Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study

Abstract

Historically, Haemophilus influenzae (Hi) serotype b (Hib) caused most invasive Haemophilus infections worldwide, mainly in children. In 1989 routine childhood vaccination against Hib was initiated in Iceland. We conducted a population-based study of all patients in the country with Haemophilus spp. isolated from sterile sites (n = 202), from 1983 to 2008. Epidemiology, clinical characteristics of the infections and serotypes of the isolates were compared during the pre-vaccination (1983-1989) and post-vaccination era (1990-2008). Following the vaccination, the overall incidence of Hib decreased from 6.4 to 0.3/100,000 per year (p <0.05) whereas the incidence did not change significantly for infections caused by Haemophilus sensu lato not serotype b, hereafter referred to as non-type b Hi (0.9 vs 1.2, respectively). The most frequent diagnosis prior to 1990 was meningitis caused by Hib, which was subsequently replaced by pneumonia and bacteraemia caused by non-type b Hi. Most commonly, non-type b Hi were non-typeable (NTHi; 40/59), followed by Hi serotype f (14/59) and Hi serotype a (3/59). Pregnancy was associated with a markedly increased susceptibility to invasive Haemophilus infections (RR 25.7; 95% CI 8.0-95.9, p <0.0001) compared with non-pregnant women. The case fatality rate for Hib was 2.4% but 14% for non-type b Hi, highest at the extremes of age. Hib vaccination gives young children excellent protection and decreases incidence in the elderly due to herd effect in the community. Replacement with other species or serotypes has not been noted. Pregnant women are an overlooked risk group.

Adhesin genes and serum resistance in Haemophilus influenzae type f isolates

“…Before vaccination against Hib became widely adopted in developed countries in the mid-1990s, serotype f was the second most common capsular serotype causing invasive H. influenzae infection (Berndsen et al, 2011;Rubach et al, 2011). In the post-Hib vaccine era, invasive disease in children due to H. influenzae is uncommon, with the majority of these infections due to unencapsulated strains, with the remainder being non-b encapsulated strains, predominantly serotypes f and a in North America and serotypes f and e in Europe (Tsang et al, 2006;Adam et al, 2010;Ladhani et al, 2010Ladhani et al, , 2012Agrawal & Murphy, 2011;Resman et al, 2011a;Rubach et al, 2011).…”

Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection

“…In addition, although NTHi is a commensal of the upper respiratory tract, it is not present as a persistent, distinct microbial community in the lower respiratory tract in health. tract, but once colonization is established, NTHi can become pathogenic itself, or contribute to the pathology of other bacteria (10) or of viral infections that lead to increased bacterial biomass (54). It can also disrupt epithelial tight junctions, which allows bacterial invasion (55).…”

“…NTHi colonization may induce airway inflammation through specific IgE-mediated hypersensitivity (9), through activation of innate immunity via Toll-like receptor (TLR)2/4, which leads to increased local production of IL-1b and IL-8 and reactive oxygen species, and through activation of adaptive immunity in which both B-and T-cell responses are implicated (6). Furthermore, NTHi can itself play an etiological role in pneumonia, either as a single pathogen (10) or in polymicrobial infection with other organisms such as Streptococcus pneumoniae (11).…”

Invasive Haemophilus influenzae Infection in Patients with Cancer

“…1,5 H influenzae type f has been reported as the most frequent non-Hib capsulated strain. [5][6][7][8][9] NTHi is also considered to be a significant cause of invasive H influenzae infection. [5][6][7][8][9][10][11][12] Several risk factors exist for invasive H influenzae infections, including malignant neoplasms, asplenia, agammaglobulinemia, alcohol use disorder, AIDS, chronic pulmonary diseases, long-term steroid use, and undergoing chemotherapy, radiotherapy, or stem cell transplantation.…”

“…[5][6][7][8][9] NTHi is also considered to be a significant cause of invasive H influenzae infection. [5][6][7][8][9][10][11][12] Several risk factors exist for invasive H influenzae infections, including malignant neoplasms, asplenia, agammaglobulinemia, alcohol use disorder, AIDS, chronic pulmonary diseases, long-term steroid use, and undergoing chemotherapy, radiotherapy, or stem cell transplantation. [2][3][4]6,11,13,14 Because malignancy is a risk factor for such infection, we report on our experience with H influenzae bacteremia since 2000 in our patients with cancer, including both solid and hematological malignancies, and their association with other comorbidities.…”