False-Positive
            <i>Mycobacterium tuberculosis</i>
            Cultures in 44 Laboratories in The Netherlands (1993 to 2000): Incidence, Risk Factors, and Consequences

Boer, Annette S. de; Blommerde, Barbara; Haas, Petra E. W. de; Šebek, M. M. G. G.; Weezenbeek, Kitty S. B. Lambregts-van; Dessens, Mirjam; Soolingen, Dick van

doi:10.1128/jcm.40.11.4004-4009.2002

Cited by 46 publications

(36 citation statements)

References 25 publications

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“…In this period, a total of 576 strains of M. tuberculosis were recovered from different patients, and 552 of these strains were received at the NIPH and analyzed consecutively. Laboratory cross-contamination was suspected when two or more strains with identical fingerprint patterns were received from the same laboratory within 7 days and with no epidemiological data connecting the patients (7). The clinical presentation of the patients and additional laboratory data were considered to determine the most likely actual patient in each case (7).…”

Section: Methodsmentioning

confidence: 99%

Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway

et al. 2003

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In this study, we determined the genetic diversity of Mycobacterium tuberculosis isolated in Norway from 1999 to 2001. The results were compared to those for strains isolated from 1994 to 1998. A total of 818 patients were diagnosed with tuberculosis (TB) during the last 3-year period. Of these cases, 576 (70%) were verified by culturing, and strains from 551 patients (96%) were analyzed by the IS6110 restriction fragment length polymorphism (RFLP) method. We excluded 13 strains (2.4%) from the analyses, since they were found to represent false-positive samples. A total of 67 strains (12%) that carried fewer than five copies of IS6110 were analyzed by spoligotyping. The strains were from 157 patients (29%) of Norwegian origin and 381 patients (71%) of foreign origin. The rate of diversity among all of the strains was 90%, while in 1994 to 1998 it was 87%. Clusters were assumed to have arisen from recent transmission; the degree of such transmission was 10% in 1999 to 2001, while for the whole 8-year period (1994 to 2001), it was 11%. Of the 109 patients diagnosed as being part of a cluster in 1999 to 2001, 89 were infected with a strain that carried more than four copies of IS6110. Among these 89 patients, 52 (58%) were infected with a strain that had already been identified in 1994 to 1998. The results indicated that most cases of TB in Norway were due to the import of new strains rather than to transmission within the country. This finding demonstrates that screening of immigrants for TB upon arrival in Norway needs to be improved. Outbreaks, however, were caused mainly by strains that have been circulating in Norway for many years.Globally, the number of tuberculosis (TB) cases is currently increasing at 2% per year (8). Programs to keep TB from rising in low-incidence countries are challenged by international traveling and immigration from high-burden countries (2-5, 14, 15, 18, 22). In Norway, patients with a foreign background contribute substantially to the TB incidence (4, 5, 11).In recent years, DNA fingerprinting of Mycobacterium tuberculosis based on restriction fragment length polymorphism (RFLP) analysis with IS6110 as a probe has given new insight into the nature of TB transmission. It has also become an indispensable tool for quality assurance of the processing and culturing of patient samples (1, 4, 5, 7, 9, 13-16, 18, 21, 22). Since 1994, IS6110 RFLP analysis has been performed on basically all strains of M. tuberculosis isolated in Norway (4, 5). However, isolates of M. tuberculosis that possess few copies of IS6110 do not generate sufficient polymorphisms to be readily distinguished by this technique. Another method, spoligotyping, involves the simultaneous detection of the presence or absence of 43 DNA spacer sequences and is superior to IS6110 RFLP analysis in discriminating isolates with fewer than five IS6110 copies (12,13,20). Spoligotyping is therefore generally used to analyze strains with fewer than five copies of IS6110 (12,13,18,20) and has been performed on such strains isolated in...

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Section: Methodsmentioning

confidence: 99%

Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway

et al. 2003

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“…A low volume of mycobacterial cultures performed annually may also increase the risk of false-positive cultures. In a 4-year nationwide study in The Netherlands, falsepositive cultures were significantly more frequent in laboratories processing Ͻ3,000 mycobacterial cultures per year (469).…”

Section: Applications Of Strain Typing To M Tuberculosis Complex Isomentioning

confidence: 99%

“…Cross-contamination events and false-positive cultures can result in unwarranted hospital admissions and drug treatment, with the potential for adverse events (469,470). In a study in the United States, the cost of three false TB diagnoses was estimated to amount to $10,873 per patient (471).…”

Section: Applications Of Strain Typing To M Tuberculosis Complex Isomentioning

confidence: 99%

Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria

et al. 2016

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SUMMARYMolecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods forMycobacterium tuberculosisand nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed.

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“…Laboratory cross-contamination is responsible for false-positive TB in 0.1% to 3% of cases (9,10). The final resolution of an alert requires genotyping the isolates involved.…”

Section: Discussionmentioning

confidence: 99%

Clonal Complexity in Mycobacterium tuberculosis Can Hamper Diagnostic Procedures

et al. 2017

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Clonal complexity is increasingly accepted in Mycobacterium tuberculosis infection, including mixed infections by Ն2 strains, which usually occur in settings with a high burden of tuberculosis and/or a high risk of overexposure to infected patients. Mixed infections can hamper diagnostic procedures; obtaining an accurate antibiogram is difficult when the susceptibility patterns of the strains differ. Here, we show how mixed infections can also prove challenging for other diagnostic procedures, even outside settings where mixed infections are traditionally expected. We show how an unnoticed mixed infection in an HIV-positive patient diagnosed in Madrid, Spain, with differences in the representativeness of the coinfecting strains in different sputum samples, markedly complicated the resolution of a laboratory crosscontamination false positivity alert.KEYWORDS tuberculosis, clonal complexity, mixed infection, diagnostic procedures C lonally complex infections are increasingly accepted in Mycobacterium tuberculosis infection. Mixed infection (i.e., the simultaneous infection by Ն2 different M. tuberculosis strains) is one of the most widely studied types of clonally complex infections (1-4). Mixed tuberculosis (TB) infection requires either simultaneous coinfection by a number of strains or, more likely, overexposure of an infected patient whose initial infection has not resolved to another patient infected by a different strain.Mixed infections are more likely in prisons, shelters, substandard overcrowded housing, and in other high-burden settings, where the possibility of overexposure is higher (2, 3, 5). The fact that mixed infections are not considered outside these contexts can hamper diagnostic procedures; for example, an unnoticed mixed infection can affect the result of antibiotic susceptibility testing. Rates of resistance are higher in regions where mixed infections are more frequent and in countries hosting immigrants from these regions; therefore, it is not uncommon for mixed infections to involve strains with different susceptibility patterns (6-8). However, although clonally complex infections are now beginning to be taken into account in the above-mentioned settings and for specific diagnostic procedures, equivalent efforts have not been made outside these contexts. Similarly, no efforts have been made to evaluate the impact of mixed infections on diagnostic procedures other than antibiotic susceptibility testing.We show how an unnoticed mixed M. tuberculosis infection in a case diagnosed in Madrid, Spain considerably hampered management of a laboratory cross-contamination alert.(The results of this study were partially presented at the 2015 ESM Meeting, Riga, Latvia.)

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False-Positive Mycobacterium tuberculosis Cultures in 44 Laboratories in The Netherlands (1993 to 2000): Incidence, Risk Factors, and Consequences

Cited by 46 publications

References 25 publications

Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway

Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway

Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria

Clonal Complexity in Mycobacterium tuberculosis Can Hamper Diagnostic Procedures

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