Successful treatment of adenovirus disease with intravenous cidofovir in an unrelated stem-cell transplant recipient.
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Adenovirus Infections, Human↗
Biomedical subjects
F Freymuth
Publications and source records attributed to F Freymuth.
[Acute respiratory Chlamydia pneumoniae infections in adults. Value of direct gene amplification diagnosis].
Chlamydia pneumoniae has been established recently as an important human respiratory pathogen. The aim of this study was to define the incidence of Chlamydia pneumoniae in acute respiratory infections by evaluating its presence in posterior nasopharyngeal aspirates or broncho-alveolar lavage specimens by polymerase chain reaction-hybridization (PCR-EIA) as well as the titres of specific antibodies in serum by a rELISA test and a micro-immunofluorescence (MIF) test. 68 adults patients were investigated. Eight patients (11.8%) were positive by either rELISA or PCR-EIA or both, with an infection rate of 5 patients with community-acquired pneumonia, 2 asthmatic patients and 1 patients with an exacerbation of chronic obstructive pulmonary disease. Serological evidence of acute infection was found in four of these patients with rELISA test and in three others with MIF test. PCR-EIA detected Chlamydia pneumoniae DNA in four patients, but there were concordant results with rELISA and PCR-EIA in only one patient. In conclusion, Chlamydia pneumoniae appears to be a common etiologic agent of acute respiratory infections in adults. The discrepancy between serological test and PCR-EIA results reflects the difficulties in routine laboratory diagnosis of Chlamydia pneumoniae. The ambiguous results of serological tests from a single serum sample assess the utility of PCR for prompt diagnosis. When PCR is negative or no feasible, a second serology to 15/21 days of interval is necessary. Further studies with optimised techniques must be developed.
Acute Disease↗
[Human coronavirus infections: importance and diagnosis].
POORLY-KNOWN VIRUS: Coronaviruses, so named because of their sun-ray-like aspect, were discovered in the sixties. The biology of these RNA viruses is complex and poorly understood. KNOWN PATHOGENS: Coronaviruses are known pathogens in veterinary medicine, causing disease states in several domestic species. In human medicine, they can cause benign respiratory infections, but few laboratories include coronaviruses in their routine diagnostic tests. SUSPECTED PATHOGENS: There is some data in the literature suggesting coronaviruses might be implicated in more severe diseases including multiple sclerosis, necrotizing enterocolitis, and lower respiratory tract infections, particularly in infants. IMPROVING DIAGNOSTIC METHODS: Due to the lack of reliable and sensitive diagnostic techniques, it is impossible to date to correctly assess the medical impact of these ubiquitous and endemic viruses. Molecular biology techniques enabling detection of human coronavirus infections should be applied to verifying the suspected implication of these viruses in diverse disease states.
Animals↗
SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases.
Pleural and pulmonary malignancies are usually associated with well-known carcinogen exposure. Recently, the presence of simian virus 40 (SV40)-like DNA sequences has been detected in brain and bone-related human cancers and in pleural mesothelioma. In order to determine whether SV40-like DNA sequences are also present in bronchopulmonary carcinoma and non-malignant lung samples, 125 frozen pleural and pulmonary samples (including 21 mesotheliomas, 63 bronchopulmonary carcinomas, 8 other tumours, and 33 non-malignant samples) and 38 additional samples distant from tumours were studied for the occurrence of SV40-like DNA sequences by polymerase chain reaction (PCR) amplification followed by hybridization with specific probes. Sequences related to SV40 large T antigen (Tag) were present in 28.6 per cent of bronchopulmonary carcinomas, 47.6 per cent of mesotheliomas, and 16.0 per cent of cases with non-neoplastic pleural and pulmonary disease. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma, but a significantly higher number of mesothelioma cases exhibited SV40-like DNA sequences in comparison with cases of non-malignant pleural or pulmonary disease (P < 0.04). Among cases positive for SV40-like DNA sequences, a history of asbestos exposure was found in 3 out of 12 bronchopulmonary carcinomas and 8 out of 10 mesotheliomas. Immunohistochemistry using monoclonal antibodies directed against Tag did not demonstrate nuclear staining. The DNA sequences were not related to BK virus sequences, but three samples were positive with probes hybridizing with JC virus DNA sequences. In conclusion, this study demonstrates the presence of SV40-like DNA sequences in pulmonary neoplasms and in non-malignant lung tissues. It appears that the presence of SV40-like DNA is not unique to cancer.
