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Infectious proxies and childhood leukaemia UKCCS Update www.UKCCS.org.uk Slide 2 www.ukccs.org Slide 3 Study population Children ( 15 years) registered for primary care with a General Practitioner (GP) Cases - ascertained from multiple sources:- Treating/referring hospitals Cross-checks with cancer registries Controls selected from primary care population registers and individually matched to cases on:- date of birth sex region of residence Slide 4 UKCCS Slide 5 Slide 6 Slide 7 Measures of exposure to infection Most direct Least direct SerologySocio-demographicproxies Clinical records Slide 8 Slide 9 Slide 10 GP consultations in the first year of life (controls N= 1031, 2-5 years old) non-infectious diagnosis/symptoms non-infectious diagnosis/symptoms N(%) N(%) infectious diagnosis/symptoms N(%) N(%) 3.0 (2.8 3.2) 3.9 (3.7 4.1) mean (95%CI) 860 (83.4) 919 (89.1) 1+ 171 (16.6) 112 (10.9) 0 Slide 11 GP consultations in the first year: mean (95% CI) ages 2-5 years 3.3(2.9-3.6)3.0(2.8-3.2)Non-infection 4.5(4.2-4.9)3.9(3.7-4.1)InfectionALLN=425ControlsN=1031Diagnosis/symptoms Slide 12 At least one infectious diagnoses in the first month (neonatal) Controls(%)Cases(%) OR(95% CI) Any18.123.81.4(1.1-1.9) Conjunctivitis7.28.21.1(0.7-1.7) URTI5.15.21.1(0.6-1.8) Fungal3.15.71.9(1.1-3.2) Gastrointestinal1.21.41.4(0.5-3.7) Slide 13 Neonatal infections & age at ALL diagnosis Number Mean(95% CI) 324 45.2(43.8-46.6) 78 45.8(42.8-48.7) 23 37.7(32.5-42.8) Neonatal infections Age at diagnosis (months) Slide 14 ALL (2-5 yrs) and infection< 1 yr Compared to controls case children had: - More episodes of infectious illness Excess apparent from birth No obvious specificity Within the case series: - Children with more infections tended to be diagnosed earlier Slide 15 Measures of exposure to infection Most direct Least direct SerologySocio-demographicproxies Clinical records Maternal illness reports Slide 16 Slide 17 Slide 18 Infectious diagnosis first year: UKCCS controls > 15mths old Number Mean (95% CI) Infectious diagnosis 12882.9(2.8-3.0) - Birth order 15612.9(2.7-3.0) 2+7232.9(2.8-3.0) - Regular social contact outside the home no6062.9(2.7-3.0) yes6822.9(2.8-3.1) - Deprivation at birth low/med10932.8(2.7-2.9) high1923.3(3.0-3.6) Slide 19 Infectious diagnosis first year: UKCCS cases > 15mths old Number Mean (95% CI) Infectious diagnosis 7033.2(3.1-3.3) - Birth order 13012.7(2.5-2.9) 2+3993.6(3.4-3.7) - Regular social contact outside the home no3873.1(2.9-3.3) yes3163.3(3.1-3.5) - Deprivation at birth low/med5653.0(2.9-3.2) high1363.8(3.5-4.1) Slide 20 Infectious diagnosis first year: UKCCS ALL controls & cases >15 mths Odds ratio (95% CI) - Birth order 10.9(0.6-1.4) 2+1.6(1.1-1.2) - Regular social contact outside the home no1.0(0.7-1.4) yes1.7(1.1-2.5) - Deprivation at birth low/med1.1(0.9-1.3) high2.7(1.2-6.0) Slide 21 ALL and prior infectious illness From birth onwards, children who develop ALL have more infectious illness episodes than those who do not The difference appears most marked in those exposed to infectious challenge from other children Slide 22 Infections first year: maternal report of infection with GP visit >15 months Odds ratio (95% CI) - Birth order 10.7(0.5-1.0) 2+0.8(0.6-1.0) - Regular social contact outside the home no0.9(0.7-1.2) yes0.6(0.5-0.9) - Deprivation at birth low/med0.7(0.6-0.9) high0.8(0.5-1.4) Slide 23 Infection (any) in the first year: UKCCS controls Mothersreport GP infection record YesNo Total (%) yes758118876(68) no297115412(32) 1055(82)233(18)1288(100) Slide 24 Infection (any) in the first year: UKCCS controls Mothersreport GP infection record YesNo Total (%) yes758118876(68) no297115412(32) 1055(82)233(18)1288(100) Slide 25 Ear infection in the first year: UKCCS controls Mothersreport Otitis media GP record YesNo Total (%) yes84146230(18) no1549041058(82) 238(19)1050(81)1288(100) Slide 26 Ear infection in the first year: UKCCS controls Mothersreport Otitis media GP record YesNo Total (%) yes84146230(18) no1549041058(82) 238(19)1050(81)1288(100) Slide 27 Ear infection in the first year: UKCCS cases Mothersreport Otitis media GP record YesNo Total (%) yes6177138(17) no102571673(83) 163(20)648(80)811(100) Slide 28 Age 3 days conjunctivitis 9 months URTI, ?otitis media 12 months Cold 13 months Cough 15 months Cough 16 months Conjunctivitis 19 months Chesty cough 2 years 7 months Pharyngitis 2 years 8 months Chesty, wheeze Infections recorded in GP notes, birth to diagnosis control Slide 29 Age 3 days conjunctivitis 9 months URTI, ?otitis media 12 months Cold 13 months Cough 15 months Cough 16 months Conjunctivitis 19 months Chesty cough 2 years 7 months Pharyngitis 2 years 8 months Chesty, wheeze Infections recalled by mother, birth to diagnosis control Slide 30 Age 2 weeks Severe oral thrush 3 weeks URTI, oral thrush, thrush nappy rash 6 weeks Severe oral thrush 7 weeks Conjunctivitis 8 weeks Conjunctivitis persists 7 months Cold 9 months Otitis media 10 months Viral infection 11 months Conjunctivitis 15 months Ringworm 16 months Diarrhoea 18 months Viral encephalitis hospitalised 19 months Cough 20 months Nasal congestion, ?chronic tonsillitis 21 months Smelly nasal discharge, ?sinusitis 2 years URTI, conjunctivitis, otitis media 2 years 1 month Otitis media 2 years 6 months Otitis media 2 years 8 months Unwell for 10 days, yellow tinge, blue lips, loose motions, leg pains, wont walk ALL Oral thrush Infections recorded in GP notes, birth to diagnosis Slide 31 Age 2 weeks Severe oral thrush* 3 weeks URTI, oral thrush, thrush nappy rash 6 weeks Severe oral thrush 7 weeks Conjunctivitis 8 weeks Conjunctivitis persists 7 months Cold 9 months Otitis media 10 months Viral infection Cold 11 months Conjunctivitis 15 months Ringworm 16 months Diarrhoea 18 months Viral encephalitis hospitalised 19 months Cough 20 months Nasal congestion, ?chronic tonsillitis 21 months Smelly nasal discharge, ?sinusitis 2 years URTI, conjunctivitis, otitis media 2 years 1 month Otitis media 2 years 6 months Otitis media 2 years 8 months Unwell for 10 days, yellow tinge, blue lips, loose motions, leg pains, wont walk ALL Infections recalled by mother, birth to diagnosis *mothers recall: one mouth infection that lasted 5 days Mother also recalled:- Otitis media x1,