The study compared the reliability and diagnostic accuracy of routine NHS laboratories and a research laboratory in diagnosing urinary tract infections (UTIs) in young children. The research laboratory showed substantially better agreement with predefined signs/symptoms of UTIs and with a clean-catch urine sample method. The NHS laboratories appeared to overdiagnose UTIs from nappy pad samples due to failure to distinguish contamination. The implications are that NHS laboratories may benefit from adopting the research laboratory's standardized methods, and clinicians should focus on obtaining higher-quality clean-catch urine samples for improved UTI diagnosis in young children.

1. Comparing the reliability and diagnostic
accuracy of routine NHS laboratories
and a research laboratory in the
Diagnosis of Urinary Tract infection in
Young children (DUTY) study
Kim Harman on behalf of the
DUTY study team

2. Research aim
Aim
To compare the reliability and diagnostic accuracy of
two different types of laboratory in the urinalysis with
regard to UTI

3. Background
There is a ‘National standard method’ for urinalysis but it is
unknown how much this is adhered to.
Few studies have compared routine NHS laboratory
reporting of results against a single standardised laboratory.
Evidence for laboratory processes is weak.

5. Whole study design
• Cross sectional diagnostic accuracy study with prospective
f/u
• ‘Open’ inclusion criteria
– Children <5 years old
– Presenting to primary care with an acute (<28 days) illness
• Constitutionally unwell and / or
• Urinary symptoms, even if clinician ‘knows’ the diagnosis
• Excluded
– Neurogenic bladder
– Antibiotics <7 days
– Trauma as main concern

6. Data collected
• Data collection
– Baseline demographics, symptoms and signs (n=63) rated
none/mild/moderate or severe
• Urine sample
– Preference clean catch, then Newcastle Nappy pad
– Urine dipstick testing
• Urine sample split and sent to
– Local NHS laboratory for routine microscopy and culture
– More detailed research laboratory (RL) analysis

7. Methods (1)
Definitions of UTI
• NHS laboratory
– Report of pure/predominant growth of a uropathogen (e.g. e.coli,
proteus, etc) at ≥105 cfu/ml
• Research laboratory
– Growth of ≥105 cfu/ml of a single uropathogen (“pure growth”)
– Or growth of ≥105 of a uropathogen with ≥3 log10 (1000-fold)
difference between growth of this and the next species
(“predominant growth”)

8. Methods(2)
Association with a priori specified variables clearly
associated with the presence of UTI from the literature
Pain/crying when passing urine
Passing urine more often
Changes in urine appearance
Temperature ≥ 39°C
Dipstick nitrite positive
Dipstick leukocyte positive
(Hay AD, Whiting P, Butler CC. How best to diagnose urinary tract infection
in preschool children in primary care? BMJ 2011; 343:d6316.)

9. General results
1. 69 Local NHS Labs involved
2. 6,079 Local NHS Laboratory urines
3. 5,107 Research Laboratory urines
4. 4,808 children with predictors from CRF & urine at
both labs

10. Study participants
Category Age <3 years Age 3-5 years
Gender Male 1439 (49.9%) 919 (47.8%)
Female 1445 (50.1%) 1005 (52.2%)
Age (years) 0 to <1 1016 (35.2%)
1 to <2 942 (32.7%)
2 to <3 926 (32.1%)
3 to <4 1099 (57.1%)
4 to <5 825 (42.9%)
Sample method Clean catch 758 (26.3%) 1861 (96.7%)
Nappy pad 2126 (73.7%) 63 (3.3%)

11. Urine sample results
Result Age <3 years Age 3-5 years
NHS laboratory Positive 189 (6.6%) 62 (3.2%)
Research
laboratory
Positive 51 (1.8%) 37 (1.9%)

12. Kappa 95% CI
Both collection methods 0.36 (0.29, 0.43)
Clean catch 0.54 (0.45, 0.63)
Nappy pad 0.20 (0.12, 0.28)
≥ 3 years 0.53 (0.41, 0.65)
Clean catch 0.55 (0.43, 0.67)
Nappy pad N/A
<3 years 0.29 (0.21, 0.36)
Clean catch 0.52 (0.37, 0.67)
Nappy pad 0.20 (0.12, 0.28)
Similar patterns were seen when comparisons were further stratified into age
groups <2 and ≥2 to <3 years. N/A is not available – too few results
Between lab comparisons

