Diagnosis Of Multidrug-resistant Tuberculosis Research Articles

Validation of the Real Time Polymerase Chain Reaction (qPCR) coupled to melting curves as an alternative tool for the diagnosis of Multi-Drug Resistant Tuberculosis

La tuberculosis es una enfermedad infecto-contagiosa, causada por diversas especies del Complejo Mycobacterium tuberculosis, actualmente se estima que un tercio de la población mundial se encuentra afectada por lo que representa una amenaza para la salud pública, principalmente por el surgimiento de cepas Multidrogorresistentes (TB-MDR). En Bolivia se reportaron 7.538 personas enfermas con Tuberculosis, los últimos datos sobre TB-MDR indican un aumento de 0,2% por año, el año 2019 se registró un 3,1% de TB-MDR. Actualmente en nuestro país se emplean métodos moleculares para la identificación de este agente infeccioso; no obstante, existen muy pocos o ningún trabajo acerca de la aplicación de métodos moleculares para la detección precisa y efectiva de cepas TB-MDR que otorguen validez a los resultados emitidos. Este trabajo resuelve el cuestionamiento de, si la PCR en tiempo real (RT-qPCR) acoplada a curvas melting es una herramienta de diagnóstico alternativo aplicable, para la identificación de Tuberculosis Multidrogorresistente. Materiales y Métodos: Se trabajó con 74 cepas de Mycobaterium tuberculosis fenotípicamente identificadas por cultivo (método de las proporciones, Canetti Rist) como gold standar. El material genético para las pruebas moleculares se obtuvo por el método de columnas, se utilizaron dos controles primarios para la determinación de resistencia a los fármacos Isoniacida y Rifampicina, tanto los controles como las muestras se procesaron por RT-qPCR acoplada a curvas melting, mediante cambios de temperatura de disociación. Resultados: Loa parámetros de test diagnóstico de la prueba demostraron sensibilidad: 67.4%, especificidad: 83.3%, Exactitud: 73.97%, VPP: 85.3%, VPN: 64.1% para Isoniacida. Mientras que para Rifampicina: Sensibilidad: 97%, especificidad: 20%, exactitud: 58.9%, VPP: 55.4% y VPN: 87.5%. Conclusión: El método evaluado para la determinación de resistencia a Isoniacida presenta un equilibrio entre sensibilidad y especificidad, por lo que representa una alternativa diagnóstica confiable, mientras que para resistencia a Rifampicina presenta una alta sensibilidad que es muy útil para países endémicos como el nuestro.

Rapid detection of multidrug-resistant tuberculosis based on allele-specific recombinase polymerase amplification and colorimetric detection.

Multidrug-resistant tuberculosis (MDR-TB) poses a serious threat to TB control. Early diagnosis and proper treatment are essential factors to limit the spread of the disease. The existing molecular tests for MDR-TB usually require specific instruments, steady power supply, and routine maintenance, which might be obstacles for low-resource settings. This study aimed to develop allele-specific isothermal recombinase polymerase amplification (allele-specific RPA) to simultaneously detect the most common mutations in the rpoB gene at codons 516, 526, and 531, which are associated with rifampicin resistance, and in the katG gene at codon 315, which is related to isoniazid resistance. Allele-specific primers targeting four major mutations, rpoB516, rpoB526, rpoB531, and katG315, were constructed and used in individual RPA reactions. The RPA amplicons were endpoints detected by the naked eye immediately after applying SYBR Green I. The optimised RPA assay was evaluated with the Mycobacterium tuberculosis wild-type strain H37Rv and 141 clinical M. tuberculosis isolates. The results revealed that allele-specific RPA combined with SYBR Green I detection (AS-RPA/SYBR) detected these four major mutations with 100% sensitivity and specificity relative to DNA sequencing. The limits of detection for these particular mutations with AS-RPA/SYBR were 5 ng. As a result of the outstanding performance of AS-RPA/SYBR, including its easy setup, speed, lack of a specific instrument requirement, and lack of cross-reaction with other bacteria, this technique may be integrated for the molecular diagnosis of MDR-TB, especially in low-resource settings.

