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Community respiratory virus infections in immunocompromised patients with cancer.

Community respiratory viruses, such as respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses, adenoviruses, and picornaviruses, are an important cause of respiratory disease in the immunocompromised adult with cancer. Recent studies have demonstrated that a minimum of 31% of adult bone marrow transplant (BMT) recipients and 18% of adults with leukemia who are hospitalized with an acute respiratory illness have a community respiratory virus infection. The temporal occurrence of these infections in immunocompromised patients tends to mirror their occurrence in the community. The clinical illnesses range from self-limited upper respiratory illnesses to fatal pneumonias, depending on the type of virus and the type and degree of immunosuppression. The pneumonias may be viral, bacterial/fungal, or mixed. The highest frequency of progression to fatal viral pneumonia has been reported for RSV infections in recently transplanted BMT recipients and myelosuppressed patients with leukemia. Studies have suggested that early therapy for RSV pneumonia with a combination of aerosolized ribavirin and intravenous immunoglobulin may be of benefit. Defining effective prophylactic and therapeutic strategies will be a challenge, given the diversity of viruses, the wide spectrum of immunocompromised patients with varying vulnerability to serious community respiratory virus disease, and the frequent presence of other opportunistic infections and medical problems. A combination of antiviral drugs and immunotherapy may need to be considered for their potential additive effect as well as to prevent the emergence of resistant virus, as occurs during monotherapy for influenza with amantadine or rimantadine. The optimal therapies need to be defined in controlled trials; however, it appears that a favorable response will hinge on the initiation of therapy at an early stage of the respiratory illness.

Adenoviridae↗

The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice.

To develop a broad understanding of the causes and patterns of occurrence of wheezing associated respiratory infections, we analyzed data from an 11-year study of acute lower respiratory illness in a pediatric practice. Although half of the WARI occurred in children less than 2 years of age, wheezing continued to be observed in 19% of children greater than 9 years of age who had lower respiratory illness. Males experienced LRI 1.25 times more often than did females; the relative risk of males for WARI was 1.35. A nonbacterial pathogen was recovered from 21% of patients with WARI; respiratory syncytial virus, parainfluenza virus types 1 and 3, adenoviruses, and Mycoplasma pneumoniae accounted for 81% of the isolates. Patient age influenced the pattern of recovery of these agents. The most common cause of WARI in children under 5 years of age was RSV whereas Mycoplasma pneumoniae was the most frequent isolate from school age children with wheezing illness. The data expand our understanding of the causes of WARI and are useful to diagnosticians and to researchers interested in the control of lower respiratory disease.

Adolescent↗

Viral infections in interferon-gamma receptor deficiency.

Interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens.

Antigens, CD↗

Antiviral activity of NMSO3 against respiratory syncytial virus infection in vitro and in vivo.

NMSO3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory syncytial virus (RSV) and other myxovirus infections in cell culture. The median effective concentration (50% effective concentration, EC(50)) of NMSO3 against replication of the Long strain of RSV in HEp-2 cells was 0.2 and 0.32 microM by optical ELISA and the plaque reduction method, respectively. On the other hand, the corresponding values for ribavirin were 10.5 and 11.2 microM, respectively. NMSO3 showed potent activity against other laboratory strains as well as fresh clinical isolates of RSV, and the average EC(50) was similar to that for Long strain. NMSO3 exhibited minimal cytotoxicity against HEp-2, MDCK, HMV-2 and Vero cells for which the median cytotoxic concentration (CC(50)) was more than 685 microM. The selectivity index [SI=(CC(50) for HEp-2/EC(50))] of NMSO3 for RSV exceeded 2978 and that of ribavirin was 6. The EC(50) of NMSO3 against influenza virus (FluV) A (H3N2) was 23.8 by the MTT method using HMV-2 cells, and 17.8 microM by the TCID(50) method using MDCK cells. NMSO3 did not inhibit replication of influenza B virus, parainfluenza virus type 2 and canine distemper virus at 103 microM. NMSO3 inhibited RSV infection of HEp-2 cells when it was added between 0 and 1.5 h after virus infection. By a temperature shift experiment during the period of contact between the virus and cells, NMSO3 inhibited both the binding of RSV to the cells and its penetration into the cells. Prophylactic and therapeutic efficacy of NMSO3 against RSV infection in cotton rats was examined. Intraperitoneal administration of 100 mg/kg per day of NMSO3 to cotton rats from 1 day before or 1 h after to 3 days after the RSV infection, once a day every day, decreased the RSV titer in lungs to 10(-1.26) to 10(-1.63) compared to the control rats which were infected with RSV and left untreated.

