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The association of respiratory viruses, temperature, and other climatic parameters with the incidence of invasive pneumococcal disease in Sydney, Australia.

BACKGROUND: Increases in incidence of invasive pneumococcal disease (IPD) during the colder months of the year in temperate regions are well recognized, but few detailed studies of possible interactions are available. We examined the relationship between virus activity, climatic parameters, and IPD during a winter in which there were separate peak incidences of influenza and respiratory syncytial virus (RSV) infection. METHODS: We performed an ecological study that correlated population-based data on IPD and respiratory virus activity in the year 2000 in metropolitan New South Wales, Australia, with climatic parameters, including weekly mean maximum and minimum temperature, relative humidity, rainfall, and wind speed. RESULTS: In children, RSV activity was significantly positively correlated with IPD activity (r = 0.578; P = .002) but not with influenza virus activity. There was a weak inverse relationship between parainfluenza virus activity and IPD activity (r = -0.401; P = .043) and a stronger inverse relationship between weekly mean maximum temperature (r = -0.458; P = .001), weekly mean minimum temperature (r = -0.437; P = .001), and IPD activity. In adults, there was no significant correlation between RSV or influenza virus activity alone and IPD, but the combination of RSV and influenza was significantly correlated with IPD (r = 0.481; P = .013). CONCLUSIONS: This study suggests that RSV infection and influenza contribute to IPD incidence peaks differently for children than for adults. Data from other geographic areas and more rigorous study designs are required to confirm these findings.

Adult↗

[Etiology of pediatric inpatients with pneumonia].

The etiology of acute pneumonia was studied in 596 pediatric inpatients at Chiba Municipal Kaihin Hospital between January 1990 and December 1991. A pathogen was identified in 389 (64.4%) episodes of pneumonia. Evidence of bacterial infection was present in 167 (28.8%) episodes, viral infection in 178 (29.9%) and Mycoplasma pneumoniae infection in 89 (14.9%). The major bacterial pathogens were H. influenzae 117 (19.6%), S. pneumoniae 51 (8.6%), M (B). catarrhalis 24 (4.0%). RS virus was the most common respiratory virus. The peak age of the patients was 7 months to 2 years old. For bacterial pneumonia, the highest rates occurred in infants. Mycoplasma pneumonia produced the highest rates in school-age children. Mycoplasma pneumonia was prevalent at two distinct times, the first emerging in the spring of 1990 and emerging again in the autumn of 1991. RS virus and influenza virus epidemics occur during the winter. Most of the parainfluenza virus have been observed during the early summer season.

Acute Disease↗

Gas chromatography for detection of viral infections.

Gas chromatograms of sertim extracts of dogs inoculated with canine infectious hepatitis virus showed two metabolites not observed in uninoculated animals. Chromatograms of extracts of tissue cultures of dog kidney, inoculated with viruses causing canine hepatitis, herpes, and distemper, and a parainfluenza virus similar to simian virus-5, each showed two or more different metabolites. Two of the distinguishing products from cultures inoculated with hepatitis virus were chromatographically indistinguishable from those found in serums of the animals.

Animals↗

Viruses and bacteria in the etiology of the common cold.

Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.

Adenovirus Infections, Human↗

Stable and noncompetitive RNA internal control for routine clinical diagnostic reverse transcription-PCR.

Clinical diagnostic tests based on nucleic acid amplification assist with the prompt diagnosis of microbial infections because of their speeds and extremely low limits of detection. However, the design of appropriate internal controls for such assays has proven difficult. We describe a reaction-specific RNA internal control for diagnostic reverse transcription (RT)-PCR which allows extraction, RT, amplification, and detection to be monitored. The control consists of a G+C-rich (60%) RNA molecule with an extensive secondary structure, based on a modified hepatitis delta virus genome. The rod-like structure of this RNA, with 70% intramolecular base pairing, provides a difficult template for RT-PCR. This ensures that the more favorable target virus amplicon is generated in preference to the control, with the control being detected only if the target virus is absent. The unusual structure of hepatitis delta virus RNA has previously been shown to enhance its stability and resistance to nucleases, an advantage for routine use as an internal control. The control was implemented in three nested multiplex RT-PCRs to detect nine clinically important respiratory viruses: (i) influenza A and B viruses, (ii) respiratory syncytial viruses A and B and human metapneumovirus, and (iii) parainfluenza virus types 1 to 4. The detection limits of these assays were not detectably compromised by the presence of the RNA control. During routine testing of 324 consecutive unselected respiratory samples, the presence of the internal control ensured that genuine and false-negative results were distinguishable, thus increasing the diagnostic confidence in the assay.

