Introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine has resulted in a dramatic reduction of Hib disease in the U.S. and an increase in the relative importance of infections caused by nontypeable strains. The current project describes the characteristics and clinical outcomes of pediatric and adult patients with invasive H. influenzae (HI) and, through multivariable analysis, identifies risk factors for in-hospital mortality.
HI cases were identified during 1999-2008 through active surveillance as part of active bacterial core surveillance (ABCs). Multivariable analysis was performed with logistic regression to identify factors predictive of in-hospital death.
4839 cases of HI were identified from 1999-2008. Children accounted for 17.1% of cases and adults 82.9%. Underlying conditions were present in 20.7% of children and 74.8% of adults. In-hospital mortality was highest in cases ≥65 years (21.9%) and <3 months (16.2%). The risk of in-hospital death in children <1 year was higher among those who were prematurely-born (<28 weeks, OR 7.1, 95% CI 3.2-15.6; 28-36 weeks OR 2.1, 95% CI 0.9-4.8) and, among children aged 1-17 years, higher in those with healthcare-associated onset and dialysis (OR 5.66, 95% CI 1.84-17.39; OR 18.11, 95% CI 2.77-118.65). In adults, age ≥40 was associated with death in nontypeable, but not encapsulated, infections. Infections with nontypeable strains increased the risk of death in cases ≥65 years (OR 1.81, 95% CI 1.31-2.52). Healthcare-associated HI, bacteremia without identifiable focus, bacteremic pneumonia, associated cirrhosis, cerebrovascular accident, dialysis, heart failure, and non-hematologic malignancy also increased the risk of death in adults.
Prematurity in infants, advanced age and certain chronic diseases in adults were associated with an increased risk of in-hospital death. Nontypeable HI was associated with higher mortality in the elderly.
"Nontypeable Haemophilus influenzae (NTHi) is a mucosal pathogen and a prevalent cause of exacerbations in patients with chronic obstructive pulmonary disease (COPD), the second most common cause of bacterial acute otitis media in children and occasionally disseminates from the respiratory tract to produce invasive disease  . Otitis media is one of the most common reasons for children seeking medical care, receiving antibiotic treatment and, in the case of reoccurrence, undergoing surgery . "
[Show abstract][Hide abstract] ABSTRACT: Nontypeable Haemophilus influenzae (NTHi) is one of the main aetiologies of childhood bacterial infections as well as exacerbations in COPD patients. Currently, no licensed NTHi vaccine exists. In the present study, we evaluated the potential of the conserved and ubiquitous surface protein Haemophilus Protein F (PF) as a vaccine candidate. Our results show that incubation of NTHi with anti-PF antibodies significantly increased the opsonophygocytosis of human promyelocytic leukemia cell line-derived granulocytes, leading to efficient killing of the bacteria (P≤0.05). The presence of anti-PF IgG titers in healthy adults (n=60) was investigated, and we found that 26% of healthy blood donors carried antibodies with the main antigenic epitope being PF(23-48). Finally, mice immunized with PF(23-48) attained a significantly increased capacity to clear NTHi as compared to a control group immunized with a peptide derived from Moraxella catarrhalis β-lactamase (P≤0.05). Taken together, our results indicate that PF is a potential NTHi-vaccine candidate.
[Show abstract][Hide abstract] ABSTRACT: SUMMARY In a world where most emerging and reemerging infectious diseases are zoonotic in nature and our contacts with both domestic and wild animals abound, there is growing awareness of the potential for human acquisition of animal diseases. Like other Pasteurellaceae, Pasteurella species are highly prevalent among animal populations, where they are often found as part of the normal microbiota of the oral, nasopharyngeal, and upper respiratory tracts. Many Pasteurella species are opportunistic pathogens that can cause endemic disease and are associated increasingly with epizootic outbreaks. Zoonotic transmission to humans usually occurs through animal bites or contact with nasal secretions, with P. multocida being the most prevalent isolate observed in human infections. Here we review recent comparative genomics and molecular pathogenesis studies that have advanced our understanding of the multiple virulence mechanisms employed by Pasteurella species to establish acute and chronic infections. We also summarize efforts being explored to enhance our ability to rapidly and accurately identify and distinguish among clinical isolates and to control pasteurellosis by improved development of new vaccines and treatment regimens.
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