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PubMed2003

[Successfully treated case with microscopic polyangiitis complicated severe varicella zoster virus infection including encephalitis and disseminated varicella zoster].

We report a case with microscopic polyangiitis (MPA) complicated by varicella zoster encephalitis. A 60-year-old woman caught a common cold and had acute otitis media in April 1998. Proteinuria and hematuria with hyaline cast were noted at the routine medical check in May, and she was referred to our hospital because of high fever and chest pain. MPA was diagnosed with acute progressive renal failure, pleuritis and elevated anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA). Corticosteroid therapy was administered under hemodialysis but MPA was flared several times with various symptoms including interstitial pneumonitis, alveolar hemorrhage and erythema multiforme exudativum. During the course of the disease she developed disseminated varicella zoster and encephalitis. Positive polymerase chain reaction to varicella zoster in cerebrospinal fluid helped to differentiate her encephalitis from central nervous system symptoms due to microscopic angiitis and herpes simplex encephalitis. Combination of corticosteroid and acyclovir therapies for MPA and varicella zoster encephalitis under hemodialysis were successful. The diagnostic process and therapies to these complicated contexts were thought to be very important.

Acute Kidney Injury↗
PubMed1994

Amplified rhinovirus colds in atopic subjects.

Evidence suggests that atopic individuals may be predisposed to more severe rhinoviral colds coupled to a worsening of existing airway disease than those with asthma. The role of atopy and IgE levels, as well as their relationship to clinical disease expression have not been defined. We hypothesized that an allergic diathesis modulates rhinoviral colds and have initiated studies of normal, atopic and asthmatic subjects employing experimental rhinoviral infection, with measurements of symptom scores, viral shedding and cultures, albumin in nasal washes and serological responses. Twenty-two subjects (11 normal, 5 atopic, 6 atopic and asthmatic) participated and were inoculated with human rhinovirus serotype 16 (HRV 16). Measurements of neutralizing antibody and viral culture were performed at screening, pre-inoculation, during the cold and at 8-10 weeks convalescence. Daily symptoms were noted, nasal washes done, IgE measured and atopy was diagnosed by skin tests. Seventeen volunteers developed clinical colds as assessed by symptom scores, virus shedding was demonstrated (with positive culture) in all subjects and a fourfold or higher seroconversion occurred in 11/22. Neutralizing HRV antibody developed unexpectedly in 10 subjects between screening and inoculation and the presence of absence of this pre-inoculation antibody determined subsequent severity of colds in normal but not in atopic subjects. Atopic antibody positive individuals developed severe clinical colds that were independent of preinoculation antibody in contrast to normal subjects who developed mild colds in the presence of a neutralizing antibody (P = 0.01). Both atopic and normal antibody negative subjects developed severe colds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

RANTES, macrophage-inhibitory protein 1alpha, and the eosinophil product major basic protein are released into upper respiratory secretions during virus-induced asthma exacerbations in children.

The presence of cytokines and the toxic eosinophil granule product major basic protein (MBP) was investigated in nasal aspirates from children with naturally occurring virus-induced asthma exacerbations and compared with levels in nasal aspirates taken from the same children when asymptomatic. Increased levels of MBP accompanied by increased levels of the chemokines RANTES and macrophage-inhibitory protein 1alpha were observed in nasal aspirates from children during the virus-induced exacerbations. Granulocyte-macrophage colony-stimulating factor was mostly undetectable in samples obtained during both symptomatic and asymptomatic periods. Interleukin-5 levels were low, but tended to increase in samples from symptomatic children. These data confirm that the eosinophil product MBP and the eosinophil chemoattractant chemokines RANTES and macrophage-inhibitory protein 1alpha are increased in upper respiratory viral infections associated with asthma exacerbations and suggest an important role for these chemokines in regulating eosinophil influx and activation. These chemokines may represent targets for therapeutic intervention in virus-induced asthma exacerbations.

Asthma↗
PubMed1988

Modification of experimental rhinovirus colds by receptor blockade.

