Respiratory Illness In Young Children Research Articles

Rapid replacement of human respiratory syncytial virus A with the ON1 genotype having 72 nucleotide duplication in G gene

Human respiratory syncytial virus (HRSV) is the main cause of severe respiratory illness in young children and elderly people. We investigated the genetic characteristics of the circulating HRSV subgroup A (HRSV-A) to determine the distribution of genotype ON1, which has a 72-nucleotide duplication in attachment G gene. We obtained 456 HRSV-A positive samples between October 2008 and February 2013, which were subjected to sequence analysis. The first ON1 genotype was discovered in August 2011 and 273 samples were identified as ON1 up to February 2013. The prevalence of the ON1 genotype increased rapidly from 17.4% in 2011–2012 to 94.6% in 2012–2013. The mean evolutionary rate of G protein was calculated as 3.275×10−3 nucleotide substitution/site/year and several positively selected sites for amino acid substitutions were located in the predicted epitope region. This basic and important information may facilitate a better understanding of HRSV epidemiology and evolution.

A replication-incompetent influenza virus bearing the HN glycoprotein of human parainfluenza virus as a bivalent vaccine

Influenza virus and human parainfluenza virus (HPIV) are major etiologic agents of acute respiratory illness in young children. Inactivated and live attenuated influenza vaccines are approved in several countries, yet no vaccine is licensed for HPIV. We previously showed that a replication-incompetent PB2-knockout (PB2-KO) virus that possesses a reporter gene in the coding region of the PB2 segment can serve as a platform for a bivalent vaccine. To develop a bivalent vaccine against influenza and parainfluenza virus, here, we generated a PB2-KO virus possessing the hemagglutinin-neuraminidase (HN) glycoprotein of HPIV type 3 (HPIV3), a major surface antigen of HPIV, in its PB2 segment. We confirmed that this virus replicated only in PB2-expressing cells and expressed HN. We then examined the efficacy of this virus as a bivalent vaccine in a hamster model. High levels of virus-specific IgG antibodies in sera and IgA, IgG, and IgM antibodies in bronchoalveolar lavage fluids against both influenza virus and HPIV3 were detected from hamsters immunized with this virus. The neutralizing capability of these serum antibodies was also confirmed. Moreover, the immunized hamsters were completely protected from virus challenge with influenza virus or HPIV3. These results indicate that PB2-KO virus expressing the HN of HPIV3 has the potential to be a novel bivalent vaccine against influenza and human parainfluenza viruses.

HMPV Lineage Nomenclature and Heparin Binding

Human metapneumovirus (hMPV), first described in 2001 [1], is responsible for causing serious respiratory illness in young children, the elderly and immunocompromised patients. Four distinct lineages of hMPV have been identified with the original nomenclature for these subgroups (A1, A2, B1 and B2), reported by van den Hoogen et al. [2], utilised by many. An alternate terminology (1A, 1B, 2A and 2B) was also published by Ishiguro et al. in 2004 [3] which has been adopted by others. However, this has caused some confusion in the interpretation of publication results as the terminology is similar yet describes different subtypes. As a result, a number of investigators have made a submission to the International Committee on Taxonomy of Viruses (ICTV, ICTV taxonomic proposal 2012.012V) for the official adoption of the original terminology as an approved nomenclature for hMPV [4]. We welcome this officially approved nomenclature which should provide clarification of these subtypes in future. Therefore to assist with the interpretation of our recently published research in the 2012 special issue of Viruses: Pneumoviruses and Metapneumoviruses entitled "Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages" [5] we have updated the Figure 3 in this letter (see Figure 1), showing the proposed ICTV terminology compared to the Ishiguro classification (used in our publication). Note that in the original publication the alphanumeric order for the Ishiguro classification was transposed (e.g., 1A was referred to as A1).

