Biomedical subjects

V O Thomsen

Publications and source records attributed to V O Thomsen.

11 recordsLinked to original sources

PubMed2004

Tuberculosis not verified by culture in a low incidence country.

The objective was to evaluate the magnitude, diagnostic basis and characteristics of patients notified with tuberculosis (TB) not verified by culture. All patients in Denmark notified with TB between 1995 and 1999 were identified through the national TB register. Nationwide culture results were obtained from the International Reference Laboratory of Mycobacteriology. The proportion of culture verification decreased from 91% in 1995 to 80% in 1999. A total of 2518 patients were notified, of which 374 (14.9%) were not verified by culture. For 80 (3.2%) patients no specimens were submitted. Instead the diagnosis was mainly based on X-ray (72.6%) for patients with pulmonary TB and histology (38.3%) for patients with extrapulmonary TB. For 216 patients aged 0-14 y, 74 (34.3%) were not verified by culture. The proportion of TB not verified by culture in Denmark is low compared to other European countries. Some cases may be well explained, e.g. children with a close contact suffering from TB or patients with extrapulmonary TB with limited number of specimens. However, for a minority group of patients with pulmonary TB there were no obvious reasons why specimens were not submitted for culture. Culture verification should remain a priority when possible.

Adolescent↗

PubMed2004

Tuberculosis in Greenland--current situation and future challenges.

OBJECTIVE: To describe the tuberculosis (TB) epidemiology in Greenland in 1998-2002 and to identify possible obstacles for reducing the TB incidence. STUDY DESIGN/METHODS: TB notification data were collected from the annual reports of the Chief Medical Officer, and culture verification data were collected from the International Reference Laboratory of Mycobacteriology at Statens Serum Institut, Denmark. RESULTS: The TB incidence in Greenland reached a peak of 185/100,000 in 2001. In 1999-2001, the majority of cases were related to an outbreak in the Southern districts. In 1998-2002, 0.5% drug-resistance was found among patients living in Greenland in contrast to 13.1% drug-resistance found previously among Inuit patients in Denmark. In 1998-2001, microscopy positive cases made up 65% of all culture confirmed cases and DNA subtyping demonstrated the emergence of Mycobacterium tuberculosis strains that were previously infrequently found. CONCLUSION: It is important to eliminate factors that fuel the epidemic and to improve general living conditions in Greenland. Treatment seems effective as limited drug-resistance is detected. TB reduction will therefore depend on early detection of active disease and thorough contact tracing. Greenland will face a pool of persons latently infected some of whom will progress to active disease. Sufficient resources need to be allocated for TB control in the years to come.

Antitubercular Agents↗

PubMed2001

[Resistant tuberculosis in Denmark].

INTRODUCTION: Increased rates of multidrug-resistant (MDR) tuberculosis (TB) has been reported from countries close to Denmark. We evaluated the incidence of drug resistance in Denmark in order to determine the magnitude of the problem. MATERIALS AND METHODS: Susceptibility testing was performed in isolates from 85.4% of all notified patients during 1991-1998. Epidemiological information was retrieved from the mandatory notification forms. RESULTS: Total drug resistance remained largely constant, although a minor increase was observed in 1997-1998. Monoresistance was observed in 7.3% of the isolates. Among 3.6% polyresistant isolates, resistance to isoniazid and streptomycin accounted for 2.8%, whereas MDR accounted for 0.5%. The MDR strains displayed different restriction fragment length polymorphism (RFLP) patterns, and no matches were identified in the international MDR database. Drug resistance in untreated Danes and foreigners were 5.9% and 14.6%, respectively. Among Danes and foreigners with previous TB, 6.2% and 22.7% had drug resistance, respectively. Increased drug resistance was found among untreated Danes aged 25-54 years mainly due to a single isoniazid- and streptomycin-resistant RFLP-cluster. Among all patients with isoniazid- and streptomycin-resistance, 77.0% had clustered strains. DISCUSSION: In conclusion, although drug resistance among untreated Danes was close to the rate estimated in good national programmes, close monitoring is needed in future years, as active transmission of isoniazid- and streptomycin-resistant Mycobacterium tuberculosis was demonstrated.

Adolescent↗

PubMed2001

Characterization of isoniazid-resistant strains of Mycobacterium tuberculosis on the basis of phenotypic properties and mutations in katG.

