Literature Alerts
This section informs healthcare professionals of the latest medical information via daily news articles on respiratory disorders and other related areas.
Recent Headlines
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J Asthma. 2010 Jun; 47(5): 551-6
Deis JN, Spiro DM, Jenkins CA, Buckles TL, Arnold DHOBJECTIVES: Parents of children who visit the pediatric emergency department (PED) for asthma exacerbations may have inadequate knowledge of preventive asthma care. The primary objective of this study was to assess knowledge and use of preventive asthma care measures among parents of children with asthma who present to the PED with asthma exacerbations. The secondary objective was to identify variables that predict adherence to four key preventive care measures. METHODS: The authors administered a 38-item questionnaire to 229 parents of children ages 2 to 18 years with asthma exacerbations who presented to two urban PEDs, one in the southeast and one in the northwest United States. Descriptive statistics were calculated to assess parental knowledge of preventive care. Multivariable logistic regression was used to identify variables associated with the use of four key preventive care measures. RESULTS: Thirty-two percent of the children had an action plan, and 52% received the influenza vaccine within the preceding year. Sixty-six percent of the children had persistent asthma by National Institutes of Health (NIH) criteria. Of these, 51% received daily inhaled corticosteroids (ICSs). When parents were asked how an ICS medicine worked, 29% (64/221) responded "immediately opens the airway," and 24% (53/221) responded "I do not know." Daily use of ICS in these children was significantly associated with parent education level beyond high school (odds ratio [OR] = 2.81; 95% confidence interval [CI]: 1.26, 6.24; p = .011). Non-African Americans were more likely to have received an action plan than African Americans (OR = 2.18; 95% CI: 1.17, 4.06; p = .014). A secondary analysis of the parent's perception of his/her ability to provide care during an asthma exacerbation was significantly associated with receipt of an action plan in a multivariable proportional odds model (OR = 3.63; 95% CI: 1.99, 6.62; p <.001). CONCLUSIONS: Parents of children with persistent asthma presenting to urban tertiary care PEDs with asthma exacerbations frequently have inadequate understanding of appropriate ICS use. Parents with less than a high school education, in particular, may benefit from focused educational interventions that address the importance of daily ICS use in asthma control. Parents who receive a written action plan are more confident in their ability to provide care for their child during an asthma exacerbation.
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BMJ. 2010; 340: c2649
Waddington CS, Walker WT, Oeser C, Reiner A, John T, Wilkins S, Casey M, Eccleston PE, Allen RJ, Okike I, Ladhani S, Sheasby E, Hoschler K, Andrews N, Waight P, Collinson AC, Heath PT, Finn A, Faust SN, Snape MD, Miller E, Pollard AJOBJECTIVES: To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom. DESIGN: Open label, randomised, parallel group, phase II study. SETTING: Five UK centres (Oxford, Southampton, Bristol, Exeter, and London). PARTICIPANTS: Children aged 6 months to less than 13 years for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures were eligible. Those with laboratory confirmed pandemic H1N1 influenza or clinically diagnosed disease meriting antiviral treatment, allergy to egg or any other vaccine components, or coagulation defects, or who were severely immunocompromised or had recently received blood products were excluded. Children were grouped by age: 6 months-<3 years (younger group) and 3-<13 years (older group). Recruitment was by media advertising and direct mailing. Recruitment visits were attended by 949 participants, of whom 943 were enrolled and 937 included in the per protocol analysis. INTERVENTIONS: Participants were randomised 1:1 to receive AS03(B) (tocopherol based oil in water emulsion) adjuvanted split virion vaccine derived from egg culture or non-adjuvanted whole virion vaccine derived from cell culture. Both were given as two doses 21 days apart. Reactogenicity data were collected for one week after immunisation by diary card. Serum samples were collected at baseline and after the second dose. MAIN OUTCOME MEASURES: Primary reactogenicity end points were frequency and severity