Haemophilus influenzae disease - Annual Epidemiological Report 2016 [2014 data]

surveillance report
Publication series: Annual Epidemiological Report on Communicable Diseases in Europe
Time period covered: Reporting on 2014 data retrieved from TESSy* on 7 July 2016
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Suggested citation: European Centre for Disease Prevention and Control. Annual Epidemiological Report 2016 – Invasive Haemophilus influenzae disease. [Internet]. Stockholm: ECDC; 2016 [cited YYYY Month DD].

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In 2014, 2 799 confirmed cases of invasive Haemophilus influenzae (H. influenzae) disease were reported to TESSy.

Key facts

  • In 2014, 2 799 confirmed cases of invasive Haemophilus influenzae (H. influenzae) disease were reported to TESSy.
  • The notification rate was 0.6 cases per 100 000 population, a similar rate as in previous years.
  • Age-specific rates were highest in infants (4.0 cases per 100 000) and the elderly (1.7 cases per 100 000).
  • The H. influenzae type b (Hib) vaccine has led to a progressive and sustained reduction of type b serotype infections. In 2014, 6% of cases with a known serotype were caused by serotype b, 57% of which were aged 25 years and over.
  • Non-capsulated strains caused the majority of cases in all age groups and 82% of all cases for which serotyping results were available.
  • Serotype f caused 9% of all cases and 72% of cases among non-b capsulated serotypes (serotypes a, c, d, e and f).
  • The changing epidemiology of invasive H. influenzae disease should be carefully monitored; disease surveillance should include all age groups, serotypes and clinical presentations.

Methods

Click here for a detailed description of the methods used to produce this annual report

  • ECDC has coordinated the surveillance of invasive H. influenzae disease at the European level since the transfer of EU-IBIS (European Union Invasive Bacterial Infections Surveillance Network) to ECDC in 2007.
  • In 2014, 29 EU/EEA Member States routinely report data on invasive H. influenzae disease to TESSy.
  • All Member States report data using the EU case definition (Commission Implementing Decision 2012/506/EU of 8 August 2012 of the European Parliament and of the Council) or use a case definition that is compatible with the EU case definition for confirmed cases.
  • The majority of Member States report data from comprehensive, passive surveillance systems with national coverage. Belgium, France and Spain report data from sentinel surveillance systems. For a summary of the surveillance systems characteristics in each Member State, please refer to the Annex.

Epidemiology

In 2014, 2 799 confirmed cases of invasive H. influenzae disease were reported by 29 countries (Table 1, Figure 1). No confirmed cases were reported by Malta. Liechtenstein and Luxembourg reported no data (Table 1). In 2014, the overall confirmed case notification rate was 0.6 cases per 100 000 population, comparable to the rates observed from 2010 to 2013, but showing a slightly upward trend. The highest rates were reported by Sweden (2.1 cases per 100 000), Denmark (1.5) and Norway (1.4) (Table 1, Figure 2).

Age and gender distribution

In 2014, invasive H. influenzae disease was predominantly found in infants and the elderly (Figure 3), with a notification rate of 4.0 confirmed cases per 100 000 population in children under one year of age, and 1.7 confirmed cases per 100 000 population in adults aged 65 years or over. For both age groups, higher rates were observed in males (Figure 3). The overall notification rate was 0.6 cases per 100 000 population for males and 0.6 for females, with a male-to-female ratio of 1.03:1.

Seasonality

The distribution of invasive H. influenzae cases by month follows a seasonal pattern, with the highest number of reported cases in the winter months, followed by a steady decrease until August and an increasing trend towards the end of the year. Compared to previous years, a higher peak was seen in May. This peak may be due to random variation as the number of reported cases was small (Figure 4). Figure 5 shows an increasing trend in the number of cases reported from 2010–2014.

Serotype

Of the 2 799 reported confirmed cases of invasive H. influenzae disease, 1 706 (61%) – reported by 20 Member States – had a known serotyping result. Of these 1 706 cases, 82% (n=1 394) were non-capsulated (non-typeable). Non-capsulated strains were the most common cause of infection in all age groups (Figure 6). The majority of invasive non-capsulated strains were observed among cases 65 years or over (Figure 7). Serotype b caused 6% (n=104) of cases in 2014. Among cases of serotype b invasive H. influenzae disease, 57% were aged 25 years or over (Figure 7).

