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Respiratory infections in cystic fibrosis patients caused by virus, chlamydia and mycoplasma--possible synergism with Pseudomonas aeruginosa.

116 cystic fibrosis patients were observed, by monthly examinations over an eight-month period, to investigate the importance of non-bacterial respiratory infections (NBI) in exacerbations of the respiratory disease. Sputum was examined for bacteria, and serum investigated for antibody response against virus, mycoplasma and chlamydia and for antibodies against Pseudomonas aeruginosa. During this period each patient had, on an average, 2.9 exacerbations of which 76% were associated with bacteria, most frequently P. aeruginosa (51%), and 20% with NBI, although bacteria were also present in most of these cases. No etiology was established in 18% of the exacerbations. The NBI were caused by respiratory syncytial virus (RSV) (9%), parainfluenza virus (5%), influenza virus (3.6%), adenovirus (2.4%), mycoplasma (0.6%) and chlamydia (0.6%). The incidence of exacerbations was higher in patients with chronic P. aeruginosa infections. RSV infections were more common in patients who developed chronic P. aeruginosa infection during the study period, and RSV infections were frequently associated with a rise of P. aeruginosa antibodies in patients who harboured these bacteria. The important role of NBI as mediators of onset of chronic P. aeruginosa infections in cystic fibrosis patients is suggested.

Adolescent↗

Effect of isoprinosine against influenza and some other viruses causing respiratory diseases.

The antiviral activity of isoprinosine was tested in tissue cultures and mice. In tissue cultures, concentrations of 25 to 100 mug/ml inhibited the infectivity of influenza and herpes hominis viruses but not parainfluenza virus, rhinovirus, or adenovirus. Among different strains of influenza A, there was considerable variability in the inhibitory concentration of isoprinosine. For influenza B, a zone effect was observed in the inhibitory drug concentration. Oral prophylactic administration of isoprinosine beginning 24 hr before infection with an intermediate challenge dose of influenza A and continued as treatment for 5 days produced a significant reduction in mortality. No protection was provided against a high dose challenge. Oral or intraperitoneal treatment of mice beginning 24 hr after infection with influenza A or B viruses significantly delayed or prevented death when the drug was administered for 10 days, but not when treatment was limited to 4 days. An increased fatality rate which occurred in treated mice given a virus dose of low lethality could not be attributed to drug toxicity.

Animals↗

Activity of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) against picornaviruses in vitro.

The newly synthesized compound 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) has been found to inhibit picornavirus replication. In multiple growth cycle experiments, 1 microgram of MDL-860 per ml caused a reduction in virus yield of at least 1.0 log10 50% tissue culture infectious doses per 0.2 ml for 8 of 10 enteroviruses and 72 of 90 rhinovirus serotypes. This antiviral activity was dependent on both compound concentration and virus inoculum size. At concentrations that had no toxic effects on cell cultures, MDL-860 did not inhibit cytopathic effect or hemadsorption activity due to coronavirus 229-E, vesicular stomatitis virus, herpes simplex virus type 1, adenovirus, influenza virus A, or parainfluenza virus 1. Compound concentrations up to 25 micrograms/ml did not cause cytopathic effect in short-term cultures of rhesus monkey, WI-38, or HeLa cells; 10 micrograms/ml did not inhibit the replication of HeLa cells. The mechanism of action of MDL-860 has not been defined, although it was not directly virucidal and appeared to inhibit picornaviruses specifically at an early step in the virus-host cell interaction.

Antiviral Agents↗

Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds.

