Common Cause Of Respiratory Infections Research Articles

NS1 Protein Mutation I64T Affects Interferon Responses and Virulence of Circulating H3N2 Human Influenza A Viruses.

ABSTRACTInfluenza NS1 protein is the main viral protein counteracting host innate immune responses, allowing the virus to efficiently replicate in interferon (IFN)-competent systems. In this study, we analyzed NS1 protein variability within influenza A (IAV) H3N2 viruses infecting humans during the 2012-2013 season. We also evaluated the impact of the mutations on the ability of NS1 proteins to inhibit host innate immune responses and general gene expression. Surprisingly, a previously unidentified mutation in the double-stranded RNA (dsRNA)-binding domain (I64T) decreased NS1-mediated general inhibition of host protein synthesis by decreasing its interaction with cleavage and polyadenylation specificity factor 30 (CPSF30), leading to increased innate immune responses after viral infection. Notably, a recombinant A/Puerto Rico/8/34 H1N1 virus encoding the H3N2 NS1-T64 protein was highly attenuated in mice, most likely because of its ability to induce higher antiviral IFN responses at early times after infection and because this virus is highly sensitive to the IFN-induced antiviral state. Interestingly, using peripheral blood mononuclear cells (PBMCs) collected at the acute visit (2 to 3 days after infection), we show that the subject infected with the NS1-T64 attenuated virus has diminished responses to interferon and to interferon induction, suggesting why this subject could be infected with this highly IFN-sensitive virus. These data demonstrate the importance of influenza virus surveillance in identifying new mutations in the NS1 protein, affecting its ability to inhibit innate immune responses and, as a consequence, the pathogenicity of the virus.IMPORTANCE Influenza A and B viruses are one of the most common causes of respiratory infections in humans, causing 1 billion infections and between 300,000 and 500,000 deaths annually. Influenza virus surveillance to identify new mutations in the NS1 protein affecting innate immune responses and, as a consequence, the pathogenicity of the circulating viruses is highly relevant. Here, we analyzed amino acid variability in the NS1 proteins from human seasonal viruses and the effect of the mutations in innate immune responses and virus pathogenesis. A previously unidentified mutation in the dsRNA-binding domain decreased NS1-mediated general inhibition of host protein synthesis and the interaction of the protein with CPSF30. This mutation led to increased innate immune responses after viral infection, augmented IFN sensitivity, and virus attenuation in mice. Interestingly, using PBMCs, the subject infected with the virus encoding the attenuating mutation induced decreased antiviral responses, suggesting why this subject could be infected with this virus.

Phylogenetic analysis of human rhinoviruses collected over four successive years in Sydney, Australia.

BackgroundHuman rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza‐like illness (ILI) to severe respiratory infection. Molecular epidemiological data are limited for HRV circulating in the Southern Hemisphere.ObjectivesTo identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009.MethodsCombined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR). Sequencing data of 5′UTR and VP4/VP2 coding regions on RT‐PCR‐positive specimens were analysed.ResultsHuman rhinoviruses were detected by real‐time PCR in 20.9% (116/555) of samples tested. Phylogenetic analysis of 5′UTR and VP4/VP2 on HRV‐positive samples was concordant in the grouping of HRV A and B species but not HRV C species. Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A. Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5′UTR tree, and one sequence showed identity to different HRV A strains in the two genes. The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032).ConclusionHuman rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere. Sequencing of multiple HRV regions may be necessary to determine exact phylogenetic relationships.

Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia-a new therapeutic strategy?

Influenza viruses (IVs) circulate seasonally and are a common cause of respiratory infections in pediatric and adult patients. Additionally, recurrent pandemics cause massive morbidity and mortality worldwide. Infection may result in rapid progressive viral pneumonia with fatal outcome. Since accurate treatment strategies are still missing, research refocuses attention to lung pathology and cellular crosstalk to develop new therapeutic options.Alveolar epithelial cells (AECs) play an important role in orchestrating the pulmonary antiviral host response. After IV infection they release a cascade of immune mediators, one of which is granulocyte and macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to promote differentiation, activation and mobilization of myeloid cells. In the lung, GM-CSF drives immune functions of alveolar macrophages and dendritic cells (DCs) and also improves epithelial repair processes through direct interaction with AECs. During IV infection, AEC-derived GM-CSF shows a lung-protective effect that is also present after local GM-CSF application. This mini-review provides an overview on GM-CSF-modulated immune responses to IV pneumonia and its therapeutic potential in severe IV pneumonia.

Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus.

Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection.

No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996–2013

BackgroundMycoplasma pneumoniae is a common cause of respiratory infections which can cause life-threatening pneumonia and serious extrapulmonary manifestations. Since the year 2000, the emergence of macrolide-resistant M. pneumoniae strains has increased with varying incidences across countries. In China more than 90% of the strains are resistant. M. pneumoniae diagnostics is mostly done with molecular methods, and in Sweden antibiotic resistance surveillance is not routinely performed. The prevalence of macrolide-resistant M. pneumoniae has not previously been studied in Sweden.Material and methodsA total of 563 M. pneumoniae–positive respiratory samples, collected from four counties in Sweden between 1996 and 2013, were screened for mutations associated with macrolide resistance using a duplex FRET real-time PCR method. The real-time PCR targets the 23S rRNA gene, and differentiation between wild-type and resistant strains was achieved with a melting curve analysis.ResultsOf the 563 samples included, 548 were analyzed for mutations associated with macrolide resistance. No mutations were found. The detection rate of macrolide-resistant M. pneumoniae in this study was 0% [0.00–0.84%].ConclusionNo macrolide-resistant M. pneumoniae has been detected in Sweden. However, the emergence and spread of macrolide-resistant M. pneumoniae strains in many countries commands continuous epidemiological surveillance.

Respiratory Syncytial Virus in Hematopoietic Stem Cell Transplantation and Solid-Organ Transplantation.

Respiratory syncytial virus (RSV), one of the most common causes of respiratory infections in immunocompetent individuals, can cause significant pulmonary morbidity and mortality in hematopoietic stem cell (HSCT) and less often in solid-organ transplant recipients. Early diagnosis and medical intervention prior to the progression from upper to lower respiratory tract viral involvement is essential to positively affect the clinical course. The greatest risk of disease progression from upper to lower respiratory tract disease is during the early posttransplant period for HSCT recipients, with lymphopenia being an important risk factor. Polymerase chain reaction has become the preferred method for rapidly diagnosing infection in this population because of higher sensitivity compared to traditional viral culture and direct viral antigen methods. Despite the lack of prospective randomized trials, retrospective pooled analyses have suggested that systemically delivered ribavirin (either aerosolized, oral, or IV; with or without immunomodulator therapy) can decrease the risk of progression of disease. Additionally, there are a number of clinical trials currently in process to evaluate several new agents that target RSV in the high-risk HSCT patient population.

WS19.3 Prevalence of small colony variants of Staphylococcus aureus from lower respiratory tract specimens

Background Staphylococcus aureus , one of the first bacteria isolated from cystic fibrosis (CF) airways, is the most common cause of respiratory infections. Small-colony phenotypic variants (SCVs) of S. aureus are selected by long-term exposure to antibiotics or co-culture with Pseudomonas aeruginosa and are often difficult to detect. The prevalence of this pathogen is largely unknown. Aim To establish the prevalence of SCV S. aureus by screening lower airway specimens from children with CF. Methods SCV S. aureus were obtained from the hospital clinical laboratory from lower airway specimens of children with CF. Each visible morphotype was subcultured onto Horse blood agar (HBA) to enable identification of SCVs. If identified, isolates required confirmation by PCR amplification of the S. aureus -specific gene, nuc and metabolic defects determined by growing isolates in the presence of haemin, menadione, thymidine and CO 2 . Paired normal and SCV S. aureus isolates were to be genotyped using pulse-field gel electrophoresis. Results 26 children (mean age 11.35(5.05) years) from the AREST CF study (Melbourne) were identified with a positive S. aureus culture from lower respiratory tract specimens collected in 2014. All children were on at least one or multiple antibiotics prior to or at time of collection, namely Augmentin (46%), Tobramycin (15%), Bactrim (11%), or other (27%). 57% of samples were visible on large MSA plates and subcultured onto wild-type HBA plates, but no SCVs of S. aureus were isolated. Conclusion SCV's were not isolated from the lower airways specimens and therefore not identified as contributing to lung infections in our cohort of young subjects with CF.

