Childhood Haemolytic uraemic syndrome in New Zealand


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Childhood Haemolytic uraemic syndrome in New Zealand

  1. 1. Childhood Haemolytic uraemic syndrome in New Zealand Dr William Wong Director, Department of Nephrology Starship Children’s Hospital
  2. 2. Headlines 3 August 1998 4 March 1999
  3. 4. 1996 Lanarkshire outbreak 10 deaths
  4. 5. Ecoli 0157 outbreak Sep-Oct 2006
  5. 6. Development of E coli associated HUS
  6. 7. <ul><li>Shiga like toxin (Stx) producing E.coli commonest cause diarrhoea associated HUS – 70% in North America & Europe </li></ul><ul><li>Stx producing Shigella dysenteriae type 1 mostly in developing countries </li></ul><ul><li>38-61% of individuals exposed to Stx-E.coli develop haemorrhagic colitis with up 9% (sporadic) 20% (epidemic) develop HUS </li></ul><ul><li>In Europe and North America distinct seasonal fluctuations – peak in warmer months </li></ul>Epidemiology
  7. 8. Epidemiology <ul><li>Most E coli 0157 H7 non sorbitol fermenters </li></ul><ul><li>Increasing resistance to sulphonamides, tetracylines, and streptomycin, reflecting the increasing use of antibiotics in food animals </li></ul><ul><li>Higher prevalence of infection in young children and elderly due to immune factors </li></ul><ul><li>Antibodies from previous infection does not give protective immunity - recurrent HUS </li></ul><ul><li>organism can survive in acid environment </li></ul>
  8. 9. Epidemiology <ul><li>Stx-E.coli colonise healthy cattle intestine, deer, goat, dogs, birds </li></ul><ul><li>Found in manure, water troughs </li></ul><ul><li>Humans infected from contamination of milk, water, meat, fruit, vegetables </li></ul><ul><li>Recovery of organism is ~100% 0-2 days after diarrhoea onset, but only 33% 6 days after onset </li></ul>
  9. 10. Clinical presentation <ul><li>Average of 3 days between exposure and illness </li></ul><ul><li>Starts with crampy abo pain & diarrhoea </li></ul><ul><li>Vomiting is common -30-60% </li></ul><ul><li>Young children tend to excrete organism for more prolonged periods </li></ul><ul><li>Increasing pallor </li></ul><ul><li>Fever in 30% </li></ul><ul><li>Diagnosis of E.coli infection dependent on isolation of organism in stools and identification of Stx antibodies </li></ul>
  10. 11. The STEC in NZ <ul><li>STEC (VTEC) E coli first isolated in 1993 from an 11 month old boy from Whakatane with HUS </li></ul><ul><li>Since 1993, steady rise in number of STEC isolates reported to ESR </li></ul>
  11. 12. STEC in NZ <ul><li>Isolates found predominately in the North Island, mainly in upper half of N.I. </li></ul><ul><li>65% occur in children <15years of age </li></ul><ul><li>predominant serotype 0157 H7, others non typeable </li></ul>
  12. 13. Comparative rates of HUS per 100,000 < age 15
  13. 14. NZPSU surveillance study <ul><li>Study commenced Jan1998-December 2007 </li></ul><ul><li>Questionnaire sent to paediatricians reporting a case </li></ul><ul><li>Case definition </li></ul><ul><ul><li>Any child less than 15 years of age with Haemolytic Uraemic Syndrome, defined as: </li></ul></ul><ul><ul><li>1. Microangiopathic haemolytic anaemia (Hb <10g/dl with microscopic evidence of fragmented red blood cells) </li></ul></ul><ul><ul><li>2. Thrombocytopenia (Platelets < 150,000 x 10 9 ) and </li></ul></ul><ul><ul><li>3. Acute renal impairment (oliguria or anuria with elevated serum urea and creatinine) </li></ul></ul><ul><li>12 mo follow up questionnaire sent for follow up information </li></ul>
  14. 15. Demographics <ul><li>98 children with HUS reported in 10yrs </li></ul><ul><ul><li>80 diarrhoeal prodrome </li></ul></ul><ul><ul><li>18 non diarrhoeal/”atypical” </li></ul></ul>
  15. 16. Ethnic composition
  16. 18. Age distribution of D(+) HUS children n=80 Number of cases
  17. 19. Population characteristics (n=98) <ul><li>Females - 45 </li></ul><ul><li>Mean age – 3.4yrs </li></ul><ul><li>Median age – 2.3yrs </li></ul><ul><li>Age range – 0.3 – 14 yrs </li></ul><ul><li>History of Diarrhoea - 80 </li></ul>
  18. 20. Distribution of D+ HUS by health region n=80 51/80(64%) from rural areas 75% in upper North Is
