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Parainfluenza type 3 meningitis. Report of two cases and review of the literature.

The authors present two immunocompetent children with parainfluenza type 3 meningitis. In each case, the outcome was favorable without detectable complications. The authors reviewed the literature, showing that central nervous system (CNS) involvement by parainfluenza viruses has rarely been described but may present with a variety of neurologic syndromes. Pediatricians and laboratory personnel should recognize that these viruses, commonly known to produce respiratory syndromes, can also be a cause of CNS infections. If additional studies confirm these observations, clinicians and virology laboratories may consider whether early hemadsorption testing to detect myxoviruses is warranted.

Female↗

Respiratory viral infections aggravate airway damage caused by chronic rejection in rat lung allografts.

Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chronic rejection is assumed to be the most important cause of bronchiolitis obliterans. However, viral infections might also be potential causes of airway damage after lung transplantation. In the present study, we investigated whether viral infections could induce airway damage in rat lung transplants in the absence or presence of chronic rejection. We compared the histopathology of the airways in 3 groups of rats: (1) nontransplanted LEW lungs, (2) LEW-to-LEW syngeneic lung transplants, and (3) BN-to-LEW allogeneic lung transplants. Nontransplanted and transplanted rats were treated with CsA to induce permanent graft acceptance of the allografts. Six months after transplantation, 4 noninfected rats of each group were killed for histological investigation (another 4 noninfected allografted rats were killed 56 days later). The remaining 16 rats in each group were infected with Sendai virus (parainfluenza type 1) intratracheally. These rats were killed for histological investigation 4, 7, 21, and 56 days after infection. In the lungs of the noninfected rats of the nontransplanted and syngeneically transplanted groups, airway changes were absent. After viral infection in these lungs, mild inflammation developed in the airways that was transient and completely resolved by day 56 after infection. In contrast, in the allogeneically transplanted lungs the viral infection caused severe and permanent damage of the airways. In the bronchioles and the large airways throughout the allogeneic lung transplants, inflammation with epithelial necrosis and formation of granulation tissue was present. On day 56 after infection, the bronchioles showed scarring in the submucosa and obliteration of the lumen, typical features of bronchiolitis obliterans. This study shows that a respiratory viral infection aggravates the airway damage in rat lung allografts with chronic rejection. The findings suggest that viral infections and chronic rejection play a synergistic role in the development of bronchiolitis obliterans after human heart-lung and lung transplantation: the virus infection may stimulate chronic rejection and rejection may hamper the local defense against the virus.

Animals↗

Effects of Sendai virus infection on function of cultured mouse alveolar macrophages.

Cultured mouse alveolar macrophages supported the growth of Sendai virus (murine parainfluenza I virus), as measured by both a 10-fold increase in extracellular virus titers and development of viral antigens on most of the cells. Synthesis of virus continued for at least 1 month without cytopathic effects. Macrophage phagocytic activity for Candida, Staphylococcus epidermidis, and opsonized erythrocytes remained unaffected by the infection, and the ability of the cells to kill S. epidermidis and S. Aureus was also unchanged. The defects in alveolar macrophage function observed in Sendai-infected mouse lungs probably are not due to a direct effect of the virus on macrophage function.

Animals↗

A group level analysis of the associations between antibodies to seven putative pathogens and respiratory disease and weight gain in Ontario feedlot calves.

The associations, at the group level, between serological titer to Pasteurella haemolytica surface antigens (Ph), Pasteurella haemolytica cytotoxin (Ph-cytox), infectious bovine rhinotracheitis virus (IBRV), bovine virus diarrhea virus (BVDV), parainfluenza-3 virus (PIV3), respiratory syncytial virus (RSV), Mycoplasma dispar (Md), M. bovis (Mb), and respiratory disease treatment rates, relapse rates, and 28 day weight gains were investigated in 14 groups of calves entering two feedlots during years 1983-1985, in Ontario. Based on least squares regression analyses, seroconversion rates to Mb and BVDV were predictive of increased respiratory disease rates, and seroconversion rates to Ph, Ph-cytox, Md and PIV3 were predictive of decreased weight gains. The R2 for predicting weight gains was much higher than for morbidity rates (0.75 vs 0.47 respectively). Titer data were not predictive of relapse rates. Group level analyses were performed because calves are managed as groups (e.g. pens) in commercial feedlots. Only BVDV seroconversion rates were related to increased risk of respiratory disease at both the individual and group levels of organization. Mycoplasma may be important factors in causing respiratory disease, and their relationship to potentiating the effects of other respiratory pathogens needs further investigation.

Animals↗

Validation of disease diagnoses reported to the National Animal Health Monitoring System from a large Colorado beef feedlot.

