John G. Bartlett,1 Scott F Dowell,2 Lionel A. Mandell,6 Thomas M. File, Jr.,3 Daniel M. Musher,4 and Michael J. Fine5 'Johns Hopkins University School of Medicine, Baltimore, Maryland, 2Centers for Disease Control and Prevention, Atlanta, Georgia, 3Northeastern Ohio Universities College of Medicine, Cleveland, Ohio, 4Baylor College of Medicine and Veterans Affairs Medical Center, Houston, Texas, and 5University of Pittsburgh, Pennsylvania, USA; and 6McMaster University, Toronto, Canada

https://www.jstor.org/stable/pdfplus/4482307.pdf

Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults

This report updates the 2009 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8] and CDC. Use of influenza A (H1N1) 2009 monovalent vaccine---recommendations of the Advisory Committee on Immunization Practices [ACIP], 2009. MMWR 2009;58:[No. RR-10]). The 2010 influenza recommendations include new and updated information. Highlights of the 2010 recommendations include 1) a recommendation that annual vaccination be administered to all persons aged >or=6 months for the 2010-11 influenza season; 2) a recommendation that children aged 6 months--8 years whose vaccination status is unknown or who have never received seasonal influenza vaccine before (or who received seasonal vaccine for the first time in 2009-10 but received only 1 dose in their first year of vaccination) as well as children who did not receive at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine regardless of previous influenza vaccine history should receive 2 doses of a 2010-11 seasonal influenza vaccine (minimum interval: 4 weeks) during the 2010--11 season; 3) a recommendation that vaccines containing the 2010-11 trivalent vaccine virus strains A/California/7/2009 (H1N1)-like (the same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; 4) information about Fluzone High-Dose, a newly approved vaccine for persons aged >or=65 years; and 5) information about other standard-dose newly approved influenza vaccines and previously approved vaccines with expanded age indications. Vaccination efforts should begin as soon as the 2010-11 seasonal influenza vaccine is available and continue through the influenza season. These recommendations also include a summary of safety data for U.S.-licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2010-11 influenza season also will be available at this website. Recommendations for influenza diagnosis and antiviral use will be published before the start of the 2010-11 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

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Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

Summary Background No published meta-analyses have assessed efficacy and effectiveness of licensed influenza vaccines in the USA with sensitive and highly specific diagnostic tests to confirm influenza. Methods We searched Medline for randomised controlled trials assessing a relative reduction in influenza risk of all circulating influenza viruses during individual seasons after vaccination (efficacy) and observational studies meeting inclusion criteria (effectiveness). Eligible articles were published between Jan 1, 1967, and Feb 15, 2011, and used RT-PCR or culture for confirmation of influenza. We excluded some studies on the basis of study design and vaccine characteristics. We estimated random-effects pooled efficacy for trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) when data were available for statistical analysis (eg, at least three studies that assessed comparable age groups). Findings We screened 5707 articles and identified 31 eligible studies (17 randomised controlled trials and 14 observational studies). Efficacy of TIV was shown in eight (67%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 59% [95% CI 51–67] in adults aged 18–65 years). No such trials met inclusion criteria for children aged 2–17 years or adults aged 65 years or older. Efficacy of LAIV was shown in nine (75%) of the 12 seasons analysed in ten randomised controlled trials (pooled efficacy 83% [69–91]) in children aged 6 months to 7 years. No such trials met inclusion criteria for children aged 8–17 years. Vaccine effectiveness was variable for seasonal influenza: six (35%) of 17 analyses in nine studies showed significant protection against medically attended influenza in the outpatient or inpatient setting. Median monovalent pandemic H1N1 vaccine effectiveness in five observational studies was 69% (range 60–93). Interpretation Influenza vaccines can provide moderate protection against virologically confirmed influenza, but such protection is greatly reduced or absent in some seasons. Evidence for protection in adults aged 65 years or older is lacking. LAIVs consistently show highest efficacy in young children (aged 6 months to 7 years). New vaccines with improved clinical efficacy and effectiveness are needed to further reduce influenza-related morbidity and mortality. Funding Alfred P Sloan Foundation.

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Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.

https://www.uphs.upenn.edu/bugdrug/antibiotic_manual/oipreventidsacdcstemcell2009.pdf

Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective.

Background: Although known as common causes of upper respiratory infections, rhinoviruses, enteroviruses, and corona-viruses are poorly studied as inducers of wheezing in infants, and their possible role in the development of childhood asthma has not been investigated. Objective: The purposes of this study were to assess the occurrence of RV, enterovirus, and coronavirus infections in wheezing infants and to evaluate the association of these viral findings with early school-age asthma. Methods: In 1999, outcome in relation to asthma was studied in 82 of 100 initially recruited children who had been hospitalized for wheezing in infancy during the period 1992-1993. In 2000, etiologic viral studies regarding the index episode of wheezing were supplemented by rhinovirus, enterovirus, and coronavirus detection by RT-PCR from frozen nasopharyngeal aspirates in 81 of the children for whom adequate samples were available. Of these children, 66 had participated in the follow-up in 1999. Results: Rhinoviruses were identified in 27 (33%) of the 81 children, enteroviruses in 10 (12%), and coronaviruses in none. Rhinoviruses were present as single viral findings in 22 (81%) of the 27 rhinovirus-positive cases, and rhinovirus infections were associated with the presence of atopic dermatitis in infancy. Enteroviruses were commonly encountered in mixed infections and had no association with atopy. As single viral findings, rhinoviruses were associated with the development of asthma ( P = .047; odds ratio, 4.14; 95% CI, 1.02-16.77 versus rhinovirus-negative cases [by logistic regression adjusted for age, sex, and atopic dermatitis on entry)]. Conclusion: Our results present rhinoviruses as important inducers of wheezing even in infancy. The association with atopy and subsequent asthma calls for reevaluation of the role of rhinoviruses in the development of asthma. (J Allergy Clin Immunol 2003;111:66-71.)

