Cause Of Acute Respiratory Illness Research Articles

Symptomatic Respiratory Syncytial Virus Infection in Previously Healthy Young Adults Living in a Crowded Military Environment

Respiratory syncytial virus (RSV) infection is a potentially important cause of acute respiratory illness in many populations, including military recruits receiving basic training. Understanding the full impact of RSV infection is challenging because of difficulties in diagnosis and the limitations of past epidemiologic studies. In this study, we set out to determine the prevalence and clinical characteristics of RSV infection and infection caused by other common viral agents in a population of previously healthy young adults, namely, military recruits receiving basic training. In addition to standard viral culture techniques, we employed serologic testing and a recently described, novel, highly sensitive real-time PCR and a molecular beacon probe assay for the detection of RSV infection. Among 256 military trainees with respiratory symptoms, RSV infection was identified in 11% by means of serologic testing and real-time PCR. Viral culture identified adenovirus in 48% of symptomatic recruits, influenza viruses in 11%, parainfluenza virus 3 in 3%, and enterovirus in <1%. The majority of recruits with RSV infection experienced a nonproductive cough, sore throat, and nasal congestion, and almost half reported symptoms of wheeze or shortness of breath. Almost all (94%) of the recruits lost > or =1 day(s) from training because of illness. This study demonstrates the challenges of diagnosis and clinical significance of RSV infection in symptomatic young adults. RSV may account for 11% of clinically important respiratory illnesses in this population, which is as much as 25% of previously undiagnosed illness. These results have implications for treatment and prevention of RSV in young adults.

Human metapneumovirus: An important cause of respiratory disease in children and adults

Human metapneumovirus is a paramyxovirus that was discovered in 2001 in the Netherlands. Epidemiologic studies have shown it to be a major cause of acute respiratory tract disease in normal infants and children worldwide, with a seasonal occurrence and spectrum of clinical illness most similar to the closely related respiratory syncytial virus. The greatest prevalence of severe disease requiring hospitalization in otherwise healthy children appears to be in those aged between 6 and 12 months, older than the peak age of hospitalizations for respiratory syncytial virus. Human metapneumovirus is also a significant cause of acute respiratory disease in adults, particularly the elderly and those with comorbid conditions such as chronic obstructive pulmonary disease, asthma, and cancer. Because there is no rapid diagnostic assay, reverse transcriptase polymerase chain reaction is most widely used. Animal models have been developed, and candidate live-attenuated vaccines are in preclinical trials, offering the potential for future interventions in high-risk groups.

First Detection of Human Metapneumovirus in Children with Acute Respiratory Infection in India: a Preliminary Report