of fever, tenderness, swelling, and erythema after vaccination. Immunogenicity was measured by microneutralisation and haemagglutination inhibition assays. The primary immunogenicity objective was a comparison between vaccines of the percentage of participants showing seroconversion by the microneutralisation assay (fourfold rise to a titre of >or=1:40 from before vaccination to three weeks after the second dose). RESULTS: Seroconversion rates were higher after the adjuvanted split virion vaccine than after the whole virion vaccine, most notably in the youngest children (163 of 166 participants with paired serum samples (98.2%, 95% confidence interval 94.8% to 99.6%) v 157 of 196 (80.1%, 73.8% to 85.5%), P<0.001) in children under 3 years and 226 of 228 (99.1%, 96.9% to 99.9%) v 95.9%, 92.4% to 98.1%, P=0.03) in those over 3 years). The adjuvanted split virion vaccine was more reactogenic than the whole virion vaccine, with more frequent systemic reactions and severe local reactions in children aged over 5 years after dose one (13 (7.2%, 3.9% to 12%) v 2 (1.1%, 0.1% to 3.9%), P<0.001) and dose two (15 (8.5%, 4.8% to 13.7%) v 2 (1.1%, 0.1% to 4.1%), P<0.002) and after dose two in those under 5 years (15 (5.9%, 3.3% to 9.6%) v 0 (0.0%, 0% to 1.4%), P<0.001). Dose two of the adjuvanted split virion vaccine was more reactogenic than dose one, especially for fever >or=38 masculineC in those aged under 5 (24 (8.9%, 5.8% to 12.9%) v 57 (22.4%, 17.5% to 28.1%), P<0.001). CONCLUSIONS: In this first direct comparison of an AS03(B) adjuvanted split virion versus whole virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine, while more reactogenic, was more immunogenic and, importantly, achieved high seroconversion rates in children aged less than 3 years. This indicates the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION: Clinical trials.gov NCT00980850; ISRCTN89141709.
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Cochrane Database Syst Rev. 2010; 5: CD000181
Ventre K, Randolph ABACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in infants and is responsible for many hospitalizations annually. Ribavirin is approved for treatment of these infections, but its use is controversial because of questions about its efficacy, concerns about occupational exposure, and its high cost. OBJECTIVES: The objective of this review is to assess the efficacy of aerosolized ribavirin for infants and children with lower respiratory tract infection due to RSV. SEARCH STRATEGY: We performed an updated electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database (EED) (The Cochrane Library 2006, issue 3) which contains the Acute Respiratory Infections Group's specialized register; MEDLINE (Ovid) (2004 to September Week 3 2006); and EMBASE (WebSpirs) (2004 to June 2006). SELECTION CRITERIA: Randomized trials comparing ribavirin with placebo in infants and children with lower respiratory tract infection attributable to RSV. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. Unpublished data were requested from trial authors when necessary. MAIN RESULTS: Twelve trials were included. All trials enrolled infants below the age of six months. In four trials with 158 participants, mortality with ribavirin was 5.8% compared with 9.7% with placebo (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.18 to 1.85). In three trials with 116 participants the probability of respiratory deterioration with ribavirin was 7.1% compared with 18.3% with placebo (OR 0.37; 95% CI 0.12 to 1.18). In three studies with 104 ventilated participants, the mean difference in days of hospitalization was 1.9 fewer days with ribavirin (95% CI -4.6 to +0.9) and the mean difference in days of ventilation was 1.8 fewer days with ribavirin (95% CI -3.4 to -0.2). No statistically significant differences in long-term pulmonary function or in incidence of recurrent wheezing following RSV infection were associated with the use of ribavirin. AUTHORS' CONCLUSIONS: Trials of ribavirin for RSV lack sufficient power to provide reliable estimates of the effects. The cumulative results of three small trials show that ribavirin may reduce the duration of mechanical ventilation and may reduce days of hospitalization. In addition, use of ribavirin may be associated with a decrease in the long-term incidence of recurrent wheezing following RSV disease. A large randomized controlled trial of ribavirin for ventilated and other high-risk participants is indicated.
