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Childhood Haemolytic uraemic syndrome in New Zealand

Childhood Haemolytic uraemic syndrome in New Zealand. Dr William Wong Director, Department of Nephrology Starship Children’s Hospital. Headlines. 4 March 1999. 3 August 1998. 1996 Lanarkshire outbreak. 10 deaths. Ecoli 0157 outbreak Sep-Oct 2006. Development of E coli associated HUS.

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Childhood Haemolytic uraemic syndrome in New Zealand

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  1. Childhood Haemolytic uraemic syndrome in New Zealand Dr William Wong Director, Department of Nephrology Starship Children’s Hospital

  2. Headlines 4 March 1999 3 August 1998

  3. 1996 Lanarkshire outbreak 10 deaths

  4. Ecoli 0157 outbreak Sep-Oct 2006

  5. Development of E coli associated HUS

  6. Epidemiology • Shiga like toxin (Stx) producing E.coli commonest cause diarrhoea associated HUS – 70% in North America & Europe • Stx producing Shigella dysenteriae type 1 mostly in developing countries • 38-61% of individuals exposed to Stx-E.coli develop haemorrhagic colitis with up 9% (sporadic) 20% (epidemic) develop HUS • In Europe and North America distinct seasonal fluctuations – peak in warmer months

  7. Epidemiology • Most E coli 0157 H7 non sorbitol fermenters • Increasing resistance to sulphonamides, tetracylines, and streptomycin, reflecting the increasing use of antibiotics in food animals • Higher prevalence of infection in young children and elderly due to immune factors • Antibodies from previous infection does not give protective immunity - recurrent HUS • organism can survive in acid environment

  8. Epidemiology • Stx-E.coli colonise healthy cattle intestine, deer, goat, dogs, birds • Found in manure, water troughs • Humans infected from contamination of milk, water, meat, fruit, vegetables • Recovery of organism is ~100% 0-2 days after diarrhoea onset, but only 33% 6 days after onset

  9. Clinical presentation • Average of 3 days between exposure and illness • Starts with crampy abo pain & diarrhoea • Vomiting is common -30-60% • Young children tend to excrete organism for more prolonged periods • Increasing pallor • Fever in 30% • Diagnosis of E.coli infection dependent on isolation of organism in stools and identification of Stx antibodies

  10. The STEC in NZ • STEC (VTEC) E coli first isolated in 1993 from an 11 month old boy from Whakatane with HUS • Since 1993, steady rise in number of STEC isolates reported to ESR

  11. STEC in NZ • Isolates found predominately in the North Island, mainly in upper half of N.I. • 65% occur in children <15years of age • predominant serotype 0157 H7, others non typeable

  12. Comparative rates of HUS per 100,000 < age 15

  13. NZPSU surveillance study • Study commenced Jan1998-December 2007 • Questionnaire sent to paediatricians reporting a case • Case definition • Any child less than 15 years of age with Haemolytic Uraemic Syndrome, defined as: • 1. Microangiopathic haemolytic anaemia (Hb <10g/dl with microscopic evidence of fragmented red blood cells) • 2. Thrombocytopenia (Platelets < 150,000 x 109) and • 3. Acute renal impairment (oliguria or anuria with elevated serum urea and creatinine) • 12 mo follow up questionnaire sent for follow up information

  14. Demographics • 98 children with HUS reported in 10yrs • 80 diarrhoeal prodrome • 18 non diarrhoeal/”atypical”

  15. Ethnic composition

  16. Age distribution of D(+) HUS childrenn=80 Number of cases

  17. Population characteristics (n=98) • Females - 45 • Mean age – 3.4yrs • Median age – 2.3yrs • Age range – 0.3 – 14 yrs • History of Diarrhoea - 80

  18. Distribution of D+ HUS by health regionn=80 51/80(64%) from rural areas 75% in upper North Is

  19. Seasonal distribution of Diarrhoeal HUS-Jan 1998-Dec 2007(n=80)

  20. Origin of infection causing D+HUS • 8 children from farms • 3 children had eaten shellfish/seafood • In most instances source of infection unknown

  21. Microbiology of D+HUS • 43/80 E.coli 0157 H7 isolated • Stx-2 toxin in all E coli 0157 • All expressed eae gene

  22. Presenting clinical features of D+HUS (n=80) Clinical feature n(%) Vomiting 60 (75%) Bloody diarrhoea 55 (68%) Jaundice 13 (16%) Anaemia 76 (95%) Anuria 40 (50%) Seizures 8(1- repetitive) Hypertension during illness 31 (38%)

  23. Time to Diagnosis of D+HUS • Duration of symptoms before Dx • Mean (days) – 7.05 ± 0.46 (SEM) • Median - 7 • Range 2-25days • 27/80(33.7%) were diagnosed within 5 days of onset • No significant difference in time to Dx in 1st 5yrs versus 2nd 5yrs of study

  24. Severity of anaemia during illness

  25. Urine output • 42 patients were anuric • Mean duration 6.4±4.8days • Median 6 days • Range 1-28

  26. Acute dialysis • 50 (62.5%) needed dialysis (mostly PD) • Dialysis duration • Mean 9.2± 6.5(CI 7.3-11.08) • Median 7 days • Range 2-38 days

  27. Complications of initial illness in D+HUS n=80 • Seizures 8 • 1 child severe seizures, died of intracranial bleed • Transient DM 0 • Cardiomyopathy 0 • Intracranial haem 1 • Pancreatitis 0 • Death 1

  28. Follow up at 12 months for D+HUS • All paediatricians requested for information on urinalysis for proteinuria, renal function, BP, growth, further attacks of HUS • 5 - unable to locate patient for further information • 67/72 of cohort available for follow up 12 mo.after initial illness

  29. Follow up at 12 months Abnormal urine sediment • significant proteinuria defined ≥1+ or urine protein to creatinine ratio of >20mg/mmol • Haematuria ≥ 1+ blood on urinalysis

  30. Results of D+HUS follow up • 39/69 normal UA at mean of 12 months after initial illness • 22/69(31.8-%) – abnormal urine (1+ bld/ protein, hypertension or reduced renal function) • 2 nephrotic proteinuria • 3 reduced GFR (34-77ml/min/1.73m2) • 2 isolated HTN

  31. Conclusions • HUS is the single most common cause of acute kidney failure in children needing acute dialysis • There is no obvious seasonal pattern • All cases are sporadic • 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 2nd five yr period of the study) • E coli 0157 is the most common organism

  32. Conclusions • Significant acute morbidity associated with the disease • Acute dialysis & its complications • Long periods of hospitalisation • Major impact on general health • Long term morbidity • Chronic renal failure • Persistent renal abnormalities in 15-20%, some will progress to chronic renal failure needing dialysis and kidney transplantation

  33. Conclusions • E coli associated HUS is a largely preventable disease • Improved public health measures are required

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