Animals↗

Respiratory viral infections in the elderly.

Viral respiratory infections represent a significant challenge for those interested in improving the health of the elderly. Influenza continues to result in a large burden of excess morbidity and mortality. Two effective measures, inactivated influenza vaccine, and the antiviral drugs rimantadine and amantadine, are currently available for control of this disease. Inactivated vaccine should be given yearly to all of those over the age of 65, as well as younger individuals with high-risk medical conditions and individuals delivering care to such persons. Live, intranasally administered attenuated influenza vaccines are also in development, and may be useful in combination with inactivated vaccine in the elderly. The antiviral drugs amantadine and rimantadine are effective in the treatment and prevention of influenza A, although rimantadine is associated with fewer side-effects. Recently, the inhaled neuraminidase inhibitor zanamivir, which is active against both influenza A and B viruses, was licensed for use in uncomplicated influenza. The role of this drug in treatment and prevention of influenza in the elderly remains to be determined. Additional neuraminidase inhibitors are also being developed. In addition, to influenza, respiratory infections with respiratory syncytial virus, parainfluenza virus, rhinovirus, and coronavirus have been identified as potential problems in the elderly. With increasing attention, it is probable that the impact of these infections in this age group will be more extensively documented. Understanding of the immunology and pathogenesis of these infections in elderly adults is in its infancy, and considerable additional work will need to be performed towards development of effective control measures.

Adolescent↗

Maternal immunization against viral disease.

The protective effect of maternal antibody against many viral diseases has been recognized. The use of maternal immunization has been considered as a means to augment this protection in the young infant against disease. Advantages of maternal immunization include the fact that young infants are most susceptible to infections but least responsive to vaccines, that pregnant women are accessible to medical care and respond well to vaccines, that IgG antibodies cross the placenta well during the third trimester, and that immunization of the pregnant woman has the potential to benefit both the mother and the infant. Disadvantages include the potential inhibition of an infant's response to active immunization or natural infection and liability issues with pharmaceutical companies and physicians. Immunization of pregnant women with viral vaccines for poliovirus, influenza viruses, and rubella has been described and maternal vaccination with these vaccines has been found to be safe for both the mother and the fetus. An open-label study of post-partum women immunized with the purified fusion protein of RSV (PFP-2, Wyeth-Lederle Pediatrics and Vaccines, Inc., Pearl River, NY) demonstrated that the vaccine was non-reactogenic and immunogenic; RSV-specific antibody was detected in breast milk. Immunization of pregnant women with purified protein or subunit vaccines could be considered against neonatal viral pathogens, such as respiratory syncytial virus, parainfluenza viruses, herpes group viruses, and human immunodeficiency virus. Further studies are needed to define the safety and efficacy of maternal immunization.

Female↗

Outbreak of vertigo in Wyoming: possible role of an enterovirus infection.

