Jim Buttery

Intussusception following rotavirus vaccine administration: Post-marketing surveillance in the National Immunization Program in Australia

INTRODUCTION In Australia, post-marketing surveillance for intussusception following vaccination commenced with funding of RotaTeq(®) and Rotarix(®) vaccines under the National Immunization Program (NIP) in July 2007. METHODS Two active surveillance mechanisms (hospital-based case ascertainment and monthly reports from paediatricians) identified intussusception cases between 1st July 2007 and 31st December 2008 in four states. Linkage to vaccination records identified cases occurring within 1-7 and 1-21 days of rotavirus vaccination. Expected cases within the post-vaccination windows were calculated by applying rates of intussusception from national hospitalisation data over 6 years (mid-2000 to mid-2006), by age and state, to numbers vaccinated (by dose) according to the Australian Childhood Immunization Register. RESULTS Combining exposure windows associated with all doses of rotavirus vaccine from 1 to 9 months of age, there was no evidence of an increased risk of intussusception following vaccination for either vaccine. However, in infants 1 to <3 months of age, there was suggestive evidence of excess intussusception cases 1-7 and 1-21 days following dose 1 (1-7 days: RotaTeq(®) relative risk (RR)=5.3, 95% confidence interval [CI] 1.1,15.4; Rotarix(®) RR 3.5, 95% CI 0.7,10.1; 1-21 days: RotaTeq(®) RR 3.5, 95% CI 1.3, 7.6; Rotarix(®)RR 1.5, 95% CI 0.4, 3.9). There was no evidence that clinical outcome of intussusception occurring within 21 days of rotavirus vaccination differed from that in cases occurring later post-vaccination. CONCLUSION Although we found no overall increase in intussusception following receipt of rotavirus vaccine, there was some evidence of an elevated risk following the first dose of both vaccines. Larger population-based studies using linked databases are required to provide more definitive evidence.

How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children's hospital.

OBJECTIVES. The primary aims of this study were to determine the volume of blood submitted for culture in routine clinical practice and to establish the proportion of blood cultures with a blood volume inadequate for reliable detection of bacteremia. METHODS. The volumes of blood samples submitted for culture from infants and children up to 18 years of age were measured over a 6-month period. Blood cultures were deemed adequate submissions if they contained an appropriate (age-related) volume of blood and were submitted in the correct blood culture bottle type. During the study, an educational intervention designed to increase the proportion of adequate blood culture submissions was undertaken. RESULTS. The volume of blood submitted in 1358 blood culture bottles from 783 patients was analyzed. Of the 1067 preintervention blood cultures, 491 (46.0%) contained an adequate blood volume and only 378 (35.4%) were adequate submissions on the basis of collection into the correct blood culture bottle type. After the intervention, there were significant increases in both the proportion of blood cultures containing an adequate blood volume (186 [63.9%] of 291 cultures) and the proportion of adequate submissions (149 [51.2%] of 291 cultures). Overall, blood cultures with an adequate blood volume were more likely than those with an inadequate blood volume to yield positive blood culture results (34 [5.2%] of 655 cultures vs 14 [2.1%] of 648 cultures). Similarly, adequate blood culture submissions were more likely than inadequate submissions to yield positive blood culture results (26 [5.1%] of 506 cultures vs 22 [2.8%] of 797 cultures). CONCLUSIONS. In routine clinical practice, a negative blood culture result is almost inevitable for a large proportion of blood cultures because of the submission of an inadequate volume of blood. Even after an educational intervention, nearly one half of blood cultures were inadequate submissions.

Performance of a whole blood interferon gamma assay for detecting latent infection with Mycobacterium tuberculosis in children

