Diagnostic performance of urine dipstick testing in children with suspected UTI: a systematic review of relationship with age and comparison with microscopy.

BACKGROUND: Prompt diagnosis of urinary tract infection (UTI) in children is needed to initiate treatment but is difficult to establish without urine testing, and reliance on culture leads to delay. Urine dipsticks are often used as an alternative to microscopy, although the diagnostic performance of dipsticks at different ages has not been established systematically. METHOD: Studies comparing urine dipstick testing in infants versus older children and urine dipstick versus microscopy were systematically searched and reviewed. Meta-analysis of available studies was conducted. RESULTS: Six studies addressed these questions. The results of meta-analysis showed that the performance of urine dipstick testing was significantly less in the younger children when compared with older children (p < 0.01). Positive likelihood ratio (LR) of both nitrite and leucocyte positive 38.54 [95% confidence interval (CI) 22.49-65.31], negative LR for both negative 0.13 (95% CI 0.07-0.25) are reasonably good, and those for young infants are less reliable [positive LR 7.62 (95% CI 0.95-51.85) and negative LR 0.34 (95% CI 0.66-0.15)]. Comparing microscopy and urine dipstick testing, using bacterial colony count on urine culture showed no significant difference between the two methods. CONCLUSION: Urine dipstick testing is more effective for diagnosis of UTI in children over 2 years than for younger children.

Mucosal immunity in the urinary tract: changes in sIgA, FSC and total IgA with age and in urinary tract infection.

The incidence of primary urinary tract infection (UTI) is greatest in the first month of life and decreases with age throughout childhood. Secretory immunoglobulin A (sIgA) is an important component of mucosal immunity. The changes in secretory IgA, IgA and free secretory component (FSC) during the first year of life were examined in relation to age, sex and in infants, feeding practice. These constituents were further compared between healthy children and those with acute and recurrent UTI. Urine was collected from 41 healthy infants (16 female: 25 male) at intervals (mean age 1.4, 9.1, 44, 91, 210 and 412 days), 139 healthy children (75 female: 64 male), 29 children with histories of recurrent UTI (25 female: 4 male) and 10 with acute UTI (8 female: 2 male). sIgA, IgA and FSC were measured by enzyme linked immunoassay. In the majority of children sIgA and IgA were undetectable at birth. SIgA and IgA rose significantly during the first year then levelled off throughout childhood. FSC was detectable from birth (geometric mean [mean of logged values]-GOM at day 1.4, 362.2 ng/ml). No sex differences were apparent for any of the three constituents at any age. Breast feeding was associated with higher levels of sIgA and IgA than bottle feeding. This was highly significant at 9.1 days when sIgA and IgA levels of breast fed compared with bottle fed infants were 64.6 ng/ml vs 21.2 and 56.2 ng/ml vs 18.7 ng/ml respectively, giving a GOM ratio of 3.04 for sIgA and 3.0 for IgA (p < 0.001 for both). No significant difference in the three parameters were demonstrable when children with recurrent UTI-with normal or abnormal renal tracts-were compared with controls. Acute UTI resulted in raised sIgA, IgA and FSC compared with controls (GOM ratio of 4.9 [p < 0.002], 4.2 [p < 0.005] and 2.7 [p < 0.001] respectively). The proportion of total IgA present as sIgA (sIgA/total IgA) was not significantly different in the acute vs control groups. Urinary sIgA and IgA may be important for the observed variation with age in infant UTI and the reduced incidence in breast fed infants but does not appear to contribute to the sex associated difference in susceptibility to infection at any age.

A urine analysis method suitable for children's nappies.