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J Sch Health. 2010 Apr; 80(4): 167-75
Cawley J, Hull HF, Rousculp MDBACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccinations for all children 6 months to 18 years of age, which includes school-aged children. Influenza immunization programs may benefit schools by reducing absenteeism. METHODS: A systematic literature review of PubMed, PsychLit, and Dissertation Abstracts available as of January 7, 2008, was conducted for school-located vaccinations, using search words "School Health Services" and "Immunization Programs"; limited to "Child" (6-12 years) and "Adolescent" (13-18 years) for PubMed and "mass or universal" and (immuniz(*) or immunis(*) or vaccin(*)) and (school or Child or Adolescen(*)) for PsychLit and Dissertation Abstracts. Fifty-nine studies met the criteria for review. RESULTS: Strategies such as incentives, education, the design of the consent form, and follow-up can increase parental consent and number of returned forms. Minimizing out-of-pocket cost, offering both the intramuscular (shot) and intranasal (nasal spray) vaccination, and using reminders can increase vaccination coverage among those whose parents consented. Finally, organization, communication, and planning can minimize the logistical challenges. CONCLUSIONS: Schools-based vaccination programs are a promising option for achieving the expanded ACIP recommendation; school-located vaccination programs are feasible and effective. Adhering to lessons from the peer-reviewed scientific literature may help public health officials and schools implement the expanded recommendation to provide the greatest benefit for the lowest cost. Given the potential benefits of the expanded recommendation, both directly to the vaccinated children and indirectly to the community, prospective, well-controlled trials to establish the cost-effectiveness of specific vaccination strategies should be high priorities for future research.
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Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age.
Influenza Other Respi Viruses. 2010 May 1; 4(3): 141-5
Belshe RB, Toback SL, Yi T, Ambrose CSBACKGROUND: It has been suggested that live attenuated influenza vaccine (LAIV) may be less effective in older individuals because of prior wild-type influenza infections. LAIV is currently approved in the United States, South Korea and Hong Kong for individuals 2-49 years of age. OBJECTIVE: To examine data from previously published pediatric studies to determine the efficacy of LAIV in various age groups. METHODS: Four studies in which the subject age range exceeded 36 months were identified: one 2-year study comparing LAIV with placebo and three 1-year studies comparing LAIV with trivalent inactivated influenza vaccine (TIV). Efficacy against any strain regardless of antigenic similarity to vaccine was analyzed by age; age groups were based on the study design and sample size. A logistic regression model was used to assess whether age, as a continuous variable, was an effect modifier on LAIV efficacy. RESULTS: The efficacy of LAIV did not vary with age in children aged 15-84 months compared with placebo or in children aged 6 months to 17 years compared with TIV. CONCLUSIONS: The available data from prospective, randomized studies in children does not support the concept that prior repeated exposure to influenza, either through wild-type infection or vaccination with live, attenuated or inactivated vaccines, reduces the efficacy of LAIV compared with placebo or TIV. The decreased immunologic responses to LAIV reported in older individuals or those with pre-existing immunity do not appear to translate into reduced protection from influenza in children.
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Lancet. 2010 May 1; 375(9725): 1545-55
Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Simões EA, Rudan I, Weber MW, Campbell HBACKGROUND: The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. METHODS: We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. FINDINGS: In 2005, an estimated 33.8 (95% CI 19.3-46.2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3.4 (2.8-4.3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000-199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. INTERPRETATION: Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. FUNDING: WHO; Bill & Melinda Gates Foundation.
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Heliox inhalation therapy for bronchiolitis in infants.