A cost-benefit analysis of the immunisation of children against respiratory syncytial virus (RSV) using the English Hospital Episode Statistics (HES) data set.

Respiratory syncytial virus (RSV) is a common cause of respiratory infection that is highly prevalent in infants, particularly those with underlying medical conditions. Severe cases of RSV require hospitalisation as well as admission to intensive care and may even result in death. The objective of the study was to measure the net benefits that could arise from an immunisation programme of infants that may well eradicate RSV to a high degree and save the direct and indirect medical care costs from hospitalisation, morbidity and the gain from potential life-time earnings by reducing the probability of mortality. In this context, the majority of existing empirical investigations are based on data from clinical trials, and where relevant facts are not available, a series of strong assumptions is derived from the published literature, whereas in this study, for the first time, the hospital episode statistics database is used to calculate the cost-benefit ratios. The methodology of the analysis adopts a cost-benefit approach to assess the impact of the immunisation and whether it is beneficial to society. The underlying assumptions of the basic model are assessed by adopting a sensitivity analysis. The results show that a number of categories are cost-effective with the use of the passive drug, which means benefits by raising the life expectancy and quality as well as reducing the resource burden on society.

The Impact of Rhinovirus Infections in Paediatric Cardiac Surgery (Risk): Study Protocol for a Prospective Cohort Study

Background: Respiratory infections are considered a potential risk of adverse events in children undergoing surgery. Rhinovirus is a common cause of respiratory infections and congenital heart disease is a risk factor for severe rhinovirus infection. However, we do not know what the impact of, clinical or subclinical, rhinovirus infections is on postoperative course following congenital heart surgery in children. Based on our clinical experience, one case-controlled study, and a case reported in the literature, we hypothesize that paediatric patients with per-operative rhinovirus positive Polymerase Chain Reaction testing have a longer paediatric intensive care unit admission, compared to children who test negative. Methods/Design: This is a prospective single-center observational study in the Leiden University Medical Center with approximately 250 children (<12 years) undergoing elective cardiac surgery, for congenital heart disease. The parents/guardians of the children will be asked to fill out a questionnaire, to asses respiratory symptoms in the last weeks, before the operation of their child. In the operating theatre, a nasopharyngeal swab will be collected. Clinical data will be collected daily during paediatric intensive care admission and paediatric intensive care unit and hospital length of stay will be recorded. If children are still intubated at day 4, a second nasopharyngeal swab and residual blood will be collected. The samples will be tested for rhinovirus with polymerase chain reaction. Primary outcome is the paediatric intensive care unit length of stay in per-operative rhinovirus-positive compared to rhinovirus-negative patients. Discussion: This is the first study to screen children for rhinovirus before undergoing cardiac surgery and to study the effects on paediatric intensive care unit length of stay. Furthermore, we aim to identify children at risk for prolonged paediatric intensive care admission after cardiac surgery.

Molecular characterization of fluoroquinolone resistance in nontypeable Haemophilus influenzae clinical isolates.

Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment.

Commonly circulating human coronaviruses do not have a significant role in the etiology of gastrointestinal infections in hospitalized children

