Early detection of Pre-XDR TB with line probe assay in a high TB burden country

Background - Worldwide, tuberculosis (TB) is one of the top 10 causes of death. Drug resistant tuberculosis has lately become a major public health problem that threatens progress made in Tuberculosis (TB) care and control worldwide. The aim of this study was to determine the prevalence of Pre-extensive drug resistant TB among MDR TB in North Central of Nigeria. Methods - This study was conducted from October, 2018 to August, 2019 with 150 samples. In Nigeria, guidelines for DR-TB as recommended by WHO is followed. All the samples from the patients who gave their consent were transported to a zonal reference TB laboratory (ZRL). Results - Mean age was 38.6 ± 13.4 years with peak age at 35-44. Out of these 103 samples processed with LPA, 101(98%) were rifampicin resistant and 2 were rifampicin sensitive, 99(96%) were INH resistant and 4 (4%) were INH sensitive, 5(5%) were fluoroquinolone resistant, 98(95%) were fluoroquinolone sensitive, 12 (12%) were Aminoglycoside + Capreomycin resistant, 91(83%) were Aminoglycoside + Capreomycin sensitive. Conclusion - Multidrug resistant TB and its severe forms (Pre-extensive & extensively drug resistant TB) can be detected early with rapid tool- Line Probe Assay rapid and prevented timely by early initiation on treatment.

A Study on Adverse Drug Reaction Profile of 2nd Line Drugs in Multi Drug Resistant (MDR) and Extensively Drug Resistant (XDR) Tuberculosis Cases Registered under DR-TB Centre in a Tertiary Care Hospital

The emergence of drug resistant mycobacterium has become a significant public health problem creating an obstacle to effective tuberculosis (TB) control. Freedom from TB is possible with timely, regular, complete treatment, with assurance, prevention and management of side effects of antitubercular drugs. Present study was conducted to evaluate common and rare adverse drug reactions (ADR) of CAT IV and CAT V to analyse demographic, radiological and bacteriological profile and treatment outcome in MDR & XDR patients. We wanted to evaluate the common and rare adverse drug reactions of intensive phase treatment of Multi Drug Resistant Tuberculosis (MDR) and Extensively Drug Resistant Tuberculosis (XDR) as per WHO-UMC Causality Assessment Scale.METHODS76 patients of MDR and XDR Tuberculosis were admitted in DR-TB (Drug Resistant TB) centre, Burdwan Medical College and Hospital and the adverse drug reaction profile of 2nd line drugs were analysed during the intensive phase from April 2016 to September 2017 after fulfilling the inclusion and exclusion criteria. Treatment was given as per the guidelines of Revised National TB Control Program PMDT (Programmatic Management of Drug-Resistant TB).RESULTSAdverse drug reactions on GI system were nausea 73 patients (96.10%), vomiting 70 (92.10%), acidity 41 (53.9%), and sulphurous belching and hepatitis 1 (1.31%) each. Peripheral neuropathy, hearing deficit, myopathy, skin rashes, hepatitis, nephrotoxicity, cardiac toxicity and convulsion were also observed. In psychosis, 3 (3.95%) had depression and made suicidal attempt. 1 each (1.31%) in hallucination and paranoia. 5 patients (6.58%) had blurring of vision, 2 patients (3.95%) had redness of eyes and one (1.31%) had eye irritation. Reactions were common in first 60 days of the regimen and in patients with BMI ≤18.CONCLUSIONSVigilant monitoring is required for these patients during the initial period and sputum smear and culture conversion is very well correlated with clinical and radiological improvement.

Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil

BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) has increased considerably worldwide. OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution. METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB). FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONS The present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB.

Analysis on drug resistance characteristics and risk factors for extensively drug resistant tuberculosis patients / 中华疾病控制杂志