Cochrane Database Syst Rev. 2010; 4: CD006915
Liet JM, Ducruet T, Gupta V, Cambonie GBACKGROUND: Acute viral bronchiolitis is associated with airway obstruction and turbulent gas flow. Heliox, a mixture of oxygen and the inert gas helium, may improve gas flow through high-resistance airways and decrease the work of breathing. OBJECTIVES: To assess heliox in addition to standard medical care for acute bronchiolitis in infants. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2), which includes the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1966 to June 2009), EMBASE (June 2009), LILACS (May 2009) and the NIH web site (May 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of heliox in infants with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We pooled data from individual trials. MAIN RESULTS: We included four trials involving 84 infants under two years of age with respiratory distress secondary to bronchiolitis caused by respiratory syncytial virus (RSV) and requiring paediatric intensive care unit (PICU) hospitalisation. We found that infants treated with heliox inhalation had a significantly lower mean clinical respiratory score in the first hour after starting treatment when compared to those treated with air or oxygen inhalation (mean difference (MD) -1.15, 95% confidence interval (CI) -1.98 to -0.33, P = 0.006, n = 69). There was no clinically significant reduction in the rate of intubation (risk ratio (RR) 1.38, 95% CI 0.41 to 4.56, P = 0.60, n = 58), in the need for mechanical ventilation (RR 1.11, 95% CI 0.36 to 3.38, P = 0.86, n = 58), or in the length of stay in a PICU (MD = -0.15 days, 95% CI -0.92 to 0.61, P = 0.69, n = 58). No adverse events related to heliox inhalation were reported. AUTHORS' CONCLUSIONS: Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. Nevertheless, there was no reduction in the rate of intubation, in the need for mechanical ventilation, or in the length of PICU stay. Further studies with homogeneous logistics in their heliox application are needed. Such studies would provide necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis.
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Etiology of bronchiolitis in a hospitalized pediatric population: prospective multicenter study.
J Clin Virol. 2010 Jun; 48(2): 134-6
Antunes H, Rodrigues H, Silva N, Ferreira C, Carvalho F, Ramalho H, Gonçalves A, Branca FBACKGROUND: In 2006, bronchiolitis due to adenovirus nosocomial infections resulted in the closure of a pediatric department in northern Portugal. OBJECTIVES: To determine the etiology of bronchiolitis in northern Portugal. STUDY DESIGN: It was a prospective multicenter study on the etiology of bronchiolitis during the respiratory syncytial virus (RSV) season (November-April). Children < or = 24 months of age admitted for a first wheezing episode were included. Nasopharyngeal specimens were analyzed by an indirect immunofluorescent-antibody assay (IFA) for RSV, adenovirus (HAdV), parainfluenza (PIV) 1-3 and influenza (IV) A and B and by polymerase chain reaction (PCR) or reverse transcription-PCR for the same viruses and for human metapneumovirus (hMPV), bocavirus (HBoV), rhinovirus (HRV), coronaviruses (229/E; NL63; OC43; HKU1) and enterovirus. RESULTS: During this period, 253 children were included, 249 IFA analyses and 207 PCRs were performed. IFA detected RSV in 58.1%; PCR increased it to 66.7%. IFA detected HAdV in 3.2%, PCR 10.0%. PCR detected IV A in 5; IV B in 2; PIV 1 in 6, PIV 2 in 4 and PIV 3 in 11 cases. HBoV, as single agent in 2 cases, and HRV were positive in 8 samples and hMPV in 11. With this virus panel, 19.7% remained without etiology. CONCLUSIONS: The most frequent agent was RSV, followed by HAdV. PCR can be cost-effective and more accurate than IFA, which is crucial for HAdV that may be associated with significant mortality (IFA alone did not detect 2/3 of the cases).
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Pneumococcal conjugate vaccines in the prevention of childhood pneumonia.
Acta Microbiol Immunol Hung. 2010 Mar; 57(1): 1-13
Ivády BLower respiratory tract infections are among the most important causes of childhood mortality worldwide, more than 2 million children die due to pneumonia every year. A number of infections caused by the main pathogens related to pneumonia can be prevented through vaccination ( S. pneumoniae, H. influenzae type-b, morbilli, pertussis, influenza). In the last decade, after the introduction of the 7-valent pneumococcal conjugated vaccine (PCV), the epidemiological background of childhood pneumonia has changed. Recently, several studies have been performed to collect data and evidences about the efficacy of PCV against noninvasive pneumococcal diseases (e.g. pneumonia, otitis media). These investigations showed 10-50% decrease of all pneumonia cases, 10-30% decrease of radiologically diagnosed pneumonia, and 50-70% decrease of the incidence of pneumococcal pneumonia in children. The aim of this review was to determine the role of the PCV in the prevention of childhood pneumonia according to the medical literature, and to summarize the efforts of global organizations (WHO, UNICEF, GAVI) in the fight against pneumonia in children.