Does Ghana's National Health Insurance Scheme provide financial protection to tuberculosis patients and their households?

Financial barriers are a key limitation to accessing health services, such as tuberculosis (TB) care in resource-poor settings. In Ghana, the National Health Insurance Scheme (NHIS), established in 2003, officially offers free TB care to those enrolled. Using data from the first Ghana's national TB patient cost survey, we address two key questions 1) what are the key determinants of costs and affordability for TB-affected households, and 2) what would be the impact on costs for TB-affected households of expanding NHIS to all TB patients?We reported the level of direct and indirect costs, the proportion of TB-affected households experiencing catastrophic costs (defined as total TB-related costs, i.e., direct and indirect, exceeding 20% of their estimated pre-diagnosis annual household income), and potential determinants of costs, stratified by insurance status. Regression models were used to determine drivers of costs and affordability. The effect of enrolment into NHIS on costs was investigated through Inverse Probability of Treatment Weighting Analysis.Higher levels of education and income, a bigger household size and an multi-drug resistant TB diagnosis were associated with higher direct costs. Being in a low wealth quintile, living in an urban setting, losing one's job and having MDR-TB increased the odds of experiencing catastrophic costs. There was no evidence to suggest that enrolment in NHIS defrayed medical, non-medical, or total costs, nor mitigated income loss. Even if we expanded NHIS to all TB patients, the analyses suggest no evidence for any impact of insurance on medical cost, income loss, or total cost.An expansion of the NHIS programme will not relieve the financial burden for TB-affected households. Social protection schemes require enhancement if they are to protect TB patients from financial catastrophe.

Determinants of Delay in Diagnosis and Treatment in Multi Drug-Resistant Tuberculosis Patients in Health Facilities

Background: Multidrug-resistant tubercu­lo­sis (MDR-TB) is a serious threat to global TB control programs. According to WHO, there are 23,000 cases of TB multidrug-/rifampicin-resistant (MDR/RR-TB) in Indonesia. In 2017, there were 442,000 of TB cases. There were 8,600 - 15,000 MDR/RR-TB cases, of which 2.4% were new cases and 13% were previously treated TB cases. This study aims to determine the factors that influence the delay in diagnosis and treatment of MDR-TB patients. Subjects and Method: This study was a cross-sectional study conducted at Dr. Moe­wardi hospital, from Sep­tem­ber to October 2017, Surakarta, Central Java. A sample of 73 MDR-TB patients with disabilities on medical records was selected for this study. The depen­dent variables were delay in diagnosis and delay in therapy of MDR-TB cases. The inde­pendent variables were age, gender, distance to health facilities, and type of health facilities. Data were collected from medical records of MDR-TB patients who were treated from March 2012 to March 2017. Data were analyzed using the chi-square model. Results: Median delay in diagnosis = 4 days. Median treatment delay = 12 days. The average patient who had delayed MDR-TB therapy (≥4 days) was 44 years old (Mean= 44.19; SD= 12.64). Delay in MDR-TB diagnosis was not significantly associated with gender (OR= 0.53; 95% CI= 0.18 to 1.57; p= 0.264), distance to health facility (OR= 1.56; 95% CI= 0.58 to 4.21; p= 0.389), and type of health facility (OR= 0.60; 95% CI= 0.26 to 1.41; p= 0.983). The average of patient who had delayed MDR-TB therapy (≥12 days) was 41 years old (Mean= 41.39; SD= 12.69). Treatment delay was not significantly related to gender (OR= 0.45; 95% CI= 0.16 to 1.26; p= 0.137), distance to health facility (OR=1.44; 95% CI= 0.55 to 3.78; p= 0.466), and type of health facility (OR= 2.31; 95% CI= 1.03 to 5.21; p= 2.967). Conclusion: There was no statistically sig­nificant relationship between gender, dis­tance from the patient's home to health facilities, and type of health facility with the delay in diag­nosis and treatment of MDR-TB patients. Keyword s : diagnosis, treatment, TB-MDR Correspondence: Yusup Subagio Sutanto. Department of Pulmo­nology and Respiratory Medicine, Faculty of Medicine Universitas Sebelas Maret/ Dr. Moe­wardi Hospital, Surakarta. Jl. Kolonel Sutarto No.132, Jebres, Surakarta, Central Java 57126. Email: dr_yusupsubagio@yahoo.com. Mobile: 0811284165. Indonesian Journal of Medicine (2021), 06(01): 14-22 https://doi.org/10.26911/theijmed.2021.06.01.02