BackgroundHuman coronaviruses (HCoVs) OC43, 229E, NL63 and HKU1 are common causes of respiratory infections. Over the years, it has been proposed that HCoVs play a possible role in gastrointestinal infections. ObjectivesTo assess the role of HCoVs in acute gastroenteritis (AGE) in children. Study designStudy was conducted at Tampere University Hospital over 2 years. Both stool and nasal swab samples were collected from 172 children with AGE, 545 with acute respiratory tract infection (ARTI) and 238 with symptoms of both. The samples were tested for HCoVs by RT-PCR. ResultsHCoVs were detected in 52 (5.4%) children: in 6.4% of those with AGE, 4.4% with ARTI and 7.1% with symptoms of both. HCoVs OC43, HKU1, 229E and NL63 were encountered in 13, 11, 13 and 15 cases, respectively. HCoVs were detected simultaneously in stool and nasal swab samples in 17 children, in nasal swabs alone in 33 children, and in the stools alone in two children. HCoVs were present in the stools of eight (4.7%) of the 172 children with AGE; in six of these cases, the nasal swab sample was also positive for the respective HCoV. Additionally, in six of the eight cases, the stool sample contained either rotavirus or calicivirus. ConclusionsHCoVs can be detected in the stools of children with AGE, but usually together with well-known gastroenteritis viruses, and concomitantly in the respiratory tract. It appears that commonly circulating HCoVs do not have a significant role in the AGE of children admitted to hospital.

Characterization of recombinant influenza A virus as a vector expressing respiratory syncytial virus fusion protein epitopes.

Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants and the elderly, and no vaccine against this virus has yet been licensed. Here, we report a recombinant PR8 influenza virus with the RSV fusion (F) protein epitopes of the subgroup A gene inserted into the influenza virus non-structural (NS) gene (rFlu/RSV/F) that was generated as an RSV vaccine candidate. The rescued viruses were assessed by microscopy and Western blotting. The proper expression of NS1, the NS gene product, and the nuclear export protein (NEP) of rFlu/RSV/F was also investigated using an immunofluorescent assay. The rescued virus replicated well in the MDCK kidney cell line, A549 lung adenocarcinoma cell line and CNE-2Z nasopharyngeal carcinoma cell line. BALB/c mice immunized intranasally with rFlu/RSV/F had specific haemagglutination inhibition antibody responses against the PR8 influenza virus and RSV neutralization test proteins. Furthermore, intranasal immunization with rFlu/RSV/F elicited T helper type 1-dominant cytokine profiles against the RSV strain A2 virus. Taken together, our findings suggested that rFlu/RSV/F was immunogenic in vivo and warrants further development as a promising candidate vaccine.

Normoxic induction of HIF-1α in macrophages is required for protection from the fungal pathogen H. capsulatum. (MPF3P.807)

Abstract Histoplasma capsulatum (Hc) is the most common cause of respiratory infection among endemic mycoses. Macrophages (MΦ) are the primary phagocytic cell that engulfs Hc. Recent data has demonstrated that the transcription factor hypoxia inducible factor 1α (HIF-1α) can be induced by pro-inflammatory cytokines or LPS in normoxia. Because HIF-1α regulates a number of factors that are potentially vital in MΦ responses to Hc, we hypothesized that myeloid HIF-1α exerts a critical role in conferring protection to Hc. Indeed, the absence of myeloid HIF-1α led to significantly higher fungal burden at 7 days post-infection and a 75% reduction in survival following Hc infection. In vitro, the HIF-1α isoform i.1 (HIFi.1) and downstream target genes were transcriptionally induced in Hc-infected bone marrow derived MΦ in normoxia. To determine if HIFi.1 induction occurs in vivo, mice were infected with a Hc strain expressing GFP. At 7 days post infection, GFP+ (infected) and GFP- (uninfected) MΦ were isolated from lungs; surprisingly both GFP+ and GFP- phagocytes exhibited induction of HIFi.1 and its target genes. Transwell assays demonstrated that a soluble mediator released from infected cells was partly responsible for HIF i.1 induction. Genetic deletion of TNFR1 or dectin-1 abrogated the in vitro induction of HIFi.1. We propose that dectin-1 mediated MΦ TNF-α production is responsible, at least in part, for induction of HIFi.1; myeloid HIF-1α is instrumental in the immune response to Hc.