@# Objective To analyze the drug resistance profile and risk factors for extensively drug resistant tuberculosis (XDR-TB) patients. Methods XDR-TB cases were identified by sixteen anti-TB drug susceptibility kits among inpatients with a diagnosis of laboratory-confirmed mycobacterium tuberculosis. Single-factor and Logistic analysis were used to analyze the risk factors for drug resistant of the first and second-line anti-TB drugs in XDR-TB patients. Results Resistant rate of rifampin, isoniazid and rifampicin were 100%, Resistant rate of streptomycin, rifampicin and dean, b sulfur isoniazid, levofloxacin and capreomycin were from 90% to 100%, resistant rate of kanamycin and amino salicylic acid were from 70% to 80%, resistant rate of amikacin from 60% to 70%, resistant rate of sulfur isoniazid was from 50% to 60%, resistant rate of ethambutol and moxifloxacin were from 40% to 50%, resistant rate of clarithromycin was from 10% to 20%, resistant rate of clofazimine 5.2%. 92.1% of XDR-TB patients were resistant to more than 10 anti-TB drugs, and the least of the patients were resistant to 6 anti-TB drugs.Logistic regression analysis showed the risk factors for XDR-TB first-and second-line anti-tb drugs included age ［20-40 year (OR=6.318, 95% CI:1.204-33.15, P=0.029;40-60 year (OR=4.772, 95% CI:0.973-23.392, P=0.054); 60 year (OR=41.366, 95% CI:2.909-588.265, P=0.006)］and anti-TB treatment history was retreatment(OR=28.013, 95% CI:3.357-233.766, P=0.002). Conclusions XDR-TB patients have serious drug resistance, but there were some drug treatable drug resistance types, and the risk factors mainly come from age and anti-TB treatment history.

A study on pre-XDR & XDR tuberculosis & their prevalent genotypes in clinical isolates of Mycobacterium tuberculosis in north India.

Background & objectives: Pre-extensively drug resistant (pre-XDR) and extensively drug resistant tuberculosis (XDR-TB) have been areas of growing concern, and are posing threat to global efforts of TB control. The present study was planned to study the presence of pre-XDR and XDR Mycobacterium tuberculosis and their genotypes in clinical isolates obtained from previously treated cases of pulmonary TB. Methods: A total of 219 isolates obtained from previously treated cases of pulmonary TB were subjected to first-line (streptomycin, isoniazid, rifampicin and ethambutol) and second-line (ofloxacin, kanamycin, capreomycin and amikacin) drug susceptibility testing on solid Lowenstein-Jensen medium by proportion method. Genotyping was done for pre-XDR and XDR-TB isolates using 12 loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR). Results: Multi-drug resistance was observed in 39.7 per cent (87/219) isolates. Pre-XDR and XDR M. tuberculosis isolates amongst 87 multi-drug resistant (MDR) TB isolates were 43 (49.4%) and 10 (11.4%), respectively. Two most dominant genotypes among pre-XDR and XDR M. tuberculosis isolates were Beijing and Delhi/CAS types. Interpretation & conclusions: Resistance to second-line anti-tubercular drugs should be routinely assessed in areas endemic for TB. Similar genotype patterns were seen in pre-XDR and XDR-TB isolates. Beijing and Delhi/CAS were predominant genotypes.

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. METHODS: Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. RESULTS: A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. CONCLUSION: This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

Drug resistance among extrapulmonary TB patients: Six years experience from a supranational reference laboratory.

Background & objectives: There is limited information available about the drug resistance patterns in extrapulmonary tuberculosis (EPTB), especially from high burden countries. This may be due to difficulty in obtaining extrapulmonary specimens and limited facilities for drug susceptibility testing. This study was undertaken to review and report the first and second-line anti-TB drug susceptibility patterns in extrapulmonary specimens received at the National Institute for Research in Tuberculosis (NIRT), Chennai, India, between 2005 and 2012. Methods: Extrapulmonary specimens received from referring hospitals were decontaminated and cultured using standard procedures. Drug susceptibility testing (DST) for Mycobacterium tuberculosis was done by absolute concentration or resistance ratio methods for the first and the second line anti-TB drugs. Results: Between 2005 and 2012, of the 1295 extrapulmonary specimens, 189 grew M. tuberculosis, 37 (19%) cases were multidrug resistant (MDR) while one was extensively drug resistant (XDR). Specimen-wise MDR prevalence was found to be: CSF-10 per cent, urine-6 per cent, fluids and aspirates-27 per cent, pus-23 per cent, lymph nodes-19 per cent. Resistance to isoniazid and ethionamide was found to be high (31 and 38%, respectively). Interpretation & conclusions: Drug resistance including MDR-TB was observed in a significant proportion of extrapulmonary specimens referred for DST. Access to culture and DST for extrapulmonary specimens should be expanded. Guidelines for MDR-TB management should have explicit sections on extra-pulmonary tuberculosis and training on laboratory techniques is urgently required.

Role of RNTCP in the management of MDR-TB.