Forty isoniazid-resistant Mycobacterium tuberculosis isolates were characterized on the basis of phenotypic properties (i.e., catalase activity, MIC of isoniazid, and growth pattern in the presence of 7 different concentrations of isoniazid) and alterations in the katG gene (codons 315 and 463). Three different growth patterns could be distinguished: concentration-dependent inhibition of growth was observed in 29 strains, similar growth at all concentrations was seen in 7 strains, and enhanced growth at low concentrations of isoniazid was evident in 4 strains. The MIC of isoniazid was < or = microg/ml for 29 of 40 strains. Mutation at codon 315 of the katG was detected in 28 of 40 strains. However, only one of the seven strains for which the MIC of isoniazid was > or = 16 microg/ml had mutation at this codon. Five of these seven strains for which the MIC was > or = 16 microg/ml had no catalase activity. The results indicate that the MIC of isoniazid for a majority of strains is below the level achievable in serum. Therefore, isoniazid may be beneficial for the treatment of some cases of multidrug-resistant tuberculosis. Determination of catalase activity aids in the detection of isolates for which MICs are high and could, in conjunction with molecular methods, provide rapid detection of most isoniazid-resistant strains.

Antitubercular Agents↗

PubMed2000

Results from 8 yrs of susceptibility testing of clinical Mycobacterium tuberculosis isolates in Denmark.

Increased rates of multidrug-resistant (MDR) tuberculosis (TB) has been reported from countries close to Denmark. This study evaluated the incidence of drug resistance in Denmark in order to determine the magnitude of the problem. Susceptibility testing was performed in isolates from 85.4% of all notified patients during 1991-1998. Epidemiological information was retrieved from the mandatory notification forms. Total drug resistance remained largely constant, although a minor increase was observed in 1997-1998. Monoresistance was observed in 7.3%, of the isolates. Among 3.6% polyresistant isolates, resistance to isoniazid and streptomycin accounted for 2.8%, whereas MDR accounted for 0.5%. The MDR strains displayed different restriction fragment length polymorphism (RFLP) patterns, and no matches were identified in the international MDR database. Drug resistance in untreated Danes and foreigners were 5.9% and 14.6%, respectively. Among Danes and foreigners with previous TB, 6.2% and 22.7% had drug resistance, respectively. Increased drug-resistance was found among untreated Danes aged 25-54 yrs mainly due to a single isoniazid and streptomycin-resistant RFLP-cluster. Among all patients with isoniazid and streptomycin-resistance, 77.0% had clustered strains. In conclusion, although drug resistance among untreated Danes was close to the rate estimated in good national programmes, close monitoring is needed in future years, as active transmission of isoniazid- and streptomycin-resistant Mycobacterium tuberculosis was demonstrated.

Adolescent↗

PubMed2000

A patient with suspected sarcoidosis died from miliary tuberculosis.

In Western Europe, awareness of tuberculous lymphadenitis (TLA) has declined. This report describes a patient who had suspected sarcoidosis for 3.5 y, who eventually died from miliary tuberculosis due to delay in diagnosis. The report includes a discussion of the differential diagnosis of TLA and sarcoidosis.

Adult↗

PubMed1999

Monitoring treatment of patients with pulmonary tuberculosis: can PCR be applied?

To assess whether PCR is applicable for monitoring the efficacy of antituberculous treatment, respiratory specimens obtained during treatment and follow-up from sputum smear-positive tuberculosis (TB) patients were examined. First, results of smear, culture, and PCR for Mycobacterium tuberculosis complex (MTB) and an internal inhibition control (MCC) were correlated retrospectively on 1,601 respiratory specimens from patients with no previous cultures of MTB. MTB optical density (OD) values increased to a maximum level of 3.5 to 4.0, with both increasing numbers of acid-fast bacilli and CFU. MTB/MCC OD ratios also increased with both smear and culture grading and correlated significantly better with both than the MTB OD value. Second, changes in MTB OD values and MTB/MCC OD ratios were compared with microscopy and culture for MTB in monthly sputa obtained during treatment and follow-up in 22 smear-positive pulmonary TB patients. Declines in MTB/MCC OD ratios during antituberculous treatment and follow-up were observed. Patients with moderate disease reached the baseline after 6 to 8 months of standard antituberculous treatment regimen, whereas patients with extensive disease were predicted to reach the baseline 1 year or more after the initiation of treatment. Although PCR detects both dead and live bacteria, we believe that PCR can be used to assess the efficacy of antituberculous treatment since increases or slow reductions in MTB/MCC OD ratios would indicate nonoptimal treatment, noncompliance, reduced bioavailability of drugs, or resistant strains of MTB and thereby would identify patients at risk for treatment failure or reactivation.

