Paediatrica Indonesiana

VOLUME 51 NUMBER 5 September 2O11

Original Article
252 Paediatr Indones, Vol. 51, No. 5, September 2011
Diagnostic tests of microscopic and urine dipstick
examination in children with urinary tract infection
Nurul Hidayah, Pungky Ardani Kusuma, Noormanto
Abstract
Background Urinarv tract infection (U1l) is common in children
and, if incorrectlv handled, mav cause lon,-term complications,
such as renal failure. 1he best test to dia,nose U1ls is urine
culture. However, urine culture is time-consumin,, takin, 3 - 5
davs. 1herefore, there is a need for faster, alternative methods.
Urinalysis is a common diagnostic test to establish the diagnosis
of U1l.
Objective 1his studv aims to determine the sensitivitv and
specificitv of urine leukocvtes, nitrite and leukocvte esterase for
UTI diagnosis.
Methods We performed dia,nostic tests at Dr Sardjito Hospital,
Yo,vakarta. We examined the presence of leukocvtes in urine bv
microscopv, urinarv nitrite and leukocvte esterase bv dipstick test,
while comparin, to urine culture as the ,old standard.
Results 1wo-hundred children were included in our studv. Bv
parallel test analvsis, we found the sensitivitv, specificitv, positive
predictive value and ne,ative predictive value of usin, all 3 tests
in combination were 95', 59', 71' and o9', respectivelv.
Conclusion 1ests for urine leukocvtes, nitrite and leukocvte
esterase have hi,h sensitivitv but low specificitv for dia,nosin,
U1ls. 1herefore, ne,ative results in these 3 tests do not rule
out the possibilitv of U1l in children. [Paediatr Indones.
2011;51:252-5].
Keywords: urinary tract infection, urine dipstick,
urine microscopic, urine culture
lrom the Department of Child Health, Oadjah Mada Universitv Medical
School, Dr. Sardjito Hospital, Yo,vakarta, lndonesia.
Reprint requests to: Pun,ki Ardani Kusuma, Department of Child Health,
Oadjah Mada Universitv Medical School, Sardjito Hospital, Jl. Kesehatan
no. 1 Yo,vakarta, lndonesia. 1el. 62-271-561616, lax.: 62-271-5o3715.
l-mail: ,injalvk_vahoo.com.
U
rinarv tract infection (U1l) is a major
health problem, particularlv in children.
lnformation on U1ls in children remains
controversial and leaves manv unanswered
questions.
1
UTI symptoms in children are not typical
or specific, makin, it difficult for phvsicians to make
a proper dia,nosis. However, U1ls require prompt
and proper mana,ement to avoid si,nificant future
complications, such as renal scarrin, or kidnev failure.
lurthermore, U1l with complication is the cause of
urosepsis, the major cause of sepsis after respiratorv
tract infections.
2
Clinicians usuallv require laboratorv examinations
to confirm a U1l dia,nosis. 1o select laboratorv tests,
one must consider two issues. lirst, a false ne,ative test
mav result in increased risk of serious complications.
Second, a false positive test could be costlv, as it could
lead to administration of unnecessarv antibiotic therapv,
which may give rise to microbial resistance.
3,1
The
,old standard examination for U1l is urine culture.
However, its main weakness is that it takes 3-5 davs to
obtain a result. U1l dia,nosis should be rapid, so that
Nurul Hidayah et al: Dia,nostic tests of microscopic and urine dipstick examination in children with urinarv tract infection
Paediatr Indones, Vol. 51, No. 5, September 2011 253
proper treatment can be given promptly. Alternative
methods to dia,nose U1ls bv urinalvsis are microscopic
urine examination (urine leukocvtes), and urine test
strips (urine nitrite and leukocvte esterase).
1
While
urinalvsis is readilv available, relativelv inexpensive, as
well as fast and simple, studies have reported varvin,
results. 1his studv aims to determine sensitivitv and
specificitv of urine leukocvtes, nitrite and leukocvte
esterase in the dia,nosis of U1l.
Methods
We performed a cross-sectional studv (Januarv-
December 2OO9) to determine the dia,nostic value of
urine leukocvtes, nitrite and leukocvte esterase tests from
suspected U1l patients, comparin, to urine culture as the
gold standard.