Gridlock from diagnosis to treatment of multidrug resistant tuberculosis (MDR-TB) in Tanzania: patients\u2019 perspectives from a focus group discussion

BackgroundMolecular diagnostics have revolutionized the diagnosis of multidrug resistant tuberculosis (MDR-TB). Yet in Tanzania we found delay in diagnosis with more than 70% of MDR-TB patients having a history of several previous treatment courses for TB signaling prior opportunities for diagnosis. We aimed to explore patients’ viewpoints and experiences with personal and socio-behavioral obstacles from MDR-TB diagnosis to treatment in an attempt to understand these prior findings.MethodsThe study was conducted in December 2016 with MDR-TB patients admitted at Kibong’oto Infectious Diseases Hospital. A qualitative approach deploying focus group discussions (FGDs) was used to gather information. Groups were sex aggregated to allow free interaction and to gauge gender specific issues in the social and behavioral contexts. The FGDs explored pathways and factors in the service delivery that may have contributed in the delay in accessing MDR-TB diagnostics and/or treatment. Collected data were coded, categorized and thematically interpreted.ResultsForty MDR-TB patients participated in six FGDs. Challenges and barriers contributing to the delay in accessing MDR-TB diagnosis to treatment were as follows: 1) Participants had a different understanding of MDR-TB that led to seeking services outside the conventional health system; 2) Socio-economic adversity made health-seeking behavior difficult and often unproductive; 3) In the health system, challenges included inadequacy of MDR-TB diagnostic centers, lack of knowledge on behalf of health care providers to consider MDR-TB and order appropriate diagnostics; 4) The specimen referral system for early diagnosis of MDR-TB was inefficient. Non-adherence of TB patients to first-line anti-TB drugs prior to MDR-TB diagnosis, given the multitude of barriers discussed, was coupled with both intentional and unintentional non-adherence of health care providers to international standards of TB care.ConclusionPatient-centered strategies bridging communities and the health system are urgently required for optimum MDR-TB control in Tanzania.

Challenges Faced by Multidrug-Resistant Tuberculosis Patients in Three Financially Affluent Chinese Cities.

PurposeThe aim of this study was to analyze socioeconomic burdens and other difficulties that multidrug-resistant tuberculosis (MDR-TB) patients in cities are facing, to identify major obstacles and which groups of patients are most affected.MethodsFace-to-face and phone-call interviews were conducted in early 2018 to follow-up with patients newly diagnosed with MDR-TB in 2017 in three tuberculosis hospitals in three financially affluent Chinese cities. Demographic data and information on their medical care, insurance coverage, and medical expenses were collected and analyzed.ResultsA total of 144 newly diagnosed MDR-TB cases were reviewed during the study period, excluding 38 who were lost to follow-up and 29 patients who refused to participate, 77 patients were enrolled in this study. A total of 61 (79%) of these patients were hospitalized after MDR-TB diagnosis with an average hospital stay of 14 days, of them 57 (74%) were sputum positive on diagnosis. The proportion of patients who failed community care were 48% married, 56% in white collar employment and 43% in temp jobs/unemployed. In terms of insurance coverage, the proportion of patients who failed community care were 23% with no insurance and/or New Rural Co-operative Medical Care Scheme (NRCMS) and 45% with Urban Employee Basic Medical Insurance (UEBMI)/Urban Residents Basic Medical Insurance (URBMI) and commercial insurance. Difficulties patients encountered were, financial pressure (33%), psychological stress (26%), adverse drug reactions (23%), repulsive reaction to injections (17%). Fourty-eight percent of the patients spent over ¥2000 (USD300) per month on TB treatment.ConclusionDespite insurance coverage, financial hardship remains the number one difficulty MDR-TB patients encountered in relatively financially affluent cities. Among them, the married working class were found to be the most financially sensitive group and have the highest tendency to fail community care. It is of utmost urgency to enhance the current medical policy to improve treatment adherence.