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Booster vaccination after neonatal priming with acellular pertussis vaccine.
J Pediatr. 2010 Apr; 156(4): 675-8
Knuf M, Schmitt HJ, Jacquet JM, Collard A, Kieninger D, Meyer CU, Siegrist CA, Zepp FAfter a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.
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Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.
Am J Clin Nutr. 2010 May; 91(5): 1255-60
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida HBACKGROUND: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza. OBJECTIVE: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren. DESIGN: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D(3) supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen. RESULTS: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D(3) group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3) compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006). CONCLUSION: This study suggests that vitamin D(3) supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. This trial was registered at https://center.umin.ac.jp as UMIN000001373.
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Pediatr Blood Cancer. 2010 May; 54(5): 716-20
Shahgholi E, Ehsani MA, Salamati P, Maysamie A, Sotoudeh K, Mokhtariazad TPURPOSE: The aim of this study was to assess the immune response of children with acute lymphoblastic leukemia (ALL) to influenza vaccine and to compare it with healthy controls. PROCEDURE: Thirty-two children aged 1-18 years with ALL on maintenance therapy and 30 healthy sibling controls were enrolled in the study. All children were vaccinated with trivalent inactivated influenza vaccine. Hemagglutinin-inhibition (HI) antibody titers were determined in sera of both patient and control groups just before and 4 weeks after vaccination. The ability of each group to mount a protective (> or =40) and/or fourfold titer was measured. RESULTS: The protective response for virus subunits among patients and healthy controls were 43.4% versus 88% for H1N1 (P = 0.04), 63.3% versus 80% for H3N2 antigens (P = 0.06), and 26% versus 73% for B antigen (P = 0.001). Responses for H1N1 and B subunits were significantly lower in patients than controls. In the patient group, the significant response to each virus was demonstrated in the analysis of pre- and post-vaccination geometric mean titer (GMT) (P = 0.001). The percentage of patients and controls with fourfold increase in HI titers were 56.2% versus 80% for H1N1 (P = 0.04), 40.6% versus 53.3% for H3N2 (P = 0.31), and 59.4% versus 83.3% for B (P = 0.038). Immune responses for H1N1 and B subunits were significantly lower in patients than controls. CONCLUSIONS: Influenza vaccine is tolerated well in ALL patients with acceptable but limited immune response compared to healthy controls. These findings support the recommendation for annual influenza vaccination in children with ALL.
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A randomized intervention of montelukast for post-bronchiolitis: effect on eosinophil degranulation.
J Pediatr. 2010 May; 156(5): 749-54
Kim CK, Choi J, Kim HB, Callaway Z, Shin BM, Kim JT, Fujisawa T, Koh YYOBJECTIVE: To investigate the effect of montelukast on eosinophil degranulation and recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis. STUDY DESIGN: Two hundred infants (age, 6-24 months) who were hospitalized with their first episode of acute RSV bronchiolitis were randomized in a double-blind, placebo-controlled, parallel comparison of 4-mg montelukast granules (RSV-MONT group) or matching placebo (RSV-PLC group) administered for 3 months. Serum eosinophil-derived neurotoxin (EDN) levels were measured (primary outcome), and recurrent wheezing was documented (secondary outcome) for 12 months. Comparisons were made with control subjects (control group, n = 50). RESULTS: At the end of the 3-month treatment period, the RSV-PLC group (n = 71) exhibited significantly elevated EDN levels (P < .0001), and the RSV-MONT group (n = 79) showed significantly decreased EDN levels (P < .01) when compared with the initial levels. As a result, EDN levels in the 2 RSV groups significantly differed at this point (P < .0001) and remained different for the entire 12-month follow-up period. Cumulative recurrent wheezing episodes at 12 months were significantly lower in the RSV-MONT group (P = .039). CONCLUSION: Montelukast treatment reduces eosinophil degranulation and is associated with a decrease in recurrent wheezing episodes in post-RSV bronchiolitis.
