Invasive disease caused by haemophilus influenzae in sweden 1997–2009; evidence of increasing incidence and clinical burden of non-type b strains

Invasive disease caused by Haemophilus influenzae in Sweden 1997–2009; evidence of increasing incidence and clinical burden of non-type b strains

Abstract
Introduction of a conjugated vaccine against encapsulated Haemophilus influenzae type b (Hib) has led to a dramatic reduction of invasive Hib disease. However, an increasing incidence of invasive disease by H. influenzae non-type b hasrecently been reported. Non-type b strains have been suggested to be opportunists in an invasive context, but information on clinical consequences and related medical conditions is scarce. In this retrospective study, all H. influenzae isolates (n = 410) from blood and cerebrospinal fluid in three metropolitan Swedish regions between 1997 and 2009 from a population of approximately 3 millionindividuals were identified. All available isolates were serotyped by PCR (n = 250). We observed a statistically significant increase in the incidence of invasive H. influenzae disease, ascribed to non-typeable H. influenzae (NTHi) and encapsulated strains type f (Hif) in mainly individuals >60 years of age. The medical reports from a subset of 136 cases of invasive Haemophilus disease revealed that 48% ofinvasive NTHi cases and 59% of invasive Hif cases, respectively, met the criteria of severe sepsis or septic shock according to the ACCP/SCCM classification of sepsis grading. Onefifth of invasive NTHi cases and more than one-third of invasive Hif cases were admitted to intensive care units. Only 37% of patients with invasive non-type b disease had evidence of immunocompromise, of whichconditions related to impaired humoral immunity was the most common. The clinical burden of invasive non-type b H. influenzae disease, measured as days of hospitalization/100 000 individuals at risk and year, increased significantly throughout the study period.

Introduction
Haemophilus influenzae is a frequent colonizer of the human respiratory tract. The species is subdivided into non-encapsulated andencapsulated strains that are typed based upon the presence of one of six antigenically distinct polysaccharide capsules designated a to f [1]. Strains that do not have a capsule are denoted non-typeable H. influenzae (NTHi). The carriage rates of NTHi in healthy pre-school children are as high as 65% [2], suggesting that NTHi is usually a commensal. However, NTHi frequently causes otitis mediaand pneumonia in children [3], and is the most common bacterial finding in exacerbations of chronic obstructive pulmonary disease [4]. Invasive NTHi cases are suggested to be opportunistic infections [3], even though information on correlated medical conditions is scarce Invasive disease by H. influenzae has historically been analogous with disease by encapsulated strain type b (Hib), a fearedcause of sepsis, epiglottitis and meningitis in children and occasionally in adults [5]. In the early 1990s, the conjugated Hib vaccine was introduced in most countries in the Western World, and a dramatically reduced incidence of invasive Hib disease occurred [6]. The incidence of bacteraemia caused by Hib in Sweden in the late 1980s was approximately 30/100 000 children, and these numbers haddecreased 10-fold by 1994 [7]. The current Swedish Hib vaccine coverage rate is 99%. Several reports on the epidemiology of invasive non-type b Haemophilus disease in the post-Hib-vaccine era have been published in recent years [8–13]. Indications of a rising incidence of invasive non-type b disease have been observed in North America [8,9,13,14]. The status in Europe is less clear, but a recent studyencompassing surveillance data from 14 European countries between 1996 and 2006 showed a small but significant increase in incidence of invasive NTHi disease [15]. In contrast, a German study covering 1998–2005 did not reveal any increase in invasive non-type b disease [16]. Even though invasive Hib disease has been successfullyrepressed following the widespread introduction of the Hib vaccine,...