Among non-b capsulated serotypes (serotypes a, c, d, e and f), f was the most commonly reported serotype (72%, n=150) and the second most common cause of invasive H. influenzae disease overall (9%). Serotype e contributed to 23% (n=47) of non-b capsulated infections and 3% of all cases. The majority of cases of serotypes e and f infection were in persons aged 45 years and over (Figure 7). Eight cases of serotype a, one case of serotype c, and two cases of serotype d were reported (Figure 6).

Among 17 Member States that consistently reported serotype data from 2010 to 2014, there was a consistent upward trend in non-capsulated strains, with a 61% increase in the number of reported cases between 2010 (n=862) and 2014 (n=1 393). No increasing trends were observed among other serotypes (Figure 8).

Clinical presentation

The clinical presentation was known for 1 519 cases (54% of all cases) reported in 2014. Of these cases, septicaemia was reported in 764 cases (50%), pneumonia in 444 (29%) and meningitis in 161 (11%). Seventeen cases presented with both septicaemia and meningitis. Three cases of epiglottitis, six cases of cellulitis, and eight cases of septic arthritis/osteomyelitis were reported. For 116 cases, the clinical presentation was reported as ‘other’. Septicaemia was the most common clinical presentation across age groups and serotypes.

Outcome

The outcome was known for 1 445 cases, 52% of all cases. There were 107 fatal cases reported, a case fatality of 7%, considering only cases with known outcome. Case fatality was highest among cases of serotype e (13%, n=4/31), followed by non-capsulated strains (8%, n=67/823), serotype b (7%, n=3/44) and serotype f (5%, n=5/100). Eighty percent of deaths occurred in persons aged ≥45 years, and 65% in those ≥65 years.

Discussion

In EU/EEA countries, cases of invasive H. influenzae disease are rare with the greatest burden in infants and the elderly, the majority caused by infection with a non-capsulated strain. As in previous years, the disease was most commonly reported in the north of Europe. This observation is possibly due to better case ascertainment and the implementation of enhanced surveillance systems. The results should be interpreted with caution because the completeness of data for some variables, such as clinical presentation and outcome, was low. In addition, there is currently no common definition of fatal outcome due to invasive H. influenzae disease in Europe.

All EU/EEA Member States have made serotype b vaccination part of their routine child immunisation schedule, and the sustained low number of serotype b cases reported highlights the success of this intervention. Indeed, serotype f is now the most common capsulated serotype observed in Europe and accounts for 9% of all cases. Before the introduction of serotype b vaccination, invasive H. influenzae disease was predominantly caused by serotype b infections in healthy young children [1]. The majority of serotype b cases were observed in ≥25 year olds, an expected shift in the age distribution, considering the impact of routine serotype b vaccination [2-5].

In the pre-vaccine era, non-capsulated H. influenzae was not a known common cause of invasive infection, however it is now the leading cause of invasive H. influenzae disease in all age groups, particularly among groups who are more susceptible to infection, e.g. neonates, the elderly, and immunocompromised persons [6-8]. The number of non-capsulated cases reported has steadily increased over the past five years, although many potential explanations exist for this increase, such as increasing survival rates among persons more susceptible to infection, the increased use of immunosuppressive therapy [8], and changes in data reporting or laboratory practices [9].

Several studies have reported increasing trends in non-capsulated H. influenzae as well as in capsulated serotypes a, e and f, following the introduction of routine Hib vaccination [2, 10-13]. There is, however, still no evidence of serotype replacement in the EU following the introduction of routine Hib vaccination [3, 4, 10, 12, 14-16].

Public health conclusions

The sustained success of serotype b vaccination is clear. Maintaining high vaccination coverage across Europe is therefore essential.

The predominance of cases caused by non-capsulated strains shows the importance of continuous monitoring for all strains, for example by genetic typing of non-capsulated strains. All age groups and clinical presentations should be monitored in order to accurately assess changes in the epidemiology and develop preventative interventions.