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Pediatr Nurs. 2009 Nov-Dec; 35(6): 335-45
Bramley AM, Bresee J, Finelli LInfluenza viruses cause annual epidemics in the United States. Although the severity of influenza epidemics vary by season, the morbidity associated with annual influenza epidemics in children is considerable from year to year. Excess pediatric outpatient clinic visits, emergency department visits, hospitalizations, and deaths occur each influenza season and are more common among younger children and those with conditions that increase their risk for developing influenza-related complications. Vaccination is the most effective way to prevent influenza and its complications and is recommended for all children 6 months through 18 years of age. Antiviral treatment is another tool to prevent influenza and reduce the duration of illness and complications. This article will review the virological, clinical, and epidemiological features of seasonal influenza, as well as discuss seasonal influenza vaccination and antiviral therapy.
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Cochrane Database Syst Rev. 2010; 2: CD007743
Robinson KA, Odelola OA, Saldanha I, McKoy NBACKGROUND: Respiratory syncytial virus (RSV) infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis (CF) are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe RSV infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing RSV hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent RSV hospitalisations and intensive care unit admissions in children with CF. OBJECTIVES: To determine the efficacy and safety of palivizumab (Synagis((R))) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from RSV infection in children with CF. SEARCH STRATEGY: We searched the Cochrane CF and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Last search: 20 January 2010. SELECTION CRITERIA: Randomised and quasi-randomised studies. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed risk of bias. MAIN RESULTS: One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N=92) to placebo (N=94) over one RSV season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to RSV; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while 5 and 4 children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio. AUTHORS' CONCLUSIONS: We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with CF. While the overall incidence of adverse events was similar in both groups, it is not possible to draw conclusions on the safety and tolerability of RSV prophylaxis with palivizumab in infants with CF because the trial did not specify how adverse events were classified. Six months after treatment, the authors reported no clinically meaningful differences in outcomes; however no data were provided. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with CF.
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Vaccine. 2010 Apr 1; 28(16): 2865-76
Zhu W, Higgs BW, Morehouse C, Streicher K, Ambrose CS, Woo J, Kemble GW, Jallal B, Yao YThe protective mechanisms of influenza vaccines in young children are not completely understood. A phase 2 clinical study was conducted in 85 children 12-35 months of age to describe and compare the immune responses to live attenuated influenza vaccine (LAIV) with trivalent inactivated influenza vaccine (TIV). To better understand the biology of vaccine effects, oligonucleotide microarrays were employed to measure the genome-wide changes in transcript profiles in whole blood at approximately 7 days after 1 dose of LAIV or TIV. Of the total 265 differentially expressed genes identified in this study, 6 clusters of genes were identified to be tightly coexpressed, many of which are likely modulated by cytokines including type 1 interferons (IFNs) and granulocyte-macrophage colony-stimulating factor. Additional functional analyses revealed that the type 1 IFN pathway and cell cycle regulation-related genes are enriched in the 6 coexpressed gene sets. Promoter characterization of these coexpressed genes also supported this conclusion. Moreover, it is suggested that the IFN-stimulated response element is likely to be a potential bidirectional promoter, and the CCAAT/enhancer-binding protein might cooperate with the E2F transcription factor family in the regulation of the cell cycle in the early immune response induced by the influenza vaccine. Overall, our study clearly indicates that the expression profile changes induced by LAIV are significantly different from those induced by TIV. These results suggest that the pattern of overexpression of type 1 IFN-stimulated genes can potentially be used as a biomarker to identify the early vaccination response of LAIV and may also explain, to a certain extent, previous clinical study observations of LAIV-induced protection against influenza-like illness in the first 2 weeks after administration.
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Risk factors for upper airway diseases.