BACKGROUND: Urinary tract infection in infancy continues to be underdiagnosed, despite its association with renal scarring and thus hypertension, renal failure, and other sequelae. Low ascertainment of urinary tract infections reflects the many difficulties in establishing a diagnosis, some of which could be eliminated by a simple, reliable method for preliminary investigation of children's urine. AIM: To assess the accuracy of a new, simple method for testing urine for nitrite and leucocyte esterase, which could be applied to children in primary care. METHODS: An in vitro study was carried out to compare the results of conventional urine analysis with urine analysis on urine soaked on to panty-liners, and with the laboratory investigation. Two urine analysis stick types were used (Boehringer Mannheim Nephur sticks and Bayer Multistix 8SG) and two brands of panty-liners. Analysis examined evidence of agreement and bias for different methods in addition to sensitivity, specificity, and negative predictive values for urine analysis. RESULTS: Pressing urine analysis test sticks on to panty-liners soaked with urine achieved consistent results compared with the results of conventional dipstick urine analysis. At a prevalence of 21.8%, sensitivity and negative predictive values of urine analysis for laboratory confirmed urinary tract infection were 94% and 98%, respectively, for Boehringer sticks, and 76% and 93%, respectively, for Bayer sticks. At prevalences of 5% and 1% (prevalences that could be expected in primary care) Bayer sticks had negative predictive values of 98.7% and 99.7%, respectively, and Boehringer sticks had values of 99.6% and 99.9%, respectively. CONCLUSIONS: Testing urine on panty-liners is accurate compared with conventional urine analysis. It may be possible to apply this method to testing unwell children presenting in primary care to identify those who require microbiological urine culture to confirm or eliminate a diagnosis of urinary tract infection.

The struggle to diagnose UTI in children under two in primary care.

BACKGROUND: The incidence of urinary tract infection (UTI) in childhood is highest in infancy and accounts for 5% of febrile infants. Reflux nephropathy following UTI in early childhood is the commonest preventable cause of chronic renal failure. Recent guidelines aim to improve the diagnosis and management of UTI in small children. OBJECTIVES: To assess management of febrile children and UTI in children under 2 years amongst GPs, and to identify some reasons for the difficulties in diagnosing UTI. METHOD: Questionnaire distributed by periodical journal. RESULTS: Eighty-two GPs responded, of whom 61 (74%) were unaware of the recent Royal College of Physicians guidelines on childhood UTI. Seventy-seven GPs (94%) would find guidelines helpful on when to send a urine sample for culture from a child under 2 years. Only 11 GPs (14%) regularly sent urine from febrile infants and toddlers; 48 GPs (63%) sent urine from only 0-10% of patients; 21 (26%) were unable to collect urine at all from these children. Several difficulties were identified by GPs regarding investigation for UTI in children. These related to practical difficulties in urine collection and culturing, lack of professional awareness of the importance of UTI and concerns about the costs of investigation. CONCLUSION: GPs frequently do not investigate for UTI in febrile children due to practical difficulties, lack of awareness and financial costs. National guidelines need to be disseminated and implemented effectively to reach target groups. Further scope for research into a simple, cheap method to collect and test urine has been highlighted as a priority to improve early diagnosis of UTI. Management of UTI in primary care can be improved with carefully evaluated strategies and this could lead to a reduction in the prevalence of renal scarring.

P1 blood group phenotype, secretor status in patients with urinary tract infections.

We have examined the distribution of P antigen, Lewis blood group phenotypes and secretor status of 65 patients with E. coli UTI (20 asymptomatic bacteriuria, 20 cystitis and normal radiology, 25 reflux nephropathy) and 45 controls who have never experienced a UTI episode. The distribution of Lewis blood group antigens was similar in all UTI groups and in the controls. The incidence of non-secretors in the reflux nephropathy group was similar to that in controls (24% versus 31%). The P1 phenotype was present in 100% of patients with asymptomatic bacteriuria, 80% with cystitis and controls and only 44% with reflux nephropathy. The combined P1/non-secretor phenotype was observed in 45% of patients with asymptomatic bacteriuria, 30% with cystitis, 12% with reflux nephropathy and in 22% of control healthy individuals. P2/secretor phenotype was demonstrated in 44% of patients with reflux nephropathy and in only 11% of controls. Our data suggest that having P2 blood group protects against asymptomatic colonization of the urinary tract, but is associated with the type of infection responsible for scarring in reflux nephropathy. It also appears that being a non-secretor does not predispose to renal scarring and that combined P2/secretor phenotype may be linked with susceptibility to reflux nephropathy.