In 2001, van den Hoogen et al. first reported the discovery of human metapneumovirus (HMPV) in respiratory patients from The Netherlands. The disease spectrum ranged from mild upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies documented circulation of HMPV for at least 50 years (8). Subsequently, this virus has been recognized as a significant cause of acute respiratory illness (ARI) in infants, children, and adults worldwide (1, 2, 5). Though respiratory diseases are highly prevalent in India (7), the role of HMPV has not been examined so far. We analyzed 17 nasopharyngeal aspirate specimens collected from the pediatric inpatient department of Sassoon General Hospital, Pune (Maharashtra state), India, and 12 throat swab and 15 nasal swab specimens from outpatient departments during July-August 2003 for detection of HMPV by reverse transcription-PCR. These were stored in transport medium at −70°C till being tested. Total RNA was extracted from 250 μl of the respiratory specimens using the TRIZOL (LS) reagent (GIBCO BRL, Life Technologies) according to the manufacturer's instructions and used for nested reverse transcription-PCR according to the published protocol and primer sequences (6). Stringent precautions were taken to avoid false positivity in the PCR. Negative controls were included between two samples and subjected to the entire PCR protocol. Pre- and postamplification procedures were performed on the different floors of the laboratory. All five HMPV-RNA-positive PCR products were sequenced directly on both strands. The phylogenetic status of HMPV-positive specimens was assessed by employing the software MEGA (3). For analysis in MEGA, the Jukes-Cantor distance was utilized, employing the neighbor-joining algorithm. The reliability of different phylogenetic groupings was evaluated by using the bootstrap test (1,000 bootstrap replications) available in MEGA. Patients with severe ARI (17 children) admitted in the inpatient department had fever and severe lower respiratory tract infection and were diagnosed as having pneumonia or bronchopneumonia. Patients with mild ARI attending outpatient departments had symptoms of common cold, pharyngitis, laryngitis, tracheitis, bronchitis, body ache, fever, and weakness in different combinations. These included 9 children and 18 adults. HMPV RNA was detected in 19.2% (5 of 26) of the children and 0 of 18 adults. Importantly, four out of five patients in whom HMPV RNA was detected were children below the age of 1 year, and one was from the age group 1 to 5 years. The GenBank accession numbers for the sequences generated during this study are {type:entrez-nucleotide,attrs:{text:AY532377,term_id:46488852,term_text:AY532377}}AY532377 to {type:entrez-nucleotide,attrs:{text:AY532381,term_id:46488860,term_text:AY532381}}AY532381. Phylogenetic analysis based on a 216-nucleotide fragment of the M gene (Figure ​(Figure1)1) demonstrated genetic heterogeneity of the Indian HMPV viral isolates with 100% bootstrap support. Four isolates (INDHMP1 and INDHMP2, both from mild cases, and INDHMP4 and INDHMP5, both from severe cases) clustered with several Canadian strains isolated in 1997, 1998, and 2000. Isolate INDHMP3 (from a severe case) belonged to a distinct second lineage comprising isolates from The Netherlands (2000) and Canada (1997, 1998, 1999, and 2002). In the second lineage, the Indian isolate (INDHMPV3) was separated from other isolates, forming a separate subgroup. FIG. 1. Phylogenetic analysis of partial M gene (216-base fragment) sequences of 24 HMPV isolates. See the text for details of the isolates and abbreviations used. Percent bootstrap support is indicated by the values at each node. The results of this preliminary study showed that during the 2-month study period, HMPV was detected in nearly five children with respiratory infections. Though none of the 18 adults were positive, unless a larger sample size is screened, infrequent infection of adults with HMPV cannot be concluded. The fact that four of the five PCR-positive patients were infants suggests importance of HMPV in this vulnerable age group. Importantly, both severe and mild cases yielded PCR positivity, demonstrating the clinical spectrum of the disease. The presence of viral RNA could be demonstrated in nasopharyngeal aspirates (n = 3) as well as nasal swabs (n = 2). The latter specimens are easy to collect. Reports from Italy have shown similar observations (4). M-gene-based phylogenetic analysis demonstrated cocirculation of distinctly different HMPV strains in Pune in 2003. The four isolates belonging to a lineage represented both mild and severe cases, whereas the only isolate belonging to the other lineage came from a severe case. In summary, the present study suggests the importance of HMPV in causing mild and severe respiratory infections among children, especially infants in India. Multicentric, long-term studies from different parts of India are needed to assess the disease burden.

Rhinovirus in adenoid tissue

Objective: Rhinovirus (RV) infection is the most common single cause of acute respiratory illness in children. The purpose of the study was to evaluate the prevalence of RV in adenoid tissue throughout the year. Material and methods: Fifty-six samples of adenoid tissue removed either due to recurrent otitis media or adenoid hypertrophy were collected for in-situ hybridization (ISH) of RV. To confirm the specificity of the ISH probe, eight adenoid biopsies were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) as well. Results: ISH was positive for RV RNA in 45% of the specimens. There was a statistically significant difference ( P=0.002) in the prevalence of RV positive adenoid biopsies from late fall to spring (65%) in comparison to late spring to early fall (20%). Children with middle ear effusion were more often ISH positive than those with dry ears, but the number of past ear infections, signs of chronic nasal obstruction or recent runny nose did not correlate to the finding in ISH. There was a good concordance between the results obtained by ISH and by RT-PCR. Conclusion: Both epithelial and/or germinal cells of adenoid tissue are frequently loaded with RV during the cold months of the year, also known to have a high incidence of RV infections among population. Children with otitis media with effusion are more likely to harbor RV in adenoid tissue than those with dry ears. Further studies are, however, needed to show whether the effusion is due to RV or whether this association exists by coincidence.

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...