Base Sequence↗

Progressive bronchial obstruction during the acute stage of respiratory tract infection in asthmatic children.

To study the time-course of infectious asthma, we retrospectively examined FEV1 from 5 days before to 10 days after the onset of illness in 31 asthmatic children (20 boys and 11 girls), aged 8 to 12 years. Infections were confirmed by a rise of at least fourfold in serum compliment fixation titers (respiratory syncytial virus, adenovirus, and Mycoplasma pneumoniae) and hemoagglutination inhibition titers (parainfluenza virus types 1, 2, and 3). All the patients had 20 percent or more fall in FEV1 from baseline value during acute phase, but were clinically tolerable and required minimum or no bronchodilators. Regardless of infectious agent, FEV1 began to fall on the first disease day or the previous day, and deteriorate for the first few days. Mean(SD) maximum fall in FEV1 ranged from 39(12) percent to 45(20) percent. Thereafter, FEV1 began to improve and returned to the preillness level by the seventh to tenth day. These results suggest that progressive bronchial obstruction may be inevitable during the acute stage of any infectious asthma.

Acute Disease↗

Recent advances in bovine vaccine technology.

A description of new commercial and experimental vaccines for viral and bacterial diseases of cattle can be broadly divided into those used for both beef and dairy cows and those used predominantly in dairy cattle. For both types of cattle, newer and experimental vaccines are directed against several of the important viral (e.g., bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, parainfluenza type 3, and foot-and-mouth disease virus) and bacterial pathogens (e.g., Pasteurella spp., Haemophilus somnus). The viral vaccines include gene-deleted, modified live, subunit, and peptide antigens. Newer bacterial vaccines, particularly those for Pasteurella spp., are composed of either modified-live vaccines or bacterins supplemented with toxoid or surface antigens. Haemophilus somnus vaccine research has concentrated mainly on defining unique surface antigens. Novel dairy cow vaccines would include the lipopolysaccharide-core (J5) antigen approach, which has been used for successful immunization against coliform mastitis. Core antigen vaccines also have reduced calf mortality from Gram-negative pathogens. Staphylococcal mastitis vaccines that contain capsular antigens, toxoids, or the staphylococcal fibronectin receptor are of active research interest. Vaccines against mastitis induced by Streptococcus agalactiae and Streptococcus uberis also are areas of intensive research. Delivery of multiple subunit antigens with optimal immune response induction has led to the investigation of attenuated heterologous viral and bacterial expression vectors such as bovine herpesvirus 1, vaccinia, and Salmonella spp. This discussion also demonstrates that molecular biology is being used to advance bovine vaccine technology.

Animals↗

Diseases and parasites of red foxes, gray foxes, and coyotes from commercial sources selling to fox-chasing enclosures.

Fifty-six red foxes (Vulpes vulpes), 18 gray foxes (Urocyon cinereoargenteus), and 13 coyotes (Canis latrans) obtained by the South Carolina Wildlife and Marine Resources Department during an investigation of suspected illegal wildlife translocation were examined for diseases and parasites. Red foxes and coyotes were confiscated from an animal dealer based in Ohio (USA), and gray foxes were purchased from an animal dealer in Indiana (USA). Emphasis was placed on detection of pathogens representing potential health risks to native wildlife, domestic animals, or humans. All animals were negative for rabies; however, 15 gray foxes were incubating canine distemper at necropsy. Serologic tests disclosed antibodies to canine parvovirus, canine distemper virus, canine adenovirus, canine coronavirus, canine herpesvirus, and canine parainfluenza virus in one or more host species. Twenty-three species of parasites (two protozoans, three trematodes, four cestodes, eleven nematodes, and three arthropods) were found, including species with substantial pathogenic capabilities. Echinococcus multilocularis, a recognized human pathogen not enzootic in the southeastern United States, was found in red foxes. Based on this information, we conclude that the increasingly common practice of wild canid translocation for stocking fox-chasing enclosures poses potential health risks to indigenous wildlife, domestic animals, and humans and, therefore, is biologically hazardous.