Using Bayesian spatial models to map and to identify geographical hotspots of multidrug-resistant tuberculosis in Portugal between 2000 and 2016

Multidrug-resistant tuberculosis (MDR-TB) is a major threat to the eradication of tuberculosis. TB control strategies need to be adapted to the necessities of different countries and adjusted in high-risk areas. In this study, we analysed the spatial distribution of the MDR- and non-MDR-TB cases across municipalities in Continental Portugal between 2000 and 2016. We used Bayesian spatial models to estimate age-standardized notification rates and standardized notification ratios in each area, and to delimitate high- and low-risk areas, those whose standardized notification ratio is significantly above or below the country’s average, respectively. The spatial distribution of MDR- and non-MDR-TB was not homogeneous across the country. Age-standardized notification rates of MDR-TB ranged from 0.08 to 1.20 and of non-MDR-TB ranged from 7.73 to 83.03 notifications per 100,000 population across the municipalities. We identified 36 high-risk areas for non-MDR-TB and 8 high-risk areas for MDR-TB, which were simultaneously high-risk areas for non-MDR-TB. We found a moderate correlation (ρ = 0.653; 95% CI 0.457–0.728) between MDR- and non-MDR-TB standardized notification ratios. We found heterogeneity in the spatial distribution of MDR-TB across municipalities and we identified priority areas for intervention against TB. We recommend including geographical criteria in the application of molecular drug resistance to provide early MDR-TB diagnosis, in high-risk areas.

English

Multi Drug Resistant Tuberculosis (MDR-TB) is a public health challenge, which itself remains a global public health problem. Its impact is worsened by co-infection with Human immunodeficiency virus (HIV). In order to institute successful TB control strategies, factors for development of MDR-TB must be understood. This study aimed to identify and describe clinical and demographic determinants for development of MDR-TB among TB patients. This was a cross sectional, hospital-based study conducted between April 2017 and December 2019 involving 428 presumptive MDR-TB patients. Specimens were subjected to GeneXpert MTB/RIF assay, microscopy and Line probe assay for diagnosis of MDR-TB. A questionnaire was used to collect demographic information from patients. The odds of having MDR-TB among patients who were cigarette smokers were four-times compared to non-smoking patients (aOR=3.94; 95%CI: 1.845-8.428, p<0.001). Alcohol abuse increased the chances of having MDR-TB by ten times (aOR=9.98: 95%CI; 2.414-41.267, p=0.001). Being HIV positive strongly increased the likelihood of having MDR-TB (aOR=2266.0: 95% CI; 407.5-2599.8, p<0.001). Compared to treatment failure, relapse and non-adherence were found to be strong predictors for MDR-TB (aOR=64.22: (95% CI; 12.786-322.507) p=0.001), and (aOR=37.44: (95% CI; 3.895-359.836, p=0.002), respectively. HIV infection, TB relapse, history of irregular treatment, cigarette smoking, alcohol abuse, and treatment failure (return) is factors development of MDR-TB. Integrated TB/HIV control programs that will include the establishment of strong diagnostic and drug delivery systems, patient management, and TB resistance surveillance systems are recommended. Key words: Tuberculosis, multi drug resistant tuberculosis (MDR-TB), HIV, M. tuberculosis, adherence; relapse.

Retrospective analysis of multidrug-resistant tuberculosis case notifications in Australia (1999-2018).

