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[Respiratory virus infections in children with acute lymphoblastic leukemia and febrile neutropenia: a prospective study].

UNLABELLED: Respiratory viruses are the most common infections in healthy children. The impact of these infections in cancer patients has been only recently recognized in Chile. AIM: To establish the frequency and epidemiological-clinical profile of respiratory virus infections in children younger than 15 years of age with acute lymphoblastic leukemia requiring hospitalization due to a febrile neutropenic episode. METHODS: All children < 15 years of age requiring hospitalization in the Regional Hospital of Valdivia, Chile, with cancer, fever and neutropenia between November 1 2002 and October 31 2004 were studied. Nasopharyngeal aspirate were obtained and tested by direct immunofluorescent assays for influenza A-B virus, parainfluenza virus type 1, 2, 3, respiratory syncytial virus (RSV) and adenovirus. RESULTS: Respiratory viruses were detected in 25% of 44 febrile neutropenia episodes occurring in 25 patients. Viruses detected were, influenza (3/11), parainfluenza (3/11) RSV (2/11), adenovirus (1/11), parainfluenza + RSV (1/11), and parainfluenza + adenovirus (1/11). Four (36%) of cases were nosocomial. Respiratory symptoms were present in 9 children, seven of whom had inferior respiratory tract symptoms. One patient died of persistent RSV infection, agranulocytosis and extensive bilateral pneumonia. CONCLUSIONS: Respiratory viruses were detected in 25% of febrile neutropenic episodes in children with ALL. This high detection rate together with the frequent involvement of the lower respiratory tract and the possibility of death strongly favors the inclusion of respiratory virus diagnostic tests in the evaluation of these children during autumn and winter season.

Adolescent↗

Respiratory viruses and chronic rejection in lung transplant recipients.

UNLABELLED: BACKGROUND; Chronic rejection manifested as obliterative bronchiolitis (OB) and bronchiolitis obliterans syndrome (BOS) continue to be major causes of morbidity and mortality after lung transplantation. Community respiratory virus (CRV) infection, including respiratory syncytial virus, parainfluenza virus, and influenza virus, can infect and also cause morbidity in lung transplant recipients. Because CRV and OB/BOS affect the small airways, we sought to determine whether CRV infections predisposed patients to OB/BOS. METHODS: To determine whether CRV predisposed to OB/BOS, a proportional hazards regression analysis of time to OB/BOS was performed with CRV as a time-dependent covariate. To determine the influence of OB/BOS on the subsequent development of CRV infection, we reversed the outcome and time-dependent covariate. To illustrate the effect of CRV on OB/BOS and the effect of OB/BOS on CRV, landmark plots were generated at specific time points. Time to development of OB/BOS was then compared using the Kaplan-Meier method. RESULTS: In our institution, we documented 40 infections caused by CRV in 33 lung transplant recipients during an 11-year period. Community respiratory virus infections occurred predominantly during seasonal community outbreaks, except for parainfluenza infections, which occurred throughout the year. The diagnosis of OB/BOS occurred throughout the year and was not associated with seasonal outbreaks of CRV. Community respiratory virus infection involving both upper and lower respiratory tracts did not predispose to OB or BOS (relative risk [RR], 1.1; 95% confidence interval [CI], 0.52-2.3; p = 0.81). However, patients with documented CRV infection of the lower respiratory tract were predisposed to high-grade BOS development (RR, 2.3; 95% CI, 1.1-4.9; p = 0.04). In addition, a patient with pre-existing OB or BOS was predisposed to developing both upper and lower respiratory tract infection with CRV (RR, 4.2; 95% CI, 1.9-9.4; p < 0.001). CONCLUSIONS: Patients with CRV infection of the lower respiratory tract were predisposed to high-grade BOS development, and patients with OB and BOS were predisposed to CRV infections.

Community-Acquired Infections↗

An epimer of 5'-noraristeromycin and its antiviral properties.