A series of novel compounds, 5-alkynyl-1-beta-D-ribofuranosylimidazole-4- carboxamides, have been identified as broad-spectrum antiviral agents. 5-Ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide (EICAR), the most potent congener of the group, showed antiviral potency about 10- to 100-fold greater than that of ribavirin. Similar in spectrum to ribavirin, EICAR was particularly active (50% inhibitory concentration, 0.2 to 4 micrograms/ml) against poxviruses (vaccinia virus), togaviruses (Sindbis and Semliki forest viruses), arenaviruses (Junin and Tacaribe viruses), reoviruses (reovirus type 1), orthomyxoviruses (influenza A and B viruses), and paramyxoviruses (parainfluenza virus type 3, measles virus, subacute sclerosing panencephalitis virus, and respiratory syncytial virus). EICAR was also cytostatic for rapidly growing cells (50% inhibitory concentration, 0.2 to 0.9 microgram/ml). EICAR inhibited vaccinia virus tail lesion formation at doses that were not toxic to the host. EICAR is a candidate antiviral drug for the treatment of pox-, toga-, arena-, reo-, orthomyxo, and paramyxovirus infections.

Adenosylhomocysteinase↗

Use of disposable micro tissue culture plates for antiviral and interferon induction studies.

A reproducible test system requiring small amounts of test compound was developed for evaluating antiviral and interferon-inducing activity. In the antiviral experiments, KB cells were grown in disposable polystyrene microplates covered with a standard domestic plastic wrap. Viruses used in the system were types 1 and 2 herpes simplex virus, vaccinia virus, type 3 adenovirus, myxoma virus, pseudorabies virus, type 3 parainfluenza virus, types 1A and 13 rhinovirus, vesicular stomatitis virus, coxsackievirus B, and type 2 poliovirus. Inhibition of viral cytopathogenic effect was the primary criterion of evaluation of antiviral activity. Reduction in cell and supernatant fluid virus titers was used as a secondary means of evaluation. The microplate system was adaptable for determining prophylactic, therapeutic, and inactivating effects against viruses. Mouse L-929 cells were used for the interferon induction studies, with vesicular stomatitis virus utilized as the indicator of interferon activity. Known active compounds evaluated in this microplate system had activity similar to that seen in macro in vitro systems.

Animals↗

Multiplex PCR for typing and subtyping influenza and respiratory syncytial viruses.

A multiplex reverse transcription (RT)-PCR method that has been developed is capable of detecting and subtyping influenza A (H1N1 and H3N2) and B viruses as well as respiratory syncytial virus (RSV) types A and B in respiratory clinical samples taken as part of a national community-based surveillance program of influenza-like illness in England and Wales. The detection of each different pathogen depended on distinguishing five amplification products of different sizes on agarose gels following RT-PCR with multiple primer sets. The multiplex RT-PCR was tested with 65 nasopharyngeal apirates from which RSV had been isolated and 237 combined nose and throat swabs from which influenza A (H1N1 and H3N2) or B virus had been detected by virus isolation, as well as 40 respiratory samples from which other viruses including cytomegalovirus, herpes simplex virus, enteroviruses, and parainfluenza viruses had been grown. For the typing and subtyping of influenza A and B viruses and RSV types A and B, the multiplex RT-PCR gave an excellent (100%) correlation with the results of conventional typing and subtyping with specific antisera. Multiplex RT-PCR can also be used to accurately detect more than one viral template in the same reaction mixture, allowing viral coinfections to be identified with the same respiratory specimen.

Child↗

Respiratory viral infections among pediatric inpatients and outpatients in Taiwan from 1997 to 1999.

The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4. 4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among hospitalized children, whereas influenza virus was the most frequently isolated virus in the outpatient group. Most respiratory viral infections (39.3%) occurred in children between 1 and 3 years old. RSV (P < 0.025) and influenza A virus (P < 0.05) infections were dominant in the male inpatient group. In addition, most pneumonia and bronchiolitis (48.4%) was caused by RSV among hospitalized children less than 6 months old. Adenovirus was the most common agent associated with pharyngitis and tonsilitis (45.5%). These data expand our understanding of the etiology of acute respiratory tract viral infections among in- and outpatients in a subtropical country and may contribute to the prevention and control of viral respiratory tract infections.

Adolescent↗

Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins.