Adult↗
[Virus bacteria interactions in acute viral pneumonia in infancy: clinical and therapeutic consequences].
Although signs and symptoms may become severe, most viral respiratory infections of infancy are self-limited and improvement usually occurs within several days. Patients hospitalized with viral pneumonia usually require supportive therapy, including oxygen and fluids, and eventually mechanical ventilation. Bacterial superinfection can occur, accompanied by purulent sputum production and isolation of pathogenic bacteria from sputum. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus are the most common secondary invaders. Appropriate antibiotherapy must be administrated after cultures. There is no evidence that prophylactic antibiotherapy is of any use to prevent bacterial superinfection in viral pneumonia.
Anti-Bacterial Agents↗
Comparison of two serological methods and a polymerase chain reaction-enzyme immunoassay for the diagnosis of acute respiratory infections with Chlamydia pneumoniae in adults.
Chlamydia pneumoniae is a common respiratory tract pathogen. Serological methods currently used for the diagnosis of C. pneumoniae infection lack specificity, give ambiguous results from a single serum sample and often provide only a retrospective diagnosis. A prospective study was undertaken to assess whether PCR could be a useful addition to the serological techniques routinely practised for diagnosis. This study investigated 68 adult patients with a diagnosis of acute respiratory infection. Acute and convalescent serological determination of antibodies to C. pneumoniae were performed by means of an rELISA test and a micro-immunofluorescence (MIF) test. Nasopharyngeal aspirates or bronchoalveolar lavage specimens and bronchial aspirates obtained from the 68 patients were evaluated by PCR-enzyme immunoassay (PCR-EIA) for the presence of C. pneumoniae and by immunofluorescence assay and cell culture for virus identification. Mycoplasma pneumoniae serology was also performed. Eight patients (11.8%) were positive by either rELISA or PCR-EIA, or both, with an infection rate of 5 (18.5%) of 27 in patients with community-acquired pneumonia, 2 (9%) of 22 in asthmatic patients and 1 (5%) of 19 in patients with an exacerbation of chronic obstructive pulmonary disease. Serological evidence of acute infection was found in four of these patients with the rELISA test and in three others with the MIF test. PCR-EIA detected C. pneumoniae DNA in four specimens, but there were concordant results with both rELISA and PCR-EIA in only one patient A positive PCR-EIA was also obtained in a patient who did not show an antibody response in acute serum. The discrepancy between serological and PCR-EIA results reflects the difficulties in routine laboratory diagnosis of C. pneumoniae infection and the necessity for further studies with optimised techniques.
Acute Disease↗
Detection of respiratory syncytial virus A and B and parainfluenzavirus 3 sequences in respiratory tracts of infants by a single PCR with primers targeted to the L-polymerase gene and differential hybridization.
A reverse transcription-PCR and hybridization-enzyme immunoassay (RT-PCR-EIA) has been developed to identify the major agents of bronchiolitis in infants: respiratory syncytial viruses A and B (RSVA and RSVB) and parainfluenzavirus 3 (PIV3). Two primer sets (P1-P2 and P1-P3) were selected in a conserved region of the polymerase L gene. In infected cell cultures, this method detected RSVA (n = 14), RSVB (n = 13), and PIV3 (n = 13), with the exclusion of PIV1 (n = 4), PIV2 (n = 3), measles virus (n = 6), mumps virus (n = 4), influenza A virus (n = 11), and influenza B virus (n = 4). The differentiation of the amplicons by restriction fragment length polymorphism (RFLP) showed a PvuII site for PIV3 strains and an AvaII site for RSV strains, with RSVA distinguished from RSVB by BglII. The hybridization-EIA, using three internal probes specific for each virus, correlated with the immunofluorescence assay (IFA) and RFLP results. Clinical aspirates from 261 infants hospitalized with bronchiolitis were tested by IFA, viral isolation technique (VIT), and RT-PCR-EIA. RT-PCR-EIA detected RSV sequences in 103 samples (39.4%), and IFA-VIT detected RSV sequences in 109 cases (41.7%). A few samples (2.6%) were IFA-VIT positive but PCR negative, and one sample was RT-PCR-EIA positive only. RT-PCR-EIA detected PIV3 sequences in 14 of the 15 IFA-VIT-positive isolates. The two methods showed very good correlation (96.9%), but RT-PCR-EIA was clearly more efficient in typing, leaving 5% non-A, non-B isolates, while IFA failed to resolve 23% of the isolates. The two methods contradicted each other for <5% of the isolates.