Animals↗

Respiratory viruses in hospital patients on the Witwatersrand. A 7-year study.

Virological investigations were carried out on 4 151 patients with respiratory disease hospitalized between May 1966 and April 1972. The groups examined were Black and White children and Black miners. Influenza viruses were more common among malnourished Black children and tended to cause more severe disease. This was also true of adenovirus and Herpesvirus hominis type 1 infections. Adenoviruses appear to be secondary invaders, frequently after a measles or influenza attack. A generalized epidemic of adenovirus type 7 occurred in 1967, the longest, coldest and most humid winter during the survey. The season of peak occurrence for respiratory syncytial (RS) virus is autumn, not winter as found elsewhere. The parainfluenza viruses differ from each other, types 1 and 2 being commoner in older children (12--48 months), mainly causing laryngotracheobronchitis (LTB), whereas type 3 is commoner in younger children (0--23 months), mainly causing pneumonia. The miners showed a preponderance of influenza A infections. The miners' origin from remote villages and high turnover rate create a situation where a given strain will persist at a moderate level for long periods, unlike in the general population where an outbreak lasts for only about 6--8 weeks. As opposed to other closed communities, adenovirus infections were rare. The reason for this is obscure.

Adenoviridae↗

Evaluation of the efficacy and duration of immunity of a canine combination vaccine against virulent parvovirus, infectious canine hepatitis virus, and distemper virus experimental challenges.

The results of this study confirmed that dogs vaccinated subcutaneously with a commercially available multivalent vaccine containing modified-live canine distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine parainfluenza virus antigens were protected against sequential experimental challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age. All 10 vaccinates were protected against clinical diseases and mortality following parvovirus and infectious canine hepatitis experimental infections. All vaccinates were protected against mortality and 90% against clinical disease following distemper challenge. These data support at least a 4-year duration of immunity for these three "core" fractions in the combination vaccine.

Adenoviruses, Canine↗

Parainfluenza and influenza virus infections in pediatric organ transplant recipients.

We retrospectively reviewed parainfluenza and influenza virus infections that occurred in pediatric organ transplant recipients at our hospital from January 1985 through September of 1992. Cultures of respiratory specimens revealed 45 infections in 42 transplant recipients (32 cases of parainfluenza and 13 cases of influenza virus infection). The following organs were transplanted: liver (28 patients), small bowel with and without liver (4), heart (3), lung with and without heart (5), and kidney (2). Clinical presentations of the patients and outcomes were similar regardless of the type of virus isolated or the type of organ transplanted. There were 20 cases in which patients had upper respiratory symptoms but did not require supplemental oxygen, nine cases in which patients required oxygen supplementation only, and eight cases in which the patients survived with mechanical ventilation. Eight patients died (five had parainfluenza, three had influenza virus infection); four children had serious concurrent infections (cytomegaloviral pneumonia in one patient, bacteremia in two, bacteremia and pneumonia in one). Factors associated with poor outcome for the entire group were age (increased morbidity and mortality if < 6 months old), augmentation of immunosuppression, and onset of infection within 1 month of transplantation. In this patient population, parainfluenza and influenza infections were important causes of morbidity and mortality.

Adolescent↗

Binding of the V proteins to the nucleocapsid proteins of human parainfluenza type 2 virus.

Interaction of the nucleocapsid (NP) and V proteins of human parainfluenza type 2 virus (HPIV-2) was investigated using a transient expression system. When the NP proteins were co-expressed with the V proteins, some of the NP proteins were translocated into the nuclei. These findings suggest that the NP protein interact with the V proteins. We examined the interaction of the NP proteins and the P, V proteins or deletion mutants of V protein using immunofluorescence and co-immunoprecipitation plus Western blotting analyses, and showed that the V proteins of HPIV-2 bind to the NP proteins and that the N-terminal domain of V protein interacts directly with the NP proteins. When the NP proteins were co-expressed with the V proteins or the N-terminal fragments (aa 1-46), the NP proteins were detected diffusely in the nuclei of the transfected cells, and were also detected in cytoplasmic inclusions. The NP and V proteins were co-localized in the nuclei or cytoplasm. Furthermore, the NP proteins were co-precipitated with the P, V, and V (1-164) proteins by a specific antibody. The P proteins interact more closely with the NP proteins than do the V proteins. These findings indicate that the V proteins have the ability to bind the NP proteins.

