The epidemiology of invasive diseases caused by Haemophilus influenzae type a (Hia), a report from IMPACT

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1 The epidemiology of invasive diseases caused by Haemophilus influenzae type a (Hia), a report from IMPACT Canadian Immunization Conference December 8, 2016 B. Tan, MD, A. McConnell, MD, MS, J. Bettinger, PhD, D. Scheifele, MD, J. Embree, MD, L. Sauve, MD, N. Bridger, MD, W. Vaudry, MD, S. Halperin, MD, S. Desai, MD, J. Rotondo, MHSc, Raymond Tsang, PhD for IMPACT investigators 1

2 Disclosure statement: I have no affiliation (financial or otherwise) with a pharmaceutical, medical device or communications organization.

3 Background Haemophilus influenzae is a bacterial pathogen which produces capsular polysaccharide (6 serotypes, Hia to Hif), or is nonencapsulated (non-typeable). 3

4 Slide courtesy of J. Rotondo (PHAC) IMPACT s first retrospective study on H. influenzae cases (western Canadian sites) Figure 1. Reported cases and crude incidence rate (per 100,000 population) of invasive disease due to B and non-b serotypes in Canada* by year, 1986 to 2015**. Data obtained from the Canadian Notifiable Disease Surveillance System. *Hi non-b data only available for QC, YK, NT, and NU in NL began reporting in 2008 and SK and MB began reporting in All provinces and territories reported from 2010 to 2015 except for ON and NS. **2015 data is preliminary. 4

5 Study purpose: To determine, over a 9 year period (from Jan 1, 2007 to Dec 31, 2015): The number and proportion of H. influenzae invasive disease cases captured at the 12 IMPACT centres attributed to Hia. The demographics, clinical presentation and outcome of invasive Hia cases over this time period. 5

6 Methods 1 Cases identified from daily admission lists and/or positive cultures for H. influenzae from sterile body fluids (blood, CSF, pleural fluid, biopsy tissue, epiglottis swab). Serotyping of isolates done at National Microbiology Laboratory (NML) in Winnipeg slide agglutination (Difco) and polymerase chain reaction (PCR). Medical charts were retrospectively reviewed for: Patient age and gender, (first 3-digit) postal code of residence, past medical history, duration of PICU and/or hospital admission, and clinical outcome. 6

7 IMPACT referrals from northern communities IMPACT hospitals admit 75,000 children annually, and have 90% of the tertiary care pediatric beds in Canada. All 12 IMPACT centres collected H. influenzae serotype data as of Edmonton Vancouver Saskatoon Calgary Winnipeg Quebec CHUSJ Ottawa MCH Toronto Halifax St. John s 7

8 Results 8

9 H. influenzae cases in 12 IMPACT centres, Total of 356 cases Non-Typeable 149 (42%) Unknown 1 (0.5%) Hif, 38 (11%) Hie 5 (1.5%) Hic 4 (1%) Hib 47 (13%) Hia 112 (32%) 9

10 # cases Hia cases in 12 IMPACT centres, Year-by-year numbers Mean 12.4/yr Median 12/yr 58% Male Most isolates From blood (87) & CSF (36)

11 # cases Hia cases in 12 IMPACT centres, Clinical presentations (as percent of total cases) (49%) 70 (62%) (31%) 29 (26%) 11 (10%) 10 (9%) 22 (19%) 5 (4%) 10 (9%) 0 20 (18%) 28 (25%) Similar in spectrum to Hib, except no epiglottitis * 11

12 Hia cases residence Circled text = # of cases from each prov/terr (regions of NU). Nunavik cases are separated from the rest of Quebec. 20 No cases from the Atlantic provinces or Yukon Vancouver 17 Edmonton Saskatoon Calgary Winnipeg N.B. Correction in conf abstract: 37 cases from northern regions (not 40) 3 Nunavik Labrador 10 Quebec CHUSJ Ottawa Halifax MCH Toronto St. John s 12

13 # cases Hia cases in 12 IMPACT centres, Ethnicity of cases (71%) (7%) 1 (1%) 0 0 Caucasian Asian African Hispanic Indigenous Canadians 1 (1%) Mixed 22 (20%)? Unknown 13

14 IMPACT Hia admission rates < 5 yrs, IMPACT hosp rate/100,000 < 5 yrs Indigenous Non-indigenous Northern region Southern region Combined regions

15 # of days Hia cases in 12 IMPACT centres, Length of stay in PICU and in hospital Hosp: n=110 Mean 16.7 days Range 0-78 days PICU: n=45 Mean 5.6 days Range 1-23 days Median 3 days PICU duration Median 13 days Hosp duration 15

16 # cases Hia cases at 12 IMPACT centers, Age groups & deaths (age-specific case fatality) (19%) 92% < 5y % < 2y Died Survived Cumulative 1 (5%) 30 1 (8%) mos 6-11 mos mos mos 2-4 yrs 5-9 yrs yrs Age groups Cumulative % 16

17 Hia cases in 12 IMPACT centres, Previous health status of cases 1 (1%) 61 (54%) 50 (45%) With normal immunity 42 (84%) With immunodeficiency, 8 (16%) 17

18 Discussion Our results are comparable to other studies in circumpolar and other surveillance systems which found Hia cases disproportionately affecting indigenous populations. Unclear if decline in Hib has unmasked Hia cases, or whether non-b serotypes have taken over the ecologic niche. Fatal cases succumbed quickly (median 2 days) after transfer to an IMPACT-PICU (1 case before arrival at an IMPACT centre). Study limitations: IMPACT admissions are dependent on referrals, hence underestimates true disease incidence (reflects the most severe cases). Determining ethnicity of patients retrospectively from hospital charts was a challenge (missing for 22 cases). 18

19 Conclusions Although Hia is not as common as Hib was, the severity of disease is comparable to Hib cases in the pre-vaccine era. Previously healthy children < 2 years were the most affected, with a small proportion having underlying disorder(s). Indigenous children in all regions of Canada (especially northern regions) were disproportionately affected, with all 9 deaths. A Hia vaccine, which is effective in infants < 6 mos-of-age and/or confers herd immunity would be useful in prevention of this disease. 19

20 Acknowledgment Data center (Vancouver) D. Scheifele, J. Bettinger, K. Marty, E. Grove, S. McCann Co-Principal Investigators S.Halperin, W Vaudry Halifax: K. Top, A. Hudgin, K. Branscombe, T. Smith, H Samson Quebec City: R. Thibeault, L. Poirier, L Gosselin, *M-France Nolin Toronto: D. Tran, * J Stapleton, S. Lee, K. Simpson Winnipeg: J. Embree, D. Coté, M. Breton Vancouver: L. Sauvé, K. Kroeker, I. Chee Ottawa: N. Le Saux, C. Bergeron, J. Bowes Calgary: T. Jadavji, * R Chawla, S. Pyra, E. Pyra Montreal: * M-A Lefebvre, D. Moore, A. Audet, T-M. Johns, L. Moisan St. John s: N. Bridger, *D. Harnum Montreal: M. Lebel, S. Bouchard, Edmonton: W. Vaudry, B. Neufeld, *C. Bon Saskatoon: B. Tan, A. McConnell, C. Cadman, B. Andreychuk Canadian Paediatric Society (Ottawa) M. Laffin-Thibodeau, M.A. Davis Public Health Agency of Canada (Ottawa) *New as of