Background: MDR-TB is defined as resistance to isoniazid and rifampicin with or without resistance to other drugs. India is one of the countries with largest burden of MDR TB in the world. Second line Anti-tuberculous therapy is now available for patients with MDR-TB under the RNTCP Category IV. but there are many challenges for MDR-TB control in india. This study was done to analyses the RNTCP data for MDR-TB maintained at a TU, in the city of Ahmedabad, Gujarat, and to compare it with the data available in literature. This study also aimed to identify challenges faced while treating MDR-TB and to address the same. Material and methods: We had restropectively analyzed 353 patients referred to the TU from the respective Direct Microscopy Center (DMC) with suspicion of MDR-TB during a period of January 2014 to December 2014. Results: Of the 353 suspected MDR_TB patients referred to the TU, 48 patients (13.597%) were diagnosed to have MDR-TB. Of these 48 patients, 46 patients had pulmonary TB (95.833%) and 2 patients had extra-pulmonary MDR-TB (4.166%). Of the 48 patients, 08 (16.67%) patients were transferred to their respective TU and 40 patients (83.33%) were enrolled for Cat IV from our TU. Of the 40 patients enrolled at our TU, 30 patients (75%) were continuing Category IV at the end of 2014 (25 were on intensive phase and 05 were on continuation phase), 03 patients (7.5%) died during treatment, 01 patient (2.5%) defaulted treatment, 05 patients (12.5%) refused treatment and 01 patient had XDR-TB (2.5%). Of the 40 patients, 05 patients (12.5%) had ofloxacin resistance. NO patient had intolerance to any oral or injectable ATT. None of the diagnosed MDR-TB patients had HIV co-infection Conclusion: Drug resistance in tuberculosis is a “man-made problem”. Anti-TB chemotherapy must be given optimally by (i) ensuring adequate absorption of drugs, (ii) timely diagnosis and management of drug toxicities and (iii) treatment adherence. To ensure that all patients get adequate treatment and to have a close follow-up of defaulters and patients who refuse treatment; we need to strengthen our existing management information system and also incorporate private sectors into our system.

First Susceptibility Testing of <i>Mycobacterium tuberculosis</i> for Second-line Anti-tuberculosis Drugs in Ghana

We performed drug susceptibility testing on first- and second-line drugs in <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) for the first time in Ghana to obtain preliminary data on drug-resistant tuberculosis. Of 21 isolates (4 new cases and 17 treated cases), 5 (23.8%) were multi-drug resistant tuberculosis (MDR-TB) and 19 (90.5%) were resistant to at least one drug, but no extensively drug-resistant TB (XDR-TB) was identified. Since the target patients were Category II, IV or smear positive at follow-up microscopy, it is understandable that there were many drug-resistant TB cases. Six isolates were resistant to one or two second-line drugs, but the second-line drugs were not approved in Ghana. It is considered that the bacilli were imported from abroad. Preventing the import of drug-resistant TB bacilli is probably one of best ways to control TB in Ghana.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): Lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of ‘new smear-positives’ diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Extensively drug-resistant tuberculosis in India: A review.

Background & objectives: Extensively drug resistant tuberculosis (XDR-TB) has become a new threat for the control of TB in many countries including India. Its prevalence is not known in India as there is no nation-wide surveillance. However, there have been some reports from various hospitals in the country. Methods: We have reviewed the studies/information available in the public domain and found data from 10 tertiary care centres in 9 cities in India. Results: A total of 598 isolates of XDR Mycobacterium tuberculosis have been reported in the studies included. However, the reliability of microbiological methods used in these studies was not checked and thus the XDR-TB data remained invalidated in reference laboratories. Interpretation & conclusions: Systematic surveillance and containment interventions are urgently needed.

Partial Extensively Drug Resistance (XDR) Tuberculosis in Children.

Emergence of resistance to two most potent first line anti-TB drugs i.e. isoniazid and rifampicin (multidrug resistant TB – MDR TB) is well known, but, the second line drugs used to treat MDR-TB are also showing resistance to the same strain of Mycobacteria (extensively drug resistance TB, XDR-TB). We report 3 children with partial XDR TB. Two responded to treatment while one was lost to follow-up.

Prevalence of XDR TB cases - A retrospective study from a tertiary care TB Hospital.