This study describes the epidemiology and treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) cases notified in Australia between 1999 and 2018, and investigates whether current data fields in the national tuberculosis (TB) dataset allow description and measurement of surveillance information pertaining to the diagnosis and clinical management of MDR-TB. In May 2019, de-identified demographic, clinical, laboratory, drug susceptibility, treatment, risk factor and outcome data for all MDR-TB case notifications were extracted from the Australian National Notifiable Disease Surveillance System. The dataset included ten treatment outcome categories, which were aggregated to four categorical outcomes for descriptive and inferential analyses. The majority of cases were overseas-born (91%). Absolute case numbers increased over time; however, the MDR-TB notification rate remained fairly stable during the study period. Treatment success was achieved in nearly two-thirds of cases (62.1%). Whilst timeframes between initial presentation, specimen collection, case notification and treatment commencement were calculated, current data fields in the national dataset precluded measurement and description of other parameters deemed important for MDR-TB surveillance. This study demonstrates that while Australia's MDR-TB burden is low, cases will continue to occur until TB control improves in countries with which Australia shares cultural and migration links. Australia should continue to support national and regional TB control programmes to sustain progress towards national elimination of TB. This study's findings support a review of data fields in the national TB dataset with potential expansion or adjustment to improve national data reporting, including the monitoring of evidence-based recommendations for the prevention and management of MDR-TB.

Treatment quality and outcome for multidrug-resistant tuberculosis patients in four regions of China: a cohort study

BackgroundChina incurs an extremely low treatment coverage of multidrug-resistant tuberculosis (MDR-TB). This study aimed to understand the experience of MDR-TB patients on quality of health care, and the clinical impact through an up to six-year follow-up.MethodsCohorts of MDR-TB patients were built in TB/MDR-TB designated hospitals in four regions of China from 2014 to 2015. Patients were followed up during treatment course, and yearly confirmation afterward until 2019. Delay in MDR-TB diagnosis and treatment was calculated upon bacteriological confirmation and treatment initiation. Risk factors for unfavourable outcomes were identified by multivariate logistic regression.ResultsAmong 1168 bacteriological-positive TB patients identified from a 12-million population, 58 (5.0%) MDR-TB cases were detected. The median delay for MDR-TB diagnosis was 90.0 days, with 13.8% having a delay above 180.0 days. MDR-TB treatment was only recommended to 19 (32.8%) participants, while the rest continued with regimen for drug-susceptible TB. In MDR-TB treatment group, 36.8% achieved treatment success, while the others had incomplete treatment (21.1%), loss to follow-up (36.8%) and TB relapse (5.3%). For non-MDR-TB treatment group, 33.3% succeeded, 25.6% relapsed, 2.6% failed, 23.1% died, and 15.4% were lost to follow-up. Overall, only 35.7% (20/56) of detected MDR-TB patients had favourable outcomes and higher education level was positively associated with it (adjusted odds ratio [aOR]: 3.60, 95% confidence interval [CI]: 1.04–12.5).ConclusionsA large proportion of patients did not receive MDR-TB treatment and had unfavourable outcomes. Delayed MDR-TB diagnosis resulted in poor quality of MDR-TB care. Rapid diagnosis, regulated patient management and high-quality MDR-TB treatment should be enhanced in China.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012\u20132017) retrospective study

BackgroundIn Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care.MethodsFor 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care.ResultsThe geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival.ConclusionsAn expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

A Rapid and Accurate Detection Approach for Multidrug-Resistant Tuberculosis Based on PCR-ELISA Microplate Hybridization Assay.

Rapid and accurate diagnosis of multidrug-resistant tuberculosis (MDR-TB) is important for timely and appropriate therapy. In this study, a rapid and easy-to-perform molecular test that integrated polymerase chain reaction (PCR) amplification and a specific 96-well microplate hybridization assay, called PCR-ELISA (enzyme-linked immunosorbent assay), were developed for detection of mutations in rpoB, katG, and inhA genes responsible for rifampin (RIF) and isoniazid (INH) resistance and prediction of drug susceptibility in Mycobacterium tuberculosis clinical isolates. We evaluated the utility of this method by using 32 multidrug-resistent (MDR) isolates and 22 susceptible isolates; subsequently, we compared the results with data obtained by conventional drug susceptibility testing and DNA sequencing. The sensitivity and specificity of the PCR-ELISA test were 93.7% and 100% for detecting RIF resistance, and 87.5% and 100% for detecting INH resistance, respectively. These results were comparable to those yielded by commercially available molecular tests such as the GenoType MTBDRplus assay. Based on the aforementioned results, we conclude that the PCR-ELISA microplate hybridization assay is a rapid, inexpensive, convenient, and reliable test that will be useful for rapid diagnosis of MDR-TB, for improved clinical care.