A derivative of 5'-noraristeromycin epimeric at the 5'-nor center ((-)-3) has been prepared enantiospecifically in three steps from (+)-((1R,4S)-4-hydroxy-2-cyclopenten- 1-yl acetate. Compound (-)-3 was evaluated for antiviral activity against a large number of viruses and found to display marked activity against varicella-zoster virus, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, reovirus, and cytomegalovirus. A similar antiviral activity spectrum was shown by the S-adenosylhomocysteine hydrolase inhibitors neplanocin A and carbocyclic 3-deazaadenosine. While equally potent as neplanocin A against most of the viruses tested, compound (-)-3 was significantly less cytotoxic. The results of this study suggest that (-)-3 should be pursued for the treatment of those virus infections [that is, pox (VV), rhabdo (VSV), paramyxo (parainfluenza), and reo] that appear to be exquisitively sensitive to the compound.

Adenosine↗

Immune responses of dairy cattle to parainfluenza-3 virus in intranasal infectious bovine rhinotracheitis-parainfluenza-3 virus vaccines.

Two hundred and fifty dairy heifers were vaccinated at three to six months of age with an intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccine. Eighteen additional heifers were tested prior to vaccination and again three to four weeks after vaccination. Neither cell-mediated nor humoral immunity was significantly raised to parainfluenza-3 virus in either group of cattle.

Administration, Intranasal↗

Surveillance of respiratory viral infections by rapid immunofluorescence diagnosis, with emphasis on virus interference.

During the 7-year period from September 1978 to August 1985, smear specimens of nasopharyngeal secretions from 3132 patients mainly hospitalized children, taken in different regions in Norway, were examined for respiratory viruses by the rapid immunofluorescence (IF) technique. A positive diagnosis for respiratory syncytial virus (RSV), parainfluenza virus type 1, 2 and 3 or influenza A and B virus was made for 896 patients (29%). The greatest prevalence for all these viruses was observed during the colder months with only sporadic cases during the summer months. A relative increase in parainfluenza virus activity, involving several parainfluenza virus types, was observed in every second autumn and during these periods only sporadic cases of RSV infection were diagnosed. Also both RSV and parainfluenza viruses were less frequently found during influenza virus epidemics and regional differences in RSV activity were observed. During the four autumn periods 1982-85 the monthly number of positive virus identifications by IF followed an epidemic curve, while the corresponding number of negative samples was relatively constant. The results of this study suggest interference between RSV, parainfluenza viruses and influenza virus in reaching their epidemiological peaks. It is suggested that interferon might be a mediator of this effect.

Child↗

[HLA system antigens in persons with differing susceptibility to the causative agents of acute respiratory diseases].

The relationship between the susceptibility of the body to infections caused by influenza A and B viruses, parainfluenza viruses, adenoviruses, Mycoplasma pneumoniae and antigens of the HLA system was studied on a group of 400 adolescents placed under clinico-epidemiological surveillance for two years. The relationship between histocompatibility antigens and acute respiratory diseases was manifested in a decrease or increase in the occurrence of recurrent diseases and infections or in the probability of the development of the diseases in infected persons. HLA B40 was associated with resistance to influenza A, B18 and B21 were associated with resistance to parainfluenza, B15 and B35 were associated with resistance to M. pneumoniae infection; susceptibility to influenza B was registered in persons with HLA B12 and to M. pneumoniae infection, in persons with HLA B16 and B18. With respect to different infective agents, the relative risk of infection varied within 1.7 and 5.0.

Acute Disease↗

Roentgenographic features of common pediatric viral respiratory tract infections.

Viral infections of the respiratory tract in infants and children are common. Little has been reported on roentgenographic findings associated with infection caused by common viruses other than with respiratory syncytial virus. We studied chest roentgenograms from 128 previously healthy infants and children who were infected with respiratory syncytial virus, parainfluenza virus, influenza virus, or adenovirus. Four common roentgenographic findings were detected: parahilar peribronchial infiltrates, hyperexpansion, segmental or lobar atelectasis, and hilar adenopathy. Diffuse interstitial infiltrates and significant pleural fluid accumulations rarely occurred in our series. We confirmed the popular but not well-documented belief that other common respiratory viruses can be associated with roentgenographic findings similar to those caused by respiratory syncytial virus. However, respiratory syncytial virus infection is associated with more abnormal chest roentgenograms than any of the other viruses regardless of the clinical syndrome. Hilar adenopathy was more common in adenovirus infection. Young infants had significantly more abnormal chest roentgenograms, with more hyperexpansion and parahilar peribronchial infiltration than older children. We also found a significant correlation between lobar atelectasis and severity of the illness. In infants and children with viral infection of the lower respiratory tract, roentgenographic information can be a useful adjunct to clinical viral diagnosis.