Rhinovirus-induced wheezing in infancy--the first sign of childhood asthma?

Objective: To investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods. Methods: Consecutive patients (ages ≥16) with aseptic meningitis or encephalitis treated in Turku University Hospital, Finland, during 1999 to 2003 were included in the study. Microbiologic tests were performed, including CSF PCR tests for enteroviruses, herpes simplex virus (HSV) 1, HSV-2, and varicella zoster virus (VZV), as well as serum and CSF antibody analysis for these viruses. Antibody testing was also performed for other pathogens commonly involved in neurologic infections. Virus culture was performed on CSF, fecal, and throat swab specimens. Results: Etiology was defined in 95 of 144 (66%) patients with aseptic meningitis. Enteroviruses were the major causative agents (26%), followed by HSV-2 (17% of all, 25% of females) and VZV (8%). Etiology was identified in 15 of 42 (36%) patients with encephalitis, VZV (12%), HSV-1 (9%), and tick-borne encephalitis virus (9%) being the most commonly involved pathogens. Etiologic diagnosis was achieved by PCR in 43% of the patients with meningitis and in 17% of those with encephalitis. Conclusions: Enteroviruses and HSV-2 are the leading causes of adult aseptic meningitis, and PCR is of diagnostic value. However, in most cases of encephalitis, the etiology remains undefined.

Etiology of aseptic meningitis and encephalitis in an adult population

BACKGROUND Influenza vaccination of healthy children is encouraged because children are frequently hospitalized for influenza-attributable illnesses. However, most children with influenza are treated as outpatients, and scarce data are available on the burden of influenza in these children. METHODS We performed a prospective study of respiratory infections in preenrolled cohorts of children < or = 13 years old during 2 consecutive respiratory seasons (2231 child-seasons of follow-up). At any sign of respiratory infection, we examined the children and obtained a nasal swab for the detection of influenza. The parents filled out daily symptom diaries. Of all the enrollees, 94% remained active participants in the study. RESULTS The average annual rate of influenza was highest (179 cases/1000 children) among children < 3 years old. Acute otitis media developed as a complication of influenza in 39.7% of children < 3 years old. For every 100 influenza-infected children < 3 years old, there were 195 days of parental work loss (mean duration, 3.2 days). CONCLUSIONS Influenza causes a substantial burden of illness on outpatient children and their families. Vaccination of children < 3 years old might be beneficial for reducing the direct and indirect costs of influenza in children.

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Burden of Influenza in Children in the Community

We evaluated a commercial immunoglobulin M (IgM)-capture immunoassay for the detection of Mycoplasma pneumoniae infections in 278 pediatric patients with community-acquired, radiographically defined pneumonia. Acute- and convalescent-phase serum samples were collected from all patients and were tested for M. pneumoniae-specific IgM and IgG antibodies by Platelia enzyme immunoassays (Sanofi Diagnostica Pasteur, Marnes la Coquette, France). Nasopharyngeal aspirates (NPAs) were collected at the time of admission to the hospital. A total of 227 NPAs were subjected to the detection of M. pneumoniae DNA by PCR, and 191 NPAs were cultured by using the Pneumofast kit (International Mycoplasma, Signeswere, France). Southern hybridization of PCR products and the IgM test with solid-phase antigen (Serion Immunodiagnostica, Wurzburg, Germany) were used for additional confirmation of a positive result, which required agreement of at least two different methods. A total of 24 (9%) confirmed diagnoses of mycoplasma infection were made, 5 (21%) of which were in children <5 years of age. Of the positive children, 24 of 24 (sensitivity, 100%) were positive by the IgM-capture test with convalescent-phase serum, 19 of 24 (79%) were positive by the IgM-capture test with acute-phase serum, 19 of 24 (79%) were positive by IgG serology, 10 of 20 (50%) were positive by PCR, and 8 of 17 (47%) were positive by culture. An additional 5 (of 254) children were positive by the Platelia IgM test alone (specificity, 98%). When the PCR with Southern hybridization result was combined with the IgM-capture test result with the acute-phase sera, the sensitivity of rapid laboratory diagnosis increased to 95%. In conclusion, the IgM serology test was the single most valuable tool for the diagnosis of M. pneumoniae pneumonia in children of any age.

https://jcm.asm.org/content/jcm/36/11/3155.full.pdf

Diagnosis of Mycoplasma pneumoniae Pneumonia in Children

Background Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness. Methods We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days. Results Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections. Conclusions Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

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Raija Vainionpää

Papers

Rhinovirus-induced wheezing in infancy--the first sign of childhood asthma?

Etiology of aseptic meningitis and encephalitis in an adult population

Burden of Influenza in Children in the Community

Diagnosis of Mycoplasma pneumoniae Pneumonia in Children

Early Oseltamivir Treatment of Influenza in Children 1–3 Years of Age: A Randomized Controlled Trial