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2012| July-September | Volume 1 | Issue 3
Online since
February 28, 2017
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ARTICLES
Drug resistance-related mutations in multidrug-resistant
Mycobacterium tuberculosis
isolates from diverse geographical regions
Senia Rosales-Klintz, Pontus Jureen, Aksana Zalutskayae, Alena Skrahina, Biao Xu, Yi Hu, Lelany Pineda-Garcia, Muayad Aghali Merza, Ionela Muntean, Freddie Bwanga, Moses Joloba, Sven E Hoffner
July-September 2012, 1(3):124-130
DOI
:10.1016/j.ijmyco.2012.08.001
Background:
Drug resistance in
Mycobacterium tuberculosis
is associated with chromosomal mutations in selected genes. These mutations can be screened for an early warning system for drug-resistant tuberculosis. The prevalence of individual mutations differs geographically, which must be considered in developing globally applicable screening tests.
Methods:
In order to analyse the geographical distribution and frequency of mutations conferring resistance to rifampicin, isoniazid and fluoroquinolones, the researchers investigated the presence of mutations in the
rpoB
gene, the
katG
gene, the
mabA-inhA
promoter region and the
gyrA
gene in clinical isolates of multidrug-resistant tuberculosis (MDR-TB) from Belarus, China, Iran/Iraq, Honduras, Romania and Uganda. For each study site, the researchers described the distribution of specific mutations in 20 clinical MDR-isolates.
Results:
The distribution of resistance-related mutations varied significantly between the study sites. Settings with a high incidence of MDR-TB, such as Belarus, showed a narrower spectrum of mutations related to rifampicin and isoniazid resistance and also a higher prevalence of fluoroquinolone resistance than study sites with a lower MDR-TB prevalence.
Conclusion:
This study confirms that there are significant geographical differences in the distribution of resistance-related mutations and suggests that an increased understanding of such differences in the specific distribution of resistance conferring mutations is crucial for development of new, generally applicable, molecular tools for rapid diagnosis of drug-resistant TB. The fact that a narrower distribution of mutations in high MDR-TB prevalence settings was seen suggests that much of the problems in these settings can be a result of an ongoing transmission of certain MDR-TB strains.
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Risk factors for multidrug-resistant tuberculosis in urban Pakistan: A multicenter case–control study
Ahsan M Ahmad, Saeed Akhtar, Rumina Hasan, Javaid A Khan, Syed F Hussain, Nadeem Rizvi
July-September 2012, 1(3):137-142
DOI
:10.1016/j.ijmyco.2012.07.007
Objective:
To evaluate risk factors for multidrug-resistant tuberculosis (MDR-TB) in an urban setting of Pakistan.
Design and methods:
In this multicenter case–control study, patients aged 15 years old or older with sputum culture and sensitivity (C/S) diagnosed with pulmonary MDR-TB were defined as cases, whereas patients aged 15 years old or older with sputum C/S diagnosed and susceptible to pulmonary TB were regarded as controls. Fifty cases and 75 controls were enrolled from three tertiary-care hospitals in Karachi.
Results:
Multivariable logistic regression models showed that cases were more likely to have had a TB patient in the house prior to the diagnosis of MDR-TB (adjusted odds ratio [OR
adj
]=3.1, 95% confidence interval [CI]: 1.2, 8.3) or had a history of prior TB treatment (OR
adj
= 4.2, 95% CI: 1.1, 15.4). Furthermore, cases compared with controls tended to be male (OR
adj
= 3.6, 95% CI: 1.4, 9.7), 15–25 years of age (OR
adj
= 3.7, 95% CI: 1.2, 11.3), of Sindhi ethnicity (adjusted OR=9.1, 95% CI: 1.9, 43.4) or with low educational attainment (OR
adj
OR=5.5, 95% CI: 1.7–17.6, for no formal schooling; OR
adj
= 3.8, 95% CI: 1.1–14.1, 1 for 1–5 school years).
Conclusions:
A TB patient in the house or a history of prior TB treatment was strongly associated with MDR-TB in this study. Furthermore, younger age, male gender, Sindhi ethnicity and poor educational attainment entailed a high risk for MDR-TB. Targeted educational intervention for patients and their contacts may minimize the noncompliance with prescribed TB treatment and lessen MDR-TB magnitude in settings like Karachi.
