Review on Drug Resistant Tuberculosis

Introduction: An estimated 9.9 million people fell ill with tuberculosis globally in 2020 with India and China contribu?ng a major percentage to the burden of TB. India is grouped under high TB, high HIV associated TB and MDR TB burden countries and 1.24 lakh fell ill with drug resistant TB out of which 56000 were started on second line treatment in 2020. Annually India accounts for 27% of missing TB cases. Diagnosis: The major forms of drug resistant TB that are of clinical importance are INH monoresistant TB, mul?drug resistant TB, pre- XDR TB and XDR TB.WHO approved newer molecular tests for MTB detec?on and drug suscep?bility tests. Treatment: Few newer drugs and few previously used drugs are showing promise when used in combina?on which have come up in recent years. Bedaquiline based regimens are showing improved cure rates. Conclusion: Guidelines based regimens should be strictly adhered to by both public and private TB case trea?ng physicians.

Fatores associados à tuberculose drogarresistente na população privada de liberdade, distribuição espacial e tendência temporal no estado do Paraná / Factors associated with drug-resistant tuberculosis in the privacy of the freedom population in the state of Paraná

Introdução: A tuberculose é um grave problema de saúde pública no mundo. Associada às condições de vida, a ocorrência e transmissão da doença são mais elevadas no sistema penitenciário, o que torna o risco de adoecimento por tuberculose na população privada de liberdade maior em comparação à população em geral. Além desse cenário, observa-se a presença da drogaresistência. Objetivo: analisar os fatores associados à tuberculose drogarresistente na população privada de liberdade do estado do Paraná, a distribuição espacial e tendência temporal da ocorrência da doença. Métodos: Estudo ecológico de casos de tuberculose resistente a medicamentos registrados no Sistema de Informação do Paraná, Brasil (2008 a 2018). Realizou-se estatística descritiva dos parâmetros quantitativos calculados com frequências absolutas. Adicionalmente, utilizou-se a regressão logística binária, no qual, foi calculado o Odds Ratio com seu respectivo intervalo de confiança. Para identificar a tendência temporal, utilizou-se o método Prais-Winsten e para verificar a associação espacial, bem como, a presença de clusters, recorreu-se a técnica Getis-Ord Gi*. Resultados: Dos 653 casos registrados como casos de tuberculose na população privada de liberdade, 98 apresentaram a tuberculose na sua forma resistente. Observou-se que ter até 8 e 11 anos de estudo, não fazer uso de tabaco e cultura de escarro apresentaram menos chances para o desenvolvimento de TBDR enquanto que, a forma clínica pulmonar e baciloscopia positiva no quarto mês de seguimento apresentaram-se favoráveis para o desenvolvimento de TBDR. A autoregressão de Prais-Winsten identificou uma tendência crescente, com APC = 15,08% (IC 95%: 0,02-0,09) de 2008 a 2018; quando analisada de 2012 a 2018, a tendência aumentou ainda mais, com APC = 23,31% (IC95%: 0,01-0,16). Foram observados hotspots nas macrorregiões norte, leste e oeste do Estado. A tuberculose pulmonar clinicamente confirmada e baciloscopia positiva no quarto mês de seguimento mostraram-se associados ao desenvolvimento de resistência aos medicamentos. Conclusão: O estudo evidenciou os fatores associados à TB resistente. Observou-se tendência crescente dos casos de TB resistente. A análise espacial revelou padrão heterogêneo da distribuição da tuberculose resistente, e sua concentração principalmente nas regiões com unidades prisionais

