Keith Grimwood

Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis

The nature and timing of lower respiratory infections in infants with cystic fibrosis is largely unknown1 because infants do not produce sputum and throat cultures may not predict lower respiratory pathogens.2 We performed a prospective cross sectional study of an unselected cohort of infants with cystic fibrosis in which bronchoalveolar lavage was used to determine lower respiratory infection and inflammation during the first three months of life. The state of Victoria, Australia (66000 births per year) has a cystic fibrosis screening programme, all patients being managed by one centre. Between February 1992 and September 1994 we recruited 45 (27 boys) of the 52 infants with newly diagnosed disease; 32 were identified by screening, 12 from meconium ileus, and one by failure to thrive, and all cases were confirmed by sweat testing. Sixteen infants had respiratory symptoms, and seven of them were receiving oral antibiotics when bronchoalveolar lavage was performed at a mean age of 2.6 (SD 1.6) months. Nine otherwise healthy infants (five boys) aged …

Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis

The objective of this study was to assess the diagnostic accuracy of oropharyngeal (OP) cultures relative to simultaneous bronchoalveolar lavage (BAL) cultures in very young children with CF, and to examine the effects of bacterial density, age, and study cohort on diagnostic accuracy. Respiratory culture data were analyzed from three independent, prospective studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF <5 years of age.

Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis

As collections of lower respiratory tract specimens from young children with cystic fibrosis (CF) are difficult, we determined whether oropharyngeal cultures predicted lower airway pathogens. During 1992–1994, 75 of 90 (83%) infants with CF diagnosed by neonatal screening had 150 simultaneous bronchoalveolar lavage (BAL) and oropharyngeal specimens collected for quantitative bacterial culture at a mean age of 17 months (range, 1–52). Ten children undergoing bronchoscopy for stridor served as controls. Total and differential cell counts and interleukin‐8 concentrations were measured in BAL fluid. A subset of bacterial pathogens were typed by pulsed field gel electrophoresis. A non‐linear relationship with inflammatory markers supported a diagnosis of lower airway infection when ≥105 colony‐forming units/ml were detected. This criterion was met in 47 (31%) BAL cultures from 37 (49%) children. Staphylococcus aureus (19%), Pseudomonas aeruginosa (11%), and Hemophilus influenzae (8%) were the major lower airway pathogens. In oropharyngeal cultures, S. aureus (47%), Escherichia coli (23%), H. influenzae (15%), and P. aeruginosa (13%) predominated. The sensitivity, specificity, and positive and negative predictive values of oropharyngeal cultures for pathogens causing lower respiratory infections were 82%, 83%, 41%, and 97%, respectively. When there was agreement between paired oropharyngeal and BAL cultures, genetic fingerprinting showed some strains of the same organism were unrelated. We conclude that oropharyngeal cultures do not reliably predict the presence of bacterial pathogens in the lower airways of young CF children. Pediatr Pulmonol. 1996; 21:267–275.

Twelve year outcomes following bacterial meningitis: further evidence for persisting effects

AIM To determine whether intellectual and cognitive impairments observed seven years following early childhood bacterial meningitis persist into adolescence. METHODS Blinded neuropsychological, auditory, and behaviour assessments were conducted in 109 (69%) subjects from an original cohort of 158 children, seven and 12 years after their meningitis, and in 96 controls. RESULTS Meningitis subjects remained at greater risk than controls for any disability (odds ratio OR 4.7, confidence interval 2.2 to 9.6). Those with acute neurological complications had more sequelae than children with uncomplicated meningitis or controls (47% v 30%v 11.5% respectively; p < 0.001). Differences in intellectual, academic, and high level cognitive function between subjects and controls were maintained at the seven and 12 year assessments. In contrast, lower order skills improved, while behaviour scores deteriorated significantly (p = 0.033). CONCLUSIONS Many of the deficits identified at the seven year follow up persist 12 years after an episode of bacterial meningitis. Key messages Bacterial meningitis in children is associated with substantial excess risk of intellectual, cognitive, and auditory impairment that persists into adolescence Continuing developmental problems of higher order language, organisation, problem solving, and central auditory function may increase learning and behavioural difficulties The risk of these adverse outcomes is greatest in, but not confined to, those who experienced acute neurological complications at the time of their illness Families, schoolteachers, and health professionals have an important role in identifying and/or helping those with learning and behavioural difficulties