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REVIEW
Division-cycle in
Mycobacterium tuberculosis
Ali Akbar Velayati, Parissa Farnia
July-September 2012, 1(3):111-117
DOI
:10.1016/j.ijmyco.2012.08.003
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CASE REPORTS
Paraplegia is not a diagnosis: Spinal tuberculosis deserves a place on the clinical radar screen: Awakening call to clinicians
Liaqat Ali Chaudhry, Marwan Zamzami, Syed Kashif Fakharudin
July-September 2012, 1(3):155-160
DOI
:10.1016/j.ijmyco.2012.07.008
Disseminated Tuberculosis(TB) occurs through lymphohaematogenous dissemination of
M. tuberculosis
. Although it is more common in young children and those who are having risk factors like having acquired or innate immunodeficiency, weak immune system being on immunosuppressive treatments; it can also occur in immunocompetent indviduals with heavy load of infection. Inhalation being the commonest mode of entry of the pathogen results in pulmonary tuberculosis being the commonest seat of primary infection,other systems commonly involved as extra-pulmonary sites are lymphnodes, bone, brain, peritonium and genitalia depending on the amount of relative blood supply and lymphatics. We present here case of a young female who was immunocompetent, having fever, progressive lower limb weakness and loss of bowel and bladder control, becoming bed bound, and admitted in our hospital for rehabilitation with a diagnosis of paraplegia.
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SHORT COMMUNICATION
Identification of
Mycobacterium tuberculosis
complex by polymerase chain reaction of Exact Tandem Repeat-D fragment from mycobacterial cultures
C Coitinho, G Greif, C Robello, J van Ingen, C Rivas
July-September 2012, 1(3):146-148
DOI
:10.1016/j.ijmyco.2012.07.002
This study evaluated an in-house polymerase chain reaction (PCR) for rapid identification of the
Mycobacterium tuberculosis
complex (MTBC) using the MTBC-specific Exact Tandem Repeat D (ETR-D) as the amplification target. In a prospective study, 801 clinical isolates identified as MTBC and 15 nontuberculous mycobacteria were analyzed. Mycobacterial DNA was extracted from automated broth cultures or from egg-based media. The amplification of the ETR-D showed to a sensitivity of 99.6% and a specificity of 100% for the correct identification of MTBC; improved extractions protocols led to 100% sensitivity. The main utility of this technique is the simplicity, rapidity, low cost and accuracy.
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ARTICLES
Multidrug and extensively drug-resistant tuberculosis in Lisbon and Vale do Tejo, Portugal, from 2008 to 2010
R Macedo, AF Antunes, M Villar, I Portugal
July-September 2012, 1(3):131-136
DOI
:10.1016/j.ijmyco.2012.07.001
Tuberculosis (TB) was explicitly recognized as a major global public health problem in the early 1990s and, if it is to be eliminated, it is essential that every country organize control activities in line with its own epidemiological situation. Portugal still remains among the countries with intermediate incidence, with 2756 cases of TB diagnosed in 2009. The incidence of multidrug-resistant (MDR) TB has been decreasing, representing an average of 1.7% of the total number of TB cases, with about 25% of extensively drug-resistant (XDR) TB, and with more than two thirds residing in the region of Lisbon and Vale do Tejo (LVT). The aim of this study is to evaluate risk factors and treatment outcomes associated with MDR and XDR-TB in LVT during the time period of 2008–2010. In 50 (2.4%) out of 2093 culture-positive TB cases from patients diagnosed in the LVT region,
Mycobacterium tuberculosis
(MTB) isolates were identified as MDR-TB; 12 (24%) met the criteria for XDR-TB. It was noted that HIV-positive status and retreatment cases are still closely associated with drug-resistant TB. Although the WHO target of about 75% treatment success rates for MDR-TB was not yet achieved, extensive drug susceptibility testing and the availability of second- and third-line drugs under strictly supervised treatment conditions permitted relatively good treatment success rates in MDR and XDR-TB cases in Lisbon.
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SHORT COMMUNICATION
Retrieval of
Mycobacterium tuberculosis
cultures suspended in phosphate buffered saline
V N. Azger Dusthackeer, P Nagarajan, Dasarathi Das, Vanaja Kumar, N Selvakumar
July-September 2012, 1(3):149-151
DOI
:10.1016/j.ijmyco.2012.08.002
One hundred and twenty-seven of 130 isolates of
Mycobacterium tuberculosis
, suspended in phosphate buffered saline (PBS) and stored at ambient conditions in the laboratory for 14 days, and another 55 of 60 cultures, suspended as above, transported from reference laboratories within 7 days, were successfully retrieved on LJ medium. Considering the maximum retrieval of
M. tuberculosis
, use of PBS can be explored further for transportation of
M. tuberculosis
cultures across laboratories.