We have generated a recombinant Newcastle disease virus (NDV) that expresses the green fluorescence protein (GFP) in infected chicken embryo fibroblasts (CEFs). This virus is interferon (IFN) sensitive, and pretreatment of cells with chicken alpha/beta IFN (IFN-alpha/beta) completely blocks viral GFP expression. Prior transfection of plasmid DNA induces an IFN response in CEFs and blocks NDV-GFP replication. However, transfection of known inhibitors of the IFN-alpha/beta system, including the influenza A virus NS1 protein and the Ebola virus VP35 protein, restores NDV-GFP replication. We therefore conclude that the NDV-GFP virus could be used to screen proteins expressed from plasmids for the ability to counteract the host cell IFN response. Using this system, we show that expression of the NDV V protein or the Nipah virus V, W, or C proteins rescues NDV-GFP replication in the face of the transfection-induced IFN response. The V and W proteins of Nipah virus, a highly lethal pathogen in humans, also block activation of an IFN-inducible promoter in primate cells. Interestingly, the amino-terminal region of the Nipah virus V protein, which is identical to the amino terminus of Nipah virus W, is sufficient to exert the IFN-antagonist activity. In contrast, the anti-IFN activity of the NDV V protein appears to be located in the carboxy-terminal region of the protein, a region implicated in the IFN-antagonist activity exhibited by the V proteins of mumps virus and human parainfluenza virus type 2.

Animals↗

Analogues of acyclic nucleosides derived from tris-(hydroxymethyl)phosphine oxide or bis-(hydroxymethyl)phosphinic acid coupled to DNA nucleobases.

A series of novel acyclic nucleoside analogues containing bis-(hydroxymethyl)phosphinic acid (BHPA) or tris(hydroxymethyl)phosphine oxide (THPO) coupled with DNA nucleobases or with 5-fluorouracil were prepared and their antiviral activity was studied against cytomegalovirus (CMV), varicella-zoster virus (VZV), parainfluenza-virus type 3, reovirus-type 1, sindbis, coxsackie B4, punta toro, vesicular stomatitis and respiratory syncytial virus, herpes simplex virus-type 1 (KOS) and type 2 (G), vaccinia virus and herpes simplex virus-1 (TK- KOS ACVr). No specific antiviral effects were noted for any of test compounds against viruses evaluated, except thymine, cytosine and adenine derivatives of BHPA exerting borderline activity against respiratory syncytial virus at the 80 mg/ml concentration.

Antiviral Agents↗

Effects of viral exposure of the two-cell mouse embryo on cleavage and blastocyst formation in vitro.

The effect of viral exposure of two-cell mouse embryos on their capacity to undergo subsequent cleavage and blastocyst formation in vitro was determined. Exposure to Coxsackie viruses B-4 and B-6, reovirus type 2, influenza virus type A, mouse cytomegalovirus, adenovirus type 5, and mouse adenovirus resulted in statistically significant inhibition of blastocyst formation. Development in vitro was unaffected by exposure to ECHO virus type 11, attenuated poliomyelitis virus type 2, parainfluenza virus type 1, mumps, rubella, and herpes simplex viruses types 1 and 2. Blastocyst formation was also unaffected by exposure of embryos to mouse interferon in a concentration 24 units/ml of culture fluid. Coxsackie virus B-4 was recovered from exposed embryos.

Animals↗

Viral etiology of acute respiratory infections among children in Porto Alegre, RS, Brazil.

Although acute respiratory infections (ARIs) are a major cause of child morbidity and mortality in Southern Brazil, little information is available on their seasonality and viral etiology. This study was conducted on children under 5 years of age with ARI to assess viral etiology in the State of Rio Grande do Sul, from 1990 to 1992. A total of 862 nasopharyngeal secretion (NPS) samples were tested using indirect immunofluorescence. The results showed that 316 (36.6%) NPS samples were positive: 26.2% for RSV, 6% for adenovirus, 1.7% for influenza viruses, 1.5% for parainfluenza viruses, and 1.2% for mixed infection. The mean viral prevalence rates in out-patient services, emergency wards, and in-patient hospital wards were 26.7%, 53% and 42.3%, respectively. Respiratory syncytial virus (RSV) and adenovirus accounted for 91.4 % of the viral diagnoses. RSV was more frequent in children under one year of age at the three levels of health care and was prevalent in infants under six months. Adenovirus was the most prevalent pathogen in hospitalized children, in 1992. Influenza A virus showed an increased prevalence with age among out-patient children. This study shows the annual occurrence of viral respiratory infections in the coldest months, with a significant annual variation in the frequency of RSV infection.