Clinical features that discriminate inhalational anthrax from other acute respiratory illnesses.

Inhalational anthrax (IA) is a rapidly progressive disease that frequently results in sepsis and death, and prompt recognition is critical. To distinguish IA from other causes of acute respiratory illness, patients who had IA were compared with patients in an ambulatory clinic who had influenza-like illness (ILI) and with hospitalized patients who had community-acquired pneumonia (CAP) at the initial health care visit. Compared with patients who had ILI, patients who had IA were more likely to have tachycardia, high hematocrit, and low albumin and sodium levels and were less likely to have myalgias, headache, and nasal symptoms. Scoring systems were devised to compare IA with ILI or CAP on the basis of strength of association. For ILI, a score of > or =4 captured all 11 patients with IA and excluded 664 (96.1%) of 691 patients with ILI. Compared with patients who had CAP, patients with IA were more likely to have nausea or vomiting, tachycardia, high transaminase levels, low sodium levels, and normal white blood cell counts. For CAP, a score of > or =3 captured 9 (81.8%) of 11 patients with IA and excluded 528 (81.2%) of 650 patients with CAP. In conclusion, selected clinical features of patients with IA differ from those of patients with ILI and are more similar to those of patients with CAP.

Detection of adenoviruses (AdV) in culture-negative environmental samples by PCR during an AdV-associated respiratory disease outbreak.

Since 1954, adenoviruses (AdV) have been recognized as an important cause of acute respiratory disease (ARD) among U.S. military recruits. Until recently, routine oral vaccination for AdV serotypes 4 and 7 eliminated epidemic AdV-associated ARD in this population. Now that the manufacturer has ceased production, vaccination has ended and AdV epidemics have reappeared. As part of a prospective epidemiological study during the high-risk ARD season, serial samples were obtained from ventilation system filters and tested for AdV by culture and PCR. An outbreak occurred during this surveillance. Of 59 air filters, 26 (44%) were AdV positive only by PCR. Sequence analysis confirmed the presence of AdV serotype 4, the implicated outbreak serotype. The number of AdV-related hospitalizations was directly correlated with the proportion of filters containing AdV; correlation coefficients were 0.86 (Pearson) and 0.90 (Spearman's rho). This is the first report describing a PCR method to detect airborne AdV during an ARD outbreak. It suggests that this technique can detect and quantify AdV-associated ARD exposure and may enable further definition of environmental effects on AdV-associated ARD spread.

Equine influenza in the United Kingdom in 1998.

In 1998, equine influenza was diagnosed by serology and nucleoprotein enzyme-linked immunosorbent assay as the cause of acute respiratory disease in vaccinated and unvaccinated horses in the UK. The signs were generally milder in vaccinated horses and completely susceptible animals showed the most severe signs, including pyrexia, inappetence, coughing, mucopurulent nasal discharge and secondary bacterial pneumonia. In a detailed investigation of an outbreak among 52 vaccinated thoroughbreds in a flat racing yard, more than 60 per cent of the horses seroconverted on the evidence of paired serum samples tested by single radial haemolysis (SRH). Preliminary sequencing and characterisation of an isolate from this outbreak indicated that it was an 'American-like' strain. In addition, in this outbreak there was a larger proportion of horses with preinfection SRH titres greater than 140 mm2 that subsequently seroconverted than in other recent outbreaks from which 'European-like' strains have been isolated. This result suggested that the cross-protectivity between circulating 'American-like' strains and the 'European-like' strains of A/equine-2 viruses present in current vaccines may be decreasing.

Role of Innate and Adaptive Immunity in the Outcome of Primary Infection withChlamydia pneumoniae, as Analyzed in Genetically Modified Mice