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CASE REPORTS
Epidemic of tuberculosis in a high school in Northern Sardinia
Alessandra Bua, Paola Molicotti, Anna Zanetti, Melania Ruggeri, Marina Cubeddu, Sara Cannas, Nanni Peana, Michela Sali, Giovanni Delogu, Stefania Zanetti
July-September 2012, 1(3):161-163
DOI
:10.1016/j.ijmyco.2012.07.003
The aim of this study was to investigate the
Mycobacterium tuberculosis
transmission among high school student and teacher populations in a high school in Northern Sardinia. Tuberculin skin-test screening, chest-X-rays, QuantiFERON-TB Gold, microbiological examination, spoligotyping and variable numbers of tandem repeats (VNTR) analysis of
M. tuberculosis
isolates were performed. This study indicates the effectiveness of the epidemiological investigation.
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Hypersensitivity pneumonitis caused by
Mycobacterium avium
subsp.
hominissuis
in a hot tub, as proven by IS1245 RFLP and rep-PCR typing☆
Rianne J.C van der Zanden, Cecile Magis-Escurra, Wiel C.M de Lange, Wouter Hoefsloot, Martin J Boeree, Jakko van Ingen, Dick van Soolingen
July-September 2012, 1(3):152-154
DOI
:10.1016/j.ijmyco.2012.07.006
A symptomatic patient had repeatedly positive cultures of Mycobacterium avium subsp.
hominissuis
after exposure to a hot tub contaminated with
M. avium
subsp.
hominissuis
. The pulmonary and tub water isolates were indistinguishable by IS1245 RFLP as well as rep-PCR typing. Discontinued use of the hot tub resulted in culture conversion.
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ARTICLES
Multidrug resistant
Mycobacterium tuberculosis
amongst Category I & II failures and Category II relapse patients from Pakistan
Abdul Ghafoor, Jaishri Mehraj, Nek Dad Afridi, Yasraba Rafiq, Hans-Uwe Wendl-Richter, Rumina Hasan
July-September 2012, 1(3):118-123
DOI
:10.1016/j.ijmyco.2012.07.004
Objective:
To determine the prevalence of multidrug-resistant tuberculosis (MDR-TB) among previously treated TB patients in Khyber Pakhtunkhwa (KP) Province, Pakistan.
Design and settings:
A cross-sectional study was conducted (January–September 2009) in 10 districts of KP. All Category (CAT) I and CAT II failures, and CAT II relapse cases were recruited within 1week following declaration of treatment outcome or re-registration of CAT II. Clinical information and sputum was collected from each patient.
Results:
Total 139 patients were enrolled.
Mycobacterium tuberculosis
bacilli (MTB) was isolated in 113 (81.3%) samples; Mycobacterium other than tuberculosis (MOTT) was isolated in 7 (5%) samples. MDR-TB was noted in 66 (58.4%) patients and extensive drug resistant (XDR-TB) in 2 (1.8%) patients. Amongst MDR patients, 20 (62.5%) were CAT I failure, 19 (76%) CAT II failure and 27 (48.2%) CAT II relapse cases. Resistance to Isoniazid was most common in 84 (74%) cases, followed by Pyrazinamide in 73 (64.6%) cases, Rifampicin in 67 (59%) cases, Streptomycin in 60 (53%) cases, Ethambutol in 58 (51%) cases, and Ofloxacin in 18 (22.2%) cases.
Conclusion:
High rate of drug resistance, including MDR observed among failures and relapse cases. This study emphasizes the need to review TB care delivery, particularly in failure cases in difficult regions such as KP that have seen considerable population displacement and conflict in recent years.
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SHORT COMMUNICATION
Performance indicators of fluorescence microscopy for sputum samples in pulmonary tuberculosis
N Selvakumar, A Syam Sunder, M Gomathi Sekar, C Ponnuraja, Vanaja Kumar
July-September 2012, 1(3):143-145
DOI
:10.1016/j.ijmyco.2012.07.005
To get insight into the sensitivity of fluorescence microscopy for diagnostic and follow-up sputum samples from pulmonary tuberculosis patients in clinical trials, the yield of smear positivity – among culture positive sputum samples – encountered in diagnostic and follow-up samples was retrospectively analyzed from the data available in a mycobacteriology laboratory in India. The sensitivity of fluorescence microscopy for diagnostic and follow-up samples respectively was found to be 94.3% and 60.7%. With these values as guidelines, the performance of fluorescence microscopy in the treatment of multi-drug resistant tuberculosis under DOTS plus program remains to be monitored and studied.
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