Acute Disease↗

Serologic survey for selected viral and rickettsial agents of brown bears (Ursus arctos) in Croatia.

Sera from 22 (13 wild and nine captive) European brown bears (Ursus arctos) from Croatia were tested to 18 viral and rickettsial agents. Serologic evidence of exposure was found to the following agents (number positive/number examined): Bhanja virus (3/15), Tahyna virus (3/15), West Nile virus (4/15), Naples sandfly fever virus (1/15), human adenovirus (1/22), influenza A (1/22) and B (1/22) virus, cytomegalovirus (1/22), parainfluenza virus 1 (2/22), Chlamydia psittaci (1/22), Coxiella burnetii (2/22), and canine parvovirus 2 (CPV-2) (7/22). Evidence of exposure to arboviruses was found exclusively among free-living bears. Evidence of exposure to agents usually transmitted directly was predominant among captive bears. Canine parvovirus 2 antibodies were the most frequently found antibodies and the only antibody common to both groups of bears. This may be the first report of antibodies to CPV-2 in bears.

Animals↗

Acute viral lower respiratory infections in children in a rural community in Thailand.

The present study was conducted as a population based cohort in a rural community of Amphoe Takhli, Nakhon Sawan province for the determination of the prevalence of acute viral lower respiratory infection (ALRI) in pediatric cases under 5 years of age from November 1998 to February 2001. There were 472 ALRI episodes during the study period; and there were 5 cases who contracted ALRI twice. The etiologic agents were determined by indirect immunofluorescence (IIF) test using specific monoclonal antibodies for the staining of exfoliated cells in nasopharyngeal aspirate (NPA) samples. The slides of fixed cells were prepared by Takhli Hospital and posted in ambient temperature to the Virology Laboratory, Siriraj Hospital where they were stained and examined. Among 472 episodes of ALRI, 170 (36.0%) viral agents were found. Viral agents were associated with 41.4 per cent of all pneumonic cases. Respiratory syncytial virus (RSV) was the most common virus observed in the present study; and it was also the most common virus associated with pneumonia and bronchitis. RSV subgrouping was performed directly in NPA samples by IIF test using a panel of subgroup specific monoclonal antibodies. RSV subgroup B predominated over subgroup A in the first study year, and it was vice versa in the second year. Overall, more cases of subgroup B were found which was in contrast to what the authors had reported in the previous study. Prevalence of RSV was seasonal dependent, the epidemic was seen during the rainy season with peaks in August or September of each year. As the method of viral identification was limited to IIF only, therefore, fewer viruses were detected. Parainfluenza viruses were detected as the second most common viral agent, the viruses spread during early summer with peaks in February or March of each year. However, its association with croup could not be demonstrated which may be due to the insensitivity of IIF in the diagnosis of non-RSV infection. Nevertheless, in terms of feasibility to investigate the disease in a rural area, IIF is economic, convenient and rapid; and gives enough information for the nationwide plan of a health care development system.

Acute Disease↗

The role of viruses and Mycoplasma pneumoniae in lower respiratory tract infections in childhood.

Acute lower respiratory tract infections are one of the major causes of childhood morbidity and mortality in developing countries. This study was undertaken at Hacettepe University Children's Hospital to determine the role of viruses and Mycoplasma pneumoniae in respiratory tract infections in children. Eighty-three patients with lower respiratory tract infections were selected at random from among the children admitted to the hospital for evaluation of respiratory symptoms. Acute and convalescent serum samples were collected from all patients for the complement-fixation test and the following antigens were used: respiratory syncytial virus (RSV), adenovirus, parainfluenza virus Type 1, influenza viruses A and B, and Mycoplasma pneumoniae. The test was positive in 39 of 83 patients (47%), and RSV was the most frequent agent detected serologically (15.7%).