Binding Sites↗

On the role of microtubules in movement and alignment of nuclei in virus-induced syncytia.

Infection of baby hamster kidney (BHK21-F) cells with the parainfluenza virus SV5 causes rapid and extensive cell fusion. Time-lapse cinematography shows that when cells fuse, their nuclei migrate straight to the center of the syncytium at rates of 1-2 micro/min. Nuclei are often arranged in long, tightly packed, parallel rows in syncytia derived from the fibroblastic BHK21-F cells. Polarization microscopy shows birefringent material between and parallel to these rows of nuclei, and electron microscopy shows bundles of cytoplasmic microtubules, approximately 250 A in diameter, and filaments, approximately 80 A in diameter, parallel to and between the rows of nuclei. Colchicine treatment causes disappearance of microtubules from BHK21-F cells and an apparent increase in the number of 80-A filaments. Although colchicine-treated, SV5-infected cells fuse, their nuclei do not migrate or form rows but remain randomly scattered through the syncytial cytoplasm. Incubation at 4 degrees C does not disrupt microtubules in BHK21-F cells. Rows of nuclei have been isolated from SV5-induced syncytia, and the nuclei in them have been found to be intimately associated with microtubules but not with other cytoplasmic structures. These results suggest that microtubules demarcate cytoplasmic channels through which nuclei migrate and that they may also be involved in the mechanism of nuclear movement.

Animals↗

Deletion of the cytoplasmic tail of the fusion protein of the paramyxovirus simian virus 5 affects fusion pore enlargement.

The fusion (F) protein of the paramxyovirus simian parainfluenza virus 5 (SV5) promotes virus-cell and cell-cell membrane fusion. Previous work had indicated that removal of the SV5 F protein cytoplasmic tail (F Tail- or FDelta19) caused a block in fusion promotion at the hemifusion stage. Further examination has shown that although the F Tail- mutant is severely debilitated in promotion of fusion as measured by using two reporter gene assays and is debilitated in the formation of syncytia relative to the wild-type F protein, the F Tail- mutant is capable of promoting the transfer of small aqueous dyes. These data indicate that F Tail- is fully capable of promoting formation of small fusion pores. However, enlargement of fusion pores is debilitated, suggesting that either the cytoplasmic tail of the F protein plays a direct role in pore expansion or that it interacts with other components which control pore growth.

Animals↗

Bronchiolitis in tropical south India.

In a prospective hospital-based study of 328 children under 5 years of age with acute lower respiratory infections, 114 (35%) were diagnosed to have acute bronchiolitis. Of them, 87 (76%) were less than 1 year and 107 (94%) were less than 2 years of age. Signs of severe lower respiratory infections, namely tachypnea (respiratory rate greater than 50/min) and subcostal retraction, were present in 95% and 93%, respectively. Of 88 children of whom roentgenographs were taken, 30 (34%) had evidence of pneumonia. No clinical signs discriminated between those with and without pneumonia. By culture or immunofluorescence antigen detection, viruses were found in 81 (71%) children with bronchiolitis; respiratory syncytial virus was the most common agent, found in 65 (57%). Parainfluenza viruses were the next most common, found in 12 (11%). Most cases of bronchiolitis occurred in outbreaks during the rainy months of August through November, coinciding with respiratory syncytial virus outbreaks. Although bacterial culture of blood was done in 56 children, no respiratory pathogen was isolated. In one child with bronchiolitis and consolidation, postmortem lung aspirate yielded Staphylococcus aureus. Thus, bronchiolitis is primarily a viral syndrome in this tropical region, just as it is in temperate regions. Eight (7%) children died (all were infants); 5 had roentgenographic pneumonia and the remaining had other abnormalities contributing to death; all had been treated with antibiotics. Since one third of lower respiratory infections are bronchiolitis, and among infants under 1 year of age bronchiolitis comprises 47% of all lower respiratory infection cases, criteria for antibiotic management must take into account the availability of roentgenographic investigation.