Hsp90 Inhibitors Exhibit Resistance-Free Antiviral Activity against Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a major cause of respiratory illness in young children, leading to significant morbidity and mortality worldwide. Despite its medical importance, no vaccine or effective therapeutic interventions are currently available. Therefore, there is a pressing need to identify novel antiviral drugs to combat RSV infections. Hsp90, a cellular protein-folding factor, has been shown to play an important role in the replication of numerous viruses. We here demonstrate that RSV requires Hsp90 for replication. Mechanistic studies reveal that inhibition of Hsp90 during RSV infection leads to the degradation of a viral protein similar in size to the RSV L protein, the viral RNA-dependent RNA polymerase, implicating it as an Hsp90 client protein. Accordingly, Hsp90 inhibitors exhibit antiviral activity against laboratory and clinical isolates of RSV in both immortalized as well as primary differentiated airway epithelial cells. Interestingly, we find a high barrier to the emergence of drug resistance to Hsp90 inhibitors, as extensive growth of RSV under conditions of Hsp90 inhibition did not yield mutants with reduced sensitivity to these drugs. Our results suggest that Hsp90 inhibitors may present attractive antiviral therapeutics for treatment of RSV infections and highlight the potential of chaperone inhibitors as antivirals exhibiting high barriers to development of drug resistance.

Hospitalization due to human parainfluenza virus-associated lower respiratory tract illness in rural Thailand

Background Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory illness in young children but little is known about their epidemiology in the tropics. Methods From 2003–2007, we conducted surveillance for hospitalized respiratory illness in rural Thailand. We performed reverse‐transcriptase polymerase chain reaction on nasopharyngeal specimens and enzyme immunoassay on paired sera Results Of 10,097 patients enrolled, 573 (5%) of all ages and 370 (9%) of children <5 years of age had evidence of HPIV infection (HPIV1=189, HPIV2=54, HPIV3=305, untyped=27). Average adjusted annual incidence of HPIV‐associated hospitalized respiratory illness was greatest in children aged <1 year (485 per 100,000 person years). Conclusions In Thailand, HPIV caused substantial illnesses requiring hospitalization in young children.

CONCENTRATION-RISK RELATIONSHIP FOR VOLATILE ORGANIC COMPOUNDS IN INDOOR AIR AND RESPIRATORY HEALTH OF CHILDREN IN LEIPZIG, GERMANY

Background and Aims: To assess the form of associations between respiratory illness in young children and domestic exposure to volatile organic compounds (VOC) and to apply a novel approach to redu...

Randomised controlled trial to reduce morbidity of bronchiolitis in young children admitted to Royal Darwin hospital in the NT

Background Bronchiolitis is the most common reason for hospital admission for infants globally(1). The use of antibiotics, in particular macrolides for treating bronchiolitis in non affluent settings remains controversial but potentially beneficial. In our region, readmission with lower respiratory illness in young children, particularly Indigenous children remains high.

Dating of human bocavirus infection with protein-denaturing IgG-avidity assays—Secondary immune activations are ubiquitous in immunocompetent adults

Background Human bocavirus (HBoV) is a widespread human parvovirus causing acute respiratory illness in young children. The HBoV primary infections are viremic and can be diagnosed serologically. Objectives To set up HBoV-IgG-avidity enzyme immuno assays (EIAs) using as antigen recombinant VP2 virus-like particles (VLPs), for diagnosis and timing of primary infections and their distinction from secondary infections or immunoactivations by this recently found virus. Study design The VLPs were utilized in setting up HBoV-IgG-avidity-EIAs of two different types. Paired sera were available from 36 wheezing children with acute primary HBoV infection, single sera from 108 nonsymptomatic university students, and 84 single or follow-up sera from 38 adults with pre-existing HBoV immunity. Results HBoV-IgG avidity for the VP2-VLPs was measured successfully by protein-denaturing EIAs of two types, employing low concentrations of urea (4.7 M and 2.5 M). The diagnostic specificities were 99.1% and 90.7%, and diagnostic sensitivities, 94.4% and 91.7%, respectively. Interestingly, of the adults followed up 44% (4/9) exhibited significant titre increases of past-immunity HBoV-IgG. Conclusions Diagnosis of HBoV primary infection can be strengthened by measurement of IgG avidity. HBoV secondary infections or anamnestic antibody responses occur ubiquitously in immunocompetent adults.