Number and Order of Whole Cell Pertussis Vaccines in Infancy and Disease Protection

lowing negative studies. Despite studies showing that echinacea does not treat cold symptoms, it is one of the best selling supplements in the United States with estimated sales exceeding

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

300 million per year. Dr Leach claims that I supported my position “through the selective reporting of a few clinical studies.” However, all studies are not equal. The studies I selected regarding gingko, chondroitin sulfate, glucosamine, garlic, St John’s wort, milk thistle, and echinacea were the best controlled, most rigorous, and most internally consistent. Indeed, most of these excellent studies were supported by NCCAM. Briggs and Killen and Leach argue that refraining from studying alternative medicine would deny the public muchneeded clinical data to make informed health care decisions. In a better world, of course, this discussion would not be happening. In a better world, dietary supplements and alternative therapies would be subject to testing before claims were allowed, as is required by the US Food and Drug Administration (FDA) for licensure of drugs, biologicals, and medical devices. Now patients are stuck with a system in which some alternative medicines might be tested after claims have been made and after nutraceutical companies have spent millions of dollars “educating” the public. At best, NCCAM functions as a post-hoc FDA, except without the FDA’s regulatory authority and without the communication skills or dollars to confront a well-heeled nutraceutical industry. Sadly, until the 1994 Dietary Supplement and Health Education Act—which essentially freed the nutraceutical industry from FDA oversight—is repealed, consumers will continue to receive bad information that could lead to bad medical decisions, NCCAM or no NCCAM.

Severe viral respiratory infections in infants with cystic fibrosis

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.

Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: A randomized trial

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991–1996 were recruited into a prospective, multiple‐birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL‐8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls.

Extended excretion of rotavirus after severe diarrhoea in young children

CONTEXT Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking. OBJECTIVE To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures. DESIGN, SETTING, AND PARTICIPANTS The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009. INTERVENTIONS BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results. MAIN OUTCOME MEASURES Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan. RESULTS Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95% confidence interval, -0.94% to 1.33%]; P = .74). CONCLUSION Among infants diagnosed with cystic fibrosis, BAL-directed therapy did not result in a lower prevalence of P. aeruginosa infection or lower total CF-CT score when compared with standard therapy at age 5 years. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000665639.

Early airway infection, inflammation, and lung function in cystic fibrosis

BACKGROUND Rotaviruses are the major cause of severe childhood diarrhoea. Knowledge of the natural history of infection, including duration of intestinal virus shedding, is important in the understanding of transmission, sources of infection, and immune responses. METHODS We carried out a study of rotavirus excretion in 37 children admitted to hospital with severe rotavirus diarrhoea. Sequential faecal specimens were collected from each child during 100 days of surveillance, and screened for rotavirus by EIA and by amplification of genome double-stranded RNA by reverse-transcription PCR. IgA coproantibody was estimated by EIA. FINDINGS Duration of rotavirus excretion ranged from 4 to 57 days after onset of diarrhoea. Excretion ceased within 10 days in 16 (43%) children, and within 20 days in 26 (70%) children. Extended excretion was detected for 25-57 days in the remaining 11 (30%) children owing mainly to continued excretion of the primary infecting strain. Extended excretion was significantly associated with antirotavirus IgA coproantibody boosts during 100 days of surveillance (p=0.001, log-rank test), and with recurrence of mild diarrhoea symptoms during convalescence (p=0.006, Fishers exact test). INTERPRETATION Severe rotavirus disease in young children may be followed by extended excretion of rotavirus. The risk of transmission to others may be greater than previously believed. Extended excretion could also explain some cases of the postgastroenteritis syndrome.