Acute Disease↗

The causes and diagnosis of influenza-like illness.

BACKGROUND: Influenza and other respiratory viruses circulate between spring and autumn in temperate climates and all year in tropical climates. These viruses cause symptoms often referred to as influenza-like illness (ILI), but are not generally distinguishable on clinical grounds alone. OBJECTIVE: This article provides a brief review of the surveillance, viral causes and current diagnostic methods used to identify viruses causing ILI. DISCUSSION: Influenza-like illness surveillance with laboratory support, conducted in most Australian stats and territories, aims to define the impact of influenza seasons in the community and provide virus strains that may be used in future vaccine formulations. Surveillance may also be useful in the early stages of an influenza pandemic. In addition to influenza, viruses known to cause ILI include respiratory syncytial virus, rhinovirus, adenovirus, parainfluenza viruses, human coronaviruses (including the virus that causes severe acute respiratory syndrome) and the recently recognised human metapneumovirus. Polymerase chain reaction assays are the most common diagnostic tests now used for the differential diagnosis of ILI.

Australia↗

[Infections in chronic obstructive pulmonery disease].

Infection plays an important role in COPD, particularly during exacerbations. The principal pathogens involved in exacerbations are viruses (influenza and parainfluenza virus, picornavirus, and respiratory syncytial virus). Bacteria (mainly Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis) are isolated from sputum in approximately 50% of exacerbations and 25% of patients with stable state. Recent data favor of a proinflammatory role of these bacteria in the natural history of the disease. The role of atypical pathogens like Chlamydia pneumoniae may be underestimated. Trials of antibiotic treatment have shown a slight but significant benefit, particularly in patients with recent-onset purulent sputum. The benefit is more significant in patients with stable severe obstructive disease. Guidelines have been published in industrialized countries on the use of antibiotics in this indication. The role of infections in the pathogenesis of obstructive lesions is controversial. Some authors have forwarded a "vicious circle" hypothesis, in which impairment of mucociliary clearance by tobacco smoke contributes to bronchial colonization by bacteria, and this further impairs mucociliary clearance and promotes airway epithelial injury. COPD is a major risk factor for community-acquired pneumonia.

Anti-Bacterial Agents↗

[Common cold: diagnostic steps? Antibiotics?].

The common cold is caused by more than 100 virus types. However, the clinical manifestation is always similar with rhinorrhea, stuffiness, sneezing, pharyngitis, laryngitis and cough. The local inflammatory reactions are not due to the presence of virus but caused by locally produced inflammatory mediators. Bacterial superinfections may cause otitis or sinusitis. Bacterial nasopharyngitis has been described in children. This entity possibly exists also in adults. Traditional viral cultures are rarely positive and are not recommended in the daily routine. In children, antigen detection for adenovirus, respiratory syncytial virus, parainfluenza and influenza virus are recommended to confirm the viral etiology or for epidemiological surveillance. The presence of group-A streptococci must be proven by culture or antigen detection before treatment with penicillin. Antiviral treatment is limited to interferon or ribavirin. New antiviral substances are in development. Today, treatment of common cold is limited to symptomatic measures, and antibiotic treatment is not justified.

Adult↗

[A simple micro-procedure in virological and serological diagnosis].

The author reports on a micro-neutralization test which makes it possible to detect the antibodies against 7 different respiratory viruses (adeno and parainfluenza viruses) using only 0.080 ml of serum from patient. Swaged PVC foil used for packing pharmaceuticals, also known here as strip packing or press-through packing for pills and dragees was employed as plates for the cultures. This material is not toxic for the cell cultures, it is cheap and suitable also for other microbiological work in the field of serology.

Adenoviridae↗