Int J Immunopathol Pharmacol. 2010 Jan-Mar; 23(1 Suppl): 13-5
Duse M, Leonardi L, Zicari AM, De Castro G, Indinnimeo LUpper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications are a burden for children, their families and society. It has been estimated that at least 6 percent of children younger than 6 yr of age presents recurrent respiratory infections, as consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still immature. Pediatricians must identify risk factors predisposing to upper respiratory tract infections and plan specific preventive strategies, ie avoidance of precocious day-care attendance and secondary smoke. Vaccination against influenza and pneumococcal diseases should always be recommended.
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A systematic review of compliance with palivizumab administration for RSV immunoprophylaxis.
J Manag Care Pharm. 2010 Jan-Feb; 16(1): 46-58
Frogel MP, Stewart DL, Hoopes M, Fernandes AW, Mahadevia PJBACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children, accounting for approximately 75,000-125,000 hospitalizations per year. It is estimated that in 2000, RSV infection accounted for 1.7 million office visits, 402,000 emergency room visits, and 236,000 hospital outpatient visits per year for children younger than 5 years of age. Palivizumab, a humanized monoclonal antibody directed against RSV, is the only immunoprophylaxis therapy approved by the FDA for prevention of serious lower respiratory tract disease caused by RSV in infants (up to 2 years of age) who meet 1 or more of the following criteria for high risk: (a) gestational age up to 35 weeks;(b) diagnosis of chronic lung disease (CLD, formerly bronchopulmonary dysplasia [BPD]); or (c) diagnosis of cyanotic or complex congenital heart disease. The RSV season typically occurs between November and March but may vary by region. During the period of our review, depending on local duration of the RSV season, infants usually required 5 monthly (every 28-30 days) intramuscular injections of palivizumab. Infants born in the middle of the season received their palivizumab doses from the time of birth to the end of the season and, therefore, may have required less than 5 doses.It is unclear if compliance with monthly doses is a problem and whether noncompliance increases the risk of RSV hospitalizations in routine clinical practice. OBJECTIVES: To (a) identify and describe compliance rates and the factors that influence parental compliance with immunoprophylaxis regimens, (b)review intervention programs and describe those that have been associated with increased compliance, and (c) summarize the association of compliance with RSV hospitalization rates. METHODS: An electronic literature search was conducted using journal databases, including Ovid, Current Contents, Embase, Medline In-Process & Other Non-Indexed Citations; Ovid Medline, PubMed, and Web of Science;and an abstract database, Medical Intelligence Solution, for citations through April 2008. Specific search terms used were palivizumab with patient compliance, patient adherence, or patient persistence. RESULTS: Twenty-five articles and abstracts met the inclusion criteria. Available studies were mostly retrospective or observational prospective.Compliance, defined in various ways across the studies, varied between 25% and 100%, and 12 studies identified some of the factors related to noncompliance. Compliance generally was lower among Medicaid patients,African American patients, and other minorities. Ten studies (3 manuscripts and 7 abstracts) investigated the association of administration of prophylaxis through monthly home visits by a health professional with parental compliance with therapy. Most of the home-based programs were associated with higher compliance rates compared with clinic or office programs.Rates as high as 94% and 64% were achieved when Medicaid infants and infants of minority descent, respectively, received their doses through a home health program. When these infants received their doses at a clinic or office, depending on the definition of compliance, rates were 61%-100% for Medicaid infants and 44% for infants of minority descent. Reminder telephone calls to parents or caregivers, comprehensive multidisciplinary programs that included extensive counseling of parents, calendars with sticker reminders, and education in the language native to parents also were associated with increased compliance, although statistical significance was reported in only 1 study. Several studies recommended educating parents on the benefits of RSV prophylaxis, alleviating transportation and language difficulties, recognizing cultural differences and biases, and clarifying misperception of RSV illness severity. Home health programs had lower rates of RSV hospitalizations than office-based programs in 3 analyses conducted in 2 studies. In 4 other abstracts, the rates of RSV hospitalization for home health programs and office-based administration did not significantly differ. In a large, 4-season, prospective outcome study, compliant infants had lower RSV hospitalization rates than those who were not compliant under one definition of compliance (doses within 35-day intervals). RSV hospitalization rates were not significantly different using another definition of compliance (receipt of anticipated doses, expected vs. observed rates).In a large survey of 10,390 infants identified from pharmacy dispensing records, RSV hospitalization rates were 1.4% in the compliant group versus 3.1% in the noncompliant group (OR = 2.2, 95% CI = 1.4-3.5, P < 0.001).Adjustment for confounding was not reported in these studies. CONCLUSION: Medicaid and minority infants were less likely to receive scheduled palivizumab doses. Home-based programs for the administration of palivizumab have been investigated more than other interventions and are associated with improved compliance compared with office-based administration. Compliance with dosing, in general, was associated with lower RSV hospitalization rates. However, these strategies should be further investigated using well-designed studies.
