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      Invasive Disease Caused by Nontypeable Haemophilus influenzae

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          Abstract

          These infections are emerging worldwide, especially in young children and the elderly.

          Abstract

          The incidence of severe Haemophilus influenza infections, such as sepsis and meningitis, has declined substantially since the introduction of the H. influenzae serotype b vaccine. However, the H. influenzae type b vaccine fails to protect against nontypeable H. influenzae strains, which have become increasingly frequent causes of invasive disease, especially among children and the elderly. We summarize recent literature supporting the emergence of invasive nontypeable H. influenzae and describe mechanisms that may explain its increasing prevalence over the past 2 decades.

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          Most cited references33

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          Non-typeable Haemophilus influenzae, an under-recognised pathogen.

          Non-typeable Haemophilus influenzae (NTHi) is a major cause of mucosal infections such as otitis media, sinusitis, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. In some regions, a strong causal relation links this pathogen with infections of the lower respiratory tract. In the past 20 years, a steady but constant increase has occurred in invasive NTHi worldwide, with perinatal infants, young children, and elderly people most at risk. Individuals with underlying comorbidities are most susceptible and infection is associated with high mortality. β-lactamase production is the predominant mechanism of resistance. However, the emergence and spread of β-lactamase-negative ampicillin-resistant strains in many regions of the world is of substantial concern, potentially necessitating changes to antibiotic treatment guidelines for community-acquired infections of the upper and lower respiratory tract and potentially increasing morbidity associated with invasive NTHi infections. Standardised surveillance protocols and typing methodologies to monitor this emerging pathogen should be implemented. International scientific organisations need to raise the profile of NTHi and to document the pathobiology of this microbe.
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            Changes in frequency and pathogens causing acute otitis media in 1995-2003.

            This study was undertaken to determine whether a change in the frequency or distribution of the causative pathogens in persistent acute otitis media (AOM) and AOM treatment failure (AOMTF) occurred after publication of the Centers for Disease Control and Prevention AOM treatment guidelines advocating high dose amoxicillin in 1998 and the universal use of the pneumococcal conjugate vaccine in 2000. This was a 9-year prospective study in a suburban, community-based private practice. To identify bacterial isolate(s), 551 children with AOM who had not responded after 1 or 2 empiric antimicrobial treatment courses (termed persistent AOM) and those who were failures after 48 h on treatment (AOMTF) underwent tympanocentesis. Three periods were compared: (1) 1995-1997 when all enrolled received standard dose amoxicillin (40-50 mg/kg/day divided 3 times daily) as the initial empiric treatment; (2) 1998-2000 when all received high dose amoxicillin (80-100 mg/kg/day divided twice daily); and (3) 2001-2003 when high dose amoxicillin and pneumococcal conjugate vaccinations were used. Persistent AOM or AOMTF for which tympanocentesis was performed occurred in 195 (16.2%) of 1,207, 204 (16.1%) of 1,278 and 152 (12.3%) of 1,232 AOM visits for 1995-1997, 1998-2000 and 2001-2003, respectively; the 24% decline in 2001-2003 in persistent AOM and AOMTF was significant (P = 0.007). Middle ear aspirates grew Streptococcus pneumoniae (48, 44 and 31%) and Haemophilus influenzae (38, 43 and 57%) for time periods 1, 2 and 3, respectively. There was a significant decline in S. pneumoniae (P = 0.017) and increase in H. influenzae (P = 0.012) isolations and of H. influenzae that were beta-lactamase-producing (P = 0.04) among middle ear fluid isolates. Also there was a trend for an increased proportion of S. pneumoniae in 2001-2003 that were penicillin-susceptible (P = 0.17). In our experience, persistent AOM and AOMTF has decreased in frequency since the introduction of high dose amoxicillin therapy and pneumococcal conjugate vaccination. It appears that H. influenzae has become the predominant pathogen of persistent AOM and AOMTF since universal immunization with the pneumococcal conjugate vaccine. Fewer S. pneumoniae AOM isolates are penicillin-resistant and more H. influenzae are beta-lactamase-producing.
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              Vaccination against colonizing bacteria with multiple serotypes.

              Conjugate vaccines protect vaccinated individuals against both disease from and nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Protection is specific to the capsular serotype(s) included in the vaccine. This specificity has raised concern that vaccination against particular ("targeted") serotypes may cause an increase in carriage of (and diseases attributable to) nontargeted serotypes. I analyzed a mathematical model designed to predict the factors affecting, and the expected extent of, such replacement in the host population. The conditions for competitive exclusion and coexistence of serotypes under mass vaccination are derived, and the equilibrium carriage of target and nontarget serotypes is determined under various ecological and epidemiological conditions. The eradication threshold for a target serotype in the presence of competing, nontarget serotypes is always lower for serotype-specific than for bivalent vaccines. In a two-serotype model, the increase in the prevalence of any single nontargeted serotype due to vaccination will not exceed the total reduction in prevalence of a targeted serotype. However, if three or more serotypes interact epidemiologically, vaccination against one type may increase carriage of a second more than it decreases carriage of the first. Carriage of a second serotype against which the vaccine offers only partial protection may initially increase and then decrease as a function of vaccine coverage. I discuss the extent to which these theoretical results can account for existing data on serotype replacement after vaccination against H. influenzae and their implications for vaccine policy.
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                Author and article information

                Journal
                Emerg Infect Dis
                Emerging Infect. Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                October 2015
                : 21
                : 10
                : 1711-1718
                Affiliations
                [1]Radboud University Medical Center, Nijmegen, the Netherlands
                Author notes
                Address for correspondence: Jeroen D. Langereis, Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Internal mail 412, P.O. Box 9101 6500 HB Nijmegen, the Netherlands; email: Jeroen.Langereis@ 123456radboudumc.nl
                Article
                15-0004
                10.3201/eid2110.150004
                4593434
                26407156
                91926580-f2c9-424d-b0ed-77720deb01cf
                History
                Categories
                Synopsis
                Synopsis
                Invasive Disease Caused by Nontypeable Haemophilus influenzae

                Infectious disease & Microbiology
                haemophilus influenzae,sepsis,meningitis,humoral immunity,cellular immunity,virulence,pathogenicity,vaccines,bacteria,invasive disease,pneumonia,nontypeable

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