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Viral pneumonia in the first month of life.

We performed a 5-year review of 40 patients less than or equal to 30 days of age with viral pneumonia. Isolates included respiratory syncytial virus (55%), enteroviruses (15%), rhinoviruses (15%), adenoviruses (10%), parainfluenza virus (7.5%) and herpes simplex virus (5%). Most infants were previously healthy but had ill family members. Nine were born at less than 37 weeks of gestation. Symptoms and signs included tachypnea, decreased feeding, cough, cyanosis, lethargy, retractions, apnea, bradycardia, seizures and depressed consciousness. Seasonality and clinical features, but not radiographic patterns, suggested specific pathogens. Patients were moderately to severely ill. The median duration of hospitalization was 7 days; therapies administered included oxygen (90%), mechanical ventilation (45%), blood transfusions (25%) and supplemental oxygen after discharge (27%). The case fatality rate was 7.5%. Prematurity, ill appearance at presentation, lobar consolidation and adenovirus infection were risk factors for severe disease.

Adenovirus Infections, Human↗

Canine viruses and multiple sclerosis.

Serum and cerebrospinal fluid from multiple sclerosis (MS) patients and control subjects were tested and compared for presence and titer of neutralizing antibody against the most common canine viruses. Canine viruses included canine distemper virus (CDV), canine adenovirus 1 (CAV-1), canine parainfluenza virus (CPIV), canine herpesvirus (CHV), canine coronavirus (CCV), and canine parvovirus (CPV). Neutralizing titers against measles virus (MV) and human adenovirus 8 (HA8) were also tested. Significantly elevated (p less than 0.05) antibody levels in sera from MS patients were found only against MV and CDV, but this depended upon the study population and the method of evaluation. The CDV-neutralizing component in serum could be absorbed on MV-infected cells. Results of this study failed to establish a link between canine viruses and MS.

Adenoviridae↗

Effect of heparin on hemagglutination by equine arteritis virus.

Heparin inhibited hemagglutination (HA) by equine arteritis virus (EAV) as well as did HA by Aujeszky's disease virus (ADV), but failed to inhibit HA by parainfluenza virus type 3 (PIV-3). The minimal concentration of heparin required to inhibit 8 HA U of EAV was 0.1 U/ml. In addition, most EAV hemagglutinin was retained by heparin acrylic beads, as was ADV hemagglutinin, but was not PIV-3 hemagglutinin. Mouse erythrocytes failed to combine with the HA inhibitory factor of heparin. However, mouse erythrocytes treated with heparinase had greatly reduced agglutinability by EAV. All these findings suggest that a heparin-like molecule on the surface of mouse erythrocytes serves as the virus-cell receptor.

Animals↗

[Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97].

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro Kourí Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in children's under 1 year of age.

Adolescent↗

[Bronchial asthma infectious exacerbations].

Bronchial asthma and asthma-like form of COPD often undergo exacerbations with symptoms of infection. Currently, there is a general agreement, that most of these infections that exacerbate asthma especially in children are caused by viruses. Several "common cold" viruses are known to cause these exacerbations (RSV, parainfluenza virus, rhinoviruses). To date, there is no certainty, if viruses exacerbate asthma alone or in combination with allergen. It is also unknown, whether they can induce primary asthma symptoms. There is a growing support for the opinion, that in infectious exacerbations of asthma also bacteria can play an important role. These include both typical as well as atypical bacterial strains (Chlamydia pneumoniae). The effectiveness of antibiotics and bacterial immunotherapy with vaccines seems to support the role of bacteria in asthma exacerbations. Another very important problem is related to the role of infectious agents in prevention of atopy. Many facts have been gathered supporting the so called "hygienic theory".

Asthma↗

The role of some viruses in acute pneumonias in adults.

Virological and bacteriological investigations were performed in 85 patients with acute pneumonias and virus isolation or serological evidence of virus infection were obtained in 37.6% of the cases. Influenza A2 and B viruses were incriminated in 14.1% of the patients; parainfluenza viruses in 7% and adenoviruses in 17.2% of the cases. Coxsackie virus was isolated from one patient's blood, and poliovirus 3 was recovered in 3 cases. In 5 cases associated virus infections were detected.

Adenoviridae↗

[Analysis of a recent laryngitis outbreak].

In the present paper the incidence and severity of croup during the months of september, october and november of the last three years is analyzed. The existence of an important outbreak of laryngitis in the autumn of 1987, with a peak of incidence during the month of october is shown. A prospective study about the children with croup admitted in a pediatric center during the epidemic period in 1987. Was done after serologic and cell-virus culture tests it became clear that the parainfluenza virus type 1 was the cause of the outbreak, as excepted. We suggest the possibility of another laryngitis outbreak in 1989 if there is not change in the epidemiologic pattern of the virus.

