Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar: an observational study.

BACKGROUND: The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. METHODS: Children (n = 677) with non-severe acute febrile illness aged 2-59 months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ("IMCI pneumonia") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia". RESULTS: Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. CONCLUSION: The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia. Trial registration Clinicaltrials.gov (NCT01094431).

Bladder/bowel dysfunction in pre-school children following febrile urinary tract infection in infancy.

BACKGROUND: An association between bladder-bowel dysfunction (BBD) and urinary tract infection (UTI) is well-known. However, a question less explored is whether children with UTI early in life also have increased prevalence of BBD after they are toilet-trained. In this study, consecutively selected children with pyelonephritis during their first year of life were assessed for BBD at pre-school age. METHODS: Ninety-two children (51 boys) hospitalized due to pyelonephritis during their first year of life were assessed for BBD at median age 5.4 years. A validated BBD questionnaire, along with urine flow and residual volume measurements, was used for diagnosing BBD. During follow-up, the group was well-characterized regarding renal status, vesicoureteral reflux (VUR), and recurrent UTI. RESULTS: BBD was diagnosed in 35/92 (38%), of which the majority was sub-diagnosed with dysfunctional voiding (DV). There was a strong association between BBD and recurrent UTI during follow-up (p < 0.0001), but only a slight association with VUR status at presentation. Nevertheless, in the group with both BBD and VUR, recurrent UTI was four times higher (12/13, 92%) than in children who had neither VUR nor BBD (23%), (p = 0.0008). BBD was also associated with kidney damage (p = 0.017). CONCLUSION: In children with pyelonephritis during the first year of life, 38% had BBD at pre-school age, regardless of whether they had VUR or not. The study shows an important association between BBD and recurrent UTI, so an assessment of BBD is therefore recommended for pre-school children with UTI, especially when they have history of pyelonephritis during infancy.

Change of urodynamic patterns in infants with dilating vesicoureteral reflux: 3-year followup.

PURPOSE: Reports concerning bladder dysfunction patterns in infants with high grade vesicoureteral reflux during the first year of life vs older children with reflux are contradictory. To describe the development of bladder function characteristics in children with congenital dilating reflux, we evaluated such infants urodynamically and followed them regularly for a 3-year period. MATERIALS AND METHODS: A total of 89 males and 25 females with grade III to V dilating reflux were evaluated 3 times using videocystometry at mean ages of 6, 20 and 40 months. RESULTS: Characteristics of the urodynamic pattern at 6 months could not be differentiated from normal patterns for that age, including low and normal bladder capacity, high voiding pressure levels, dyscoordination at voiding (80%) and overactivity during filling (60%). However, at 20 months the overall pattern was different, including increased bladder capacity and residual volume, normal voiding pressure, persistent overactivity during filling and dyscoordination at voiding. Bladder dysfunction was seen in 48 children (42%) at 20 months, of whom 34 primarily had high bladder capacity with incomplete emptying (dilated bladder dysfunction) and 14 had overactive bladder. Predictors for development of dilated bladder dysfunction at followup were high residual urine at 6-month examination and recurrent urinary tract infections. Recurrent infections were significantly correlated to high residual urine at all investigations and to detrusor overactivity at the 20-month examination. CONCLUSIONS: Urodynamic patterns changed between the first and second year of life in patients with dilating reflux, from an immature pattern with high pressure levels to high capacity bladder with incomplete voiding. Therefore, bladder dysfunction, which was seen in 42% of patients, was only possible to diagnose after the first year of life and was mainly seen as high capacity bladder with incomplete voiding.

Longitudinal development of renal damage and renal function in infants with high grade vesicoureteral reflux.

PURPOSE: We sought to study renal abnormality and renal function through time in infants with high grade vesicoureteral reflux. MATERIALS AND METHODS: This prospective observational study included 115 infants (80 boys and 35 girls) younger than 1 year with grade III to V vesicoureteral reflux. The diagnosis was made after prenatal ultrasound in 26% of the patients and after urinary tract infection in 71%. Patients were followed by renal scintigraphy, 51chromium edetic acid clearance and video cystometry. Median followup was 62 months. RESULTS: Renal abnormality, which was found in 90% of the children at followup, was generalized in 71% and focal in 29%. The abnormality was bilateral in 28% of the affected patients. Total glomerular filtration rate was less than 80% of expected in 30% of the patients. Single kidney function was less than 40% of expected total glomerular filtration rate in 71% of the patients. Renal status (parenchymal abnormality and function) remained unchanged through time in 84 of 108 available cases (78%), improved in 5 (5%) and deteriorated in 19 (18%). Predictive factors for deterioration were recurrent febrile urinary tract infection, bilateral abnormality and reduced total glomerular filtration rate. Deteriorated renal status was more common in cases diagnosed prenatally than in those detected after urinary tract infection. CONCLUSIONS: Among these infants with high grade vesicoureteral reflux renal abnormality was frequent and was associated with subnormal filtration of one of the kidneys. Decreased total glomerular filtration rate was seen in about a third of the patients. Overall deterioration of renal status was seen in only a fifth of the patients. Infection control seems to be an important factor to minimize the risk.

Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar - Aetiologies, Antibiotic Treatment and Outcome.

BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.

Megarectosigmoid in children with anorectal malformations: long term outcome after surgical or conservative treatment.

PURPOSE: Megarectosigmoid (MRS) is commonly seen in children with anorectal malformations (ARM) and contributes to the high incidence of constipation. Surgical resection has been advocated by some, whereas others propose intense bowel management as the treatment of choice. The aim of this study was to evaluate outcome of both bowel function and configuration after surgical or conservative treatment of MRS in ARM patients. MATERIALS AND METHODS: The study included 79 patients with ARM, excluding perineal fistula, (48 boys, 31 girls) from 1986 to 2007. MRS was diagnosed at colostomy formation or contrast enema performed in the neonatal period. Early in the period, the majority of the patients were treated surgically, whereas in the late 1990 s, a conservative approach with intensified bowel treatment was implemented. Contrast enema and bowel function investigations were performed repeatedly during follow-up. RESULTS: MRS, according to radiological criteria, was diagnosed in 26/79 (33%) of the ARM children. Bowel functional outcome was similar regardless of surgical or conservative treatment and comparable to function in ARM children with non-MRS. The radiological signs of rectal dilatation and elongation disappeared after surgical intervention, but normalisation of the rectosigmoidal configuration was also seen with age in the conservative group. CONCLUSIONS: Bowel functional outcome in ARM children with MRS was similar after either surgical or conservative treatment during follow-up. The radiological signs of rectal dilatation and elongation disappeared also in the conservatively treated patients over time.

Is the mode of occurrence of vesicoureteral reflux correlated to bladder function and spontaneous resolution?

PURPOSE: To investigate whether mode of occurrence of vesicoureteral reflux (VUR), during micturition (M), during filling without increase in pressure (passive, P) or in response to an overactive contraction (OA), can be explained by differences in bladder function. Also, to study if the mode of occurrence of VUR can predict spontaneous resolution. MATERIALS AND METHODS: There were 93 infants (68 boys and 25 girls) with VUR (grade III-V) included. Videocystometry was performed at median ages 5, 22 and 32 months registering grade and mode of reflux and bladder function characteristics. RESULTS: Mode of occurrence of reflux changed with age. During infancy P, OA and M reflux comprised almost equal parts. At follow up, P reflux had increased and both OA and M reflux had decreased. This was partly due to a significantly higher probability of spontaneous resolution for M than P reflux, at 40 months (42 vs 18%). P and M reflux were significantly correlated to bladder function characteristics. P reflux was seen in children with high bladder capacity and occurred early in filling. Other predictors were higher age within the respective group and female sex. M reflux was correlated to lack of residual urine, low bladder capacity and absence of overactivity. Other indicators were male sex and low-grade reflux. CONCLUSIONS: P and M reflux correlate to different bladder patterns: P with high bladder capacity and M with low bladder capacity and without signs of bladder dysfunction. M seems to be benign with a higher resolution rate.

Spontaneous resolution of high grade infantile vesicoureteral reflux.

PURPOSE: We studied the spontaneous resolution rate in a group of infants with high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS: This prospective study comprised 115 infants (80 boys and 35 girls) with high grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The majority of patients (71%) were diagnosed after UTI during infancy and only 26% were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were followed according to a program of repeat video cystometry and noninvasive 4-hour voiding observations. Median followup was 39 months. RESULTS: The overall spontaneous resolution rate to grade II or less for all grades was 39% with no difference between boys and girls. However, when comparing the more severe grades IV and V, we found a significantly higher resolution rate in boys during the infant year. No difference in VUR disappearance could be detected when comparing the groups according to presentation, prenatal ultrasound or pyelonephritis. Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and they significantly correlated with VUR nonresolution. Bladder dysfunction was found in 37% of patients and it also significantly correlated with nonresolution. CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V) congenital VUR was high in boys during the infant year (29%), whereas in girls and boys after the infant year the resolution rate was 9% yearly during followup. Negative prognostic factors for resolution were recurrent UTIs and bladder dysfunction.