5
Subjects were obtained bv consecutive
samplin, and included 2OO children with possible U1l,
a,ed 2 months - 1o vears. Subjects were treated in Dr
Sardjito Hospital as inpatients or outpatients. Criteria
for clinical U1l dia,nosis varied accordin, to a,e ,roup.
lor infants, the criteria were non-specific svmptoms
such as vomitin, and/or diarrhea, anorexia, irritabilitv,
fussiness, fever of unknown cause, late onset jaundice
in the presence of elevated levels of bilirubin (direct or
indirect), and failure to thrive. lor pre-schoolers, the
criteria were dvsuria, ur,encv, frequencv, unusual urine
smell, fever, failure to thrive, and abdominal or pelvic
pain. lor school-a,ed children, dvsuria, frequencv,
fever, unusuallv foul-smellin, urine, vomitin,, anorexia,
and abdominal pain. We excluded children who had
alreadv received antibiotics or vitamin C, and those who
had ,lucosuria, proteinuria, urine of specific ,ravitv >
O.O3O or pH <5 and patients or families who refused to
participate.
Based on U1l prevalence data, we calculated the
minimum sample size required in our studv to be 2OO
subjects. Urinalvsis was performed in the Department
of Clinical Patholo,v, Dr Sardjito Hospital. Urine
specimens were collected bv obtainin, mid-stream urine.
lxamination of leukocvtes in urine was performed bv
centrifu,ation followed bv microscopv and countin, of
cells bv Neubauer haemocvtometer. leukocvtes were
reported per hi,h power field (HPl) and considered
positive for U1l if the number of leukocvte cells was
~ 5 cells/HPl. Dipstick urine test was used to measure
levels of nitrites and leukocvte esterase visuallv, and
the results compared with the reference colours on the
box. Anv colour chan,e indicated a positive result for
U1l. Urine culture was performed with MacConkev
and CllD a,ar, with cultures incubated at 37
o
C and
examined after 21-1o hours. 1he number of bacterial
colonies was counted. Positive U1l was indicated bv
presence of bacteria ~ 1O
5
cfu/ml.
laboratorv examinations were performed bv
two analvsts, with kappa value of O.62, indicatin,
a,reement. 1his studv was approved bv the Medical
lthics Committee of Oadjah Mada Universitv.
Subjects were collected bv consecutive samplin,,
and a descriptive analvsis was performed on subject
characteristics and dia,nostic test results (urine
leukocvtes, nitrite and leukocvte esterase) combined,
compared to urine culture as the ,old standard.
Sensitivitv, specificitv, positive predictive value (PPV),
ne,ative predictive value (NPV), positive likelihood
ratio (lR ) and ne,ative likelihood ratio (lR -) were
then computed.
Results
1wo hundred eli,ible subjects were included in this
studv. Baseline characteristics collected were a,e, sex,
circumcised state for males, and clinical svmptoms
associated with UTI. (Table 1)
Table 1. Characteristics of subjects suspected of having UTIs
Characteristic n = 200 Percentage, %
Age
2 mo 1 yr
>1 5 yrs
>5 10 yrs
>10 18 yrs
Gender
Boy
Girl
Circumcised state (boys)
Circumcised
Not circumcised
Symptoms
Fever
Abdominal Pain
Vomiting
Dysuria
Frequency
Urgency
Enuresis
Constipation
Icterus
Positive Urine Culture
50
69
45
36
65
135
22
43
102
59
48
28
15
9
9
8
4
95
25
35
22
18
33
67
34
66
51
30
24
14
8
4
4
3
2
48
Nurul Hidayah et al: Dia,nostic tests of microscopic and urine dipstick examination in children with urinarv tract infection
254 Paediatr Indones, Vol. 51, No. 5, September 2011
1he most common patho,en causin, U1l was
Escherichia coli (3o'), followed bv Pseudomonas
aeruginosa (29'). ther patho,ens were coa,ulase-
negative Staphylococcus, Klebsiella pneumonia,
Citrobacter sp, Proteus vulgaris, and Candida sp (13',
o', 3', 2' and 2', respectivelv). (Table 2)
For single parameter diagnostic test analysis,
leukocvte esterase had the hi,hest sensitivitv of oo'
(95' Cl: o2 to 95) with specificitv of 3O' (95' Cl:
21 to 3o). Urine leukocvtes had sensitivitv of o7'
(95' Cl: o1 to 91) and specificitv of 26' (95' Cl:
17 to 31). Urine nitrite test had the lowest sensitivitv
of 1O' (95' Cl: 3O to 5O), but showed the hi,hest
specificitv of o1' (95' Cl: 7 to oo) compared to other
diagnostic tests. (Table 3)
1he parallel test analvsis with the combination of
3 parameters, (urine leukocvtes, nitrite and leukocvte
esterase) is shown in Table 4. This combination
increased the sensitivitv to 95' (95' Cl: o7 to 1OO)
and specificitv to 59' (95' Cl: 11 to 77).
