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Occurrence and aetiology of acute respiratory diseases: results of a longterm surveillance programme.

Totals of 58,661,000 acute respiratory disease (ARD) cases, 1,376,651 bronchitis and pneumonia complications, and 93,042 deaths from influenza, bronchitis, pneumonia or chronic pulmonary affection were notified during 11 years of ARD surveillance from 1975 to 1986. All ARD seasons started with the first phase in September-December; this increase in morbidity was caused chiefly by adenoviruses, parainfluenza viruses, rhinoviruses and M. pneumoniae. Second wave of ARD morbidity occurring in January-April used to be explosive and was associated with an influenza epidemic in 9 of the 11 seasons; only in 1978/79 and 1984/85 the ARD epidemics were caused by adenoviruses and especially RSV, the share of influenza being minimal. Pneumonia and bronchitis excesses occured during epidemics caused by M. pneumoniae in 1975/76, 1980/81 and 1985/86. Particularly high mortality excesses occurred in 1976, 1977 and 1983 during epidemics elicited by a new drift variants of influenza A(H3N2). Identification of viral agent of M. pneumoniae attempted in 5474 ARD cases was successful at 37.4%. The respective contributions of parainfluenza viruses, adenoviruses, influenza A virus and RSV to overall aetiologically identified morbidity were 14.2, 13.9, 13.8, and 12.0%. Mixed infections (2-3 agents identified simultaneously) accounted for 14.6% of cases. Type B influenza virus, rhinoviruses, enteroviruses and herpes simplex virus contributed only by 5.6-7.8%. In ordinary seasons the share of M. pneumoniae in aetiologically identified ARD morbidity was 0.6-3.8%; this agent displayed predominance at 5-year cycles, when accounting for 20.5-38.9% of cases. The most frequently detected agents in individual age groups were as follows: in preschool children parainfluenza (18.6%), RSV (16.6%), and adenoviruses (17.4%); in school children M. pneumoniae (26%), influenza A and B (10.2 and 14.7% respectively), and adenoviruses (10.7%); in adolescents and young adults influenza type A (20.2%), M. pneumoniae (15.0%), and rhinoviruses (13.3%); in adults above 25 years age influenza A virus (38%), and other respiratory viruses at a frequency lower than 10% each.

Adolescent↗

Experimental panencephalitis induced in suckling mice by parainfluenza type 1 (6/94) virus. I. Clinical and pathological features.

Intracerebral inoculation of two strains of suckling mice with 6/94 virus, a parainfluenza type 1 virus originally isolated from two patients with multiple sclerosis, produced clinical disease 1-2 weeks after inoculation. Of 528 animals inoculated, 33% died (26% of the ICR strain and 76% of the BALB/c strain) usually between two or three weeks after injection. Animals that recovered appeared to develop normally. Pathological changes were of two types. Initially, there was a necrotizing panencephalitis with virus-specific intracytoplasmic inclusions in choroid and ependymal epithelial cells and neurons. The second major lesion appeared about 6 weeks post inoculation and consisted of a noninflammatory spongiform degeneration of white matter that primarily involved the cerebral hemispheres; a diffuse vacuolar encephalapathy primarily affecting the brain stem; and a persistent minimal inflammation.

Animals↗

Serological relationships between certain avian and animal paramyxoviruses.

An avian paramyxovirus designated Robin/Hiddensee/19/75 proved to be related to the Yucaipa virus group in cross haemagglutination inhibition test (HIT). Whereas the prototype parainfluenza viruses did not react with the antiserum raised against the Robin virus, a newly isolated bovine parainfluenza 3 virus was shown to be inhibited up to half the homologous titre. Possible antigenic relationships between avian, mammalian and human paramyxoviruses are discussed.

Animals↗

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

The safety, infectivity, immunogenicity, and phenotypic stability of the cold-passaged (cp) candidate vaccine cp-45, a cold-adapted (ca), temperature-sensitive (ts) mutant of the JS strain of human parainfluenza virus type 3 (HPIV-3), was evaluated in 114 children 6 months to 10 years old in a randomized, placebo-controlled, double-blind trial. The cp-45 vaccine was well tolerated when given intranasally to parainfluenza virus type 3 (PIV-3)-seropositive and -seronegative children. With 10(4) or 10(5) TCID50 of cp-45 vaccine, 86% of seronegative vaccines were infected, 83% of whom shed virus at a mean peak titer of 10(22) pfu/mL. Virus present in respiratory specimens retained the ts phenotype, and each of 86 PIV-3 isolates tested retained both the ca and ts phenotypes. One dose of 10(5) TCID50 of vaccine induced a serum hemagglutination-inhibiting antibody response in 81% of vaccinees; the geometric mean titer was 1:32. These studies indicate that the cp-45 HPIV-3 vaccine is satisfactorily attenuated, infectious, immunogenic, and phenotypically stable and merits further evaluation in infants and young children.