Background: The diagnosis of latent Mycobacteriumtuberculosis (MTB) infection with a tuberculin skin test (TST) in children is complicated by the potential influence of prior exposure to Bacille Calmette Geurin (BCG) vaccination or environmental mycobacteria. A whole blood assay has recently been developed to quantitatively measure interferon gamma (IFN-γ) production by lymphocytes specific to the MTB antigens ESAT-6 and CFP-10, but its use and assessment in children has been limited. A study was undertaken to compare the performance of the whole blood IFN-γ assay with the TST in diagnosing latent tuberculosis (TB) infection or TB disease in children in routine clinical practice. Methods: One hundred and six children with a high risk of latent TB infection or TB disease were enrolled in the study. High risk was defined as contact with TB disease, clinical suspicion of TB disease, or recent arrival from an area of high TB prevalence. The whole blood IFN-γ assay was undertaken in 101 children. Results: Seventeen (17%) of the 101 assays yielded inconclusive results due to failure of positive or negative control assays. There was poor correlation between the whole blood IFN-γ assay and the TST (kappa statistic 0.3) with 26 (70%) of the 37 children defined as latent TB infection by TST having a negative whole blood IFN-γ assay. There were no instances of a positive whole blood IFN-γ assay with a negative TST. Mitogen (positive) control IFN-γ responses were significantly correlated with age (Spearman’s coefficient = 0.53, p<0.001) and, in children with latent TB infection identified by TST, those with a positive IFN-γ assay were older (median 12.9 v 6.92 years, respectively, p = 0.007). The whole blood IFN-γ assay was positive in all nine children with TB disease. Conclusion: There was poor agreement between the whole blood IFN-γ assay and TST for the diagnosis of latent TB. The whole blood IFN-γ assay may have lower sensitivity than the TST in diagnosing TB infection in children. A significant proportion of whole blood IFN-γ assays fail when used as a screening assay in routine practice.

Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule

Introduction: Rotavirus vaccines were introduced into the funded Australian National Immunization Program (NIP) in July 2007. Due to purchasing arrangements, individual states and territories chose either a 2-dose RV1 (Rotarix, GSK) regimen or 3-dose RV5 (Rotateq, Merck/CSL) regimen. This allowed comparison of both vaccines in similar populations with high infant vaccination coverage. Methods: Admission and rotavirus identification data from the major pediatric hospitals in 3 states (2 using RV5, 1 RV1), together with state-based hospitalization and vaccination data from Queensland (RV5) were analyzed for the years before, and up to 30 months following rotavirus vaccine introduction. Emergency encounters and short-stay unit admissions for gastroenteritis are also described. Results: Rotavirus vaccine coverage in Australia is high, with 87% of infants receiving at least 1 dose. Hospital admissions for both rotavirus gastroenteritis and nonrotavirus-coded gastroenteritis were reduced following vaccine introduction in all states, not only for the age group eligible for NIP rotavirus vaccination, but also for children born prior. RV5 vaccine efficacy in Queensland has been estimated at 89.3%. Marked reductions in acute gastroenteritis emergency presentations and short-stay unit admissions have also been observed. Conclusions: Early evidence from the NIP in Australia has demonstrated high rotavirus coverage with both RV1 and RV5. The introduction of both vaccines has been associated with a marked reduction in gastroenteritis admissions, supportive of both direct vaccine protection, as well as with indirect herd protection.

A three-way comparison of tuberculin skin testing, QuantiFERON-TB gold and T-SPOT.TB in children.

Background There are limited data comparing the performance of the two commercially available interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease. Methods and Findings The results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, κ = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, κ = 0.50) or T-SPOT.TB (75%, κ = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-γ responses was significantly influenced by TB contact history, but only the TST was influenced by age. Conclusions Although a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.

Intussusception Risk and Disease Prevention Associated With Rotavirus Vaccines in Australia's National Immunization Program

BACKGROUND Estimates of the risk of intussusception (IS) associated with currently licensed rotavirus vaccines (RV1 [Rotarix; GSK] and RV5 [RotaTeq; Merck]) diverge. Contemporaneous introduction of both vaccines in Australia enabled a population-based assessment of risk. METHODS Confirmed cases of IS in infants aged 1 to <12 months were identified from national hospitalization databases, supplemented by active hospital-based surveillance, from July 2007 through June 2010. Vaccination histories were verified by the Australian Childhood Immunisation Register, which was also used to identify age-matched controls. Self-controlled case series and case-control methods were used to assess the risk of IS associated with both vaccines in prespecified periods after vaccination. The estimated burden of vaccine-attributable IS was compared with estimated reductions in gastroenteritis hospitalizations. RESULTS Based on 306 confirmed cases of IS, the relative incidence of IS in the 1-7-day period after the first vaccine dose, was 6.8 (95% confidence interval, 2.4-19.0; P < .001) for RV1, and 9.9 (95% confidence interval, 3.7-26.4; P < .001) for RV5. There was a smaller increased risk 1-7 days after the second dose of each vaccine. The case-control analysis gave similar results. We estimate an excess of 14 IS cases and >6500 fewer gastroenteritis hospitalizations in young children annually in Australia after vaccine introduction. CONCLUSIONS We found a similarly increased risk of IS after both vaccines, but the balance of benefits and risks at population level was highly favorable, a finding likely to extend to other settings despite varying incidence of IS and potentially higher morbidity and mortality from both gastroenteritis and IS.

