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 Children’s Hospital

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Page 1: Childhood Haemolytic uraemic syndrome in New Zealand

Childhood Haemolytic uraemic syndrome in New Zealand

Dr William Wong Director, Department of NephrologyStarship Children’s Hospital

Page 2: Childhood Haemolytic uraemic syndrome in New Zealand

Headlines

3 August 1998 4 March 1999

Page 4: Childhood Haemolytic uraemic syndrome in New Zealand

1996 Lanarkshire outbreak

10 deaths

Page 5: Childhood Haemolytic uraemic syndrome in New Zealand

Ecoli 0157 outbreak Sep-Oct 2006

Page 6: Childhood Haemolytic uraemic syndrome in New Zealand

Development of E coli associated HUS

Page 7: Childhood Haemolytic uraemic syndrome in New Zealand

• 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

EpidemiologyEpidemiology

Page 8: Childhood Haemolytic uraemic syndrome in New Zealand

EpidemiologyEpidemiology

• 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

Page 9: Childhood Haemolytic uraemic syndrome in New Zealand

EpidemiologyEpidemiology• 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

Page 10: Childhood Haemolytic uraemic syndrome in New Zealand

Clinical presentationClinical 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

Page 11: Childhood Haemolytic uraemic syndrome in New Zealand

The STEC in NZThe 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

Page 12: Childhood Haemolytic uraemic syndrome in New Zealand

STEC in NZ 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

Page 13: Childhood Haemolytic uraemic syndrome in New Zealand

Comparative rates of HUSper 100,000 < age 15

0.67 0.641.3

7.9

0

1

2

3

4

5

6

7

8

U.S. U.K Aust N.Z. Argent

Page 14: Childhood Haemolytic uraemic syndrome in New Zealand

NZPSU surveillance studyNZPSU 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

Page 15: Childhood Haemolytic uraemic syndrome in New Zealand

DemographicsDemographics• 98 children with HUS reported in 10yrs

– 80 diarrhoeal prodrome– 18 non diarrhoeal/”atypical”

Page 16: Childhood Haemolytic uraemic syndrome in New Zealand

Ethnic compositionEthnic composition

40, 68%

16, 27%

2, 3% 1, 2%

NZE

Maori

PI

Indian

Page 17: Childhood Haemolytic uraemic syndrome in New Zealand

Childhood haemolytic uraemic syndrome and VTEC isolates, 1998-

2007

0

10

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0N

umbe

r of

cas

es

D+HUS 14 4 5 6 9 10 8 8 10 10

All paed HUS 14 7 7 6 12 12 10 10 12 12

Total STEC 39 46 46 59 49 79 57 62 54 65

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Page 18: Childhood Haemolytic uraemic syndrome in New Zealand

Age distribution of D(+) HUS childrenn=80

0

10

20

30

40

50

60

<1yrs 1-5yrs 5-10yrs >10yrs

age group

Number of cases

Page 19: Childhood Haemolytic uraemic syndrome in New Zealand

Population characteristics Population characteristics (n=98)(n=98)

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

Page 20: Childhood Haemolytic uraemic syndrome in New Zealand

Distribution of D+ HUS by health regionn=80

0 2 4 6 8 10 12 14 16 18

Northld

Akld

Waikat

Bay of Pl

Tairawhiti

Hawkes B

Lakes

Taranaki

Wangan

Mid Cent

Wgtn

Waiarap

Nels-Mar

Cant

West Coast

Southld

Otago 51/80(64%) from rural areas

75% in upper North Is

Page 21: Childhood Haemolytic uraemic syndrome in New Zealand

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

0

2

4

6

8

10

12

14

16

J F M A M J J A S O N D

Month of Year

No

. of

D+

case

s

Page 22: Childhood Haemolytic uraemic syndrome in New Zealand

Origin of infection causing D+HUSOrigin of infection causing D+HUS

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

Page 23: Childhood Haemolytic uraemic syndrome in New Zealand

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

Page 24: Childhood Haemolytic uraemic syndrome in New Zealand

Presenting clinical features of D+HUS Presenting clinical features of D+HUS (n=80)(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%)

Page 25: Childhood Haemolytic uraemic syndrome in New Zealand

Time to Diagnosis of D+HUSTime 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

Page 26: Childhood Haemolytic uraemic syndrome in New Zealand

Severity of anaemia during illness

0

10

20

30

40

50

60

30-50g/L 51-70g/L >70g/L

haemogloblin

No

. o

f p

atie

nts

Page 27: Childhood Haemolytic uraemic syndrome in New Zealand

Urine output

• 42 patients were anuric– Mean duration

6.4±4.8days– Median 6 days– Range 1-28

31, 72%

10, 23%

2, 5%

1-7 days

8-14 days

>14 days

Page 28: Childhood Haemolytic uraemic syndrome in New Zealand

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

28, 56%14, 28%

8, 16%

1-7 days

8-14 days

>14 days

Page 29: Childhood Haemolytic uraemic syndrome in New Zealand

Complications of initial illness in Complications of initial illness in D+HUS D+HUS n=80n=80

• Seizures 8– 1 child severe seizures, died of intracranial bleed

• Transient DM 0• Cardiomyopathy 0• Intracranial haem 1• Pancreatitis 0• Death 1

Page 30: Childhood Haemolytic uraemic syndrome in New Zealand

Follow up at 12 months for Follow up at 12 months for D+HUS 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

Page 31: Childhood Haemolytic uraemic syndrome in New Zealand

Follow up at 12 monthsFollow up at 12 monthsAbnormal urine sediment• significant proteinuria defined ≥1+ or urine

protein to creatinine ratio of >20mg/mmol• Haematuria ≥ 1+ blood on urinalysis

Page 32: Childhood Haemolytic uraemic syndrome in New Zealand

Results of D+HUS follow up 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

Page 33: Childhood Haemolytic uraemic syndrome in New Zealand

ConclusionsConclusions• 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

Page 34: Childhood Haemolytic uraemic syndrome in New Zealand

ConclusionsConclusions• 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

Page 35: Childhood Haemolytic uraemic syndrome in New Zealand

ConclusionsConclusions• E coli associated HUS is a largely preventable

disease• Improved public health measures are required