Coronavirus infection and hospitalizations for acute respiratory illness in young children

There is only limited knowledge on the burden of disease due to both new (HCoV‐NL63 and HKU‐1) and previously discovered coronaviruses (OC43 and 229E) in children. Respiratory specimens and clinical data were prospectively collected in an active, population‐based surveillance study over a 2‐year period from children aged <5 years hospitalized with acute respiratory symptoms or fever. These samples were retrospectively tested by real‐time RT‐PCR for HCoV‐NL63, HKU1, OC43, and 229E. Human coronaviruses (HCoVs) were identified in 2.2% of study children <2 years of age. Rates of HCoV‐associated hospitalization per 10,000 were 10.2 (95% CI 4.3, 17.6), 4.2 (95% CI 1.9, 6.9), and 0 (95% CI 0, 3.7) in children aged <6 months, 6–23 months, and 24–59 months, respectively. Coronaviruses were identified in a modest number of hospitalized children. J. Med. Virol. 81:853–856, 2009. © 2009 Wiley‐Liss, Inc.

Prophylaxis against respiratory syncytial virus in young children with cystic fibrosis

In cystic fibrosis (CF) patients, respiratory syncytial virus (RSV) infection is associated with significant morbidity. Although passive prophylaxis with palivizumab lowers hospitalization rate for RSV infection in populations at risk of severe infection, its use is not recommended in infants with CF disease. To determine the effect of palivizumab prophylaxis on hospitalization for acute respiratory illness in young children with CF during the first RSV season following the diagnosis of CF. In this retrospective study, medical records of patients diagnosed with CF between the years 1997 and 2005 inclusively and on whom the diagnosis was made before 18 months of age were reviewed. Collected data included age at diagnosis, palivizumab prophylaxis, occurrence of hospitalization for acute respiratory tract illness during the RSV season and identification of RSV infection. A diagnosis of CF was made in 76 young children and data collected from 75 children. Of those, 40 did not receive RSV prophylaxis while 35 received palivizumab injection monthly during the RSV season. Among non-recipient children, 7 out of 40 were hospitalized for acute respiratory illness during the RSV season. Of these seven patients, RSV detection was positive in nasopharyngeal secretions in three patients, negative in one patient and not requested in the others. Among palivizumab recipients, 3 out of 35 children were hospitalized for acute respiratory illness (P > 0.05 compared to non-recipients group). In these three palivizumab recipients, RSV detection was negative in nasopharyngeal secretions. Palivizumab recipients experienced fewer hospital days per patient for acute respiratory illness (mean +/- SD: 0.8 +/- 3.07 days) as compared to non-recipients (mean +/- SD: 1.73 +/- 4.27 days) but this difference did not reach statistical significance. CF infants may benefit from RSV immunoprophylaxis with palivizumab.

Inhibition of Human Coronavirus NL63 Infection at Early Stages of the Replication Cycle

Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, beta-D-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 microg/ml, 2 microM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 microM, >200 nM, >200 nM, >100 microM, and 80 microM, respectively). These agents may be investigated further for the treatment of coronavirus infections.

A cluster randomized controlled trial comparing three methods of disseminating practice guidelines for children with croup [ISRCTN73394937

BackgroundThe optimal management of croup – a common respiratory illness in young children – is well established. In particular, treatment with corticosteroids has been shown to significantly reduce the rate and duration of intubation, hospitalization, and return to care for on-going croup symptoms. Furthermore treatment with a single dose of corticosteroids does not appear to result in any significant adverse outcomes, and yields overall cost-savings for both families and the health care system.However, as has been shown with many other diseases, there is a significant gap between what we know and what we do. The overall aim of this study is to identify, from a societal perspective, the costs and associated benefits of three strategies for implementing a practice guideline that addresses the management of croup.Methods/designsWe propose to use a matched pair cluster trial in 24 Alberta hospitals randomized into three intervention groups. We will use mixed methods to assess outcomes including linkage and analysis of administrative databases obtained from Alberta Health and Wellness, retrospective medical chart audit, and prospective telephone surveys of the parents of children diagnosed to have croup. The intervention strategies to be compared will be mailing of printed educational materials (low intensity intervention), mailing plus a combination of interactive educational meetings, educational outreach visits, and reminders (intermediate intensity intervention), and a combination of mailing, interactive sessions, outreach visits, reminders plus identification of local opinion leaders and establishment of local consensus processes (high intensity intervention). The primary objective is to determine which of the three intervention strategies are most effective at lowering the rate of hospital days per 1,000 disease episodes. Secondary objectives are to determine which of the three dissemination strategies are most effective at increasing the use of therapies of known benefit. An economic analysis will be conducted to determine which of the three intervention strategies will most effectively reduce total societal costs including all health care costs, costs borne by the family, and costs stemming from the strategies for disseminating guidelines.