Radiological assessment of constipation.

A scoring system for faecal loading was constructed by two experienced observers using the abdominal radiographs of 20 children. Four other observers independently graded the radiographs using this system and there was a high degree of agreement between all six observers (p < 0.001), suggesting that radiological assessment of constipation can be standardised.

Radiological evidence of constipation in urinary tract infection.

Little objective evidence has been published to support the claim that constipation is an important contributory factor in recurrent urinary tract infection (UTI) in childhood. Using a radiological scoring system, two observers assessed faecal loading from abdominal radiographs of children with proved UTIs. There was a significant increase in the degree of faecal loading in children with UTI when compared with controls (r = 0.237). This difference was mainly accounted for by girls with recurrent (greater than five) UTIs. This study confirms an association between recurrent UTI and faecal loading. Further studies are needed to establish if there is a causal relationship and benefits from treatment.

Absorption of a new oral formulation of cyclosporin A in a child on parenteral nutrition.

A 2-year-old child underwent renal transplantation in the presence of a post-viral enteropathy rendering him dependent on total parenteral nutrition. As part of his immunosuppression, he was given a new oral formulation of cyclosporin A (Neoral), which he was able to absorb satisfactorily, using conventional doses, during the 6 weeks he was dependent on intravenous nutrition and in the face of intermittent severe diarrhoea. An unusual pharmacokinetic profile was observed.

Outcome of pregnancy in an Oxford-Cardiff cohort of women with previous bacteriuria.

To investigate the influence of asymptomatic bacteriuria in childhood on subsequent pregnancy, we reviewed the outcome of 139 pregnancies in 88 women who were first identified during a programme of screening schoolgirls for asymptomatic bacteriuria carried out between 1970-1972. Data were analysed for the following groups: 50 pregnancies in 28 women with known renal scars (group 1); 16 pregnancies in 14 women with normal kidneys and reflux (group 2); 73 pregnancies in 46 women with normal urinary tracts (group 3); 139 healthy controls. Women in group 1 had a 3.3-fold increased relative risk of hypertension (p < 0.01) and a 7.6-fold increased risk of pre-eclampsia (p < 0.05) compared to controls, and a higher rate of obstetric interventions, including emergency caesarean section. Women in groups 2 and 3 appeared to carry a slightly increased risk of hypertension during the last trimester (RR = 1.8) but there were no significant differences in this or the incidence of pre-eclampsia or mode of delivery. Bacteriuria was more prevalent in all index groups compared to controls (37 per cent vs. 8 per cent, p < 0.01) and included four cases of acute pyelonephritis in in the study group. Fetal outcome was satisfactory in all cases. These results suggest that women with renal scars are at risk of hypertension and pre-eclampsia during pregnancy but that modern obstetric care minimizes these risks.

Covert bacteriuria: long term follow up.

In a longitudinal prospective study 58 schoolgirls with covert bacteriuria were followed up for an average of 11.2 years (range 8.8 to 13.5 years). Intravenous urography was carried out at the start of the study (aged 4 to 11 years) and after completion of the follow up period (aged 14.8 to 22.3 years). After random allocation 27 of these girls received intermittent treatment for covert bacteriuria for the first four years and the control group received no treatment. The effect of covert bacteriuria, treatment, vesicoureteric reflux, and reflux nephropathy at presentation on the final renal length, progression of scarring, and development of new scars was analysed. No new scars were found in girls with bilaterally normal kidneys. In girls with reflux nephropathy, three kidneys showed progression of existing scars and two kidneys developed new scars. It was shown that final renal length was not influenced by vesicoureteric reflux or treatment, but reduced renal length at final assessment was associated with the presence of kidney scarring at initial assessment.