Adenoviridae Infections↗

Improved detection of rhinoviruses in nasal and throat swabs by seminested RT-PCR.

A seminested RT-PCR (nRT-PCR) was used to detect picornavirus (PV) RNA in cell cultures inoculated with rhinoviruses (HRVs) and enteroviruses (EVs). PCR tests in which a primary "touchdown" PCR was followed by secondary reactions using PV or HRV specific primers were able to differentiate HRVs of 48 serotypes from EVs. PVnRT-PCR and HRVnRT-PCR were then used to test nasal and throat swabs from adult subjects with naturally acquired respiratory virus infections. The swabs were also analysed for respiratory viruses by cell culture techniques and the rates of PV identification by the two methods were compared. PVnRT-PCR was found to be at least five times more sensitive than cell culture for the detection of PVs in these clinical specimens. Paired acute and convalescent serum samples were tested for complement fixing antibodies to adenovirus, influenza A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, and 3, Myco plasma pneumoniae, and Chlamydia psittaci. An enzyme-linked immunosorbent assay (ELISA) was used to detect rises in antibody level to coronavirus types 229E and OC43. The overall rate of pathogen identification in 159 swabs from adult asthmatics increased from 28% when only cell culture and serology were used to 57% when these methods were supplemented by PVnRT-PCR.

Adult↗

Detection and typing of respiratory adenoviruses in a single-tube multiplex polymerase chain reaction.

A multiplex polymerase chain reaction (PCR) assay that is capable of detecting and typing six serotypes of respiratory adenovirus (Ad) was developed, using multiple sets of type-specific primers. The detection of each different serotype depended on distinguishing different numbers and sizes of amplification products on agarose gels following PCR. The multiplex PCR was tested with 26 clinical Ad isolates and other respiratory viruses including influenza viruses, parainfluenza viruses, and respiratory syncytial viruses as well as respiratory bacterial pathogens such as Chlamydia pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. The multiplex PCR for the detection and typing of Ads gave an excellent correlation with the results by conventional typing with type-specific antisera. This assay may serve as a rapid means of confirming Ad with simultaneous serotype identification of the isolates. It will also have relevance as an adjunctive tool to conventional serotyping for diagnostic and epidemiological purposes.

Adenovirus Infections, Human↗

Recent influenza virus A infections in forensic cases of sudden unexplained death.

84 forensic necropsy cases with a history of sudden unexpected death and where no acceptable cause of death was found at autopsy (= cases of sudden unexplained death, SUD) were found to have a significantly higher rate of influenza A (H 3 N 2) infection than did matched controls of the general population and a group of forensic necropsy cases with known cause of death (NON-SUD cases). By contrast, the group of SUD cases was found to have no significantly increased infection rate with influenza H 1 N 1 and B virus, parainfluenza viruses, RS virus, adenovirus, and cytomegalovirus. The influenza A associated SUD cases had a significantly higher rate of pathological and histological findings previously described for cases of primary viral pneumonia than did SUD cases without recent influenza A infection and NON-SUD cases. These findings suggest that virological examination of SUD cases could be helpful in order to determine the probable cause of death. A considerable portion of the influenza associated SUD cases occurred during interepidemic influenza periods. Therefore, such cases could be a useful source for monitoring the interepidemic spread of influenza virus.

Autopsy↗

Serological evidence of recent influenza virus A (H 3 N 2) infections in forensic cases of the sudden infant death syndrome (SIDS).

40 forensic SIDS cases were found to have a significantly higher rate of serologic evidence of recent influenza A (H 3 N 2) infection than did matched controls. In contrast, the SIDS cases had serologically no significantly increased infection rate with influenza H 1 N 1 and B virus, parainfluenza virus, RS virus, adenovirus, and cytomegalovirus. SIDS cases with recent influenza infection had a significantly higher rate of histological findings as described for primary viral pneumonia than did SIDS cases without influenza infection. SIDS cases with recent influenza infection occurred much more frequently during epidemic than during interepidemic influenza A (H 3 N 2) periods. Our results confirm previous reports that SIDS cases have an increased rate of respiratory virus infections. However, they cannot prove a causal relationship between influenza infection and death. Since our SIDS cases comprised 75 per cent of cases aged more than three months, our results pertain essentially to cases of this age group.