An epidemiologic investigation was conducted to characterize and evaluate the possibility of a viral aetiology of an outbreak of acute vertigo in Hot Springs Country, Wyoming, during autumn 1992. Case-finding identified Hot Springs County residents who sought medical attention for new onset vertigo during 1 August, 1992-31 January 1993. Thirty-five case-patients and 61 matched controls were interviewed and serum specimens were obtained during January 1993. Case-patients were more likely than controls to report symptoms (e.g. fatigue, sore throat, fever, diarrhoea) of antecedent acute illness. Case-patients did not have a significantly greater prevalence or mean titre of IgG antibodies to respiratory syncytial virus, parainfluenza viruses, Epstein-Barr virus, and cytomegalovirus than controls. Serologic evidence of recent enterovirus infection (IgM antibodies) was found for 74% of case-patients compared with 54% of controls (P < 0.05), suggesting a possible association between vertigo and enterovirus infection. Future studies are needed to define the role of enteroviruses in innerear diseases.

Adolescent↗

Prevalence of various respiratory viruses in the middle ear during acute otitis media.

BACKGROUND: Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media. Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown. METHODS: We determined the prevalence of various respiratory viruses in the middle-ear fluid in 456 children (age, two months to seven years) with acute otitis media. At enrollment and after two to five days of antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were obtained for viral and bacterial cultures and the detection of viral antigens. The viral cause of the infections was also assessed by serologic studies of serum samples obtained during the acute illness and convalescence. RESULTS: A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent). Respiratory syncytial virus was the most common virus identified in middle-ear fluid: it was detected in the middle-ear fluid of 48 of the 65 children (74 percent) infected by this virus (P< or =0.04 for the comparison with any other virus). Parainfluenza viruses (15 of 29 children [52 percent]) and influenzaviruses (10 of 24 children [42 percent]) were detected in the middle-ear fluid significantly more often than enteroviruses (3 of 27 children [11 percent]) or adenoviruses (1 of 23 children [4 percent]) (P< or =0.01 for all comparisons). CONCLUSION: Respiratory syncytial virus is the principal virus invading the middle ear during acute otitis media. An effective vaccine against upper respiratory tract infections caused by respiratory syncytial virus may reduce the incidence of acute otitis media in children.

Acute Disease↗

Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus.

BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as "children") for HBoV. METHODS: Children for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1-3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004. RESULTS: Twenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in > or =50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period. CONCLUSIONS: HBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children.

Bocavirus↗

A community-based study of acute respiratory tract infection in Thai children.

A 2-year longitudinal study was conducted among the population of a socioeconomically depressed urban community in Bangkok, Thailand, from January 1986 through December 1987 to determine the incidence, etiologic agents, and risk factors associated with acute respiratory tract infection (ARI) in children less than 5 years of age. Data were obtained for a total of 674 children, who were visited twice weekly for detection of signs and symptoms of ARI. During the first year of the study, throat-swab specimens were obtained for bacterial culture from both ill and healthy children and a nasal wash was performed on mildly ill children for detection of virus. During both years of the study, nasopharyngeal aspiration for identification of virus was performed for children with more severe infection. The overall incidence of ARI was 11.2 episodes per child-year. The highest (14.9) and lowest (8.8) rates per child-year occurred in age groups 6-11 months and 48-59 months, respectively. Respiratory syncytial virus, parainfluenza virus, adenovirus, Streptococcus pneumoniae, and Haemophilus influenzae were the prevalent pathogenic agents identified. Factors associated with higher risk of ARI were low family income, working mothers, mothers with allergies, chronic malnutrition, and crowding in the home.

Acute Disease↗

Association of rhinovirus infection with poor bacteriologic outcome of bacterial-viral otitis media.

Viruses--both alone and in combination with bacteria--have been shown to be a cause of acute otitis media (AOM). Moreover, the presence of virus in middle ear fluid (MEF) interferes with the bacteriologic response to antibiotic treatment in AOM. We studied various factors related to the eradication of bacteria from the MEF of infants and children who had AOM associated with a combination of bacteria and viruses. Of 622 cases of AOM diagnosed and treated between 1985 and 1991, 71 were due to such a combination. Bacteria were eradicated from MEF by 2-4 days of antibiotic treatment in 50 (70%) of these 71 cases; in the remaining 21 cases, the originally identified bacteria persisted or a new pathogenic bacterial species was detected after such treatment. These two groups of cases were compared with respect to the patients' age, sex, race, history of recurrent AOM, duration of respiratory symptoms, and compliance; the type of antibiotic treatment administered; the type of pathogenic bacteria and viruses identified in MEF; the presence of single or multiple pathogens; and the laterality of the disease. The only difference noted was in the type(s) of virus found in MEF. The presence of rhinovirus was associated with a higher rate of bacteriologic failure than was that of respiratory syncytial virus, parainfluenza virus, influenza virus, or other viruses. Our data suggest that the bacteriologic response to antibiotic treatment in bacterial-viral AOM may depend in part on the type(s) of virus present in MEF.