Urinary tract infection in febrile convulsions.

A retrospective review of the casenotes of 403 children admitted to hospital with febrile convulsions was performed to estimate the frequency of symptomatic urinary tract infection and examine medical practice in making this diagnosis. A total of 228 (56%) children had urine cultured: 150 bag specimens, 76 clean voided samples, and two suprapubic aspirates. There were 13 'probable' and six 'possible' infected urine samples together representing 5% of the whole study population (n = 403), 8% of those having urine cultured (n = 228), and 12% of those providing uncontaminated urine samples (n = 155). Those with first febrile convulsions and those aged under 18 months were more likely to have urine examined. Practices varied significantly between different hospitals. These results suggest that there has indeed been a need for practice guidelines, and that further audit of practice is required to assess their impact.

Vesicoureteric reflux: screening of first degree relatives.

Thirty three healthy infants and children with a family history of reflux nephropathy or vesicoureteric reflux in first degree relatives were screened for upper urinary tract abnormalities (renal scarring or pelvicaliceal dilatation) using ultrasound scanning or intravenous urography, or both. In addition, micturating cystourethrography was carried out in all infants and children under 2 years old (n = 20) and in children over 2 years old in whom abnormalities of the upper renal tract (renal scarring) had been found (n = 3). Upper renal tract abnormalities were found in four of the total of 33 children (12%) and vesicoureteric reflux in 12 of the 23 who underwent micturating cystourethrography (52%). Screening of infants and children was acceptable to parents. This approach has enabled the diagnosis of vesicoureteric reflux to be made in an appreciable number of children before the development of urinary tract infections and reflux nephropathy. Prospective follow up of this group will provide more information about the natural history of sterile vesicoureteric reflux.

Serum Tamm-Horsfall protein levels in childhood: relationship with age and glomerular filtration rate.

Serum Tamm-Horsfall protein (THP) levels were measured in 157 infants and children, 46 cord blood samples and 75 adults using an enzyme-linked immunosorbent assay. THP levels increased significantly across the age groups, suggesting a positive relationship with age. There was a strong positive relationship between serum THP and estimated glomerular filtration rate among children with chronic renal failure.

Effect of symptomless bacteriuria in childhood on subsequent pregnancy.

The outcome of 52 pregnancies in 34 women who had had bacteriuria in childhood was compared with that of normal control pregnancies. The prevalence of bacteriuria at the first antenatal visit was significantly higher (p less than 0.001) in previously bacteriuric women (35%) than in controls (5%), and acute pyelonephritis developed in 10% compared with 4% of controls. Pre-eclampsia (arterial pressure above 140/90 mm Hg with proteinuria above ++) developed in 4 of 12 previously bacteriuric women known to have renal scarring (5 of 16 pregnancies), in only 1 of 22 previously bacteriuric women without scars (1 of 36 pregnancies), and in 1 of 52 controls (p less than 0.001). Women with renal scars were also more likely to undergo induction of labour (44% of pregnancies) and operative delivery (57% of pregnancies) than previously bacteriuric mothers without scars (17%, 22%) or control mothers (16%, 20%). The infants of previously bacteriuric mothers were not significantly smaller than those of healthy control mothers, but Apgar scores were lower among offspring of previously bacteriuric mothers with scarred or normal kidneys (p less than 0.001). Fetal outcome was, however, satisfactory in all cases.

Survival time in cystinosis. A collaborative study.

In a retrospective study the overall survival time of 205 cystinotic patients of six countries was determined. The median survival time was 8.5 years. The median time for 'renal death' (age at death due to uraemia or age at starting renal replacement therapy) was 9.2 years. The youngest patient dying of renal death was 5.2 years. No sex difference in survival time was noticed. Furthermore no difference in survival time was noted between the different countries. The analysis of the overall survival curve indicates no clear differences between the infantile and adolescent types of cystinosis.