Patient Level Delay in Diagnosis of Multi-Drug Resistant Tuberculosis among Patients Attending Tertiary Care Hospital in Haryana

Background: Multi-Drug Resistant Tuberculosis (MDR-TB) besides increasing cost and duration of treatment also increases the mortality and morbidity. Less awareness in the community and diagnostic constraints for MDR-TB at patient level is a major cause of delay in diagnosis. Objective: To find out the delay in diagnosis of MDR-TB and factors affecting this delay among MDR-TB patients attending tertiary care hospital, PGIMS Rohtak, Haryana, India. Material and Methods: It is a hospital based cross-sectional study carried out in the department of Respiratory Medicine, PGIMS Rohtak, Haryana from March 2018 to February 2019 among 125 admitted patients of MDR-TB in tertiary care hospital, PGIMS Rohtak. A pre-designed, pre-tested, semi-structured interview schedule was used and data were analysed using SPSS version 20.0 and Chi square test was applied. Result: The mean and median patient delay was found to be 31.11 days and 21 days, respectively. Extent of patient delay was significantly associated with socio-demographic factors like age, sex, literacy status, occupation, addiction and past history of TB in patients. Conclusion: In this study, it was concluded that there was significant delay in the diagnosis as well as seeking treatment at patient level which was associated with socio-demographic factors. Thus, there is urgent need to boost up the Information, Education and Communication (IEC) activities to increase awareness among general public about the importance of early diagnosis and treatment of MDR-TB. &nbsp; How to cite this article:Jain RB, Gupta R, Sharma S, Kumar T, Agrawal G, Choudhary P et al. Patient Level Delay in Diagnosis of Multi-Drug Resistant Tuberculosis among Patients Attending Tertiary Care Hospital in Haryana. Epidem Int 2019; 4(4): 8-15. DOI: https://doi.org/10.24321/2455.7048.201918

Molecular Detection of Isoniazid and Rifampin Resistance in Mycobacterium tuberculosis Isolates from Lorestan Province, Iran from 2014 to 2017

Background: A rise in multidrug-resistant tuberculosis (MDR-TB), which is defined as the resistance to the two most effective first-line therapeutic drugs, Isoniazid (INH) and Rifampin (RIF), threatens global public health worldwide. Resistance of Mycobacterium tuberculosis to INH results from mutations in several genes most commonly in katG gene, and resistance to RIF is due to mutations in rpoB gene. Therefore, rapid diagnosis of MDR-TB is of high importance in controlling the disease progress and outcome. The accurate detection of the resistant TB strains can be accelerated by developing molecular tests. Objectives: The aim of the present local study was to isolate MDR-TB from the patients who were the residents in the west of Iran and examination the frequency of MDR-TB between patients of Lorestan province for the first time and assess the mutations in the regions related to RIF/INH resistance via PCR and sequencing methods. Methods: In this study, 106 isolates of M. tuberculosis were selected in health centers of Lorestan, Iran from 2014 to 2017. After culturing M. tuberculosis isolates on Lowenstein-Jensen medium, classical susceptibility testing proportional method against INH and RIF was performed. After DNA extraction, PCR and sequencing were used to detect mutations related to RIF and INH resistance. Results: The results demonstrated 3.8%, 0.9%, and 0.9% frequency for INH + RIF, INH and RIF resistance, respectively. Importantly, 4 out of 6 isolates harbored mutations in codon290 of katG gene. Also, these isolates contained mutations in codon339 of rpoB gene. No mutation was observed in inhA gene of M. tuberculosis isolates. Conclusions: The results suggest that molecular techniques can be used as a rapid method for the identification of drug resistance in clinical isolates of M. tuberculosis. DNA sequencing has a high sensitivity for the detection of resistance mutations to RIF and INH in MDR-TB cases. Also, the results showed that the most frequent resistance associated-mutations occurred in codon290 of katG and codon 339 rpoB gene segments.