References

  1. Peltola H. Haemophilus influenzae type b disease and vaccination in Europe: lessons learned. Pediatr Infect Dis J. 1998 Sep;17(9 Suppl):S126-32.
  2. MacNeil JR, Cohn AC, Farley M, Mair R, Baumbach J, Bennett N, et al. Current epidemiology and trends in invasive Haemophilus influenzae disease – United States, 1989-2008. Clin Infect Dis. 2011 Dec;53(12):1230-6.
  3. Georges S, Lepoutre A, Dabernat H, Levy-Bruhl D. Impact of Haemophilus influenzae type b vaccination on the incidence of invasive Haemophilus influenzae disease in France, 15 years after its introduction. Epidemiol Infect. 2013 Sep;141(9):1787-96.
  4. Giufre M, Cardines R, Caporali MG, Accogli M, D'Ancona F, Cerquetti M. Ten years of Hib vaccination in Italy: prevalence of non-encapsulated Haemophilus influenzae among invasive isolates and the possible impact on antibiotic resistance. Vaccine. 2011;29(22):3857-62.
  5. Kastrin T, Paragi M, Kolman J, Cizman M, Kraigher A, Gubina M, et al. Characterisation of invasive Haemophilus influenzae isolates in Slovenia, 1993-2008. Eur J Clin Microbiol Infect Dis. 2010 Jun;29(6):661-8.
  6. Puig C, Grau I, Marti S, Tubau F, Calatayud L, Pallares R, et al. Clinical and molecular epidemiology of Haemophilus influenzae causing invasive disease in adult patients. PloS one. 2014;9(11):e112711.
  7. van Wessel K, Rodenburg GD, Veenhoven RH, Spanjaard L, van der Ende A, Sanders EA. Nontypeable Haemophilus influenzae invasive disease in the Netherlands: a retrospective surveillance study 2001-2008. Clin Infect Dis. 2011 Jul 1;53(1):e1-7.
  8. Collins S, Vickers A, Ladhani SN, Flynn S, Platt S, Ramsay ME, et al. Clinical and molecular epidemiology of childhood invasive nontypeable Haemophilus influenzae disease in England and Wales. Pediatr Infect Dis J. 2016 Mar;35(3):e76-84.
  9. Voldstedlund M, Haarh M, Molbak K, MiBa Board of Representatives. The Danish Microbiology Database (MiBa) 2010 to 2013. Euro Surveill. 2014 Jan 9;19(1). pii: 20667.
  10. Ladhani SN, Collins S, Vickers A, Litt DJ, Crawford C, Ramsay ME, et al. Invasive Haemophilus influenzae serotype e and f disease, England and Wales. Emerg Infect Dis. 2012 May;18(5):725-32.
  11. Resman F, Ristovski M, Ahl J, Forsgren A, Gilsdorf JR, Jasir A, et al. Invasive disease caused by Haemophilus influenzae in Sweden 1997-2009; evidence of increasing incidence and clinical burden of non-type b strains. Clin Microbiol Infect. 2011 Nov;17(11):1638-45.
  12. Ladhani S, Slack MP, Heath PT, von Gottberg A, Chandra M, Ramsay ME, et al. Invasive Haemophilus influenzae Disease, Europe, 1996-2006. Emerg Infect Dis. 2010;16(3):455-63.
  13. Desai S, Jamieson FB, Patel SN, Seo CY, Dang V, Fediurek J, et al. The epidemiology of invasive Haemophilus influenzae non-serotype b disease in Ontario, Canada from 2004 to 2013. PloS one. 2015;10(11):e0142179.
  14. Ladhani S, Stark, M.E., Chandra, M., Slack, M.P. No evidence for Haemophilus influenzae serotype replacement in Europe after introduction of the Hib conjugate vaccine. Lancet. 2008;8:275-6.
  15. Berndsen MR, Erlendsdottir H, Gottfredsson M. Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study. Clin Microbiol Infect. 2012 Sep;18(9):918-23.
  16. Kalies H, Siedler A, Grondahl B, Grote V, Milde-Busch A, von Kries R. Invasive Haemophilus influenzae infections in Germany: impact of non-type b serotypes in the post-vaccine era. BMC Infect Dis. 2009 Apr 20;9:45.