Near patient testing for influenza in children in primary care: comparison with laboratory test

Influenza is an important cause of acute respiratory illness in young children. Common complications include febrile convulsions, otitis media, bronchiolitis, and croup. In epidemic years attack rates among preschool children...

Limiting the Spread of Resistant Pneumococci: Biological and Epidemiologic Evidence for the Effectiveness of Alternative Interventions

Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an "antiresistance vaccine" that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.

Limiting the spread of resistant pneumococci: biological and epidemiologic evidence for the effectiveness of alternative interventions.

Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an "antiresistance vaccine" that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.

Parental smoking and respiratory illnesses in Australian children aged 0-4 years: ABS 1989-90 National Health Survey results

ObjectiveThis study investigated the associations between parental smoking and respiratory infections in Australian children aged 0-4 years. MethodsData from the ABS 1989-90 National Health Survey were used. The exposure variables examined were maternal, paternal and combined family smoking. Outcome variables were parent-reported chronic or recent asthma, asthma wheeze, bronchitis, influenza, common cold, cough, otitis media and other respiratory conditions. Logistic regression techniques were used to control for confounding by socio-economic status, child's sex, maternal education, place of residence, ethnicity and family size. ResultsOf the 4,281 children in the sample, 45% lived in households with one or more current smokers and 29% had a mother who smoked. Maternal (but not paternal) smoking was significantly associated with asthma (OR 1.52, 95% CI 1.19-1.94) and asthma wheeze (OR 1.51, 95% CI 1.26-1.80). No other significant associations were observed. Positive and significant dose response relationships were found between the amount of maternal smoking and both asthma variables. Population attributable risks were calculated and almost 13% of asthma and asthma wheeze in 0-4 year old Australian children in 1989-90 was estimated to be due to maternal smoking. ConclusionLarge numbers of Australian children live in households with smokers. This study, like others, has shown an association between maternal smoking and respiratory illnesses in young children. Further strategies are needed to prevent or reduce young children's exposure to environmental tobacco smoke in their homes.

Serious respiratory illness associated with rhinovirus infection in a pediatric population

Background: Rhinoviruses have long been associated with mild upper respiratory illness in both adults and children. However, the role of rhinoviruses as lower respiratory tract pathogens has not been fully characterized. Previous data suggests that rhinoviruses may cause severe lower respiratory illness in young children or infants. Objectives: The present study describes the clinical presentations, severity of illness and outcomes for a large cohort of pediatric patients with documented rhinovirus infections. Subjects and methods: A retrospective chart review was done on 93 pediatric patients from whom 101 nasopharyngeal or endotracheal specimens were positive by viral culture for a rhinovirus. All patients were hospitalized or seen in the pediatric emergency department at The Children’s Hospital of Philadelphia between 1 January, 1990 and 31 May, 1996. Results: Of the 93 patients, 52 were male and 41 female. The age range was 0 days to 18 years with 25 (27%) less than 3 months, 42 (45%) between 3 and 12 months and 26 (28%) over the age of 12 months. Clinical presentations on evaluation in the emergency department or admission included 78 (84%) patients with acute respiratory illness, 13 (17%) with fever and suspected sepsis and 11 (12%) with other complaints. Reported physical findings on examination included one or more lower respiratory symptoms or signs of acute distress and fever greater than or equal to 38.1°C. A total of 64 (69%) children were noted to have significant past medical histories, including 28 (44%) with prematurity or complicated neonatal courses, 11 (17%) with prior reactive airways, 8 (12%) with congenital cardiac disease and 7 (11%) with neurologic disorders. Of the patients, 29 (31%) were considered to be otherwise healthy children with no underlying dysfunctions. The mean duration of hospitalization for 69 patients admitted with respiratory illness who did not develop subsequent unrelated complications was 3.7 days. No significant bacterial or fungal pathogens were identified in 91% of the cases. Conclusions: This study shows that rhinoviruses were associated with severe lower respiratory illness and hospitalization in a large pediatric population and that rhinovirus infection was a complicating factor in those patients with underlying or predisposing conditions.