AbstractInfection with Chlamydia pneumoniae is a common cause of acute respiratory disease in man and is also associated with atherosclerotic cardiovascular disorder. Herein, we have compared bacterial load and immune parameters of C. pneumoniae-infected mice genomically lacking T cell coreceptors, cytokine receptors, or cytotoxic effector molecules. A protective role for CD8+ cells is shown by the enhanced severity of infection of CD8−/− or TAP-1−/−/β2-microglobulin −/− mice. CD8+ cells hindered a parasite growth-promoting role of CD4+ T cells, as indicated by the higher sensitivity to early infection of CD8−/− than CD4−/−/CD8−/− mice, which was further confirmed in experiments in which SCID mice were reconstituted with either CD4+ or CD4+ plus CD8+ T cells. Interestingly, CD4+ T cells played a dual role, detrimental early (14 and 24 days) after infection but protective at later time points (60 days after infection). The CD8+ T cell protection was perforin independent. The early deleterious role of CD4+ in the absence of CD8+ T cells was associated with enhanced IL-4 and IL-10 mRNA levels and delayed IFN-γ mRNA accumulation in lungs. In line with this, IFN-γR−/− (but not TNFRp55 −/−) mice showed dramatically increased susceptibility to C. pneumoniae, linked to reduced inducible nitric oxide synthase (iNOS) mRNA accumulation, but not to diminished levels of specific Abs. The increased susceptibility of iNOS−/− mice indicates a protective role for iNOS activity during infection with C. pneumoniae. The higher sensitivity of IFN-γR−/− mice to C. pneumoniae compared with that of SCID or recombination-activating gene-1−/− mice suggested a relevant protective role of IFN-γ-dependent innate mechanisms of protection.

A Case of Fulminant Bronchiolitis Obliterans Organizing Pneumonia

Bronchiolitis obliterans organizing pneumonia(BOOP) is a type of diffuse interstitial lung disease that has emerged in the past decade as an important cause of acute respiratory illness in adult. Clinically, the entity usually starts with a subacute influenza-like illness, followed by cough, progressive dyspnea, and weight loss. Organized inflammatory polypoid materials predominantly affecting distal bronchioles, alveolar ducts, and peribronchial alveolar spaces are a key pathologic findings. BOOP is characterized by a good response to glucocorticoid and an excellent prognosis. However, there is a subset of BOOP who presents with a fulminant course leading to death or chronic severe fibrosis with marked impairment of lung function. Recently, we have experienced a case of rapidly progressive BOOP, diagnosed by open lung biopsy and showed a reluctant response to corticosteroid.

Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.

From 1 November 1992 through 1 May 1993 and from 1 November 1993 through 1 May 1994, we conducted a prospective surveillance study at the University of Texas M.D. Anderson Cancer Center (Houston) to evaluate the role of community respiratory virus infections in hospitalized adult bone marrow transplant (BMT) recipients, Respiratory secretions were obtained from all adult BMT recipients with acute respiratory illnesses. During these two winters, a community respiratory virus was isolated from 37 (36%) of 102 patients and 30 (26%) of 115 patients, respectively. Approximately half (49%) of these infections were due to respiratory syncytial virus (RSV); the remainder were due to influenza virus (18%), picornaviruses (18%), parainfluenza virus (9%), or adenovirus (6%). Fifty-eight percent of these infections were complicated by pneumonia, with an associated mortality of 51%. The pneumonias that complicated RSV infection were almost exclusively viral in origin and were associated with a mortality of 100% if not treated promptly with antiviral agents. In contrast, many of the pneumonias that complicated the other viral infections, such as influenza, appeared to be either self-limited viral pneumonias or secondary bacterial or fungal pneumonias. Community respiratory viruses are frequent causes of acute respiratory illnesses in adult BMT recipients hospitalized during the winter and are associated with substantial morbidity and mortality.

Hantaviruses and hantavirus pulmonary syndrome.

logical testing and autopsy findings did not indicate any known cause of acute respiratory illness and shock. Persons who were affected lived in rural areas of northwestern New Mexico and northeastern Arizona, but there was no obvious epidemiologic connection between patients. Recognition and reporting of this outbreak led to an unprecedented multiagency response that involved the collaborative efforts of clinicians, field epidemiologists, biologists, laboratory researchers, and public health educators. Specimens from the patients were tested for a wide variety of agents at the Centers for Disease Control and Prevention (CDC) [1]. Within 3 weeks of the recognition of the outbreak, the first evidence of the cause of illness was found. IgM and IgG antibodies to several hantaviruses were detected in the sera of patients with use of enzyme immunoassay (EIA), suggesting that illness was due to a previously unrecognized but serologically cross-reactive hantavirus. Additional evidence that a hantavirus was the etiologic agent accumulated in short order. Antigen was detected in the endothelia of multiple organs of these patients on immunohistochemical testing when a monoclonal antibody reactive with conserved hantaviral nucleoprotein epitopes was used, and hantaviral nucleotide sequences were detected in patient tissue specimens by reverse transcriptase polymerase chain reaction (RT-PCR). Nichol and colleagues [2] confirmed that the etiologic agent was a unique hantavirus on the basis of results of nucleotide sequence analysis of RT-PCR-amplified viral genetic material. The respiratory illness associated with hantavirus infection has been designated hantavirus pulmonary syndrome (HPS) [3]. Clinical illness associated with hantavirus infection first