Blood cultures in newborns and children: optimising an everyday test

Effective use of blood cultures is a key component of the management of septic newborns and children. The technical and practical aspects of paediatric practice and the heightened susceptibility of children to infection because of immunological immaturity make automatic extrapolation of adult data difficult and potentially unfounded.

Multiresistant Pseudomonas aeruginosa outbreak in a pediatric oncology ward related to bath toys.

BACKGROUND Nosocomial outbreaks of Pseudomonas aeruginosa in pediatric hospitals frequently involve neonates and immunosuppressed patients and can cause significant morbidity and mortality. OBJECTIVE To describe the investigation of a multidrug-resistant P. aeruginosa outbreak in a pediatric oncology ward at the Royal Childrens Hospital, Melbourne, Australia. DESIGN AND METHODS Specimens were collected from infected patients and the ward environment. Bacterial isolates were characterized by antibiotic susceptibility patterns and bacterial DNA fingerprinting performed by pulsed-field gel electrophoresis (PFGE). A case-control study was carried out to assess possible risk factors for infection. RESULTS Eight patients had clinical illnesses including bacteremia (n = 5) and infections of skin (n = 2), central venous catheter site (n = 1) and urinary tract (n = 1). The environmental ward survey yielded isolates of multiresistant P. aeruginosa from a toy box containing water-retaining bath toys, as well as from three of these toys. Pulsed-field gel electrophoresis of bacterial DNA demonstrated identical band patterns of the isolates from patients, toys and toy box water. A case-control study involving the 8 cases and 24 disease-matched controls demonstrated a significant association between P. aeruginosa infection and use of bath toys (P = 0.004), use of bubble bath (P = 0.014), duration of stay (P = 0.007) and previous antibiotic exposure (P = 0.026). Cultures from the bubble bath liquid were negative. CONCLUSION This is the first description of a nosocomial outbreak associated with toys. We caution against the use of water-retaining bath toys in wards treating immunocompromised children.

Comprehensive health assessment for newly arrived refugee children in Australia

Abstract:  Providing appropriate and responsive care to refugees from diverse backgrounds and with unique health needs is challenging. Refugee children may present with a wide range of conditions, which may be unfamiliar to health professionals in developed countries. Additionally, refugees may experience unfamiliarity with the Australian health system and distrust of authority figures and/or medical practitioners. This article provides an overview of the priority areas in health and health management for paediatric refugee patients for paediatricians as well as other relevant health care providers caring for this group. Specific issues covered include general health assessment, infectious diseases, immunization, growth and nutrition, oral health, development and disability, mental health and child protection. Comprehensive health assessment can assist in identifying children at risk of poor health and to provide them with timely and effective care, advocacy and appropriate referral.

An outbreak of necrotizing enterocolitis associated with norovirus genotype GII.3.

Background: Necrotizing enterocolitis (NEC) is an acute abdominal emergency of unknown etiology predominantly affecting preterm infants. We describe a cluster of NEC in a level III NICU involving 15 infants over a 6-month period. Cohorting and stringent infection control measures were associated with termination of the cluster. A case-control study was used to investigate potential risk factors associated with development of NEC. Methods: Stool samples were collected from 55 infants (10 of 15 NEC and 45 non-NEC controls). Enteric pathogens were identified by culture and/or molecular diagnostic techniques. For the case-control study, controls were selected from admitted neonates during the same time and in the preceding 6-month period, matched for gestation and birthweight. Results: Forty percent (4/10) of NEC infants had norovirus RNA detected compared with 9% (4/45) of non-NEC infants (OR: 6.83, 95% CI: 1.3–34.9, P = 0.021). A lower rate of prolonged rupture of membranes and a higher rate of maternal smoking was also observed in NEC infants than in controls. No significant differences in incidences of chorioamnionitis, intrapartum antibiotics, volume of feedings, time of first formula feeding, and rates of patent ductus arteriosus or intrauterine growth retardation were detected. Conclusions: Infants who developed NEC had an increased incidence of norovirus detection in their stool following diagnosis. This further strengthens the case for an etiologic role of norovirus in the pathogenesis of NEC.