THE ROLE OF QUANTITATIVE C-REACTIVE PROTEIN , WHITE BLOOD CELL COUNT AND PYURIA IN PREDICTING URINARY TRACT INFECTION AMONG FEBRILE INFANTS AND CHILDREN Affiliation

Introduc on Urinary tract infec on (UTI) is among the commonest bacterial infec ons in infants and children that warrants early detec on and management to prevent long term consequences in kidney causing significant morbidity. The prevalence of UTI varies according to age, gender, race, circumcision status of children but it occurs in 1% of boys and 1 to 3% of girls. There have been studies that have highlighted the importance of C-reac ve as an inflammatory marker involved during urinary tract infec on in children.


Objec ves
To find out how Quan ta ve C-reac ve protein level, white blood cell count and pus cells in urine are associated in febrile infants and children with UTI.
To find out the an bio c sensi vity pa ern of UTI.

Methodology
A prospec ve cross sec onal study was conducted to evaluate febrile infants and children of 2 months to 13 years of age with suspected UTI for a period of six months.Venous blood samples were sent for Quan ta ve es ma on of CRP, White blood cell count and urine samples were sent for urine microscopy and culture sensi vity.Sta s cal analysis of data was done using SPSS so ware version 16.

INTRODUCTION
Urinary tract infec on is one of the common bacterial infec on in infants and children that warrants early detec on and management to prevent long term consequences in kidney causing significant morbidity.Urinary tract infec on not only involves bladder but the infec on can ascend up to the kidney causing scarring of kidney that can cause hypertension and chronic kidney 1, 2 disease etc.The prevalence of UTI varies according to age, gender, race & circumcision status of children.but it 3 occurs in 1% of boys and 1 to 3% of girls.There is male preponderance for UTI in less than 1 year age group whereas it is more common in female a er infancy.One of the study done in Dhulikhel Hospital, Nepal reported UTI to 4 be twice more common in female than male.
There have been studies that highlighted the importance of C-reac ve as an inflammatory marker involved during urinary tract infec on in children and also underscoring the predic ng value of raised WBC counts,ESR, mean platelet volume and lymphocyte -neutrophil ra o in detec ng UTI 5 -7 early on.Different studies done to look at sensi vity and specificity of C-reac ve protein, White blood cell count & pyuria have provided good evidence to support that they 8 are useful in predic ng UTI.
The most common causa ve agents for UTI are fecal flora that colonizes around the perineal region and enters the bladder through urethra.Once infec on commences , immune system gets ac vated leading to inflammatory response in the body.
Urine culture remains gold standard test for UTI but it takes 72 hours to isolate the organism and tes ng for sensi vity 9 to the an bio cs that might delay treatment.
Hence to predict the possibility of UTI very early on among febrile infants and children, we aimed to do this study to see whether quan ta ve es ma on of CRP, WBC Count and pus cells in urine could predict UTI.We also aim to find out local sensi vity pa ern for the common pathogens causing UTI.