Humans↗

Febrile exudative tonsillitis: viral or streptococcal?

A prospective 1-year study of acute febrile exudative tonsillitis in 110 children was carried out. Viral infection was associated with 42% of the cases, beta-hemolytic streptococci with 31% (12% group A), Mycoplasma pneumoniae with 5%, and unknown cause with 35%. More than one agent was implicated in 14% of the cases. Adenovirus was the viral agent most frequently (19%) recorded. Other viruses involved were Epstein-Barr virus, parainfluenza, influenza A, herpes simplex, and respiratory syncytial viruses. The responsible agent was found by rapid viral antigen detection in 20% of all cases and by rapid test for group A streptococcal antigen detection in 10%. Age was the most important factor in predicting the causative agent. Viral tonsillitis was most common in children younger than 3 years of age and group A beta-hemolytic streptococci tonsillitis in children 6 years of age or more. Clinical analysis of the illness, WBC count, and ESR did not reveal differences that could help in differentiating bacterial from viral tonsillitis. All patients were treated with a regimen of oral penicillin. Fever associated with group A beta-hemolytic streptococci tonsillitis responded to penicillin therapy significantly more rapidly than fever associated with viral infections. These observations demonstrate the prominent role of viruses in the etiology of febrile exudative tonsillitis, especially in young children, and reinforce the benefit of rapid tests before antibiotic therapy is started.

Adolescent↗

Value of serological tests in the diagnosis of viral acute respiratory infections in adults.

The dynamics of the antibody response to influenza viruses A (H1N1), A (H3N2) and B, to parainfluenza viruses 1, 2, 3, to adenoviruses and respiratory syncytial virus was studied in paired serum samples collected from 110 patients hospitalized with acute respiratory infections (ARI) and in 40 patients suffering from other diseases. Rises in serum antibody titers to 1--5 of the above mentioned antigens were detected in many of the patients of both groups. The fact is most likely due to the presence of some epidemiologically and clinically uncharacteristic viral ARI (influenza included); simultaneous or successive infections with influenza virus and different other viruses were very frequent. A greater efficiency of the etiological diagnosis of viral ARI can be achieved only by the association of epidemiological and clinical criteria with serological data, the visualization of viral antigens and virus isolation.

Acute Disease↗

Establishment of a canine cell line: derivation, characterization, and viral spectrum.

A cell line, designated A-72, for virus studies was established from a tumor surgically removed from a female, 8-year-old Golden Retriever dog. Following explant culture, the cells were serially passaged 135 times. The A-72 cells maintained a fibroblastic appearance and, at the 123rd passage, had a population doubling time of approximately 27 hours. Karyotypic analysis of the high passage cells showed the modal 2n chromosome number was 92 to 93. Using starch gel electrophoresis for enzyme characterization, the electrophoretic mobilities of enzymes extracted from A-72 cells were identical with those of canine peritoneal fibroblasts and primary canine kidney cells. The A-72 cells were susceptible to infection with infectious canine hepatitis virus, canine adenovirus type II, canine herpesvirus, canine parainfluenza virus, and canine coronavirus, but were not susceptible to canine distemper virus or the minute virus of canines. These cells have been particularly useful for studies of the fastidious canine coronaviruses, as the commonly used primary canine kidney cells exhibit varied susceptibility to these viruses.

Animals↗

[Asthma and infection: risk or prevention?].

Upper respiratory tract infections and wheezing illnesses occur frequently in early childhood. Most viral infections associated with wheeze in infancy are attributable to respiratory syncitial virus, whereas in older children rhinovirus, influenza and parainfluenza virus prevail. The detection rate of viruses has increased since PCR techniques have been used. A British study for example showed that in 80% of episodes in asthmatic children aged 9-11 years viruses could be detected in nasal aspirates which had been taken within 4 days of the wheezing attack. In most cases rhinovirus was identified. Two major hypotheses have been proposed to explain the association between respiratory tract infections and subsequent respiratory abnormalities. One hypothesis states that viral infections early in life damage the growing lung or alter host immune regulation. The second hypothesis holds that respiratory infections are more severe in infants and children with some underlying predisposition. These notions await further clarification. Early childhood bacterial and viral infections may, however, also be associated with a reduced risk of developing atopic sensitization or allergic conditions, as the results of several recent studies suggest.

Asthma↗

Conserved epitopes on the hemagglutinin-neuraminidase proteins of human and bovine parainfluenza type 3 viruses: nucleotide sequence analysis of variants selected with monoclonal antibodies.