Bronchiolitis↗
[Adult multi-nuclear cell hepatitis. A study in 17 patients].
OBJECTIVES: Giant-cell hepatitis is rare in adults and its significance has not been clarified. We report the clinical and histological characteristics and outcome in a group of adult patients with giant-cell hepatitis. METHODS: Seventeen patients with giant-cell hepatitis, hospitalized in our unit between 1976 and 1992, were studied retrospectively. Giant-cell hepatitis was defined as at least two hepatocytes with four or more nuclei per cell on liver biopsy. Clinical and biochemical parameters, liver histology, and the serological profile of HAV, HBV, HCV, HIV, HSV, EBV, CMV, and paramyxovirus were evaluated. Paramyxovirus immunochemistry was performed in 6 liver biopsies. RESULTS: There were 11 females and 6 males, an average of 48 years old (range: 29-80). Four patients had a well-defined etiology: acute hepatitis B infection with a favorable outcome in 2 cases, clometacine induced-hepatitis resulting in death from liver failure in one case, and chronic hepatitis B and C in one patient with AIDS. Among the 13 patients in which the etiology could not be determined, histologically defined acute hepatitis was observed in 8 and chronic hepatitis in 5. Nine patients were treated with immunosuppressive drugs. One patient was lost to follow-up. Eight patients responded to treatment, but 5 patients progressed to cirrhosis between 5 months and 7 years. Two of the 4 patients with unexplained liver disease who did not receive any treatment died of liver failure. CONCLUSION: In patient with acute or chronic hepatitis without an identified cause (with or without autoimmune abnormalities), the presence of giant-cell hepatitis seems to have a similar evolution as active autoimmune hepatitis. The poor prognosis of these patients suggests that early immunosuppressive treatment is justified.
Adult↗
[Comparison of the in vitro sensitivity to cidofovir and ganciclovir of clinical cytomegalovirus isolates. Coordinated Action Group 11].
Cidofovir (CDF) or Vistid is a monophosphate nucleoside analogue that inhibits the DNA polymerase of herpes viruses including the cytomegalovirus (CMV). CDF is active on GCV-resistant strains with a mutation on the phosphotransferase gene (UL97). However, DNA polymerase gene mutations that induce resistance to GCV are responsible for cross-resistance to CDF. Resistance phenotypes to GCV and CDF were determined for 57 CMV strains isolated from blood and urine samples. Sixteen strains were recovered after CDF therapy. Of the remaining 41 CDF-naive strains, 34 were susceptible and seven resistant to GCV. Fifty percent inhibitory concentrations (IC50) for CDF were in the 0.2-2.6 microM range for CDF-naive strains susceptible to GCV. For GCV-resistant strains, IC50 values for CDF were < or = 3 microM for strains with a low level of resistance to GCV (GCV IC50 < 30 microM) and > or = 6 microM for three of the five strains with a high level of resistance to GCV (GCV IC50 > or = 30 microM).
Antiviral Agents↗
Detection of SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma and other pulmonary diseases.
Mesotheliomas are pleural-based tumours mainly associated with asbestos exposure (70% of cases) and the incidence is still raising. Recently, a possible viral connection was reported and 60% of mesotheliomas were demonstrated to contain and express SV40-like DNA sequences. In this study, the presence of SV40-like DNA sequences were investigated in mesotheliomas (15 tissue samples and six cell lines) and in 63 additional bronchopulmonary carcinomas, one parietal osteosarcoma and non-malignant lung samples as well as in organizing pleuritis (8). Finally, 163 samples were analysed by the polymerase chain reaction (PCR) with a set of primers PYV.for and PYV.rev to amplify a 173 bp region of the SV40 Tag. and a 179 bp region JC virus (JCV) as well as a 182 bp region BK virus (BKV). PCR amplification and hybridization with a probe specific for SV40 Tag revealed that 47.6% of mesotheliomas, 28.6% of primary bronchopulmonary carcinomas and 16% of non-neoplasic lung diseases contained SV40-like DNA sequences. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma. However, a significantly higher number of mesothelioma cases exhibited SV40- like DNA sequences in comparison with non-malignant pleural and pulmonary tissues. The DNA sequences were not related to BK and JC virus sequences. These results indicate that SV40-like DNA sequences are present in mesotheliomas as well as in bronchopulmonary carcinomas and non-malignant pleuropulmonary diseases.
