Increase in invasive nonvaccine pneumococcal serotypes at two hospitals in Barcelona: was replacement disease to blame?

AIM: To describe an increase in the incidence of invasive pneumococcal disease (IPD) caused by serotypes not contained in the heptavalent pneumococcal conjugate vaccine (PCV7) in children in two hospitals in Barcelona with different vaccine uptake. METHODS: Cumulative incidences of IPD, vaccine and nonvaccine serotypes (NVSTs), and main clinical presentations before (1998-2001) and after vaccine introduction (2005-2008) were compared. RESULTS: The incidence of IPD in children aged <2 years at Hospital Germans Trias i Pujol covering a population in which PCV7 was not widely used showed a nonsignificant increase from 29.9 to 58.8 per 100,000 child-years between both periods. Following vaccine introduction, there was a 2.5-fold increase in IPD caused by NVSTs in children aged <5 years. Analysis of trends in the almost fully vaccinated population of Hospital de Barcelona revealed a nonsignificant reduction in IPD incidence in children aged <2 years from 63.1 to 26.0 per 100,000 child-years. NVSTs in children aged <5 years showed a nonsignificant 1.7-fold increase in the vaccine period at this centre. CONCLUSIONS: The paradoxical increase in invasive infections caused by NVSTs in these populations with different vaccine use suggests that these changes were not driven only by PCV7.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Impact of neonatal morbidity on the risk of developmental delay in late preterm infants.

BACKGROUND: Late preterm infants (LPI) have a higher risk of developmental delay (DD) than term-born infants. The association of perinatal complications with specific morbidity is not clear. AIM: (1) To compare the risk of DD at 4years of age between LPI who have presence or absence of any morbidity associated with the prematurity at birth, called complicated (cLPI) or uncomplicated (uLPI), and term-born infants, (2) to determine maternal and perinatal factors associated with risk of DD, and (3) to analyze, in LPI, the association between perinatal morbidity and risk of DD. METHODS: A retrospective cohort study including 163 LPI - 47 cLPI and 116 uLPI - and 158 term-born infants (Terms) was conducted. Parents completed the Ages & Stages Questionnaires®3rd Spanish version (ASQ3). Risk of DD was defined as the presence of any ASQ3 domain scoring below the mean minus 2 SD. Association between risk of DD and maternal and perinatal factors was analysed using a multivariate logistic model. Incidence of risk of DD was analysed according to specific morbidity. RESULTS: Compared to Terms, cLPI have a higher risk of DD in the communication domain. Respiratory pathology was associated with a higher risk in the communication domain. Caesarean delivery was the only maternal perinatal risk factor for DD, especially in gross motor domain. CONCLUSIONS: At the age of 4years cLPI, especially those with respiratory morbidity, had a higher risk of communication delay. Caesarean delivery was the only perinatal risk factor associated with risk of DD.

Enhanced culture detection of Kingella kingae, a pathogen of increasing clinical importance in pediatrics.

Osteoarticular infection and occult bacteremia are the 2 invasive infectious pathologies most frequently associated in childhood with Kingella kingae. We report a series of 11 patients in whom osteomyelitis predominates over septic arthritis, which is the reverse of other series, probably as a consequence of inoculation of samples during surgery on agar media, used in combination with or as an alternative to inoculation into blood culture bottles. Although K. kingae infections usually follow a benign clinical course, we noted 2 patients with mild orthopedic sequelae.

Outbreaks of influenza A virus infection in neonatal intensive care units.

BACKGROUND: Outbreaks of nosocomial influenza virus infections have been described rarely during childhood and even less so in the neonatal period. METHODS: We report 30 neonates admitted to 2 neonatal intensive care units with nosocomial influenza A virus infection, which occurred in 2 outbreaks during 1999. Risk factors for infection were evaluated, and control measures were adopted. Virus was detected by indirect immunofluorescence antibody screen. Any infant with nasopharyngeal aspirate positive for influenza A virus was considered infected. RESULTS: Of 95 infants screened 30 were positive for influenza A virus (31.5%). Mean birth weight was 1622 g, and mean gestational age was 31 weeks in the infected group. In the noninfected group mean birth weight was 2594 g and mean gestational age was 36.4 weeks. Low birth weight, short gestational age, twin pregnancy and mechanical ventilation were identified as risk factors for infection. Clinical symptoms were seen in 22, and 8 were asymptomatic. Clinical features were predominantly respiratory and digestive. The outcome was favorable in all cases. CONCLUSIONS: Infection by influenza virus has to be considered as a possible cause of nosocomial infection in the neonatal period. Control measures and prevention are important.