Anti-Bacterial Agents↗

Acute laryngotracheitis in the rat induced by Sendai virus: the influx of six different types of immunocompetent cells into the laryngeal mucosa differs strongly between the subglottic and the glottic compartment.

OBJECTIVES: Acute laryngotracheitis is a disease in which mainly the subglottic area is infected, whereas adjacent parts of the larynx, especially the narrow glottic fold, remain unaffected. The reason for the difference between these two directly adjacent regions is unknown. Therefore, in the present study the influx of dendritic cells, neutrophils, T and B lymphocytes, natural killer cells, and macrophages into the mucosa of different laryngeal compartments was investigated after Sendai virus infection in the rat. The aims were to study both the influx of immunocompetent cells and the adhesion of the pathogen and to correlate them to the different reactions of the laryngeal areas during pseudocroup. METHODS: Acute laryngotracheitis was induced by intranasal application of Sendai virus in brown Norway rats. This virus is exclusively pneumotropic in rodents and belongs to the parainfluenza virus type 1, the main pathogen of acute laryngotracheitis in children. The numbers of dendritic cells, neutrophils, T and B lymphocytes, natural killer cells, and macrophages were determined in the supraglottic, glottic, subglottic, and tracheal mucosa on days 2, 5, 7, and 14 after virus application. Furthermore, the nucleoprotein of the virus and major histocompatibility complex (MHC) Class II expression were detected immunohistologically on the laryngeal epithelium. RESULTS: All cell subsets entered the laryngeal mucosa during inflammation. The highest influx was detected among dendritic cells subglottically. This was accompanied by a strong virus adhesion and MHC Class II expression on the subglottic epithelium. In contrast, only a few immunocompetent cells entered the adjacent glottic mucosa, and on the glottic epithelium staining for virus nucleoprotein and MHC Class II expression was weak. CONCLUSIONS: The inflammatory response of the laryngeal mucosa shows great regional differences in this animal model during experimental viral infection. The response was characterized by a strong subglottic and a weak glottic reaction. A possible reason for this difference might be region-specific viral adhesion on the epithelium of the laryngeal areas, as well as differences in MHC Class II expression. Thus, these data agree with the clinical observation during acute laryngotracheitis and may explain why the subglottic part of the larynx is affected preferentially during pseudocroup. The molecular mechanisms mediating the different reactions await clarification.

Acute Disease↗

[Research on substances with antiviral activity. II. Derivatives of N-substituted 2-chloro-3-formylindoles].

Thiosemicarbazones and amidinohydrazones of N-substituted 2-chloroindole-3-aldehydes were synthesized and investigated for antiviral activity against RNA virus (parainfluenza type 3, HA-I/CR-8 stock) and DNA virus (vaccinia virus, HID stock). The thiosemicarbazones of 1-(o,m,p,-chlorobenzoyl)-2-chloroindole-3-aldehydes were more active than methisazone against vaccinia virus.

Amidines↗

Mechanisms of bacterial superinfections in viral pneumonias.

Although it was once thought that bacterial infection was merely a function of the virulence of the microbe it is now known that other pathogens can alter host resistance. With respect to bacterial superinfection during viral pneumonias, three important factors must be considered; the role of the virus, the role of the bacterium, and the immune status of the host. The fact that no one bacterial species is responsible for all human cases of postinfluenzal bacterial pneumonia indicates that there is a general impairment of pulmonary antibacterial defenses brought about by the viral infection. The fact that the rate of intrapulmonary killing varies with different bacterial species indicates that the superinfecting organism can itself play a role in the dual disease process. Finally, it has been amply demonstrated that the resistance of the host is dependent on a variety of factors which include innate variables such as genetic endowment and a multitude of imponderable variables acquired through life experiences which can be considered under the general category of "host factors". All three factors interact and collectively impinge upon the resistance of the host. Lastly, as influenza virus infections occur most frequently in epidemic outbreaks, the relationship between influenza virus and secondary bacterial infections is the classic example. However, there is growing evidence that an association exists between other virus groups and bacterial pathogens in respiratory tract infections. Adenovirus, parainfluenza virus, and rhinovirus are among the agents that appear to pave the way for bacterial pneumonias. Mycoplasma pneumoniae, once considered to be a virus and the cause of primary atypical pneumonia, may also render the respiratory tract susceptible to bacterial invasion.

Animals↗