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Immunization updates and challenges.
Curr Opin Pediatr. 2010 Apr; 22(2): 234-40
Keeton VF, Chen AKPURPOSE OF REVIEW: Childhood vaccination recommendations in the United States have increased throughout the years. Many providers, patients, and families are overwhelmed and have concerns regarding the safety and efficacy of vaccines. Various barriers and challenges exist for healthcare providers to successfully implement the vaccination recommendations. This review will discuss the 2009 and newly released 2010 immunization recommendations, as well as challenges and strategies to improve vaccination in children and adolescents. RECENT FINDINGS: Seasonal influenza immunization continues to be promoted for all children, and recommendations for vaccination against novel influenza A have emerged as well. Concerns surrounding vaccine safety and necessity may cause increasing rates of vaccine refusal among some parents, but clear messages from providers and unbiased information about benefits and risks of immunization may counteract these doubts. Barriers to immunizing adolescents continue as access to healthcare in this age group changes. SUMMARY: Pediatric providers currently face numerous challenges in improving rates of immunization among children and adolescents. Promoting coverage through the influenza vaccines, counseling parents with clear information about the risks and benefits of vaccines, and taking advantage of nonpreventive visits for immunization are some strategies suggested to address these challenges.
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Targeted antiviral prophylaxis with oseltamivir in a summer camp setting.
Arch Pediatr Adolesc Med. 2010 Apr; 164(4): 323-7
Kimberlin DW, Escude J, Gantner J, Ott J, Dronet M, Stewart TA, Jester P, Redden DT, Chapman W, Hammond ROBJECTIVE: To describe the effectiveness of containment of novel influenza A(H1N1) infection at a summer camp. DESIGN: Targeted use of oseltamivir phosphate by individuals in close contact with influenza-confirmed cases. SETTING: Boys' camp in Alabama in July 2009. PARTICIPANTS: A total of 171 campers, 48 camp counselors, and 27 camp staff. INTERVENTIONS: Campers with confirmed influenza received oseltamivir and were immediately isolated and sent home. All boys and counselors in the infected child's adjoining cabins received prophylactic oseltamivir for 10 days, including 8 campers at higher risk for influenza infection (eg, those with asthma, seizure disorder, or diabetes). Alcohol-based hand sanitizer was provided at each of the daily activities, in the boys' cabins, and in the dining hall, and counselors were educated by the medical staff on the spread of influenza and its prevention through good hand hygiene. All cabins, bathrooms, and community sports equipment were sprayed or wiped down with disinfectant each day. Main Outcome Measure Virologic confirmation of influenza. RESULTS: Three of the 171 campers tested positive for influenza A during the course of the 2-week fourth session, for an attack rate of 1.8%. The probability of observing 3 or fewer infected campers if the attack rate was 12% is less than 1 in 10,000,000 (P < .0000001). An exact 95% confidence interval based on 3 events among 171 individuals estimates the attack rate to be between 0.3% and 5.0%. While 31% to 57% of campers, counselors, or staff experienced nausea with the treatment, this did not result in discontinuation of therapy. No campers tested positive for influenza A after returning home at the end of the camp session. CONCLUSION: In conjunction with comprehensive hand sanitization and surface decontamination, a targeted approach to antiviral prophylaxis contained the spread of influenza in a summer camp setting.
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