

Age Factors↗
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Interactive effect of genes associated with immunoglobulin allotypes and HLA specificities on susceptibility to Haemophilus influenzae disease.

Genes associated with immunoglobulin (Ig) allotype determinants are important in regulation of immune responses to bacterial polysaccharides. Furthermore, loci associated with Ig allotypes have been reported to interact with those associated with the major histocompatibility complex and affect susceptibility to certain diseases. In the present study we determined the frequencies of certain Gm phenotypes in patients with Haemophilus meningitis or epiglottitis and in controls. HLA-A, -B and -DR specificities had previously been determined in the majority of these subjects. Although no Ig phenotype was associated with increased or decreased relative risk of disease, the frequencies of several combinations of HLA specificities and Ig phenotypes were significantly different from those of controls. Thus, for subjects with the Gm phenotype (1, 3, 17; 23; 5, 13, 21), the risk of Haemophilus meningitis or epiglottitis was lower in individuals with HLA-B5 than in those without this specificity (odds ratio less than 0.1, P less than 0.004). In contrast, for subjects with the closely related Gm phenotype differing only by the absence of Gm(23), (1, 3, 17; ; 5, 13, 21), the risk of disease was higher in those with HLA-DR3 than in individuals who lacked DR3 (odds ratio = 11.0, P = 0.02). Although the present data require confirmation in an independent sample, they suggest that complex interactions between genes at two independent loci controlling HLA and Ig allotypes, respectively, may affect susceptibility to Haemophilus disease.

Child↗