Synthesis, biological activity and structure–activity relationship of 4,5-dimethoxybenzene derivatives inhibitor of rhinovirus 14 infection

Human rhinoviruses are a common cause of respiratory infections, and thus constitute an important target for medicinal chemistry. Still, no drug has been approved for clinical use. We report herein the discovery of dibenzenic derivatives with potent and specific in vitro anti-rhinoviral 14 activity. A total of 99 structural analogues were synthesized by an original synthesis method, i.e. through one organic agent Tetrakis(DimethylAmino)Ethylene (TDAE) and a structure–activity relationship was established. It was shown that 4,5-dimethoxy scaffold and the presence of a C-4 substituted aromatic moiety were necessary to the in vitro activity of these original agents. However, modifications on liker were not convincing. The benzonitrile derivative 23 was identified as the most potent and selective inhibitor of rhinovirus replication in these series (EC50 of 2 ± 0.5 μM, CC50 of 184 μM, selectivity index of 92).

Pulmonary immune response to Streptococcus pneumoniae

Streptococcus pneumoniae is a common cause of respiratory infection associated with significant morbidity and mortality. The immune response to S. pneumoniae is complex, multi-layered and incompletely understood. The lung has non-specific defence mechanisms that include cellular and secreted components. The initial response to bacteria that adhere to or breach the epithelium is mediated by the innate immune system and recognition of non-specific motifs common to many pathogens. This stimulates the inflammatory response and subsequently the development of the more specific adaptive immune system. Better understanding of the immune response to S. pneumoniae will underpin future progress in both the prevention of infection and adjuvants to existing treatments.

Clinical Presentation and Laboratory Findings of Mycoplasma pneumoniae Respiratory Infections in Children

Mycoplasma pneumoniae is a common cause of respiratory infections in children and adults, but the most severe presentations tend to be in older children and adolescents. The organism causes up to 30% of primary atypical pneumonia (PAP), but it is now recognized that these severe manifestations of infection represent only a small percentage of respiratory infections due to this species of bacteria. Typical incubation times until the development of symptoms are remarkably slow for a bacterial infection, usually between 2 and 3 weeks. The typical presentation includes flulike symptoms with cough, often with sore throat, headache, malaise, and fever. Symptoms, particularly cough, may be very prolonged despite appropriate antibiotic therapy, sometimes lasting up to 3 months. Cough, initially dry, may become productive of purulent sputum as the illness progresses. Examination of the throat may reveal some erythema but usually no exudates or associated lymphadenopathy. Auscultation of the chest in patients with PAP often demonstrates fine inspiratory rales, particularly at the lung bases, and occasionally expiratory wheezing. Chest films may show streaky unilateral or bibasilar infiltrates, peribronchial thickening, and not infrequently small pleural effusions. Computed tomographs of the chest are very likely to show peribronchial thickening and centrilobular nodules with a tree-in-bud pattern and patchy areas of airspace consolidation. Accurate diagnosis of M. pneumoniae infections is complicated by a current lack of rapid diagnostic techniques with appropriate sensitivity and specificity.

Respiratory Syncytial Virus Infection Induces Higher Toll-Like Receptor-3 Expression and TNF-α Production Than Human Metapneumovirus Infection

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are common causes of respiratory infections in children. Diseases caused by hMPV are generally considered to be less severe than those caused by RSV; the underlying mechanisms, however, remain unknown. In the present study, the expressions of TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV were measured in an attempt to explore the differences in the airway inflammation caused by the two viruses. Our results demonstrate that both hMPV and RSV infection upregulated the expressions of TLRs and inflammatory cytokines. Specifically, the TLR3 expression was revealed to be elevated in vitro and in mouse lungs. IFN-α produced by A549 cells after RSV or hMPV infection remained undistinguishable, whereas production of TNF-α was significantly higher after RSV infection than hMPV infection either in the presence or absence of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV infection may be due to the greater magnitude of induction of airway inflammation by RSV involving TLR3 activation and production of TNF-α.