Measles Vaccination During the Respiratory Virus Season and Risk of Vaccine Failure

To determine whether measles vaccine failure is more common in persons who were vaccinated during the respiratory virus season, when they were more likely to have had concurrent minor illnesses. Population-based case series and case-control study. Wisconsin and Ohio. The case series included all 545 of the states' residents who had confirmed measles reported during 1985 through 1990 and a history of receiving a single dose of measles vaccine during 1975 through 1988 at 15 to 59 months of age. In a case-control study restricted to 1984 through 1988 vaccinees, season of vaccination was compared in 170 case children and 6070 control students. Risk of clinical vaccine failure after measles vaccination during the respiratory virus season (September through May) or the peak season (November through March) compared with summertime (June through August), after adjustment for age at vaccination and place of residence. In the case series of persons with vaccine failure, the proportion who had been vaccinated during the respiratory virus season (74.7%) was no greater than expected (September through May = 74.8% of the year). In the case-control study, vaccination during the respiratory virus season (odds ratio, 0.92; 95% confidence interval, 0.66 to 1.30) or the peak season (odds ratio, 0.93) did not increase the risk of vaccine failure. Despite the high and strongly seasonal prevalence of viral respiratory illness in young children, routine childhood measles vaccination during the respiratory virus season does not increase their risk of vaccine failure. Findings provide epidemiologic support for recently strengthened recommendations that measles vaccination not be deferred in children with minor respiratory illnesses.

Age-Related Development of Human Memory T-Helper and B-Cell Responses toward Parainfluenza Virus Type-1

Human parainfluenza-1 virus (hPIV-1) infections are a major cause of respiratory illness in young children. While children and adults are each susceptible to hPIV-1 infection, the clinical symptoms in adults are mild and hospitalizations are rare. One explanation for the differences in disease severity is that immune memory responses are simply inferior in children as compared to adults and cannot counter virus growth. Alternatively, it has been suggested that immune (particularly T-helper (TH) cell) responses toward respiratory viruses are superior in children versus older individuals, and that these responses contribute to, rather than protect from, disease symptoms. As a test of these possibilities, we analyzed hPIV-1-specific T-helper (TH) and B-cell memory responses among individuals of various ages, including children hospitalized with hPIV-1-induced croup. Experiments revealed: (1) hPIV-1-specific B-cell and class-II restricted TH-Cell proliferative responses were present in all tested adults. (2) TH-cells responded to internal viral proteins as well as to the external glycoprotein, hemagglutinin-neuraminidase. (3) Immune responses were highly cross-reactive with Sendai virus. (4) Memory B-cell and TH-cell responses were extremely poor in young children, inclusive of children tested upon hospital entry for hPIV-1-induced croup. In total, results did not support the theory that naturally induced hPIV-specific memory responses cause respiratory illness. Rather, results showed a correlation between memory and a good clinical outcome and highlighted Sendai virus as a strong candidate for an hPIV-1 vaccine.

On the health effects of environmental tobacco smoke.

Possible adverse health effects of breathing environmental tobacco smoke include lung cancer, respiratory illnesses in young children, decreased pulmonary function, decreased lung growth, allergy to tobacco, and exacerbation of angina. These effects are reviewed to aid informed discussion on this health issue. Some of the constituents of tobacco smoke are found in the home, the outdoor environment, and the workplace in permissible concentrations and are considered unlikely to cause ill health. A double standard, one in the workplace and another for the public, may be evolving for acceptable health risks.