  19. 21. Seasonal distribution of Diarrhoeal HUS- Jan 1998-Dec 2007 (n=80)
  20. 22. Origin of infection causing D+HUS <ul><li>8 children from farms </li></ul><ul><li>3 children had eaten shellfish/seafood </li></ul><ul><li>In most instances source of infection unknown </li></ul>
  21. 23. Microbiology of D+HUS <ul><li>43/80 E.coli 0157 H7 isolated </li></ul><ul><li>Stx-2 toxin in all E coli 0157 </li></ul><ul><li>All expressed eae gene </li></ul>
  22. 24. Presenting clinical features of D+HUS (n=80) <ul><ul><li>Clinical feature n(%) </li></ul></ul><ul><li>Vomiting 60 (75%) </li></ul><ul><li>Bloody diarrhoea 55 (68%) </li></ul><ul><li>Jaundice 13 (16%) </li></ul><ul><li>Anaemia 76 (95%) </li></ul><ul><li>Anuria 40 (50%) </li></ul><ul><li>Seizures 8(1- repetitive) </li></ul><ul><li>Hypertension during illness 31 (38%) </li></ul>
  23. 25. Time to Diagnosis of D+HUS <ul><li>Duration of symptoms before Dx </li></ul><ul><ul><li>Mean (days) – 7.05 ± 0.46 (SEM) </li></ul></ul><ul><ul><li>Median - 7 </li></ul></ul><ul><ul><li>Range 2-25days </li></ul></ul><ul><ul><li>27/80(33.7%) were diagnosed within 5 days of onset </li></ul></ul><ul><ul><ul><li>No significant difference in time to Dx in 1 st 5yrs versus 2 nd 5yrs of study </li></ul></ul></ul>
  24. 26. Severity of anaemia during illness
  25. 27. Urine output <ul><li>42 patients were anuric </li></ul><ul><ul><li>Mean duration 6.4 ±4.8days </li></ul></ul><ul><ul><li>Median 6 days </li></ul></ul><ul><ul><li>Range 1-28 </li></ul></ul>
  26. 28. Acute dialysis <ul><li>50 (62.5%) needed dialysis (mostly PD) </li></ul><ul><li>Dialysis duration </li></ul><ul><ul><li>Mean 9.2 ± 6.5(CI 7.3-11.08) </li></ul></ul><ul><ul><li>Median 7 days </li></ul></ul><ul><ul><li>Range 2-38 days </li></ul></ul>
  27. 29. Complications of initial illness in D+HUS n=80 <ul><li>Seizures 8 </li></ul><ul><ul><li>1 child severe seizures, died of intracranial bleed </li></ul></ul><ul><li>Transient DM 0 </li></ul><ul><li>Cardiomyopathy 0 </li></ul><ul><li>Intracranial haem 1 </li></ul><ul><li>Pancreatitis 0 </li></ul><ul><li>Death 1 </li></ul>
  28. 30. Follow up at 12 months for D+HUS <ul><li>All paediatricians requested for information on urinalysis for proteinuria, renal function, BP, growth, further attacks of HUS </li></ul><ul><ul><li>5 - unable to locate patient for further information </li></ul></ul><ul><ul><li>67/72 of cohort available for follow up 12 mo.after initial illness </li></ul></ul>
  29. 31. Follow up at 12 months <ul><li>Abnormal urine sediment </li></ul><ul><li>significant proteinuria defined ≥ 1+ or urine protein to creatinine ratio of >20mg/mmol </li></ul><ul><li>Haematuria ≥ 1+ blood on urinalysis </li></ul>
  30. 32. Results of D+HUS follow up <ul><li>39/69 normal UA at mean of 12 months after initial illness </li></ul><ul><li>22/69(31.8-%) – abnormal urine (1+ bld/ protein, hypertension or reduced renal function) </li></ul><ul><ul><li>2 nephrotic proteinuria </li></ul></ul><ul><ul><li>3 reduced GFR (34-77ml/min/1.73m 2) </li></ul></ul><ul><ul><li>2 isolated HTN </li></ul></ul>
  31. 33. Conclusions <ul><li>HUS is the single most common cause of acute kidney failure in children needing acute dialysis </li></ul><ul><li>There is no obvious seasonal pattern </li></ul><ul><li>All cases are sporadic </li></ul><ul><li>Most cases occur in the North Is, but more recently, cases have been appearing in the South Is as well (almost all occurring in the 2 nd five yr period of the study) </li></ul><ul><li>E coli 0157 is the most common organism </li></ul>
  32. 34. Conclusions <ul><li>Significant acute morbidity associated with the disease </li></ul><ul><ul><li>Acute dialysis & its complications </li></ul></ul><ul><ul><li>Long periods of hospitalisation </li></ul></ul><ul><ul><li>Major impact on general health </li></ul></ul><ul><li>Long term morbidity </li></ul><ul><ul><li>Chronic renal failure </li></ul></ul><ul><ul><li>Persistent renal abnormalities in 15-20%, some will progress to chronic renal failure needing dialysis and kidney transplantation </li></ul></ul>
  33. 35. Conclusions <ul><li>E coli associated HUS is a largely preventable disease </li></ul><ul><li>Improved public health measures are required </li></ul>