Antibodies, Viral↗

Virus isolation and titration at 33 degrees and 37 degrees C.

Various prototype viruses and original specimens were comparatively titrated in cell cultures at 33 degrees and 37 degrees C. Higher titers at 37 degrees were consistently obtained with adenoviruses; for other viruses (enteroviruses, herpesvirus hominis, vaccinia virus, parainfluenza viruses) the titers were mostly identical at either temperature. Original specimens and prototye strains showed the same behavior. The habit to cultivate viruses from throat swabs at 33 degrees C is unsatisfactory for adenoviruses.

Adenoviridae↗

Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn's disease.

BACKGROUND/AIMS: Infectious agents have long been suspected of playing a role in the initiation of Crohn's disease. The objective of this study was to search for likely microbial agents in diseased tissues using immunocytochemical techniques. METHODS: Intestines and mesenteric lymph node specimens of 21 patients from two French families with a high frequency of Crohn's disease and from Connecticut were studied. The microbial agents searched for included Bacteroides vulgatus, Borrelia burgdorferi, Escherichia coli, Listeria monocytogenes, Streptococcus spp., bovine viral diarrhea virus, influenza A virus, measles virus, parainfluenza virus, and respiratory syncytial virus. RESULTS: Seventy-five percent of the patients with Crohn's disease (12 of 16) were positively labeled with the antibody to Listeria. Macrophages and giant cells immunolabeled for this antigen were distributed underneath ulcers, along fissures, around abscesses, within the lamina propria, in granulomas, and in the germinal centers of mesenteric lymph nodes. In addition, 57% (12 of 21) of the cases contained the E. coli antigen, and 44% (7 of 16) contained the streptococcal antigen. The immunolabeling for the latter two agents also occurred within macrophages and giant cells, distributed in a pattern similar to that of Listeria antigen. CONCLUSIONS: The results suggest that Listeria spp., E. coli, and streptococci, but not measles virus, play a role in the pathogenesis of Crohn's disease.

Antigens, Bacterial↗

Sequence analysis of the mumps virus mRNA encoding the P protein.

The nucleotide sequence of the mumps virus phospho- or polymerase-associated (P) protein mRNA has been determined by sequencing a full-length cDNA clone and confirmed by partially sequencing the mRNA and the genome. The mRNA contains 1311 nucleotides excluding the poly(A) and encodes a protein of 390 amino acids with a calculated molecular weight of 41,574. Three small polypeptides were seen in in vitro translation of viral mRNA and hybrid-selected P mRNA, possibly representing internal initiation in the same reading frame of the P protein. A second overlapping reading frame is predicted from the sequence which has a capacity to code for two polypeptides of 56 and 34 amino acids, respectively. Whether these two polypeptides are expressed in infected cells is not known. Comparison of the P protein sequence with that of Sendai virus, measles virus, parainfluenza virus type 3, and canine distemper virus (CDV) showed no distinct homology but comparison with the P protein of Newcastle disease virus (NDV) showed 25.6% homology.

Amino Acid Sequence↗

Radioimmunoassay of measles virus hemagglutinin protein G.

Guinea pig and rabbit antisera from animals immunized with purified measles virus hemagglutinin (G) protein were used to establish a solid-phase four-layer radioimmunoassay for quantitative measurement of the G protein. The sensitive of the assay was 2 ng of purified G protein, and 200 micrograms of protein from uninfected Vero cells neither decreased the sensitivity nor reacted non-specifically in the assay. Radioimmunoassay standard dose-response curves were established and unknown values interpolated from these using the logit program of a desktop computer. Using this procedure, a measles virus growth curve in infected Vero cells was determined by measurement of G protein production. Under these same conditions, hemagglutination was not sensitive enough to detect early hemagglutinin production. Viral antigens in canine distemper virus, Newcastle disease virus, parainfluenza viruses 1-4, simian virus 5, and respiratory syncytial virus-infected cell lysates did not cross-react in the radioimmunoassay. A small degree of cross-reactivity was detected with mumps viral antigens, both with Vero cell-derived (wild-type strain) and egg-derived (Enders strain) purified virus preparations and with a cell lysate antigen prepared from wild-type mumps virus-infected Vero cells.

Animals↗

Validation of syndromic surveillance for respiratory infections.