Antibodies, Viral↗

Isolation of respiratory bovine coronavirus, other cytocidal viruses, and Pasteurella spp from cattle involved in two natural outbreaks of shipping fever.

OBJECTIVE: To identify cytocidal viruses and Pasteurella spp that could be isolated from cattle involved in 2 natural outbreaks of shipping fever. ANIMALS: 105 and 120 castrated male 4- to 8-month-old feedlot cattle involved in 1997 and 1998 outbreaks, respectively. PROCEDURES: Nasal swab specimens and blood samples were collected, and cattle were vaccinated on arrival at an order-buyer barn from 4 local auction houses. Four days later, they were transported to a feedlot, and additional nasal swab specimens and blood samples were collected. Nasal swab specimens were submitted for virus isolation and bacterial culture; blood samples were submitted for measurement of respiratory bovine coronavirus (RBCV) hemagglutinin inhibition titers. RESULTS: 93 of 105 cattle and 106 of 120 cattle developed signs of respiratory tract disease during 1997 and 1998, respectively, and RBCV was isolated from 81 and 89 sick cattle, respectively, while at the order-buyer's barn or the day after arrival at the feedlot. During the 1997 outbreak, bovine herpesvirus 1 was isolated from 2 cattle at the order-buyer's barn and from 5 cattle 7 and 14 days after arrival at the feedlot, and parainfluenza virus 3 was isolated from 4 cattle 14 days after arrival at the feedlot. During the 1998 outbreak, bovine herpesvirus 1 was isolated from 2 cattle at the order-buyer's barn and on arrival at the feedlot and from 5 cattle 7 and 14 days after arrival at the feedlot, and parainfluenza virus 3 was isolated from 1 animal the day of, and from 18 cattle 7 and 14 days after, arrival at the feedlot. Pasteurella spp was cultured from 4 and 6 cattle at the order-buyer's barn and from 92 and 72 cattle on arrival at the feedlot during the 1997 and 1998 outbreaks, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that RBCV may play a causative role in outbreaks of shipping fever in cattle. More than 80% of the sick cattle shed RBCV at the beginning of 2 outbreaks when the Pasteurella spp infection rate was low.

Animals↗

Cell-mediated immunity to viral antigens and tuberculin in multiple sclerosis.

Lymphocyte transformation responses to measles, mumps, herpes simplex and parainfluenza virus antigens and purified protein derivative of tuberculin were determined in both 78 normal controls and 40 patients with multiple sclerosis, 16 of whom were studied serially. Patients with multiple sclerosis showed significantly reduced responses to all antigens except herpes simplex. Impaired responses occurred at all stages of clinical activity, but were lowest during recovery from an acute exacerbation or in patients with chronic disease. The transformation responses to measles, mumps and parainfluenza virus antigens correlated significantly with the numbers of circulating T cells, which, similarly, showed parallel fluctuations with disease activity.

Adult↗

Isolation of a paramyxovirus from the cerebrospinal fluid of a dog with posterior paresis.

A paramyxovirus was isolated from cerebrospinal fluid of a dog with a history of incoordination and posterior paresis. The virus apparently was not related to canine distemper virus (CDV), considering the lack of virus neutralization with CDV-specific antibody, negative immunofluorescence with CDV-specific conjugate, and avirulence for ferrets. The virus was antigenically related to a prototype strain of canine parainfluenza virus, as determined by positive immunofluorescence with canine parainfluenza virus-specific conjugate and virus neutralization tests.

Animals↗

Recognition of viral antigens in 6/94 virus-induced T-cell-mediated cytotoxicity.

Distinct events in the virus-stimulated T-cell-mediated cytotoxicity (V-CMC) have been investigated: 1.) The induction of V-CMC is possible by immunizing mice with infectious as well as UV-inactivated virus (parainfluenza type 1 strain 6/94), or with virus-infected cells either compatible or imcompatible with the recipient. 2). Recognition of viral antigens by the effector cells occurs independently of the H2 environment: Fractionation of effector cells on columns loaded with virus-infected cells eliminates virus-specific cytotoxic cells. Effector cells and cells on the column need not share H-2 antigens. The findings are discussed with regard to the H2 restriction of the virus induced T-cells mediated cytotoxicity.

Animals↗

Respiratory virus infections in adults with hematologic malignancies: a prospective study.