We have previously identified 11 epitopes located in two topologically nonoverlapping antigenic sites (A and B) and a third bridging site (C) on the human type 3 parainfluenza virus (PIV3) hemagglutinin-neuraminidase (HN) glycoprotein by using monoclonal antibodies (MAbs) which inhibit hemagglutination and virus infectivity (K. L. Coelingh, C. C. Winter, and B. R. Murphy, Virology 143:569-582, 1985). We have identified three additional antigenic sites (D, E, and F) on the HN molecule by competitive-binding assays of anti-HN MAbs which have no known biological activity. Epitopes in sites A, D, and F are conserved on the bovine PIV3 HN glycoprotein and also among a wide range of human isolates. The dideoxy method was used to identify nucleotide substitutions in the HN genes of antigenic variants selected with neutralizing MAbs representing epitopes in site A which are shared by human and bovine PIV3. The deduced amino acid substitutions in the variants were located in separate hydrophilic stretches of HN residues which are conserved in the primary structures of the HN proteins of both human and bovine PIV3 strains.

Animals↗

A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants.

BACKGROUND: Parainfluenza type 3 virus (PIV-3) infections cause lower respiratory tract illness in children throughout the world. A licensed PIV-3 vaccine is not yet available. METHODS: A live attenuated cold-adapted (ca) and temperature-sensitive (ts) PIV-3 vaccine, designated cp-45, was evaluated sequentially in open label studies in 20 adults and in placebo-controlled, double blind studies in 24 PIV-3-seropositive children, 52 PIV-3-seronegative infants and children and 49 infants 1 to 2 months old. A single dose of this intranasal vaccine was evaluated in adults [106 plaque-forming units (pfu)] and seropositive children, and 104 and 105 pfu were evaluated in seronegative children. In the infant study, two 104 pfu doses of vaccine were administered at 1- or 3-month intervals. Safety, infectivity, immunogenicity and phenotypic stability of the vaccine were evaluated in all cohorts. RESULTS: The cp-45 vaccine was well-tolerated in all age groups and infected 94% of vaccinated seronegative children and 94% of vaccinated infants. Although immunization with the first dose of cp-45 diminished the replication of a second dose in all infants, those immunized after 3 months shed vaccine virus more frequently than those immunized after 1 month (62% vs. 24%, respectively). Antibody responses to PIV-3 were readily detected in seronegative children with a variety of assays; however, the IgA response to the viral hemagglutinin-neuraminidase was the best measure of immunogenicity in young infants. Of 109 vaccine virus specimens recovered from nasal washes, 98 were ts and 11 were temperature-sensitive intermediate (tsi) viruses, with pinpoint plaques visible at 40 degrees C. tsi viruses appeared transiently at the time of peak viral replication, represented a very small proportion of the total virus shed and were not associated with changes in clinical status. ca revertants were not detected. CONCLUSIONS: The cp-45 vaccine is appropriately attenuated and immunogenic in infants as young as 1 month of age. Further development of this vaccine is warranted.

Age Factors↗

Age-related changes in the immune system of mice of eight medium and long-lived strains and hybrids. II. Short- and long-term effects of natural infection with parainfluenza type 1 virus (Sendai).

Studies on the effects of natural infection with parainfluenza type 1 virus (Sendai) on the immune system of 8 strains and hybrids of aging mice revealed that (a) 55 of 63 indices tested were abnormal as late as 8 months after the disappearance of clinical systoms, (b) thymus weight and cell indices and lymph node T cell activity still exhibited a statistically significant negative correlation with age following infection, and (c) immunologically immature young and immunodeficient old mice suffered more severe sequelae following viral infection than did adult or middle-aged mice as determined by accelerated decline of thymus indices, mortality, IgM Coombs' titer, and in the case of old mice, anemia. These findings suggest that chronic viral infection can accelerate immunologic aging and that viral infection in utero can suppress or retard the development of the T cell component of the immune system. In support of our previous study, they also suggest that the thymus regulates immunologic aging and that genetic factors regulating immunologic aging are not easily influenced by environmental factors.

Aging↗

Experimental panencephalitis induced in suckling mice by parainfluenza I (6/94) virus. III. Ultrastructural studies.

Intracerebral inoculation of newborn mice with Parainfluenza I (6/94) virus produces a chronic panencephalitis. Electron microscopic studies were carried out over 125 days of the infection. Productive infection of choroidal and ependymal epithelial cells was seen from postinoculation days 2nd to the 8th. Fusion of adjacent choroid and ependymal cells resulted in giant cell formation. Completed virions were seen adsorbed to circulating macrophages and these cells replicated intracytoplasmic nucleocapsids. Neuronal infection was evident on the 3rd postinoculation day, was widespread by the 6th day postinoculation and persisted to the 35th day postinoculation. Nucleocapsid alignment and budding from neuronal plasma membranes was never seen. An initially intense mononuclear cell infiltrate subsided by the 35th day but residual inflammation persisted throughout the study. Late in the course of the infection, vacuolation of the neuropil and a periventricular and deep cerebral spongiform change was seen which could not be directly associated with local viral replication. These ultrastructural findings are correlated with prior light microscopic, virological and immunofluorescent studies of the infection and compared to other experimental models of myxovirus central nervous system infections.

