Childhood Haemolytic uraemic syndrome in New Zealand

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Childhood Haemolytic uraemic syndrome in New
Zealand

• Dr William Wong
• Director, Department of Nephrology
• Starship Childrens Hospital

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Headlines
4 March 1999
3 August 1998
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1996 Lanarkshire outbreak
10 deaths
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Ecoli 0157 outbreak Sep-Oct 2006
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Development of E coli associated HUS
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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

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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

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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

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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

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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

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STEC in NZ

• Isolates found predominately in the North Island,
  mainly in upper half of N.I.
• 65 occur in children lt15years of age
• predominant serotype 0157 H7, others non typeable

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Comparative rates of HUS per 100,000 lt age 15
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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
  lt10g/dl with microscopic evidence of fragmented
  red blood cells)
• 2. Thrombocytopenia (Platelets lt 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

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Demographics

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

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Ethnic composition
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Age distribution of D() HUS childrenn80
Number of cases
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Population characteristics (n98)

• Females - 45
• Mean age 3.4yrs
• Median age 2.3yrs
• Age range 0.3 14 yrs
• History of Diarrhoea - 80

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Distribution of D HUS by health regionn80
51/80(64) from rural areas 75 in upper North
Is
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Seasonal distribution of Diarrhoeal HUS-Jan
1998-Dec 2007 (n80)
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Origin of infection causing DHUS

• 8 children from farms
• 3 children had eaten shellfish/seafood
• In most instances source of infection unknown

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Microbiology of DHUS

• 43/80 E.coli 0157 H7 isolated
• Stx-2 toxin in all E coli 0157
• All expressed eae gene

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Presenting clinical features of DHUS (n80)

• 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)

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Time to Diagnosis of DHUS

• 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

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Severity of anaemia during illness
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Urine output

• 42 patients were anuric
• Mean duration 6.44.8days
• Median 6 days
• Range 1-28

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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

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Complications of initial illness in DHUS n80

• Seizures 8
• 1 child severe seizures, died of intracranial
  bleed
• Transient DM 0
• Cardiomyopathy 0
• Intracranial haem 1
• Pancreatitis 0
• Death 1

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Follow up at 12 months for DHUS

• 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

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Follow up at 12 months

• Abnormal urine sediment
• significant proteinuria defined 1 or urine
  protein to creatinine ratio of gt20mg/mmol
• Haematuria 1 blood on urinalysis

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Results of DHUS 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

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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

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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

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Conclusions

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