Prevalence of Multidrug-Resistant Tuberculosis at a Regional Drug-Resistant Tuberculosis Center of Maharashtra

Introduction: Multidrug-resistant tuberculosis (MDR-TB) has created a significant health problem in most of the countries, and it is an obstacle to effective TB control. Aims and Objectives: The study aims to study the prevalence of MDR-TB among new cases, retreatment cases and to study the rate of MDR-TB detection among suspected cases of Category I (CAT I) failure, CAT II failure and at the start of CAT II. Patients and Methods: The present retrolective study was conducted by reviewing the records of diagnosed MDR-TB patients at a drug-resistant TB center from January 2012 to December 2013. The data of new and retreatment pulmonary TB (PTB) cases diagnosed during that period were collected. The data were analyzed to find out the prevalence of MDR-TB, and the rate of MDR-TB detected among each CAT. Results: The prevalence of MDR-TB in new cases was 0.10% and that of retreatment cases was 4.3%. The rate of MDR-TB detection among suspected cases of CAT I failure was 16.8%, 52.4% in CAT II failure, 11.6% at the start of CAT II, 11.7% among sputum positive during any month follow-up, 6.6% among MDR-TB contacts. Conclusion: Timely suspicion and diagnosis of MDR-TB and treatment are important in new and retreatment cases. All relapse or defaulter patients should be screened for MDR-TB at the start of CAT II treatment. MDR-TB should be suspected in any sputum-positive TB patient during treatment/sputum positive relapse/defaulter PTB.

Auditory Evaluation with Pure Tone Audiometry and DPOAE in Kanamycin Treatment of Multidrug-Resistant Tuberculosis

Background: Kanamycin treatment is mainly used in multidrug-resistant tuberculosis (MDR-TB) patients. Hearing impairment associated along with the treatment leads to be permanently. Audiology assessments and monitoring may benefits to detect early on hearing loss. This study aimed to determine the evaluation of hearing alteration after kanamycin injection in the first month treatment. Method: We conducted a prospective study, observational longitudinal analytic with pre and post design in patients treated with kanamycin-based regimens in MDR-TB Outpatients Pulmonology Department Dr. Soetomo general hospital Surabaya. Assessment of hearing result using Pure Tone Audiometry and DPOAE, compared between baseline data and after 4 weeks treatments. Statistical analysis for hearing threshold and cochlear dysfunction based on overall frequency and specific frequency DPOAE examination, using Wilcoxon ranks test and Mc Nemar test. Results: A total of 15 patients (8 males and 7 females) with confirmed diagnosis of MDR-TB were included in this study conducted within 3 months in 2018. There were 15 ears represented with based line and compared to 4 weeks after treatment, showed on Audiometry and DPOAE on overall frequencies, found no significant difference (p &gt; 0.05), but in DPOAE at frequency of 10,000 Hertz (Hz) was found a significant difference (p = 0.002). Conclusion: DPOAE at high frequency (10,000 Hz) may benefits for early detection on hearing impairment. A baseline data with DPOAE is recommended, besides Audiometry for ototoxicity monitoring in Kanamycin treatment in MDRTB patients.

A novel approach for eliciting adolescent MDR-TB treatment tolerability: qualitative data from South Africa.

SETTING: Treatment tolerability among adolescents diagnosed with multidrug-resistant tuberculosis (MDR-TB) is underexplored. We present qualitative study data from adolescents participating in an observational cohort in the Western Cape, South Africa.OBJECTIVE: To elicit adolescent experiences of MDR-TB diagnosis and treatment with qualitative body-mapping activities and discussions.DESIGN: Adolescents in an observational MDR-TB cohort received routine toxicity and audiology screenings from clinicians. We enrolled eight participants (age 10-16 years) to participate in additional body-mapping activities and in-depth interviews. A thematic deductive analysis was conducted. We present a comparison of the clinical assessments and qualitative discussions.RESULTS: Adolescent participants reported few adverse effects on standard toxicity and audiology reports. Only nausea and vomiting were reported in >10% of cases, all of which were grade 1 (causing no/minimal interference) adverse effects (AEs). However, when comparing toxicity reports with qualitative body-mapping activities and interviews, we found previously unreported AEs (neurosensory alteration, neuromuscular weakness, pain); underestimated severity of AEs (nausea, itching); and missed psychosocial symptoms (signs of depression).CONCLUSION: Adolescents receiving treatment for MDR-TB experienced treatment-related AEs that were not reported during routine clinical assessments. Psychosocial experiences of adolescents are not taken into account. More research is needed to understand the experiences of this vulnerable group. We recommend that drug safety monitoring be adapted to include more creative and patient-driven reporting mechanisms for vulnerable groups, including children.