Adult↗

PubMed1999

Disseminated infection with Mycobacterium genavense: a challenge to physicians and mycobacteriologists.

In the present study we compared the clinical presentations of patients with a clinical diagnosis of AIDS and disseminated Mycobacterium genavense infection (n = 12) with those of patients with AIDS and disseminated M. avium complex (MAC) infection (n = 24). Abdominal pain was seen more frequently in the group of patients infected with M. genavense than in patients infected with MAC (P = 0. 003). Analysis of microbiological data revealed that stool specimens from patients infected with M. genavense were more often smear positive than stool specimens from patients infected with MAC (P = 0. 00002). However, M. genavense could be cultured on solid media from only 15.4% of the stool specimens, whereas MAC could be cultured from 71.4% of the specimens. Bone marrow and liver biopsy specimens yielded growth of M. genavense within a reasonably short time, allowing species identification by DNA technology. Microbiological data clearly demonstrated the importance of acidic liquid medium for primary culture, the avoidance of pretreatment and the use of additives in culture, and the necessity for prolonged incubation if M. genavense is suspected. Susceptibility testing showed that M. genavense is sensitive to rifamycins, fluoroquinolones, and macrolides, whereas it is resistant to isoniazid. Susceptibility to ethambutol and clofazimine could not be evaluated. The mean survival times of patients in the two groups were similar.

AIDS-Related Opportunistic Infections↗

PubMed1998

Diagnosis of pulmonary tuberculosis. Application of gen-probe amplified Mycobacterium tuberculosis direct test.

The purpose of this investigation was to evaluate the Amplified Mycobacterium tuberculosis Direct Test (AMTDT) for the diagnosis of pulmonary tuberculosis (TB). Six hundred and forty-six sputum samples were analysed by microscopy for acid-fast bacilli, by culture for mycobacterial growth, and by AMTDT for the presence of M. tuberculosis complex rRNA. If there were discrepant results, information as to whether the patient had a history of TB was obtained. The sensitivity was 85.7% (smear positive 100% and smear negative 71.4%, respectively) and the specificity was 96.8% compared with culture. By retesting, 12 of 13 false-positive samples could be divided into two major categories. The samples in one category were retest positive, had highly positive results, and the patients had previous culture-proven TB. The samples in the other category had less positive AMTDT results, were retest negative, and the patients were not notified as having TB. This investigation shows that AMTDT is a sensitive supplementary method for rapid detection of M. tuberculosis complex in respiratory specimens, that there is a risk of contamination which has to be monitored closely, and that positive samples should be retested.

DNA Probes↗

PubMed1997

False-positive results from cultures of Mycobacterium tuberculosis due to laboratory cross-contamination confirmed by restriction fragment length polymorphism.

During 1994, a cross-contamination problem leading to false-positive cultures of Mycobacterium tuberculosis was revealed in a mycobacteriology laboratory processing 30,000 to 35,000 samples per year. Molecular strain typing based on restriction fragment length polymorphism confirmed the contaminations. Out of 1,439 positive cultures of Mycobacterium tuberculosis, 49 samples from 48 patients were suspected to be cross-contaminated. In 37 cases, growth was observed both in BACTEC vials and on solid media, indicating that the contamination took place during the processing of the samples. The majority of the contaminated samples had been handled by the same technician.

Bacterial Typing Techniques↗

PubMed1996

Utility of PCR in diagnosing pulmonary tuberculosis.

At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy. However, this technique is insensitive and many cases of pulmonary tuberculosis cannot be initially confirmed. Nucleic acid amplification techniques are extremely sensitive, but when they are applied to tuberculosis diagnosis, they have given variable results. Investigators at six centers in Europe compared a standardized PCR system (Amplicor; Roche) against conventional culture methods. Defined clinical information was collected. Discrepant samples were retested, and inhibition assays and backup amplification with a separate primer pair were performed. Mycobacterium tuberculosis complex organisms were recovered from 654 (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two of the M. tuberculosis isolates from 204 patients were smear positive and culture positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4% for smear-positive specimens and 60.9% for smear-negative specimens, with a specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens with discrepant results revealed that 130 were from patients with recently diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27 discrepancies were due to presumed uneven aliquot distribution and 11 were due to presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor enables laboratories with little previous experience with nucleic acid amplification to perform PCR. Disease in more than 60% of the patients with tuberculosis with smear-negative, culture-positive specimens can be diagnosed at the time of admission, and potentially all patients with smear-positive specimens can immediately be confirmed as being infected with M. tuberculosis, leading to improved clinical management.

Bacteriological Techniques↗