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Epidemiology of Invasive Haemophilus influenzae Serotype a Disease—United States, 2008–2017

The Pediatric Infectious Disease Journal: November 2021 - Volume 40 - Issue 11 - p 1028
doi: 10.1097/INF.0000000000003346
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Soeters HM, Oliver SE, Plumb ID, et al. Clin Infect Dis. 2021;73:e371–e379.

After the introduction of Haemophilus influenzae serotype b (Hib) vaccines in the 1980s–1990s, the incidence of invasive H. influenzae disease among children <5 years of age decreased by more than 99% in the United States. Following this dramatic reduction, the serotype distribution of invasive H. influenzae cases shifted. Although nontypeable H. influenzae and H. influenzae serotype f now cause the majority of invasive disease in the United States, H. influenzae serotype a (Hia) is of particular concern because incidence increased by an average of 13% annually from 0.02 per 100,000 in 2002 to 0.14 per 100,000 in 2015, and elevated incidence has been reported among children and indigenous populations in the United States and Canada. In Alaska, the epidemiology of Hia is distinct from that in the rest of the United States, and multiple invasive Hia disease outbreaks have occurred. Hia can cause disease of similar clinical presentation and severity as Hib, and Hib vaccines offer no cross-protection against Hia. Data from active, population- and laboratory-based surveillance during 2008–2017 to describe the current epidemiology of invasive Hia disease in the United States and Alaska are reported.

Active, population- and laboratory-based surveillance for invasive H. influenzae disease was conducted as part of Active Bacterial Core surveillance, supported by the Centers for Disease Control and Prevention (CDC). The population under surveillance represented 11.9% and 13.7% of the US population in 2008 and 2017, respectively. A case of invasive Hia disease was defined as isolation of Hia from a normally sterile site. Epidemiologic and clinical information was abstracted from medical records. Statewide laboratory-based surveillance for invasive H. influenzae disease in Alaska was conducted by CDC’s Arctic Investigations Program in Anchorage, AL.

From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children <5 years of age (incidence: 0.64), with highest incidence among children <1 year of age (1.60). Case fatality rate was 7.8% overall and was highest among adults ≥65 years of age (15.1%). Among children <5 years old, the incidence was 17 times higher among American Indian and Alaska Native children (8.29) than among children of all other races combined (0.49).

Information on clinical syndrome was available for 99.7% of cases: 41.3% had bacteremic pneumonia; 32% had bacteremia, 23.9% had meningitis, 7.8% had septic arthritis, 4.4% had cellulitis and 3.9% had epiglottitis (syndromes were not mutually exclusive). All of the patients with epiglottitis were >50 years of age.

In Alaska, incidences among all ages (0.68) and among children <1 year of age (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among American Indians and Alaska Natives.

Comment: Most reports of Hia have been from North America and Brazil; surveillance elsewhere in the world has rarely detected invasive Hia disease. However, reporting of H. influenzae in many locations is still limited to Hib versus nonserotype b, with no serotyping capacity for Hia. Therefore, the true geographic range and disease burden of Hia globally is unknown.

Previous reports have shown that Hia can cause disease with clinical severity similar to Hib, perhaps influenced by the close similarity between the Hia and Hib capsular polysaccharides. A chart review of a subset of Active Bacterial Core surveillance Hia cases from 2011 to 2015 found evidence of severe disease, and that children younger than 1 year had the highest proportion of cases with both short- and long-term adverse clinical outcomes, including hearing loss, developmental delay, and speech delay (CDC, unpublished data).

According to the latest (2021–2024) 32nd edition of the Red Book, clinicians can consider chemoprophlylaxis of household contacts of index cases of invasive Hia disease in those households with a child younger than 4 years or with an immunocompromised child. A similar approach as Hib also may be considered for preschool and child care contacts in consultation with local or state public health departments (American Academy of Pediatrics (Haemophilus Influenzae Infections). In: Kimberlin DW, Barnett ED, Lynfield R, et al, eds. Red Book: 2021 Report of the Committee on Infectious Diseases.

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