Anti-Bacterial Agents↗

Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis.

The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status.

Adult↗

Rheumatoid factor in acute viral infections: interference with determination of IgM, IgG, and IgA antibodies in an enzyme immunoassay.

IgM rheumatoid factor (RF), an autoantibody to the Fc fragment of IgG, was determined by solid-phase enzyme immunoassay (EIA). RF levels were significantly higher in patients with rubella virus infection than in patients with infections due to influenza virus, cytomegalovirus, respiratory syncytial virus, parainfluenza virus, adenovirus, mumps virus, or herpes simplex virus. To evaluate the role of RF in EIA determinations of viral antibodies, IgM RF from IgM-IgG cryoglobulin or control IgM was added to patient sera before assay for viral antibodies. IgM RF inhibited virus-specific IgG and IgA reactions and gave nonspecific IgM reactions in EIA for antibodies to rubella and influenza viruses, but had little or no effect on antibodies to cytomegalovirus. The minimal effective amounts of RF were 100-500 ng/ml for inhibition of IgG, 300-1,000 ng/ml for IgA, and 25-500 ng/ml for IgM. The control IgM preparation gave no such effects. These studies reinforce the need to eliminate RF interference in solid-phase EIA.

Acute Disease↗

Clinical evaluation of radioimmunoassay of nasopharyngeal secretions and serology for diagnosis of viral infections in children hospitalized for respiratory infections.

Viral diagnosis was performed using radioimmunoassay (RIA) for virus antigen in nasopharyngeal secretions (NPS) and complement-fixation (CF) tests of paired sera from specimens of 90 children hospitalized for acute respiratory infection. Major respiratory viruses sought for by both methods (adenoviruses, influenza A and B viruses, parainfluenza virus type 3, respiratory syncytial virus) were detected in 40 (44%) of the patients; 15% of the diagnoses were made by NPS-RIA alone. Serologic diagnosis of other viral infections was confirmed in six additional cases. In the different clinical entities a viral diagnosis was established as follows: pneumonia, 50%; upper or middle respiratory infection with no wheezing, 43%; acute laryngitis, 54%; and wheezing bronchitis, 29%. In each clinical entity the virus-positive and virus-negative patients had similar total leukocyte counts, mean C-reactive protein levels and mean erythrocyte sedimentation rates. There was no difference in the duration of hospitalization between the patients with positive and negative viral studies. It was not possible to divide the patients into clinical subgroups according to the presence or absence of detectable viral infection.

Antigens, Viral↗

Epidemiology of documented viral respiratory infections and acute otitis media in a cohort of children followed from two to twenty-four months of age.