Additional information

ECDC Surveillance Atlas of Infectious Diseases

ECDC surveillance report on invasive bacterial diseases in Europe 2012: https://ecdc.europa.eu/en/publications-data/surveillance-invasive-bacterial-diseases-europe-2012

ECDC surveillance report on invasive bacterial diseases in Europe 2011: https://ecdc.europa.eu/en/publications-data/surveillance-invasive-bacterial-diseases-europe-2011

ECDC surveillance report on invasive bacterial diseases in Europe 2010: https://ecdc.europa.eu/en/publications-data/surveillance-invasive-bacterial-diseases-europe-2010

ECDC surveillance report on invasive bacterial diseases in Europe 2008/2009: https://ecdc.europa.eu/en/publications-data/surveillance-invasive-bacterial-diseases-europe-20082009

European Invasive Bacterial Disease Surveillance Network (EU-IBD): https://ecdc.europa.eu/en/about-us/networks/disease-and-laboratory-networks/eu-ibd

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* The European Surveillance System (TESSy) is a system for the collection, analysis and dissemination of data on communicable diseases. EU Member States and EEA countries contribute to the system by uploading their infectious disease surveillance data at regular intervals

Publication data

Data

Table 1. Reported, confirmed cases of invasive Haemophilus influenzae disease: number and rate per 100 000 population, EU/EEA, 2010–2014

table -
Period: 01 Jan 2014 - 31 Dec 2014

Reported, confirmed cases of invasive Haemophilus influenzae disease: number and rate per 100 000 population, EU/EEA, 2010–2014

Data

Figure 1. Number of reported, confirmed cases of invasive Haemophilus influenzae disease, EU/EEA, 2014

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Period: 01 Jan 2014 - 31 Dec 2014

Number of reported, confirmed cases of invasive Haemophilus influenzae disease, EU/EEA, 2014

Data

Figure 2. Number of reported, confirmed cases of invasive Haemophilus influenzae disease per 100 000 population, EU/EEA, 2014

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Period: 01 Jan 2014 - 31 Dec 2014

Number of reported, confirmed cases of invasive Haemophilus influenzae disease per 100 000 population, EU/EEA, 2014

Data

Figure 3. Reported, locally acquired Invasive Haemophilus influenzae disease cases, by age and gender, EU/EEA, 2014

graph -
Period: 01 Jan 2014 - 31 Dec 2014

Reported, locally acquired Invasive Haemophilus influenzae disease cases, by age and gender, EU/EEA, 2014

Data

Figure 4. Seasonal distribution of reported, confirmed cases of invasive Haemophilus influenzae disease, EU/EEA, 2014 compared with 2010−2013

graph -
Period: 01 Jan 2014 - 31 Dec 2014

Seasonal distribution of reported, confirmed cases of invasive Haemophilus influenzae disease, EU/EEA, 2014 compared with 2010−2013

Data

Figure 5: Trend and number of reported cases of invasive Haemophilus influenzae disease, EU/EEA, 2010−2014

graph -
Period: 01 Jan 2014 - 31 Dec 2014

Trend and number of reported cases of invasive Haemophilus influenzae disease, EU/EEA, 2010−2014

Data

Figure 6: Serotype distribution of reported, confirmed cases of invasive H. influenzae disease by age group, EU/EEA, 2014

graph -
Period: 01 Jan 2014 - 31 Dec 2014

Serotype distribution of reported, confirmed cases of invasive H. influenzae disease by age group, EU/EEA, 2014

Data

Figure 7: Age group distribution of reported, confirmed cases of invasive H. influenzae disease by serotype, EU/EEA, 2014

graph -
Period: 01 Jan 2014 - 31 Dec 2014

Age group distribution of reported, confirmed cases of invasive H. influenzae disease by serotype, EU/EEA, 2014

Data

Figure 8: Trend and number of reported, confirmed cases of invasive H. influenzae disease by serotype, EU/EEA, 2010−2014

graph -
Period: 01 Jan 2014 - 31 Dec 2014

Trend and number of reported, confirmed cases of invasive H. influenzae disease by serotype, EU/EEA, 2010−2014