Prevalence of Multidrug-Resistant Tuberculosis: A Six-Year Single-Center Retrospective Study in Tehran, Iran

Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the main challenges to TB control, particularly in developing countries such as Iran. Continuous TB drug resistance surveillance is required for the effective management of TB patients. Methods: The antibiotic susceptibility patterns of clinical Mycobacterium tuberculosis isolates were retrospectively analyzed from April 2012 to March 2018. Conventional and molecular methods were used for the identification and drug susceptibility testing (DST) of M. tuberculosis isolates. Results: A total of 3,012 clinical specimens were collected form TB-suspected patients. Of them, 100 (3.3%) were culture-positive and assigned as M. tuberculosis by phenotypic and molecular methods. According to DST, 17 (17%) isolates were MDR-TB. Conclusions: Improved diagnosis and treatment of MDR-TB may lead to better control of the disease in Iran.

Survival time and influencing factors in multidrug-resistant tuberculosis patients in Wuhan, 2006-2014

Objective: To investigate the survival time of multidrug-resistant tuberculosis (MDR-TB) patients and the influential factors in Wuhan. Methods: The relevant information were collected from TB management information system, cause of death reporting system and medical records by trained doctors. The univariate and multivariate Cox proportional hazards model were applied to analyze the factors affecting survival time of patients. Results: A total of 552 patients with MDR-TB were included in the analysis. After the diagnosis of MDR-TB, the cumulative survival rates from the first year to the third year were 0.94, 0.88, and 0.80, respectively. The mortality density of MDR-TB patients was 6.52/100 person-years, and the median survival time was (89.52±1.85) months. Kaplan-Meier analysis showed that the cumulative survival rate of the standardized treatment group was significantly higher than that of the non-standardized treatment group (Log rank=101.070, P<0.001). Compared with the patients aged <30 years, the HR of the patients aged 30-years and ≥60 years were 2.987 (95%CI: 1.268-7.036), 4.957 (95%CI: 1.942-12.653). Compared with the patients with the education level of high school and above, the HR of the patients with education level of junior high school/primary school and below were 1.908 (95%CI: 1.152-3.160), 1.681(95%CI: 1.033-2.735). Compared with the patients without diabetes, the HR of the patients with diabetes was 1.961(95%CI: 1.347-2.854). Compared with the patients without other serious diseases, the HR of the patients with other serious diseases was 2.597 (95%CI: 1.820-3.706). Compared with the patients who had been treated less than one time, the HR of the patients having previous treatment with more than 2 times was 1.611 (95%CI: 1.077-2.409). Compared with patients receiving standard MDR regimen treatment, the HR of the patients receiving no standard MDR regimen treatment was 3.155 (95%CI: 2.132-4.670). Conclusions: The cumulative survival rate of MDR-TB patients without standard treatment was significantly lower than that of patients with standard treatment. Older age, low educational level, diabetes mellitus, other serious diseases, more than two times treatment in the past, and receiving no multi-drug resistance regimen treatment were the risk factors affecting the survival of MDR-TB patients.

Family cluster of multi-drug resistant tuberculosis in Kingdom of Saudi Arabia

We describe the clinical and genetic characteristics of multi-drug resistant tuberculosis (MDR-TB) in a family cluster in the western region of Kingdom of Saudi Arabia diagnosed between 2012 and 2016. All cases had risk factors for tuberculosis acquisition and they were not household contacts of the index case. Genetic analysis detected both MDR-TB and pre-extensively drug-resistant tuberculosis (pre-XDR TB) strains in the index case and confirmed tuberculosis transmission between two cases. Lack of early diagnosis of MDR-TB by molecular testing and lack of extended contact tracing contributed to the transmission of MDR-TB among this family cluster over four years.