Animals↗

Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent.

The relative in vitro antiviral activities of three related nucleoside carboxamides, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), and selenazole (2-beta-D-ribofuranosylselenazole-4-carboxamide), were studied against selected DNA and RNA viruses. Although the activity of selenazole against different viruses varied, it was significantly more potent than ribavirin and tiazofurin against all tested representatives of the families Paramyxoviridae (parainfluenza virus type 3, mumps virus, measles virus), Reoviridae (reovirus type 3), Poxviridae (vaccinia virus), Herpes-viridae (herpes simplex virus types 1 and 2), Togaviridae (Venezuelan equine encephalomyelitis virus, yellow fever virus, Japanese encephalitis virus), Bunyaviridae (Rift Valley fever virus, sandfly fever virus [strain Sicilian], Korean hemorrhagic fever virus), Arenaviridae (Pichinde virus), Picornaviridae (coxsackieviruses B1 and B4, echovirus type 6, encephalomyocarditis virus), Adenoviridae (adenovirus type 2), and Rhabdoviridae (vesicular stomatitis virus). The antiviral activity of selenazole was also cell line dependent, being greatest in HeLa, Vero-76, and Vero E6 cells. Selenazole was relatively nontoxic for Vero, Vero-76, Vero E6, and HeLa cells at concentrations of up to 1,000 micrograms/ml. The relative plating efficiency at that concentration was over 90%. The effects of selenazole on viral replication were greatest when this agent was present at the time of viral infection. The removal of selenazole from the medium of infected cells did not reverse the antiviral effect against vaccinia virus, but there was a gradual resumption of viral replication in cells infected with parainfluenza type 3 or herpes simplex virus type 1 (strain KOS). However, the antiviral activity of ribavirin against the same viruses was reversible when the drug was removed.

Animals↗

Sequence analysis and expression of the human parainfluenza type 1 virus nucleoprotein gene.

The nucleotide sequence of the human parainfluenza type 1 (Pl1) virus nucleoprotein (NP) gene was determined from cDNA clones of the mRNA. A cDNA clone, 4-31, containing a 1.7-kb insert, was identified as a Pl1 NP-specific clone by partial nucleotide sequence analysis and sequence comparison with Sendai virus (SV) NP. Using a vaccinia virus transient expression system, a polypeptide with electrophoretic mobility similar to that of Pl1 NP was synthesized from this clone, which reacted specifically with both polyclonal and monoclonal antibodies against Pl1 virus and Pl1 NP, respectively. The complete nucleotide sequence of this clone was determined and was found to contain a single open reading frame that can encode a protein of 524 amino acids with a predicted molecular weight of 57,547. Comparison of the amino acid sequence of Pl1 NP with that of other paramyxoviruses showed that two conserved amino acid sequences found within other paramyxoviruses are also present in Pl1 NP. Although Pl1 and SV showed a high sequence homology, approximately 100 amino acids at the C-terminal region were highly divergent as found also among other paramyxoviruses.

Amino Acid Sequence↗

The wheezy infant -- immunological and molecular considerations.

Most of the data on the pathogenesis of asthma is based on information obtained through bronchial biopsies and bronchoalveolar lavage in adults and young adults. Ethical considerations linked to the invasive nature of airway endoscopy have limited the studies on the pathophysiology of asthma in infancy and early childhood. Although there is evidence that an asthma-like inflammation, with increased inflammatory cells and thickening of the lung basement membrane, may be present also at a very early age, clinical and epidemiologic studies suggest that asthma manifestations in preschool children may significantly differ from those observed in older subjects. In western countries, the vast majority of infants and young children has episodic (or intermittent) asthma, and the exacerbations generally defined "wheezing episodes" occur more frequently with a seasonal pattern being usually related to acute viral infections. There is strong epidemiological evidence that approximately 2/3 of all children who wheeze because of viral infections in early life (and are not atopic) have a transient condition that tends to disappear during early school years. All respiratory viruses may be implicated in the wheezing episodes, the principal being respiratory syncytial virus (RSV) and, with a lower frequency, adenovirus and parainfluenza viruses during the first 3 years of life, and rhinoviruses after that age. Infants and preschool children have on average 6-8 "colds" per year, but the illness tends to be limited to the upper respiratory tract alone in a considerable proportion of individuals, without causing symptomatic involvement of the lower respiratory tract. The variety of factors determining the different outcomes are only partially known, but complex interactions between the intrinsic pathogenicity of the virus and host factors, including the socio-economic conditions of the family, are central to define the type of manifestations and the severity of the process.

Antigen-Antibody Reactions↗