Bovine respiratory syncytial virus protects cotton rats against human respiratory syncytial virus infection

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory infections in infancy. No vaccine against this virus has yet been protective, and antiviral drugs have been of limited utility. Using the cotton rat model of HRSV infection, we examined bovine respiratory syncytial virus (BRSV), a cause of acute respiratory disease in young cattle, as a possible vaccine candidate to protect children against HRSV infection. Cotton rats were primed intranasally with graded doses of BRSV/375 or HRSV/Long or were left unprimed. Three weeks later, they were challenged intranasally with either BRSV/375, HRSV/Long (subgroup A), or HRSV/18537 (subgroup B). At intervals postchallenge, animals were sacrificed for virus titration and histologic evaluation. Serum neutralizing antibody titers were determined at the time of viral challenge. BRSV/375 replicated to low titers in nasal tissues and lungs. Priming with 10(5) PFU of BRSV/375 effected a 500- to 1,000-fold reduction in peak nasal HRSV titer and a greater than 1,000-fold reduction in peak pulmonary HRSV titer upon challenge with HRSV/Long or HRSV/18537. In contrast to priming with HRSV, priming with BRSV did not induce substantial levels of neutralizing antibody against HRSV and was associated with a delayed onset of clearance of HRSV upon challenge. Priming with BRSV/375 caused mild nasal and pulmonary pathology and did not cause exacerbation of disease upon challenge with HRSV/Long. Our findings suggest that BRSV may be a potential vaccine against HRSV and a useful tool for studying the mechanisms of immunity to HRSV.

Acute respiratory illness in Adelaide children — the influence of child care

To test the hypothesis that children attending child care centres are more likely to be prone to acute respiratory illness. A case-control study. A community-based study in the Adelaide metropolitan area. A randomly selected sample of Adelaide children whose births were registered in 1983. A respiratory illness score was calculated for each child, based on parents' reports of acute respiratory illness in the previous 12 months. Information was obtained by postal survey for 2618 children (mean age at time of study, 26 months). Eight hundred and nineteen of these children (31%) were reported to be regular or occasional attenders of child care centres or crèches. Home interviews were carried out with parents of children whose respiratory illness scores fell in the top 20% of the range and those whose score was in the bottom 20%. Children prone to respiratory illness were more likely to be users of child care centres or crèches than the children who were not prone (odds ratio = 2.28; 95% confidence interval, 1.53-3.40). The risk of being prone to respiratory illness increased with the frequency of use of child care, and tended to be greater the younger children were when they first attended child care centres. Adjustment in multivariate analysis for confounding factors made little difference to the strength of the association of proneness to respiratory illness with the use of child care (adjusted odds ratio = 2.23; 95% confidence interval 1.38-3.61). Use of child care centres is an important cause of acute respiratory illness among Australian children.

A serological survey for equine influenza in New Zealand horses

Abstract Extract Madam:— Equine influenza is one of the main causes of acute respiratory disease of horses in many parts of the world. Clinically the disease is not recognised as being present in New Zealand (1) or Australia (3) but with the increasing international movement of horses the risks of introducing the virus are high. This survey was undertaken to determine if there was serological evidence of equine influenza in New Zealand, and if so, to ascertain the prevalence rate.