Human rhinovirus (HRV) infection can be inhibited in vitro by antibody directed against the cellular receptor for the major HRV group representing 90% of serotypes. We assessed the prophylactic effectiveness and safety of intranasally administered rhinovirus receptor murine monoclonal antibody (RRMA) in two double-blind, place-controlled, randomized studies of volunteers experimentally inoculated with HRV-39. In the first study, RRMA administration (135 micrograms/subject in 9 applications, -17 to +48 h) did not reduce infection (RRMA 12/15 vs. placebo 13/15) or illness (8/12 vs. 7/13) rates or modify the clinical course of experimental HRV-39 colds. In the second trial, a higher RRMA dosage (1 mg/subject in 10 applications, -3 to +36 h), similarly did not reduce overall infection (11/13 vs. 12/13) or illness (7/11 vs. 9/12) rates, but was associated with a 1-2 day delay in the onset of viral shedding and cold symptoms and with significant reductions in viral titers and nasal symptoms on the second day after challenge and in mucus weights on the third day after challenge. No toxicity related to RRMA was recognized. The results indicate that intranasal RRMA modified infection and illness after experimental HRV-39 challenge and suggest that blockade of host cell receptors offers a novel antiviral approach against HRV infections.

Administration, Intranasal↗
PubMed1995

Anaesthesia in children with viral respiratory tract infections.

The effects and consequences of anaesthesia in a child with a respiratory tract infection (RTI) are controversial. There is a high incidence of viral RTI in children presenting for surgery and anaesthesia. The social and economic impact of postponing the procedure is significant; for the child, family and institution. The clinical effects of the common cold are well known, affecting the respiratory tract from the nose down to the small airways and lung parenchyma. The systemic effects of the toxic viraemic phase are also well recognized but not so the potential risk of a viral myocarditis. There is an increased incidence of intra- and postoperative respiratory related complications up to six weeks after a RTI. These include airway obstruction, laryngeal spasm, vagally mediated reflex bronchoconstriction, increased bronchial secretions, desaturation, atelectasis and postoperative respiratory complications. Children with symptoms of a moderate to severe RTI presenting for elective surgery should be postponed for six weeks. Emergency surgery should proceed with a mask anaesthetic for minor surgery or by adopting a modified rapid sequence induction (atropine but no cricoid pressure) to gain rapid control of the airway to avoid laryngeal spasm and vagally mediated reflex bronchoconstriction; IPPV, awake extubation, postoperative monitoring of respiratory function and appropriate analgesia.

Anesthesia↗
PubMed1999

Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

BACKGROUND: Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. OBJECTIVE: Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. METHOD: The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). RESULTS: Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of vaccine safety, immunogenicity, and efficacy; postlicensure measurements of the public health impact of the vaccine and a track record of the vaccine's safety and acceptance with large-scale use; and the critical need for international collaborations to evaluate vaccines against diseases of global importance that are rare in the United States (eg, typhoid fever). It was clear that the critical step-up from bench scale to pilot lots and then to large-scale production, which depends on a small group of highly trained individuals, is often a particularly vulnerable point in the development process. CONCLUSIONS: One fundamental lesson learned is that within the varied and comprehensive US vaccine development infrastructure, multiple and rather distinct paths can be followed to reach vaccine licensure. The National Vaccine Advisory Committee review process should be conducted periodically in the future to ascertain that the US vaccine development network, which has been enormously productive heretofore and has played a leadership role globally, is adapting appropriately to ensure that new, safe, and efficacious vaccines become available in a timely manner.

Drug Approval↗
PubMed2001

The association between respiratory viruses and symptoms in 2-week-old infants at high risk for asthma and allergy.

OBJECTIVES: The role of viral respiratory tract infections in the onset of childhood asthma and allergy is controversial, partly because of limited understanding about postnatal viral exposures. We investigated the prevalence of 3 common respiratory viruses and associated respiratory symptoms in 2-week-old infants at high risk for having asthma and allergy. STUDY DESIGN: Frozen nasal specimens from 2-week-old children at high risk (n = 495) underwent reverse transcription-polymerase chain reaction (RT-PCR) for picornavirus-, parainfluenza-, and respiratory syncytial virus-specific nucleic acid. RT-PCR findings were related to respiratory symptoms (cold, cough, and wheeze) and to characteristics implicated with increased risk for asthma and allergy. RESULTS: Viral RT-PCR was positive in 199 (40.2%) of 495 specimens examined, with picornavirus and parainfluenza significantly associated with respiratory symptoms. Viral prevalence was significantly higher in children born during the winter and summer months. CONCLUSIONS: A high percentage (40.2%) of infants at high risk for asthma and allergy had been exposed to common respiratory viruses at 2 weeks of age. RT-PCR is a powerful diagnostic method that can be used in epidemiologic studies examining the role of viral respiratory tract infections in the pathogenesis of pediatric asthma and allergy.

Asthma↗
PubMed1974

Viruses associated with acute respiratory infections 1961-71.