Clinical observation and collection of biological specimens from a large beef feedlot (approximately 30,0000 animals) were used to evaluate 6 approaches for validation of a disease reporting system. Data collected during a 12-month period were used to evaluate each approach. A subsample of disease cases reported to the National Animal Health Monitoring System (NAHMS) was compared with the clinical observations of the investigators. Although the agreement between clinical diagnosis by the NAHMS veterinarian and by feedlot health crews was high, the sensitivity and specificity of specific diagnoses varied from 100 to 18% and from 99 to 76%, respectively, which suggests that regular clinical observations by a veterinarian are needed to validate disease diagnoses reported to NAHMS by producers. Subsampling of a group of cattle by means of paired serologic determination of antibodies to infectious bovine rhinotracheitis virus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza-3 virus revealed a high serologic conversion rate to infectious bovine rhinotracheitis, and high levels of preexisting antibody to bovine respiratory syncytial and parainfluenza-3 viruses. It was concluded that the current method of data collection for Colorado feedlots provides an acceptable level of sensitivity and specificity for the program. However, disease events that are not of economic importance to the feedlot operator will be underestimated. If an objective of NAHMS is to develop a base line of animal health conditions, diagnosis of diseases by current methods will be satisfactory. Occasional validation through clinical observations by a veterinarian will suffice to monitor quality of collected data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A simplified plaque assay for respiratory syncytial virus--direct visualization of plaques without immunostaining.

Due to their generally small size, detection of respiratory syncytial virus (RSV) plaques commonly relies on immunostaining using either polyclonal antisera or a pool of monoclonal antibodies against the surface fusion glycoprotein. Disadvantages include the costs of the antibodies and substrate, and microscopic examination is often needed for counting of plaques. By optimizing many parameters, greatly improved plaque assays for RSV A2, Long and RSV B 18537 strains using Vero or HEp-2 cells have been developed. Although many groups use Vero cells for plaquing, after optimization plaques were much larger in HEp-2 cells. Both cell types needed to be confluent at infection and agarose was more suitable than carboxymethyl cellulose for the overlay. Overlay medium for HEp-2 was DMEM/F12, 0.3% agarose, and for Veros it was Liebovitz L15, 5% fetal calf serum, 0.3-0.5% agarose. After 5-7 days, monolayers were fixed with 1% formal saline overnight, agarose was removed and monolayers were stained with 0.05% neutral red in water. Plaques were readily visible by eye and plates could be dried and stored permanently. Parainfluenza virus type 3 also formed large plaques in HEp-2 cells under the conditions optimal for RSV.

Animals↗

New transtracheal bronchoalveolar lavage technique for the diagnosis of respiratory disease in sheep.

A new transtracheal bronchoalveolar lavage technique for the diagnosis of respiratory disease in sheep under field conditions was tested in 76 sheep. The sheep were divided into three groups, normal sheep, sheep with clinical signs of respiratory disease and housed sheep, on the basis of their respiratory disease history and husbandry conditions. The detection of Mannheimia haemolytica and Mycoplasma ovipneumoniae or parainfluenza virus type 3 and bovine respiratory syncytial virus antigen in the lavage samples was closely correlated with clinical disease. The sheep with clinical respiratory disease had a higher mean percentage of neutrophils in the lavage fluid than the sheep in the other two groups.

Animal Husbandry↗

[Effect of tuberculin and levamisole on the immune response after vaccinating calves against para-influenza and Salmonella infections].

Studied was the effect of tuberculin and levamizole on the immune response following vaccination of calves against parainfluenza and Salmonella infections. It was found that in calves that had colostrum antibodies against parainfluenza the immunogenic stimulation with the two agents first led to a drop of the total protein and of the antibody titer of the blood serum; in later periods the antibody titer grew severalfold. The stimulation with tuberculin and levamizole in the case of Salmonella infection substantiated more abrupt humoral immune response as against the case of animals that were not stimulated. More effective was the stimulation when lemvamizole was applied on the 7th day following vaccination. It was established that both tuberculin and levamizole stimulated the phagocytic activity of the blood of calves vaccinated against a parainfluenza virus and did not influence essentially the same activity in calves vaccinated against Salmonella infection. The amount of erythrocyte-rosette forming cells (E-POK) also remained visibly unchanged by the effect of tuberculin and levamizole with the use of the two vaccines.

Adjuvants, Immunologic↗

Adult croup: a rare but more severe condition.

We report the first adult patient with virologically confirmed croup caused by parainfluenza virus type 3 and review 10 cases of adult croup described in the English-language literature. Circumstantial evidence of viral infection was present in only 1 other case, in which there was a rise in antibody titer against influenza B virus. Ten patients (91%) required intensive care support. None of the 11 patients died. A comparison was also made between the 11 adults with croup and 43 children hospitalized with severe croup described in a representative paper published in 1984. Adult croup represents an apparently more severe disease entity than pediatric croup.

