childhood haemolytic uraemic syndrome in new zealand
TRANSCRIPT
Childhood Haemolytic uraemic syndrome in New Zealand
Dr William Wong Director, Department of NephrologyStarship Children’s Hospital
Headlines
3 August 1998 4 March 1999
1996 Lanarkshire outbreak
10 deaths
Ecoli 0157 outbreak Sep-Oct 2006
Development of E coli associated HUS
• 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
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
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
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
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
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
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
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
DemographicsDemographics• 98 children with HUS reported in 10yrs
– 80 diarrhoeal prodrome– 18 non diarrhoeal/”atypical”
Ethnic compositionEthnic composition
40, 68%
16, 27%
2, 3% 1, 2%
NZE
Maori
PI
Indian
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
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
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
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
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
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
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
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%)
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
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
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
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
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
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
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
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
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
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
ConclusionsConclusions• E coli associated HUS is a largely preventable
disease• Improved public health measures are required