Influenza-like illness, cold and sore throat was the diagnosis given in over 80% of 5177 acute respiratory illnesses in patients swabbed over a 10-year-period. A pathogenic organism was isolated twice as frequently from patients with a sore throat or an influenza-like illness as from those diagnosed as suffering from croup or laryngitis and bronchitis. A laboratory diagnosis was commoner in school children than in older or younger persons.Most of the organisms isolated were found in association with all types of acute respiratory illness but, with increasing age of the patient, one particular agent or group of agents was more likely to be of aetiological significance.

Acute Disease↗
PubMed1990

The sore throat. When to investigate and when to prescribe.

Sore throats are most commonly due to infections, many of which are viral and do not require specific treatment. Symptoms and signs of the common cold, influenza or croup, the occurrence of conjunctivitis in some adenoviral infections, generalised lymphadenopathy and splenomegaly in glandular fever or the presence of vesicles characteristic of herpangina (Coxsackie A virus) or of herpes simplex infection, occasionally enable a clinical diagnosis and avoid the need for antibiotic therapy. In the case of treatable conditions a typical membrane may suggest diphtheria, a scarlatiniform rash infection due to Streptococcus pyogenes or to Corynebacterium haemolyticum, and a cherry-red epiglottis Haemophilus influenzae type b. Associated atypical pneumonia suggests infection with Mycoplasma pneumoniae or Chlamydia pneumoniae. Pharyngitis due to Neisseria gonorrhoeae may be accompanied by infection at other sites or by other sexually transmitted diseases. Candidal infection, in the appropriate clinical circumstance, should suggest HIV infection. Surgical drainage is required in the case of peritonsillar or retropharyngeal abscess. Noninfectious cases of sore throat, e.g. thyroiditis, are relatively uncommon considerations in the differential diagnosis of acute febrile pharyngitis. The most common problem is to recognise streptococcal pharyngitis, which requires antibiotic treatment for 10 days to avoid the risk of rheumatic fever.

Humans↗
PubMed2005

Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life.

BACKGROUND: Viral infections are the major cause of acute wheezing illnesses in childhood. Variations in immunologic responses at birth may be determinants of the risk of acquiring these illnesses. OBJECTIVES: To determine the immunologic risk factors for virus-induced wheezing in high-risk infants. METHODS: The study involves 285 children with a parental history of asthma and/or respiratory allergies. Mononuclear cells obtained at birth (umbilical cord blood) and at 1 year of age were incubated with phytohemagglutinin, respiratory syncytial virus, or rhinovirus, and supernatants were analyzed for IL-5, IL-10, IL-13, and IFN-gamma. Nasal secretions obtained at well child visits and during respiratory illnesses were analyzed for common respiratory viruses. RESULTS: Respiratory syncytial virus-induced wheezing was associated with reduced phytohemagglutinin-induced IL-13 responses (medians, 213 vs 304 pg/mL; P = .026) from cord blood cells, and similar trends were found for wheezing in general. Furthermore, median IL-13 responses diminished by 28% in non-wheezing children by age 1 year, versus only 3% in wheezing children (P = .013). Children with > or =2 episodes of wheezing had lower phytohemagglutinin-induced IFN-gamma responses and were less likely to have rhinovirus-induced IFN-gamma responses at birth (P < .05). Finally, children with measurable cord blood IFN responses to respiratory syncytial virus were less likely to wheeze in their first year (odds ratio, 0.43 [0.23, 0.79]). CONCLUSION: In children with a family history of allergies and/or asthma, mononuclear cell phytohemagglutinin-induced IL-13 and virus-induced IFN-gamma responses at birth are indicative of the risk for wheezing in the first year of life.

Common Cold↗
PubMed2004

The common cold: a review of the literature.

Respiratory viral infections, also known as the common cold, are the most common infections in humans. Despite their benign nature, they are a major cause of morbidity and mortality on a worldwide basis. Several viruses have been associated with such illness, of which rhinovirus is the most common. Symptom production is a combination of viral cytopathic effect and the activation of inflammatory pathways. Therefore, antiviral treatment alone may not be able to prevent these events. The optimal use of such agents also requires earlier initiation; therefore, it is important to develop accurate and rapid diagnostic techniques for respiratory viruses. Before any reliable and effective treatment is available, symptomatic therapies may remain the only possible choice of management.

Journal Article↗
PubMed1977

Therapeutic efficacy of inosiplex (Isoprinosine) in rhinovirus infection.