METHODOLOGY
A prospec ve cross sec onal hospital based study was conducted for a period of six months commencing from May 2017 to October 2017 at Biratnagar Aspatal Pvt. Ltd. unit of Birat Medical College & Teaching Hospital, Biratnagar.
All the children (2 months-13 years) with fever( 38.4 ) and suspected to have urinary tract infec on were included in this study.The symptoms included for the suspicion of UTI were vomi ng, back pain, pain abdomen, foul smelly urine, urinary frequency & urgency etc.Those children also underwent history and physical examina on.The children with diagnosed renal disorders & history of intake of an bio cs over the last one week period were excluded from the study.
Informed consents were taken from the parents and ethical approval was obtained from the research and ethics commi ee of the hospital.The blood was collected using BD Vacutainer from the peripheral vein using all asep c precau on and serum was separated by centrifuging the vacutainer.The quan ta ve analysis of CRP was done on MISPA13 automated protein analyzer.Quan ta ve nephelometry method was used to quickly and accurately measure the specific level of CRP in serum.A smart card was inserted in the analyzer.A pre filled cartridge of CRP was taken and was tapped to remove any air bubble.Eighty microlitre of sample was added to the dedicated well in the cartridge and it was placed in the cartridge carrier.The start bu on is pressed and sample was analyzed.The test results were measured in mg/dl keeping a cut off of <0.6 mg/dl.
Appropriately collected urine sample was sent for microscopic examina on of urine and culture sensi vity.The physical examina on of urine was done to note the colour, odour, clarity and cloudiness .The chemical examina on of urine was done by dips ck method using DEKA PHAN dips cks from ERBA LACHEMA for protein, sugar, blood, specific gravity, pH, Ketones nitrites and leucocytes and urobilinogen.
Urine culture was considered gold standard test for UTI.For standard urine analysis pyuria was defined as >10 WBC count in centrifuged urine sample.Inocula on of urine was done using 0.01ml(x100) loop onto nutrient and Maconkey Agar.Loop full of urine was taken and streaked across the plate perpendicular to the original inoculum (Lawn Culture).
Plates were inoculated at 37 C for 24-48 hours.Organisms were iden fied by doing naked eye examina on (color) of the colonies and further by doing biochemical examina on.The an bio c sensi vity test was done on Muller-Hinton Agar.
All the data were entered in excel and transferred to SPSS version 16.The descrip ve and inferen al sta s cs were used for data analysis.The test of significance was done by chi square test.The sensi vity, specificity, nega ve predic ve value and posi ve predic ve value were calculated for CRP, WBC Count and Pyuria using Urine culture as the gold standard.A p value < 0.05 was considered significant.

DISCUSSION
Early diagnosis and treatment of UTI is of great importance due to its implica on of renal scarring and its long term morbidity.Several studies done in various se ngs have clearly suggested that there is a raised inflammatory 1,2 marker during urinary tract infec on.
This study tried to look at the role of common inflammatory markers such as C-reac ve protein and white blood cell count that we commonly use in our se ng.In our study we found slightly higher prevalence of UTI (31%) among female children as compared to male children (28.6%).
Our study also noted that the prevalence of UTI is higher in infants (40%) as compared to children of 1-5 yrs age group (31%) or children of more than 5 yrs of age group (29.5 %).
In our study we observed that the increased White blood cell counts of >12000/dl had sensi vity of 56.5% and specificity of 87.8% in predic ng posi ve urine culture whereas the posi ve predic ve value and nega ve predic ve value were 66% and 83% respec vely.However, Benador et al found a sensi vity of 89% and specificity of 10 25% in his study.
In this study, we noted sensi vity and specificity of 77% and 81% respec vely for CRP > 1 mg/dl taking Urine culture as the gold standard whereas PPV and NPV were 63% and 90% respec vely which is different from the study done by Ayazi P et al in which the sensi vity was much higher(96%) and specificity was very low but Posi ve predic ve value and

CONCLUSION
Quan ta ve C-reac ve protein and White blood cell count in blood can predict UTI in febrile infants and children with high sensi vity and specificity .Pyuria ( pus cells>10/HPF) also has good sensi vity , posi ve and nega ve predic ve value for predic ng UTI.E coli being the commonest organism isolated.There is growing resistance of organism that warrants development of an bio c guideline locally.

LIMITATION OF STUDY
This study was conducted for 6 months period only.Similar study for longer dura on would have had be er external validity.

Figure 2 :
Figure 2: An bio c Sensi vity Pa ern

Table 1 : Demographics of pa ents with posi ve culture results Age group
*Sta s cally significantFigure 1 : Isolates of Urine Culture

Table 3 : Sensi vity, PPV, NPV of lab results
Amoxy clavulinic acid(71.7%)and even to Ampicilin (41.6%) was found.Although this finding was quite different from our study, it highlighted the importance knowing local an bio c sensi vity pa ern to provide 16 ra onal an bio cs prescrip on to treat infec on.In a study done by Ojha A et al. in Nepal, Nitrofurantoin(93%) and Amikacin(93%) were the most sensi ve which is comparable to our study.The finding from Gallegos J et al noted even higher percentage of sensi vity to Amikacin (100%) and