STUDY OBJECTIVE: A key public health question is whether syndromic surveillance data provide early warning of infectious outbreaks. One cause for skepticism is that biological correlates of the administrative and clinical data used in these systems have not been rigorously assessed. This study measures the value of respiratory data currently used in syndromic surveillance systems to detect respiratory infections by comparing it against criterion standard viral testing within a pediatric population. METHODS: We conducted a longitudinal study with prospective validation in the emergency department (ED) of a tertiary care children's hospital. Children aged 7 years or younger who presented with a respiratory syndrome or who were tested for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus, adenovirus, or enterovirus between January 1993 and June 2004 were included. We assessed the predictive ability of the viral tests by fitting generalized linear models to respiratory syndrome counts. RESULTS: Of 582,635 patient visits, 89,432 (15.4%) were for respiratory syndromes, and of these, 7,206 (8.1%) patients were tested for the viruses of interest. RSV was significantly related to respiratory syndrome counts (adjusted rate ratio [RR] 1.33; 95% confidence interval [CI] 1.04 to 1.71). In multivariate models including all viruses tested, influenza virus was also a significant predictor of respiratory syndrome counts (RR 1.47; 95% CI 1.03 to 2.10). This model accounted for 81.6% of the observed variability in respiratory syndrome counts. CONCLUSION: Respiratory syndromic surveillance data strongly correlate with virologic test results in a pediatric population, providing evidence of the biologic validity of such surveillance systems. Real-time outbreak detection systems relying on syndromic data may be an important adjunct to the current set of public health systems for the detection and surveillance of respiratory infections.

Boston↗

Vaccines and immunotherapies for the prevention of infectious diseases having cutaneous manifestations.

Although the development of antimicrobial drugs has advanced rapidly in the past several years, such agents act against only certain groups of microbes and are associated with increasing rates of resistance. These limitations of treatment force physicians to continue to rely on prevention, which is more effective and cost-effective than therapy. From the use of the smallpox vaccine by Jenner in the 1700s to the current concerns about biologic warfare, the technology for vaccine development has seen numerous advances. The currently available vaccines for viral illnesses include Dryvax for smallpox; the combination measles, mumps, and rubella vaccine; inactivated vaccine for hepatitis A; plasma-derived vaccine for hepatitis B; and the live attenuated Oka strain vaccine for varicella zoster. Vaccines available against bacterial illnesses include those for anthrax, Haemophilus influenzae, and Neisseria meningitidis. Currently in development for both prophylactic and therapeutic purposes are vaccines for HIV, herpes simplex virus, and human papillomavirus. Other vaccines being investigated for prevention are those for cytomegalovirus, respiratory syncytial virus, parainfluenza virus, hepatitis C, and dengue fever, among many others. Fungal and protozoan diseases are also subjects of vaccine research. Among immunoglobulins approved for prophylactic and therapeutic use are those against cytomegalovirus, hepatitis A and B, measles, rabies, and tetanus. With this progress, it is hoped that effective vaccines soon will be developed for many more infectious diseases with cutaneous manifestations.

Bacterial Infections↗

A multi-centre pilot proficiency programme to assess the quality of molecular detection of respiratory viruses.

OBJECTIVES: To assess the quality of molecular detection of respiratory viruses in clinical diagnostic laboratories. STUDY DESIGN: Respiratory virus proficiency panels were produced from diluted stocks of respiratory viruses provided and tested by four reference laboratories. The panels consisted of strong positive, positive, low positive and negative samples for influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1 and 3, adenovirus serotypes 4 and 7, human rhinovirus serotypes 16, 72 and 90, human coronaviruses OC43 and 229E. The panels were sent to 17 participants; results and information on methodology was collected. RESULTS: All laboratories returned results, of which five submitted complete data sets. So, for analysis all results were combined. Samples were correctly identified by participants in 93.75%, 76.75% and 47.03% for the high positive, positive and low positive samples, respectively. One false positive was reported for all data sets (1.1%). The overall score for all assays using different methodologies was 78.8%. Laboratory performance was not dependant on methodology as all in-house methodologies could achieve optimal results, but dependant on careful optimisation and procedures specific to the laboratory. CONCLUSIONS: The first proficiency panel showed that in general all participants performed well. Although, it also highlights areas for improvement for all participants in order to generate robust results for use in clinical diagnostics.

Adenoviruses, Human↗