Background: The emergence of XDR –TB strains is a major roadblock in the successful implementation of TB control programmes. This further leads to high morbidity and mortality, especially in immuno-compromised patients. Identification and observation of resistance patterns of XDR-TB strains may help clinicians manage MDR-TB cases, the treatment line of which is expensive, time-taking and involves intake of toxic drugs with many side-effects. Our study is aimed to find out the prevalence of XDR-TB among the MDR-TB strains isolated in a tertiary care hospital. Material & Methods: The study population consisted of 223 patients of tuberculosis who were culture positive and Mycobacterium tuberculosis was resistant to Rifampicin and Isoniazid during January 2007 to December 2009. Each patient had submitted two sputum samples i.e. spot and morning. The identified Mycobacterium tuberculosis complex was subjected to drug sensitivity testing by first and second line drugs by proportion and absolute concentration methods as per standard procedure . Results : The results showed that 20.17% strains (45/223) were XDR-TB strains. Most of these strains showed resistance to four drug combination viz. KM, ETH, OFX & PAS (5.82%), KM & OFX (3.13%), OFX, KM and ETH (1.79%), 1.34% strains showed resistance to all the drugs i.e. pan resistance and other combinations in the remaining strains. Nearly 80% of the XDR-TB strains showed resistance to three or more drugs combination pattern. Conclusion: The multidrug resistant TB cases need urgent and timely sensitivity report for second line ATT drugs to help clinicians start proper drug combinations to treat MDR-TB patients.

Extensively drug resistant tuberculosis (XDR-TB): An overview.

Tuberculosis or TB is a common and often deadly infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis in humans. Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is spread through the air, when people who have the disease cough, sneeze, or spit. Most infections in humans result in anasymptomatic, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of its victims. Extensively drugresistant tuberculosis (XDR TB) is a relatively rare type of multi drug-resistant tuberculosis (MDR TB). It is resistant to almost all drugs used to treat TB, including the two best first-line drugs: isoniazid and rifampin. XDR TB is also resistant to the best second-line medications: fluoroquinolones and at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin). One in three people in the world is infected with dormant TB germs (i.e. TB bacteria). Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person’s immunity, such as HIV, advancing age, or some medical conditions. TB can usually be treated with a course of four standard, or first-line, anti- TB drugs. If these drugs are misused or mismanaged, multidrug-resistant TB (MDRTB) can develop. MDR-TB takes longer to treat with second-line drugs, which are more expensive and have more side-effects. XDR-TB can develop when these second-line drugs are also misused or mismanaged and therefore also become ineffective. Because XDR-TB is resistant to first- and second-line drugs, treatment options are seriously limited. It is therefore vital that TB control is managed properly. This article presents a brief review of extensively drug-resistant tuberculosis with an emphasis on its various aspects associated i.e. introduction, symptoms, transmission, diagnosis, treatment, vaccines as well as prevention; the article reveals the different approaches in the management of Multi-drug resistant tuberculosis and correlation between XDR-TB as well as HIV/AIDS.

Prevalence of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: a retrospective hospital-based study.

Background & objective: Extensively drug-resistant tuberculosis (XDR-TB) is a difficult-to-treat form of multidrug-resistant tuberculosis (MDR-TB). High rates of XDR-TB have been reported from India. We sought to ascertain the prevalence of XDR-TB among patients with MDR-TB treated at a tertiary care centre in New Delhi, India. Methods: Case records of patients treated for MDR-TB at the All India Institute of Medical Sciences hospital, New Delhi, between 1997 and 2003 were retrospectively reviewed. All patients underwent a pretreatment drug-susceptibility testing (DST) to first- as well as second-line drugs. XDR-TB was defined as TB caused by bacilli showing resistance to rifampicin and isoniazid in addition to any fluoroquinolone and to at least one of the three following injectable drugs: capreomycin, kanamycin, and amikacin. Results: A total of 211 laboratory-confirmed cases of MDR-TB were reviewed. The mean age of the patients was 33 ± 12 yr. Fifty one (24%) patients were females. All patients were sero-negative for human immunodeficiency virus infection. Five of the 211 MDR-TB patients had XDR-TB. The prevalence of XDR-TB was 2.4 per cent among MDR-TB patients. Interpretation & conclusion: Our results showed that XDR-TB was rare among patients with MDR-TB treated between 1997 and 2003 at our centre. Unreported selection bias might have been responsible for the high prevalence of XDR-TB reported in previous hospital-based studies from India.

Extensively drug-resistant tuberculosis: a case report and literature review

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.

Trends in multidrug-resistant tuberculosis: [review]

Multidrug-resistant tuberculosis (MDR-TB) is an increasing global problem. The extent and burden of MDR-TB varies significantly from country to country and region to region. Globally, about three per cent of all newly diagnosed patients have MDR-TB and the proportion is higher in patients who had previously received anti-tuberculosis (anti-TB) treatment reflecting the failure of programs designed to ensure complete cure of patients with tuberculosis. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services and implementation of DOTS-Plus strategy.