Deoxyribonucleic Acid Relatedness of Chlamydia sp. Strain TWAR to Chlamydia trachomatis and Chlamydia psittaci

Chlamydia sp. strain TWAR is an important cause of acute respiratory disease in humans. To determine the genetic relatedness of the TWAR organism to Chlamydia trachomatis and Chlamydia psittaci, solution hybridization followed by SI nuclease assays were performed, and guanine-plus-cytosine (G+C) contents were determined. Deoxyribonucleic acid (DNA) preparations from three TWAR isolates were radioactively labeled and hybridized against DNAs from three serovars ofC. trachomatis and five strains of C. psittaci. Reciprocal experiments were also done by using radioactively labeled C. trachomatis and C. psittaci DNAs against TWAR DNA. In all cases, the degree of DNA relatedness between TWAR and the two Chlamydia species was 10% or less. Within the group of TWAR isolates, there was 94% or greater sequence similarity. The G+C values for TWAR were intermediate between the G+C values for C. trachomatis and C. psittaci. The degrees of DNA relatedness among the strains within the species C. psittaci ranged from 20 to 100%.

Infections with Legionella pneumophila in children.

To learn the role of Legionella pneumophila, the agent of Legionnaires' disease, in childhood illness, a prospective study was conducted among 52 children younger than four years of age with acute disease of the lower respiratory tract. Viral, mycoplasmal, and bacterial cultures and acute- and convalescent-phase sera were obtained during 64 episodes of acute illness; additional sera were drawn annually for three to five years. On the basis of serologic evidence, none of the acute episodes appeared to be due to L. pneumophila serogroup 1 or 2. However, examination of annual serum specimens showed that 27 (52%) of the children had rises in titer of indirect immunofluorescent antibody (a fourfold or greater rise to a reciprocal titer of ⩾128). Most rises in titer were in response to the serogroup 2 antigen. These results suggest that L. pneumophila is not a common cause of acute respiratory disease in early childhood in the study area but that children are frequently exposed to the organism. Alternatively, the serologic responses might be to unrelated cross-reacting microorganisms.

Influenza Mortality and Morbidity

To the Editor.— Elsewhere in this issue (p 115), Gregg and his associates have addressed analysis of the contribution of influenza to mortality and morbidity in nonepidemic years by Albert B. Sabin, MD (237:2823, 1977). I wish only to comment on Dr Sabin's wish to equate influenza with all other causes of acute respiratory disease, as he does in the following statement: The attempt by some to limit the clinical diagnosis of influenza to disease caused by the influenza viruses and to dismiss the remainder of the clinical syndrome responsible annually for many millions of days of bed disability (exclusive of the many millions of days of bed disability attributed separately to acute infections of the upper respiratory tract or to pneumonia), is, in my judgement, unrealistic and counterproductive in dealing with the total influenza problem. It seems retrogressive to despair of separating the manifold causes of acute respiratory disease at

Rapid Detection of Mycoplasma Antibody

Abstract Mycoplasma pneumoniae is a significant nonviral cause of acute respiratory disease in children and young adults. The clinical expression of mycoplasmal respiratory tract infection ranges from minor upper respiratory symptoms to acute bronchitis and atypical pneumonia. Indistinguishable respiratory syndromes are commonly caused by several viral agents (1). Mycoplasma pneumonia responds to antibiotics in contrast to the other common respiratory pathogens, but treatment is often inappropriate because mycoplasma infections cannot be distinguished from other causal agents without laboratory aids. Laboratory confirmation by culture is of limited diagnostic use because the organism grows very slowly and may be found in the absence of clinical infection (2, 3). Thus, serodiagnosis, demonstrating changing levels of complement-fixing (CF)3 antibodies to mycoplasma, has become the most widely accepted routine diagnostic tool (4). The CF test, although fairly sensitive and reliable, is a tedious, cumbersome technique, especially for the small laboratory.

Protective effect of antibody to parainfluenza type 1 virus.

PARAINFLUENZA Type 1 virus is an important cause of acute respiratory disease in infants and children.1 , 2 During primary infection the lower respiratory tract is often involved, and illness may be quite severe. Initial infection usually occurs during childhood, and most older children and adults have serum neutralizing antibody to this virus.2 Reinfection with Type 1 virus has been observed in adults under both experimental and natural conditions despite the presence of serum neutralizing antibody.3 4 5 Illness associated with reinfection is generally mild and limited to the upper respiratory tract.Adults and older children undergoing reinfection probably constitute an important source of . . .