Antigens, Polyomavirus Transforming↗
[Infection with cytomegalovirus in a premature infant secondary to contamination by breast milk].
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Cytomegalovirus Infections↗
[Drugs active against respiratory viruses].
Few molecules are active against respiratory viruses. In upper respiratory tract infections, which are frequent and fortunately not severe, their deficiency is not a problem. However some molecules are able to block in vitro the interaction between a rhinovirus and its receptor: anti-receptor antibodies, soluble ICAM-1, capsid-binding agents. The lower respiratory tract infections (bronchiolitis, pneumonia...), mainly due to respiratory syncytial virus and influenza viruses are potentially more severe, and 2 groups of compounds are or have been used in these infections: amantadine and ribavirin. Ribavirin is effective in respiratory infections due to respiratory syncytial, influenza and parainfluenza viruses, and on many other viruses. Its toxicity needs to administrate it as an aerosol, and in France, ribavirin is used as compassional treatment in severe forms of bronchiolitis or pneumonia due to respiratory syncytial virus, and in high-risk children. Anti-parkinsonian drugs, related to amantadine (Mantadix, Roflual) are no longer on sale. Therefore there is no active molecule yet available against these viruses.
Amantadine↗
Detection of human cytomegalovirus in renal transplantation: comparison of four diagnostic methods: DNA in sera by polymerase chain reaction (PCR), DNA in leukocyte by PCR, pp65 leukocytic antigenemia, and viremia.
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Cytomegalovirus↗
Detection of respiratory syncytial virus, parainfluenzavirus 3, adenovirus and rhinovirus sequences in respiratory tract of infants by polymerase chain reaction and hybridization.
BACKGROUND: Immunofluorescence assay (IFA) of viral antigens in nasal aspirates is largely used for the diagnosis of respiratory syncytial virus (RSV), parainfluenzavirus (PIV) type 3 and adenovirus (AdV) infections, whilst rhinovirus (RV) are detected by virus isolation technique (VIT) only. Using the two techniques, IFA and VIT, a significant number of specimens remain negative in spite of clinical and epidemiological presumptions of viral infection. OBJECTIVES AND STUDY DESIGN: The polymerase chain reaction (PCR) should improve the sensitivity of viral detection in clinical specimens. From October 1995 to March 1996, 277 nasal aspirates from hospitalized infants were tested simultaneously by IFA, VIT, polymerase chain reaction and hybridization with a DNA enzyme immunoassay (PCR-EIA) for RSV, PIV-3, AdV and RV. RESULTS: RSV were detected in 177 (64%) samples, PIV-3 in 23 (8%), RV in 40 (14%), and AdV in 30 (10%). PCR-EIA detected RSV in more samples 173 (62%) than IFA/VIT: 109 (39%) (P < 10(-7)). In most cases (79%), RSV-infected infants had lower respiratory tract disease, and routine and PCR techniques were positive. Out of the 23 PIV-3 infections, 12 were IFA/VIT- and PCR-EIA-positive, and 11 IFA/VIT-negative and PCR-EIA-positive. For RV, 35 (87%) specimens were PCR EIA-positive and 11 (27%) culture-positive; for AdV 30 samples were PCR-EIA-positive and four were culture-positive. Simultaneous viral infections were revealed in a significantly higher proportion than in conventional techniques: 18% (50/277) versus 2.5% (7/277); P < 10(-7). One RSV infection in four was associated with the presence of another virus, mainly PIV-3 (16 cases) and AdV (13 cases). CONCLUSIONS: PCR-EIA detects more positive-specimens than IFA/VIT, 1.5 times more for RSV, 1.9 for PIV-3, 4 for RV and 10 for AdV, respectively. This increased sensitivity of viral detection by PCR-EIA compared to the IFA/VIT could suggest that samples containing low levels of virus are missed by routine methods IFA/VIT, and consequently, RSV or PIV-3, and above all RV or AdV are overlooked as agents of respiratory diseases. However, apart from the fact that the economic and convenient aspects of virus diagnostic cannot be missed, it is difficult to answer the following questions: what is the meaning of the detection of a viral sequences in nasal aspirates of infants, or may PCR have detected virus in patients who would not developed disease?
Adenoviridae↗
Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women.