Aged↗

Survey of antibodies against various infectious disease agents in racing camels in Abu Dhabi, United Arab Emirates.

Prevalence of antibodies against some important disease agents in sera from racing camels in Abu Dhabi (United Arab Emirates) is reported. Antibodies against Brucella abortus were detected in 1.5% of racing camels, but only 0.76% had titres sufficient for the animals to be considered infected. The complement fixation test revealed antibodies against Coxiella burnetii (causative agent of Q fever) in 7.9% of camels (with a geometrical mean titre of 13) and against parainfluenza virus type 3 in 5.6% of camels (with a geometrical mean titre of 20). Serological evidence did not show the presence of Aspergillus spp., while antibodies against Leptospira interrogans were seen in 4.1% of camels. Antibodies against Echinococcus polymorphus were observed in 2.6% of the animals, while a large number of racing camels (30.9% and 36.4%) possessed antibodies against Toxoplasma gondii, as determined by direct agglutination and indirect haemagglutination, respectively.

Animals↗

Neutral endopeptidase and neurogenic inflammation in rats with respiratory infections.

Neuropeptides such as substance P are implicated in inflammation mediated by sensory nerves (neurogenic inflammation), but the roles in disease of these peptides and the peptidases that degrade them are not understood. It is well established that inflammation is a prominent feature of several airway diseases, including viral infections, asthma, bronchitis, and cystic fibrosis. These diseases are characterized by cough, airway edema, and abnormal secretory and bronchoconstrictor responses, all of which can be elicited by substance P. The effects of substance P and other peptides that may be involved in inflammation are decreased by endogenous neutral endopeptidase (NEP; also called enkephalinase, EC 3.4.24.11), which is a peptidase that degrades substance P and other peptides. In the present study, we report that rats with histories of infections caused by common respiratory tract pathogens (parainfluenza virus type 1, rat corona-virus, and Mycoplasma pulmonis) not only have greater susceptibility to neurogenic inflammatory responses than do pathogen-free rats but also have a lower activity of NEP in the trachea. This reduction in NEP activity may cause the increased susceptibility to neurogenic inflammation by allowing higher concentrations of substance P to reach tachykinin receptors in the trachea. Thus decreased NEP activity may exacerbate some of the pathological responses in animals with respiratory tract infections.

Animals↗

[Variants of parainfluenza type 2 viruses].

A comparative study of the antigenic and biological properties of parainfluenza type 2 viruses revealed the existence of two variants among them. The first variant includes strains isolated up to 1965 inclusive, the 2nd those isolated in 1966--1974. The strains of the 2nd variant are characterized by poor interaction with antibody in immune sera to the reference virus which appears to be due to a loss of one of the antigens in them. Besides, they have comparatively low immunogenicity and the hemagglutinating activity and higher sensitivity to inhibitors. The paper emphasized the necessity of using immune sera to strains isolated in recent years, in addition to reference sera, for identification of new isolated of parainfluenza type 2 virus.

Genetic Variation↗

Immunoelectron microscopy of parainfluenza virion glycoproteins with polyclonal and monoclonal antibodies: movement of glycoprotein with monoclonal antibody.

Two glycoproteins (HN and F) of parainfluenza virus were immunogold-labeled with polyclonal and monoclonal antibodies, respectively, and their labeling patterns were compared. Both glycoproteins HN and F were efficiently and homogeneously labeled with polyclonal antibodies, whereas they were labeled much less and heterogeneously with monoclonal antibodies. When either protein was initially labeled with monoclonal antibody, and then the other one, with polyclonal antibody, immunolabels of two glycoproteins were almost completely segregated. Although this segregation deformed virion morphology, it supported the concept of monoclonal antibody-mediated movements of glycoproteins.

Animals↗

Individual contributions of the human metapneumovirus F, G, and SH surface glycoproteins to the induction of neutralizing antibodies and protective immunity.

We evaluated the individual contributions of the three surface glycoproteins of human metapneumovirus (HMPV), namely the fusion F, attachment G, and small hydrophobic SH proteins, to the induction of serum HMPV-binding antibodies, serum HMPV-neutralizing antibodies, and protective immunity. Using reverse genetics, each HMPV protein was expressed individually from an added gene in recombinant human parainfluenza virus type 1 (rHPIV1) and used to infect hamsters once or twice by the intranasal route. The F protein was highly immunogenic and protective, whereas G and SH were only weakly or negligibly immunogenic and protective, respectively. Thus, in contrast to other paramyxoviruses, the HMPV attachment G protein is not a major neutralization or protective antigen. Also, although the SH protein of HMPV is a virion protein that is much larger than its counterparts in previously studied paramyxoviruses, it does not appear to be a significant neutralization or protective antigen.