Discussion
Dicknson estimated the risk of U1ls in bovs a,ed 2-11
vears to be 1.6/1OOO/vear, while in ,irls thev found the
risk to be 3.o/1OOO/vear.
6
f the children suspected to
have U1ls in our studv, the lar,est a,e ,roup was 1-5
vears old. 1here were more females than males and
the majoritv of males were uncircumcised.
Clinical svmptoms of U1l are non-specific
and in some patients even occur without svmptoms.
However, the most common complaint of our subjects
was fever. ln lower U1ls, patients usuallv complain
of pain or burnin, sensation in the urethra durin,
urination with small amount of urine excreted and
discomfort in the suprapubic re,ion. ln upper U1ls,
svmptoms of headache, malaise, nausea, vomitin,,
fever, chills, and/or flank pain can be found. ln
neonates, the symptoms are not typical so UTIs
often manifest as svmptoms of sepsis. Svmptoms
in newborns mav include jaundice, pallor, cvanosis,
respiratory distress, decreased appetite, decreased
bodv wei,ht, diarrhea, and central nervous svstem
svmptoms such as anxietv, seizures, and hvpotonia.
Svmptoms are more specific in older children.
1,7
Rehman et al. documented clinical svmptoms of U1l
to include fever (91'), dvsuria (65'), failure to ,row
(1O'), vomitin, (2o'), and abdominal pain (22').
7
We also found that fever was the most common
complaint (51') in our studv subjects.
Prais et al. su,,ested that most common causes
of U1ls were E. coli (o6',) followed bv Klebsiella sp
(6') and other patho,ens (o').
o
Waisman et al. found
the most common bacterial pathogens to be E. coli
(77.3'), followed bv Pseudomonas, enterococcus, and
Klebsiella (5.7' for each) and ,roup B Streptococcus
and coa,ulase-ne,ative Staphylococcus (2.o' each).
9
ther studies also reported E. coli to be the most
common cause of U1l. Similarlv, we found E. coli
Table 2. Microbes causing UTI
Microbes n Percentage
Escherichia coli
Pseudomonas aeruginosa
Coagulase-negative Staphylococcus
Klebsiella pneumoniae
Citrobacter sp
Proteus vulgaris
Candida sp
38
29
13
8
3
2
2
40
31
14
8
3
2
2
Total 95 100
Table 3. Single parameter diagnostic test results
Results Urine leukocytes Urine nitrites Urine leukocyte esterase
Sensitivity, %
Specifcity, %
PPV, %
NPV, %
LR (+)
LR (-)
87 (95% CI 81 to 94)
26 (95% CI 17 to 34)
52 (95% CI 44 to 59)
69 (95% CI 55 to 84)
1.18 (95% CI 1.03 to 1.35)
0.49 (95% CI 0.26 to 0.91)
40 (95% CI 30 to 50)
81 (95% CI 73 to 88)
66 (95% CI 53 to 78)
60 (95% CI 52 to 68)
2.10 (95% CI 1.32 to 3.34)
0.74(95% CI 0.61 to 0.90)
88 (95% CI 82 to 95)
30 (95% CI 21 to 38)
53 (95% CI 45 to 61)
74 (95% CI 61 to 87)
1.25 (95% CI 1.09 to 1.45)
0.39 (95% CI 0.21 to 0.74)
Table 4. Parallel analysis of diagnostic tests based on three
parameters
Urine leukocytes + nitrites +
leukocyte esterase
Value
Sensitivity, %
Specifcity, %
PPV, %
NPV, %
LR (+)
LR ( - )
95 (95% CI 87 to 100)
59 (95% CI 41 to 77)
74 (95% CI 62 to 87)
89 (95% CI 76 to 100)
2.29 (95% CI 1.47 to 3.55)
0.09 (95% CI 0.02 to 0.37)
Nurul Hidayah et al: Dia,nostic tests of microscopic and urine dipstick examination in children with urinarv tract infection
Paediatr Indones, Vol. 51, No. 5, September 2011 255
was the most common cause of U1ls in our subjects
(1O').
ln previous studies, the dia,nostic tests of
urinalvsis varv accordin, to the research settin,s.
lor urine nitrite, Rehmani found the sensitivitv,
specificitv, NPV, and PPV was o1', o7', 73', and
91', respectivelv. leukocvte esterase had sensitivitv
of 77', specificitv 51', NPV 13', and PPV o5'.