During a 2-year period, 157 consecutive episodes of respiratory virus infections that occurred in 130 patients with upper or lower respiratory tract infection were analyzed for respiratory viruses. A respiratory virus was identified in 75 episodes (48%), and several viruses were found in 13 episodes: there were a total of 56 influenza A virus infections, 14 respiratory syncytial virus infections, 8 adenovirus infections, 8 infections with parainfluenza virus types 1 or 3, and 7 enterovirus infections. On multivariate analysis, the only variable that predicted progression to pneumonia in patients with an upper respiratory tract infection was the presence of respiratory syncytial virus, whereas lymphocytopenia had a nonsignificant trend. Also, among the 38 patients who had pneumonia at any time during the episode, both respiratory syncytial virus and lymphocytopenia were commonly found. For both epidemiological and therapeutic considerations, frequent screening for respiratory viruses should be incorporated into the routine diagnostic study of patients with hematologic malignancies.

Adenoviridae↗

Sendai virus-induced alterations in lung structure/function correlate with viral loads and reveal a wide resistance/susceptibility spectrum among mouse strains.

The Paramyxoviridae family includes some of the most important and ubiquitous disease-causing viruses of infants and children, most of which cause significant infections of the respiratory tract. Evidence is accumulating in humans that genetic factors are involved in the severity of clinical presentation. As a first step toward the identification of the genes involved, this study was undertaken to establish whether laboratory mouse strains differ in susceptibility to Sendai virus, the murine counterpart of human type-1 parainfluenza virus which, historically, has been used extensively in studies that have defined the basic biological properties of paramyxoviruses in general. With this purpose in mind, double-chamber plethysmography data were collected daily for 7 days after inoculation of Sendai virus in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values closely reflected the success of viral replication in the lungs and revealed a pattern of continuous variation with resistant, intermediate, and susceptible strains. The results unambiguously suggest that BALB/c (resistant) and 129Sv (susceptible) strains should be used in crossing experiments aimed at identifying the genes involved in resistance to Paramyxoviridae by the positional cloning approach.

Animals↗

Presence of specific viruses in the middle ear fluids and respiratory secretions of young children with acute otitis media.

The purpose of the study was to investigate the presence of different viruses in middle ear fluids and nasopharyngeal aspirates in young children with acute otitis media. Two cohorts of children (N = 329 and 611) were followed from 2 to 24 months of age in Finland in two prospective studies (Finnish Otitis Media Cohort Study and Finnish Otitis Media Vaccine Trial). During the study period, nasopharyngeal and middle ear fluid specimens for each acute otitis media event were examined for eight (Cohort Study) or ten (Vaccine Trial) common respiratory viruses; adenoviruses, influenza viruses A and B, parainfluenza viruses 1, 2, and 3, respiratory syncytial virus (RSV), enteroviruses, parechoviruses, and rhinoviruses. Picornaviruses (rhinoviruses, enteroviruses, and parechoviruses) were determined by reverse transcription PCR while antigen detection was used for the other viruses. A virus was present in either nasopharyngeal or middle ear specimen in 54% of events in the first cohort and in 67% of events in the second. Rhinoviruses formed the most common virus group detected (41-32%), followed by enteroviruses (25%, sought in the second cohort only) and respiratory syncytial virus (RSV) (10%). All the other viruses represented jointly 8-10% of the events. In conclusion, using the methods described in this study, a specific virus infection was diagnosed in two thirds of all acute otitis media events in young children. Picornavirus RNA was detected in association with more than a half of all acute otitis media events. The use of PCR-based methods for the other respiratory viruses might have increased further the overall virus detection rate in acute otitis media.

Acute Disease↗

Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections.

The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS-CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS-CoV infection. Therefore, SARS-CoV replication was suppressed by pretreatment with IFN. SARS-CoV and RSV induced high levels of IL-6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling-3 (SOCS3) by SARS-CoV was significantly lower than that by RSV in spite of the significant production of IL-6. Toll-like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS-CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with "severe" inflammation in SARS.

Caco-2 Cells↗

Paramyxovirus strategies for evading the interferon response.

Two genera, the Respirovirus (Sendai virus (SeV) and human parainfluenza virus (hPIV3) and the Rubulavirus (simian virus (SV) 5, SV41, mumps virus and hPIV2), of the three in the subfamily Paramyxovirinae inhibit interferon (IFN) signalling to circumvent the IFN response. The viral protein responsible for the inhibition is the C protein for respirovirus SeV and the V protein for the rubulaviruses, both of which are multifunctional accessory proteins expressed from the P gene. SeV suppresses IFN-stimulated tyrosine phosphorylation of signal transducers and activators of transcription (STATs) at an early phase of infection and further inhibits the downstream signalling without degrading any of the signalling components in most cell lines. On the contrary, the Rubulavirus V protein targets Stat1 or Stat2 for degradation. Proteasome-mediated degradation appears to be involved in most cases. Studies on the molecular mechanisms by which paramyxoviruses evade the IFN response will offer important information for modulating the JAK-STAT pathway, designing novel antiviral drugs and recombinant live vaccines, and improving paramyxovirus expression vectors for gene therapy.

Antiviral Agents↗