Animals↗

Sequence analyses of the 3' genome end and NP gene of human parainfluenza type 2 virus: sequence variation of the gene-starting signal and the conserved 3' end.

We cloned and determined the nucleotide sequences of cDNAs against nucleocapsid protein (NP) mRNA and the genomic RNA of human parainfluenza type 2 virus (PIV-2). The 3' terminal region of genomic RNA was compared among PIV-2, mumps virus (MuV), Newcastle disease virus (NDV), measles virus (MV), PIV-3, bovine parainfluenza type 3 virus (BPIV-3), Sendai virus (SV), and vesicular stomatitis virus (VSV), and an extensive sequence homology was observed between PIV-2 and MuV. Although no significant sequence relatedness was observed between PIV-2 and other viruses, the terminal four nucleotides were identical in the viruses compared, implying a specific role of these nucleotides on the replication of paramyxoviruses. A primer extension analysis elucidated the major NP mRNA initiation site with the sequence UCUAAGCC, which showed a moderate homology with the gene-starting consensus sequences of other paramyxoviruses. On the other hand, the NP mRNA was terminated at the nucleotide stretch AAAUUCUUUUU, and this sequence was conserved in all the PIV-2 genes, indicating that the oligonucleotides will form a part of the gene attenuation signal of PIV-2. Comparisons of NP protein sequence indicated a possible subgrouping of the paramyxoviruses into two groups, one of which is a group including PIV-2, PIV-4, MuV, and NDV, and another is a group including PIV-3, BPIV-3, and SV. This result supports an idea from our previous studies using polyclonal and monoclonal antibodies. Furthermore, our data indicated that the PIV-2 NP protein sequence was more closely related to MV and CDV than to other parainfluenza viruses, PIV-3 and SV.

Amino Acid Sequence↗

An outbreak of acute pneumonia in young, single-suckled calves.

An outbreak of acute severe pneumonia which affected six to 14-week-old single-suckled calves, resulted in 45/77 requiring treatment. The examination of paired sera from all affected calves revealed that neither an adenovirus, non infectious bovine rhinotracheitis virus nor parainfluenza 3 virus was involved. The acute exudative interstitial pneumonia found at post mortem was typical of pneumonic pasteurellosis.

Animals↗

A novel covalent enzyme-linked immunoassay (CELIA) for simultaneously measuring free and immune complex bound antibodies with a defined specificity. II. Application to immune complexes containing viral antigens in human sera.

The coupling of viral antigens from parainfluenza virus (PIV-1), cytomegalovirus (CMV) and human immunodeficiency virus (HIV-1) to chemically functionalized polystyrene plates has permitted us to develop a covalent enzyme-linked immunoassay (CELIA) for measuring the titers of free antibody (Ab) and immune complex (IC) bound Ab directed against each of these viruses. The method was first validated for experimentally produced IC (PIV-anti-PIV) and then applied to the analysis of IC in human sera. In the case of a renal transplant patient with CMV viremia whose free Ab titers were less than 100, the method unambiguously permitted the IC bound anti-CMV titers to be determined. In the case of a survey for HIV-1 Ab, it also allowed us to identify a sub-group of seropositives with IC anti-HIV. In view of the ease and rapidity with which CELIA can be performed, this technology should enable determinations of IC bound Ab of defined specificity to be undertaken routinely in seroepidemiological surveys.

Animals↗

Antibodies to paramyxovirus nucleoproteins define regions important for immunogenicity and nucleocapsid assembly.

To help illuminate the surface topography of paramyxovirus nucleocapsids, epitopes recognized by monoclonal antibodies have been mapped on the primary structure of human parainfluenza virus type 1 (hPIV1) nucleoprotein (NP). Full-size NP (524 amino acids) was used, as well as a series of truncated proteins with segments resected from either their carboxyl or their amino termini. Immunoprecipitation by three anti-hPIV1 NP monoclonal antibodies required the presence of amino acids within the carboxyl-terminal 23% of NP. This was consistent with an earlier study of the closely related Sendai virus (SV) NP which mapped all epitopes to regions near the carboxyl terminus. However, in contrast to those results, we found that three other antibodies specific for hPIV1 NP recognized epitopes in the amino-terminal 30% of the molecule. Two of these antibodies also cross-reacted with SV NP and with SV nucleocapsid complexes, showing that the same epitopes were present in the SV protein and were accessible on the nucleocapsid surface. Differences in immunogenicity of these epitopes in the hPIV1 and SV nucleoproteins may reflect sequence differences elsewhere in each NP molecule. In addition, two antibodies to epitopes near the NP carboxyl terminus caused P protein to be released from SV nucleocapsid complexes and prevented binding of exogenous P protein to nucleocapsids. Antibody inhibition of P protein binding helps to locate the NP domains important for attachment of P protein during nucleocapsid assembly.

Antibodies, Monoclonal↗