4
lor urine leukocvte test bv microscopv, Simerville et
al. found that more than 5 leukocvtes per field of view
had a sensitivitv of 1o' - 11' and a specificitv of oo'
- o9', PPV 56' - 59' and NPV o3' - 95'.
1O
ln our
studv, the hi,hest sensitivitv test was urine leukocvte
esterase (oo'), but this test had low specificitv (3O'),
with PPV and NPV of 53' and 71', respectivelv.
lurthermore, the hi,hest specificitv values were found
for urine nitrite (o1'), but it had low sensitivitv
(1O'), with PPV of 66' and NPV of 6O'. 1his result
implies that there are a hi,h proportion of patients
who do not experience U1l if their urine nitrite test
shows a ne,ative result. ln this studv, we combined
the three common parameters of urine leukocvtes,
nitrite and leukocvte esterase in order to increase the
sensitivitv and specificitv of urinalvsis for detectin,
U1ls. 1he combination of these three dia,nostic
tests improved sensitivitv to 95' and specificitv to
59'. PPV and NPV also increased to 71' and o9',
respectivelv. A studv bv lohr et al. also documented
increased sensitivitv of 1OO' when all dia,nostic tests
were positive, with specificitv of 66.1'.
11
We found
the sensitivitv to be lower than that of lohr et al.,
probablv due to the urine not bein, analvsed within
an hour of collection, which mav cause a hi,her rate
of false positives due to contamination. 1his is one
weakness of our studv. lor future studies, suprapubic
aspiration is recommended to minimize the possibilitv
of bacterial contamination.
We conclude that the combination of urine
leukocvtes, nitrite and leukocvte esterase tests had
hi,h sensitivitv, but low specificitv for dia,nosin,
U1ls. 1herefore, ne,ative results of these 3 tests do
not rule out the possibilitv of U1ls in children.
Acknowledgments
We would like to thank lndv Parvanto, lita Wirastuti, latifah
Hanum, and Retno Palupi for their technical assistance.
References
1. zorc JJ, Kiddoo DA, Shaw KN. Dia,nosis and mana,ement
of paediatric urinarv tract infections. Clin Microbiol Rev.
2OO5,1:117-22.
2. Man,atas SM, Suwitra K. Dia,nosis dan penatalaksanaan
infeksi saluran kemih terkomplikasi. Dexa Medica.
2OO1,17:12-1.
3. Downs SM. 1echnical report: Urinarv tract infection in febrile
infants and voun, children. Pediatrics. 1999,1O3:1-6.
1. Rehmani R. Accuracv of urine dipstick to predict urinarv
tract infections in an emer,encv department. Pediatrics.
199o,9o:1O1-2.
5. Puspone,oro HD. Uji Dia,nostik. Dalam: Sastroasmoro S,
lsmael S, editors. Dasar - dasar metodolo,i penelitian klinis.
2
nd
ed. Jakarta: Sa,un, Seto, 2OO7. p. 166-o5.
6. Dickinson JA. lncidence and outcome of svmptomatic
urinarv tract infection in children. Br Med J. 1979,1:133O
-2.
7. Rehman, A, Jahanzeb M, Siddiqui, 1S, ldris, M. lrequencv
and clinical presentation of U1l amon, children of
Hazara Division, Pakistan. J Avub Med Coll Abbottabad.
2OOo,2O:63-5.
o. Prais D, Straussber, R, Avitzur Y, Nussinovitch M, Harel
l, Amir J. Bacterial susceptibilitv to oral antibiotics in
communitv acquired urinarv tract infection. Arch Dis Child.
2OO3,oo:215-o.
9. Waisman Y, zerem l, Aamir l, Mimouni M. 1he validitv of
the uriscreen test for earlv detection of urinarv tract infection
in children. Pediatrics. 1999,1O1:e11.
1O. Simerville JA, Maxted Wl, Pahira JJ. Urinalvsis: a
comprehensive review. Am lam Phvsic. 2OO5,71:1153-62.
11. lohr JA, Portilla MO, Oeuder 1O, Dunn Ml, Dudlev SM.
Makin, a presumptive dia,nosis of urinarv tract infection bv
usin, a urinalvsis performed in an on-site laboratorv. J Pediatr.
1993,122:22-5.