Respiratory viral infections and effects of meteorological parameters and air pollution in adults with respiratory symptoms admitted to the emergency room

BackgroundRespiratory viral infections (RVIs) are the most common causes of respiratory infections. The prevalence of respiratory viruses in adults is underestimated. Meteorological variations and air pollution are likely to play a role in these infections.ObjectivesThe objectives of this study were to determine the number of emergency visits for influenza-like illness (ILI) and severe acute respiratory infection (SARI) and to evaluate the association between ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city of Porto Alegre, Brazil, from November 2008 to October 2010.MethodsEleven thousand nine hundred and fifty-three hospitalizations (adults and children) for respiratory symptoms were correlated with meteorological parameters and air pollutants. In a subset of adults, nasopharyngeal aspirates were collected and analyzed through IFI test. The data were analyzed using time-series analysis.ResultsInfluenza-like illness and SARI were diagnosed in 3698 (30·9%) and 2063 (17·7%) patients, respectively. Thirty-seven (9·0%) samples were positive by IFI and 93 of 410 (22·7%) were IFI and/or PCR positive. In a multivariate logistic regression model, IFI positivity was statistically associated with absolute humidity, use of air conditioning, and presence of mold in home. Sunshine duration was significantly associated with the frequency of ILI cases. For SARI cases, the variables mean temperature, sunshine duration, relative humidity, and mean concentration of pollutants were singnificant.ConclusionsAt least 22% of infections in adult patients admitted to ER with respiratory complaints were caused by RVI. The correlations among meteorological variables, air pollution, ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate factors as significant underlying contributors to the prevalence of RVI.

A cost-effectiveness analysis of respiratory syncytial virus (RSV) prophylaxis in infants in the United Kingdom.

BackgroundRespiratory syncytial virus (RSV) is a common cause of respiratory infection that is highly prevalent in infants. Severe cases of RSV infection require hospitalisation; this is most likely to occur in infant populations at high risk. The study assesses the cost-effectiveness of palivizumab versus no prophylaxis in infants at high risk of hospitalisation with RSV in the United Kingdom (UK).MethodsA decision tree model was developed to reflect the clinical pathway of infants at high risk of severe RSV infection who receive either prophylaxis with palivizumab or no prophylaxis. The main outcome was the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the degree of uncertainty surrounding the results. A threshold analysis considered the impact of clinical and environmental risk factors on the cost-effectiveness in the subgroup of preterm infants 33–35 weeks gestational age (wGA).ResultsProphylaxis with palivizumab compared with no prophylaxis is associated with the following ICERs; £33,216 for infants with congenital heart disease; £19,168 for infants with chronic lung disease; £3,845 for preterm infants < 29 wGA; £30,205 for preterm infants 29–32 wGA; and £99,056 for preterm infants 33–35 wGA. One-way sensitivity analysis suggests that these results are highly sensitive to the input data. Threshold analysis in the preterm 33–35 wGA subgroup demonstrates that an adjusted RSV-hospitalisation baseline risk of 17.94% or higher would result in an ICER below the £30,000 per quality-adjusted life-year threshold.DiscussionPalivizumab is cost-effective compared to no prophylaxis in the United Kingdom in many of the subgroups considered, showing that palivizumab would be a cost-effective use of National Health Service resources.

Comparison of Throat and Nasopharyngeal Swab Specimens for Molecular Diagnosis of Mycoplasma pneumoniae

Mycoplasma pneumoniae is a common cause of respiratory infections in humans. Although it is usually associated with mild acute respiratory infections such as sore throat, pharyngitis, rhinitis and tracheobronchitis. The aim of this study was to evaluate the prevalence of M. pneumoniae among the patients of respiratory tract infection (RTI) in hospitalized patients. A total of 290 patients were included and one specimen of throat and Nasopharyngeal swabs from each patient was taken. The mean age of the patients was 34.5 (±9.80) years and 57.2% were males. The prevalence of Mycoplasma pneumoniae was significant higher (15.5%) among NPS samples compare with throat (7.9%) samples (RR=0.51, 95%CI=0.32-0.82, p=0.005). The prevalence of Mycoplasma pneumoniae was found to be decreased with increase in the age of the patients among both throat and Nasopharyngeal swabs, however, this was statistically insignificant (p>0.05). The prevalence was higher among male patients compared with female among both throat and Nasopharyngeal swabs, and this was statistically significant (p<0.05). There was seasonal variations in the prevalence of Mycoplasma pneumoniae. The prevalence was higher in winter season than summer among both throat (Winter=5.9%, Summer=9.3%) and Nasopharyngeal (Winter=2.1%, Summer=6.2%) swabs.