Using linked health data to better understand the causes of acute rheumatic fever and other poststreptococcal
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1 Using linked health data to better understand the causes of acute rheumatic fever and other poststreptococcal diseases Michael Baker* Jane Oliver, Sally Thomas, Jane Zhang, Arlo Upton, Nevil Pierse, Nikki Moreland, Debbie Williamson *HEIRU, University of Otago, Wellington
2 Outline Group A Streptococcus (GAS) infections Post-streptococcal autoimmune sequelae Methods Results - Sequelae of: GAS+ve throat swabs GAS+ve skin swabs Hospitalisations for streptococcal infections Conclusions / Implications Limitations / Further work
3 Background Group A Streptococcus (GAS): Superficial infection Pharyngitis Impetigo, Pyoderma Invasive diseases Septicaemia, Pneumonia, Osteomyelitis Necrotising fasciitis Toxin mediated diseases Scarlet fever Streptococcal toxic shock syndrome Post-streptococcal autoimmune sequelae Acute Rheumatic Fever (ARF) Rheumatic Heart Disease (RHD) Acute Post-streptococcal glomerulonephritis (APSGN)
4 Background RHD is one of NZs biggest ID killers (~140 deaths pa) Large cause of health iniquities with most ARF/RHD cases in Maori and Pacific
5 Conventional wisdom Background GAS (Strep) sore throat?? Acute Rheumatic fever (ARF) Rheumatic heart disease (RHD) GAS skin infection eg Impetigo Acute Post Streptococcal Glomerulonephritis (APSGN)
6 Methods GAS exposure data sources Laboratory throat swab and skin swab test data, community labs (Labtests), Auckland Region (pop= 1.5 million), Hospitalisations for specific clinical conditions (eg Strep pharyngitis, skin infections) NZ (pop=4.5 million), Disease outcome data sources Hospitalisation data on first admissions for ARF (ICD.10 I00, I01, I02) APSGN (ICD.10 N00, N05) Linked to exposure using unique patient number (encrypted NHI)
7 Methods Analytic method Calculation of disease rates in cohorts: Exposed (test +ve) vs. unexposed (test ve) Exposed (following hosp for Strep. disease) vs. Unexposed (same population 12 months later ie case-cross over design) RR and 95%CI across cohorts, stratified by time intervals and other characteristics Exposed group Unexposed group
8 ARF cases (number) Methods - Time window ARF (N=165 cases) incidence by week, following GAS+ve throat swab test results, Auckland day window day window day window Weeks from swab to ARF hospitalisation
9 ARF / 100,000 swabs / year Results - ARF following GAS +ve throat swab ARF cases (N=155) in 365 days following GAS+ve throat swabs vs. risk ARF (N=378) following GAS & Group C/G -ve throat swabs All ages, 8-90 days, RR elevated significantly Total 5-19 years, 8-90 days, RR elevated significantly Māori 5-19 years, 8-90 days, RR elevated significantly Pacific 5-19 years, 8-90 days, RR elevated significantly GAS+ve swab GAS-ve swab 8-90 days days days Time period following throat swab collection
10 APSGN / 100,000 swabs / yr Results - APSGN following GAS+ve throat swab APSGN cases (N= 44) in 365 days following GAS+ve throat swabs vs. risk APSGN (N=233) following GAS & Group C/G -ve throat swabs All ages, 8-90 days, RR no significant effect Total 5-19 years, 8-90 days, RR no significant effect Māori 5-19 years, 8-90 days, RR no significant effect Pacific 5-19 years, 8-90 days, RR no significant effect GAS+ve swab GAS-ve swab 8-90 days days days Time period following throat swab collection
11 APSGN / 100,000 swabs / year Results - APSGN following GAS +ve skin swab APSGN cases (N=18) in 365 days following GAS +ve skin swabs vs. risk APSGN (N=17) following GAS & Group C/G -ve skin swabs All ages, 8-90 days, RR elevated significantly Total 5-19y olds, 8-90 days: RR elevated significantly Māori 5-19y olds, 8-90 days: RR elevated, CI overlaps 1.00 Pacific 5-19y olds, 8-90 days: RR elevated, CI overlaps GAS +ve GAS -ve 8-90 days days days Time period following skin swab collection
12 ARF / 100,000 swabs / year Results - ARF following GAS +ve skin swab ARF cases (N= 23) in 365 days following GAS +ve skin swab vs. risk ARF (N= 18) following GAS & Group C/G -ve skin swabs All ages, 8-90 days, RR elevated significantly Total 5-19y olds, 8-90 days: RR elevated significantly Māori 5-19y olds, 8-90 days: RR elevated, CI overlaps 1.00 Pacific 5-19y olds, 8-90 days: RR elevated, CI overlaps GAS +ve GAS -ve 8-90 days days days Time period following skin swab collection
13 Results - ARF risk following hospitalisations for potentially causal infections Hosp condition Hosp admits 1 ARF 8-90 days (N) ARF days (N) RR (95%CI) Strep pharyngitis & tonsillitis NC Skin infection Elevated significantly IDs (total) Elevated significantly 1 Māori and Pacific aged 5-19 years, admitted Rate of subsequent initial ARF per 100,000 person years, two time periods: 8-90 days, and days (baseline)
14 Results - APSGN risk following hospitalisations for potentially causal infections Hosp condition Hosp admits 1 APSGN 8-90 days (N) APSGN days (N) RR (95%CI) Strep pharyngitis & tonsillitis NC Skin infection Elevated significantly IDs (total) Elevated significantly 1 Māori and Pacific aged 5-19 years, admitted Rate of subsequent initial ARF per 100,000 person years, two time periods: 8-90 days, and days (baseline)
15 Conclusions and Implications Conventional wisdom GAS (Strep) sore throat X Acute Rheumatic fever (ARF) Rheumatic heart disease (RHD) GAS skin infection eg Impetigo Acute Post Streptococcal Glomerulonephritis (APSGN)
16 Conclusions and Implications Risk of ARF is markedly elevated in 90 days following a GAS+ve throat swab and GAS+ve skin swab (and following related hospitalisations) Risk of ARF not significantly elevated following Group C/G+ve throat swab (small numbers) Risk of APSGN is markedly elevated following a GAS+ve skin swab (but not GAS+ve throat swab) Support for treatment of GAS+ve skin infections as part of ARF (and APSGN) prevention programmes Children participating in RF prevention programme
17 Limitations and further work (1) GAS exposure effects reduced by antibiotic use Study of GP cases with linked antibiotic data to measure risk in treated and untreated cohorts (2) Limits of observational data Study of immune response to GAS throat and skin infections (HRC funded project underway)
18 Acknowledgements Funders: University of Otago, HRC, NZCPHM Support: Labtests, for provision of testing data Collaborators on related work: Susan Jack, Dianne Sika-Paotonu, Matire Harwood, Gordon Purdie, Julian Crane, Jonathan Carapetis
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