BACKGROUND: Viral upper respiratory infections (URIs) are considered major risk factors for acute otitis media (AOM) in young children. We studied the epidemiology and relative roles of different viruses in respiratory infections in a cohort of 329 Finnish children followed from 2 months to 2 years of age. METHODS: A nasopharyngeal aspirate (NPA) was collected whenever the child had signs and/or symptoms of URI and tested for the presence of common respiratory virus antigens or infectivity/nucleic acid (only rhinoviruses). Possible repeated detections of a given virus during a 30-day period were considered to represent a single designated virus-specific episode. AOM and URI episodes were defined in a similar way. RESULTS: At least one virus was detected in 837 (41.7%) of the 2005 NPA specimens examined. Rates of URI and virus-specific episodes showed expected seasonal variation with major peak occurrences coinciding with or preceding those of AOM. The proportions of rhinoviruses, respiratory syncytial (RS) virus, parainfluenza virus (PIV) type 3, influenza virus A and adenoviruses were 63.1, 14.7, 6.7, 6.7 and 6.2% of the total of 761 virus-specific episodes. Influenza virus B, PIV1 and PIV2 were each responsible for approximately 1% of the episodes. AOM was diagnosed in 870 URI cases (43.4%) and in 43.3% of cases associated with a virus-positive NPA. The latter figure was clearly higher (57.7%) for RS virus-positive specimens. CONCLUSIONS: The seasonal coincidence of URI and AOM demonstrated the obvious role of URI in the pathogenesis of AOM. The occurrence of rhinoviruses and RS virus in URI was strikingly more common than that of any other virus tested. Although rhinoviruses were definitely the most frequently found viruses in NPA specimens, the association of RS virus with concurrent AOM was relatively higher than that of any other virus.

Acute Disease↗

Virus antibody levels in IgA deficiency.

IgA-deficient blood donors and their age- and sex-matched controls were compared for the occurrence of complement-fixing antibodies in serum against several viruses. The level in the IgA-deficient persons was slightly higher against several respiratory pathogens (adenoviruses, type B influenza virus, parainfluenza virus, and respiratory syncytial virus) that give rise to localized infections, and against coxsackie B group of viruses. No corresponding difference was observed in mumps, varicella, and cytomegalovirus infections, where viraemia is a characteristic feature, or in Mycoplasma pneumoniae infection.

Adenoviruses, Human↗

[Isolation of Chlamydia pneumoniae and antibodies to the agent in patients with acute bronchitis].

Isolation of Chlamydia pneumoniae and serologic tests were performed on 85 children and adults patients with acute bronchitis admitted to the Kitasato Institute Hospital from January 1989 to May 1991. C. pneumoniae was isolated from sputa or tonsillar swabs in 11 of 57 (19%) patients examined. Of these, 10 patients were tested serologically and 9 (90%) had 16 or higher titer of IgG antibody. A total of 68 patients were tested serologically, and 17 (25%) revealed positive; 14 had a fourfold rise or more in the titer of IgG antibody, or IgM titer of 16 or more, and 3 had IgG antibody with a titer of 512 or greater. In 34 patients, sera were tested for evidence of acute infections not only with C. pneumoniae, but also with Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenovirus, respiratory syncytial virus, coxackie A9 virus, parainfluenza virus type I, II, and III. Two of the 34 patients were associated with influenza A virus, 4 with influenza B virus, whereas 6 were associated with C. pneumoniae. The data available suggest that C. pneumoniae cause bronchitis much more than has been suspected, and also confirm earlier suggestions that the agent played an important role in respiratory tract infections. Chlamydia trachomatis was recovered from sputa and tonsillar swabs in 6 adults patients with acute bronchitis. Studies are needed for a better understanding of the epidemiology and clinical relevance of this microorganism to lower respiratory tract diseases in adults.

Adolescent↗

Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5'-nor derivatives.

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were studied for their broad-spectrum antiviral potential. 3-Deazaneplanocin A, DHCA, and DHCDA proved specifically effective against vesicular stomatitis virus, vaccinia virus, parainfluenza virus, reovirus, and rotavirus. Their selectivity was greater than that of neplanocin A, particularly against vesicular stomatitis virus and rotavirus. As could be expected from adenosine analogs that are directly targeted at AdoHcy hydrolase, 3-deazaneplanocin A, DHCA, and DHCDA were fully active in adenosine kinase-deficient cells, implying that their activity did not depend on phosphorylation by adenosine kinase. None of the AdoHcy hydrolase inhibitors showed selective activity against human immunodeficiency virus (type 1). 3-Deazaneplanocin A at a dose of 0.5 mg/kg per day conferred marked protection against a lethal infection of newborn mice with vesicular stomatitis virus.

Adenosine↗