This study assessed the diagnostic value of the cytomegalovirus (CMV)-specific IgG avidity index (AI) for pregnant women without a history of CMV seroconversion. Sera were studied from 40 women with CMV seroconversion (group I), 70 with past CMV infection (group II), 10 (20 sera) with serologic reactivation (group III), and 41 with CMV-specific IgM without proven seroconversion (group IV). Sera from women in group I collected <14 weeks after seroconversion had a low AI (mean, 30% +/- 12%), whereas all sera from women in group II had an AI >60% (mean, 88% +/- 9%). Among the 41 babies born to group IV women, only 4 were infected with CMV (all born to mothers with a low [<30%] AI early in pregnancy). These results suggest that AI determination may help to date a primary CMV infection in pregnant women who lack seroconversion history.
Antibodies, Viral↗
[Viral bronchiolitis and pneumopathies in infants].
Acute bronchiolitis is the most common severe lower-respiratory-tract infection of infancy. Although signs and symptoms may become severe, most viral respiratory infections are self-limited and improvement occurs within a few days. Patients hospitalized with bronchiolitis usually require supportive therapy, including oxygen and fluids, and may require mechanical ventilation. A trial of aerosolized beta 2-agonist is warranted in patients with bronchiolitis. Systemic corticosteroids have not been proved efficacious. Inhaled corticosteroids may be useful in reducing the severity of chronic wheezing that may follow acute bronchiolitis. Ribavirin may be considered in patients with severe disease of those at high risk for severe disease.
Acute Disease↗
Evaluation of virological procedures to detect fetal human cytomegalovirus infection: avidity of IgG antibodies, virus detection in amniotic fluid and maternal serum.
Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection and fetal damage largely due to maternal primary infection. Virological procedures which are able to detect HCMV fetal infection were evaluated. HCMV IgG antibodies were detected in 62.5% of the pregnant women and 1.47% had a primary infection. From March, 1992 to August, 1995, 29 seroconversions were observed, and in 64 other cases. HCMV IgM antibodies were detected in the first serological test. The mean IgG antibody avidity test (AI) was 31% for the 11 seroconversions tested and 74% in 32 cases where IgG and IgM HCMV antibodies were detected in the first serum. In the 29 HCMV seroconversions, 19 amniocentesis were carried out and 12 fetuses (41.4%) were infected in utero. In four amniotic fluids positive in culture and PCR, the fetus or newborns were infected and in one out of the two cordocentesis undertaken, hepatitis, anemia, and thrombocytopenia were noted. In four other cases, investigations seeking HCMV in amniotic fluid were negative whereas infants were infected at birth. Among the 64 cases with positive HCMV IgM and IgG antibodies detected in the first serological test, three fetuses were infected in utero, but no amniotic fluid was available in these cases. Amniotic fluids were studied in 39 cases, and HCMV detection by culture and PCR-hybridization was negative. HCMV DNA was detected in the maternal sera of five out of 21 pairs of seroconversions and in two cases on the first negative serum. The assay was also carried out on 50 of the 64 HCMV IgM positive sera. Two had detectable HCMV DNA.
Amniotic Fluid↗
Multicenter evaluating of a commercially available PCR assay for diagnosing enterovirus infection in a panel of cerebrospinal fluid specimens.
Thirteen laboratories participated in blind tests of a panel of 20 coded cerebrospinal fluid specimens (7 uninfected samples, 3 samples infected with 1 50% tissue culture infective dose [TCID50]/0.1 ml [nonenterovirus strains], and 10 samples infected with 10, 1, or 0.1 TCID50/0.1 ml [three different enterovirus serotypes]) on the Amplicor enterovirus PCR assay (Roche Diagnostic Systems). The panel was also evaluated by in-house PCR (two nested-PCR and three one-step PCR assay) or tissue culture (eight laboratories). The viral load was shown to influence greatly the sensitivity of the assay. The average sensitivity of the Amplicor test ranged from 67 to 98% for viral titers of 1 to 10 TCID50/0.1 ml, respectively; titers of 0.1 TCID50/0.1 ml resulted in a sensitivity of only 16%. The overall specificity of the Amplicor test was 98%. The Amplicor assay compared favorably to the five in-house PCR tests (no significant difference in either sensitivity or specificity) and was much more sensitive than tissue culture (P < 0.001), even for high viral loads. It was easy to perform, rapid (about 6 h), well-standardized, and appeared to be suitable for the diagnosis of enterovirus meningitis on a routine basis in laboratories trained in molecular biology techniques.
Base Sequence↗