13. Associations with variables
Clean catch Nappy pad
Research laboratory
AUC (95% CI) 0.86 (0.79, 0.92) 0.79 (0.70,0.88)
NHS laboratories
AUC (95% CI) 0.75 (0.69,0.80) 0.65 (0.61,0.70)

14. 00.51
1 0.5 0
Clean catch
UTI + ve in NHS
00.51
1 0.5 0
Nappy pad
00.51
1 0.5 0
UTI +ve in RL
00.51
1 0.5 0
Sensitivity
Specificity
Between lab comparisons

15. Summary of main results
• There is worse than expected agreement between
the labs and between collection methods
• Associations of microbiological positivity with pre-
specified signs/symptoms were lower for:
– NHS positivity than for research laboratory positivity
– Nappy pad samples than for clean catch samples

16. Implications - microbiological
NHS labs may wish to adopt the methods of the research
laboratory.

17. Implications – clinical
More effort should be spent on obtaining higher
quality (clean catch) samples, even in the very young

18. Implications - research
Leading hypothesis is that for nappy pad samples
the NHS labs overdiagnose UTI because of failure to
identify contamination

19. NIHR disclaimer
This project was funded by the NIHR Health Technology
Assessment Programme (project number 08/66/01) and will
be published in full as a Health Technology Assessment.
The views and opinions expressed therein are those of the
authors and do not necessarily reflect those of the HTA
programme, NIHR, NHS or the Department of Health.

20. Thank you team
Investigators
Alastair Hay (co-CI) Study Managers
Chris Butler (co-CI) Jonathan Sterne Harriet Downing
Peter Brindle Judith van der Voort Marilyn Peters
Brendan Delaney Penny Whiting Kate Rumsby
Jan Dudley Data Manager Emma Thomas-Jones
Margaret Fletcher Cathy Lisles Cherry-Ann Waldron
Will Hollingworth Database manager Statisticians
Kerenza Hood Stevo Durbaba Kate Birnie
Robin Howe Microbiologist Michael Lawton
Paul Little Mandy Wootton Tim Pickles
Alasdair MacGowan Health economist DUTY nurses / CSOs
Kathy O’Brien John Busby
Primary care clinicians
Children & their families

21. Associations in Research Lab
Central laboratory
Clean catch Nappy pad
OR (95% CI) p OR (95% CI) p
Pain/crying passing urine 6.0 (3.0, 11.8) <0.001 1.4 (0.3, 7.0) 0.716
Passing urine more often 0.8 (0.4, 1.7) 0.543 1.2 (0.3, 4.4) 0.839
Change in urine appearance 3.1 (1.6, 6.1) 0.001 3.1 (1.2, 7.9) 0.019
Temperature ≥39°C 1.7 (0.6, 5.1) 0.333 1.1 (0.1, 8.8) 0.930
Dipstick: nitrite +ve 11.2 (5.4, 23.1) <0.001 5.2 (2.4, 11.3) <0.001
Dipstick: leukocyte +ve 5.3 (2.8, 10.0) <0.001 4.1 (1.9, 8.9) <0.001
AUC (95% CI) 0.86 (0.79 0.92) 0.79 (0.70, 0.88)

22. Associations in NHS labs
NHS laboratory
Clean catch Nappy pad
OR (95% CI) p OR (95% CI) p
Pain/crying passing urine 2.9 (1.6, 5.1) <0.001 1.1 (0.4, 3.1) 0.838
Passing urine more often 0.6 (0.3, 1.1) 0.073 0.7 (0.3, 1.5) 0.370
Change in urine appearance 3.0 (1.8, 4.9) <0.001 2.1 (1.3, 3.5) 0.005
Temperature ≥39°C 1.7 (0.8, 3.8) 0.157 0.7 (0.2, 2.2) 0.526
Dipstick: nitrite +ve 7.6 (4.1, 14.1) <0.001 2.0 (1.4, 2.9) 0.001
Dipstick: leukocyte +ve 3.1 (1.9, 5.1) <0.001 3.1 (2.1, 4.4) <0.001
AUC (95% CI) 0.75 (0.69, 0.80) 0.65 (0.61, 0.70)

23. 0.1.2.3.4
s.e.ofkappa
-.5 0 .5 1
kappa
Funnel plot 95% confidence limits