Inosiplex (Isoprinosine), the paracetamidobenzoic acid salt of inosine dimethylaminoisopropanol, has shown antiviral activity in cell culture and in animals. Controlled challenge studies using the drug in a prophylactic fashion, however, have been disappointing. In vitro studies, as well as uncontrolled clinical trials, have suggested that the drug might be more effective when used therapeutically. We therefore undertook to test inosiplex in a controlled, double-blind, therapeutic study of volunteers challenged with rhinovirus. Thirty-nine volunteers were randomly divided into groups receiving either inosiplex or placebo tablets. Drug or placebo was started either at the time of, or 48 hours after challenge with rhinovirus Type 21. Illness was assessed in terms of the classical common cold symptoms, and infection was also determined by viral isolation from daily nasal wash specimens and by serum antibody rises. Five of 19 volunteers in the inosiplex group became ill, whereas 14 of 20 in the placebo group were sick (p less than 0.01). There was no difference between the control and inosiplex groups in the number of volunteers from whom rhinovirus was isolated. There was, however, a reduction in the duration of virus shedding in the inosiplex group. Seroconversion was also slightly less common in the inosiplex group. Immunologic studies suggest that inosiplex stimulates the lymphocyte mitogenic response. The results suggest that inosiplex exerts significant therapeutic benefits in rhinovirus infection.

Adult↗
PubMed1999

An update on the pathophysiology of rhinovirus upper respiratory tract infections.

Upper respiratory tract infections are one of the most common infectious diseases in man and are characterized by relatively mild symptoms. However, complications of bacterial super-infection or asthma exacerbations are not seldomly seen. Most upper respiratory tract infections are caused by rhinoviruses. The rhinovirus is a non-enveloped 30 nm RNA-virus with over 100 serotypes that belongs to the Picornaviridae family and only replicates in primates. It is characterized by a single positive stranded genome acting not only as a template for RNA synthesis, but also encoding for a single polypeptide necessary for viral replication. The viral capsid has an icosahedral symmetry and demonstrates deep canyons, with a receptor-binding domain. Rhinoviruses are transmitted mainly via direct- or indirect contact with infected secretions and invade their host by binding to the ICAM-1 receptor on the nasal epithelium. Typical for rhinovirus upper respiratory tract infections are isolated scattered foci of infected epithelium, not showing any striking damage or cytopathic alterations, between large areas of normal epithelium. Today there is still little detailed knowledge on the pathophysiology of common cold, especially on the aspect of cellular migration and defense. A better understanding in mechanisms underlying this cellular response would not only have therapeutical consequences, but may also explain the relationship between viral infectious rhinitis and asthma or atopy. During a rhinovirus infection, a selective neutrophil and monocyte recruitment is observed. In vitro and in vivo data have demonstrated a time-limited, rhinovirus-induced increase in bradykinin, cytokine, chemokine and sICAM-1 concentrations. Epithelial derived proinflammatory cytokines initiate an adhesion cascade and activate T lymphocytes that create a TH1-type cytokine environment within the infected tissue, necessary to eradicate the virus infection. The selective recruitment of neutrophils seems linked to increased concentrations of the chemokine IL-8 and common cold symptoms. It is doubtful that the cytokine-regulated-production of specific neutralising immunoglobulins is necessary for recovery from viral illnesses and presumably only contributes to a late and temporary protection against rhinovirus reinfection. These observations confirm the crucial role that cytokines and mediators play in the pathogenesis of a rhinovirus infection by mediating chemotaxis, transmigration and activation of inflammatory- and immunocompetent cells.

Animals↗
PubMed1970

Viruses associated with acute respiratory infections in Royal Air Force personnel.

All respiratory illnesses which were reported to the medical officers between September 1966 and December 1967 on a Royal Air Force station of 350 men were studied virologically.THREE PERIODS OF INCREASED RESPIRATORY INFECTIONS WERE OBSERVED: two occurred in the autumn, one in each year, and the third in the winter during January and February. The autumnal outbreaks were associated mainly with rhinovirus infections, and high isolation rates (82.1, 65.9%) were achieved at these times. Few of the illnesses during the winter outbreak could be diagnosed in the laboratory, and no evidence was found of infection with ;coronaviruses'.Despite the entrance of 30 fresh recruits direct from civilian life every 5 weeks, the respiratory infections encountered on the station were very similar to those in the local population and were not predominantly infections with adenoviruses, Coevirus, and Mycoplasma pneumoniae, as previously reported from larger military recruit centres.

Adenoviridae Infections↗