Introduction: Tuberculosis is a serious public health problem in the world. Associated with living conditions, the occurrence and transmission of the disease are higher in the penitentiary system, which makes the risk of becoming ill from tuberculosis in the population deprived of liberty greater compared to the general population. In addition to this scenario, the presence of drug resistance is observed. Objective: to analyze the factors associated with drug-resistant tuberculosis in the population deprived of liberty in the state of Paraná, the spatial distribution and temporal trend of the disease's occurrence. Methods: Ecological study of cases of drug-resistant tuberculosis registered in the Information System of Paraná, Brazil (2008 to 2018). Descriptive statistics were performed on the quantitative parameters calculated with absolute frequencies. Additionally, binary logistic regression was used, where the Odds Ratio with its respective confidence interval was calculated. To identify the temporal trend, the Prais-Winsten method was used and to verify the spatial association, as well as the presence of clusters, the Getis-Ord Gi* technique was used. Results: Of the 653 cases registered as cases of tuberculosis in the prison population, 98 had tuberculosis in its resistant form. It was observed that having up to 8 and 11 years of study, not using tobacco and sputum culture were less likely to develop TBDR, while the pulmonary clinical form and positive bacilloscopy in the fourth month of follow-up were favorable for the development of TBDR. Prais-Winsten autoregression identified an increasing trend, with APC = 15.08% (95% CI: 0.02-0.09) from 2008 to 2018; when analyzed from 2012 to 2018, the trend increased even more, with APC = 23.31% (95% CI: 0.01-0.16). Hotspots were observed in the North, East and West macro-regions of the State. Clinically confirmed pulmonary tuberculosis and positive bacilloscopy in the fourth month of follow-up were associated with the development of drug resistance. Conclusion: The study highlighted the factors associated with resistant TB. There was a growing trend in resistant TB cases. Spatial analysis revealed a heterogeneous pattern of distribution of resistant tuberculosis, and its concentration mainly in regions with prison units

Outcomes of multi drug resistant tuberculosis under programmatic conditions: the experience

Background: Tuberculosis is the most common cause of death from an infectious disease worldwide after HIV/AIDS. Drug resistant tuberculosis continues to be a public health crisis. India stands, one among 27 “high burden” MDR countries and has over 2 million new TB cases every year and TB kill’s nearly 1000 people every day. The WHO 2018 Global Tuberculosis Report estimated that, worldwide, approximately 3.5 percent of all new TB cases and 18 percent of previously treated cases are caused by MDR or rifampicin-mono resistant strains.Methods: Presumptive drug resistance TB cases were subjected for CBNAAT or LPA to detect resistance patterns. About 231 cases of MDR/RR TB cases after pre-treatment evaluation started on CAT- IV regimen and both interim and final outcomes were analyzed.Results: Out of 231cases 172(74.4%) were males and 59(25.6%) were females with age between 13-75yrs. Total of 194 cases culture conversion occurred out of which 28 cases the cultures were reverted back to positives. Final Outcomes were, cured in 84 (36.3%) cases, treatment completed in 42 (18.18%) cases, defaulters in 31 (13.4%) cases, turned to be XDR in 10 (4.32%) cases, treatment failure in 10 (4.32%) cases, 50 (21.6%) cases died, 3(1.29%) cases were transferred out.Conclusions: Approximately 2/3rd of MDR/RR TB cases are retreatment sputum positive cases. Successful outcome observed in 54.54% of cases only. High rates of deaths and defaulters alarm the necessity of more effective implementation and surveillance of the programme.

Utility of cartridge based nucleic acid amplification test in the diagnosis of extra pulmonary tuberculosis

Background: Tuberculosis is one of the top 10 cause of death globally. Extra-pulmonary tuberculosis is an important clinical problem. Extra-pulmonary tuberculosis range from 30%-53% in India. Diagnosis of extra-pulmonary tuberculosis is still challenging despite many investigations. World Health Organization recommends Gene-Xpert Mycobacterium Tuberculosis/Rifampicin (Cartridge Based Nucleic Acid Amplification Test-CBNAAT) over conventional tests for diagnosis of extra-pulmonary tuberculosis which permits rapid tuberculosis diagnosis through detection of the genetic sequence of DNA of mycobacterium tuberculosis and simultaneous identification of a majority of the mutations that confirm Rifampicin resistance which is highly predictive of multi-drug resistant tuberculosis.Methods: Study was carried out over a period of one year. Patients with suggestive of extra-pulmonary tuberculosis were included in study. Diagnosis of extra-pulmonary tuberculosis carried out by clinical, radiological, biochemical analysis, cytological, bacteriological confirmation. Based on mycobacterium tuberculosis result, the study population were divided into ‘Mycobacterium Tuberculosis detected’ and ‘Mycobacterium Tuberculosis not detected’ groups. Mycobacterium Tuberculosis detected group was further divided into ‘Rifampicin resistant’ and ‘Rifampicin sensitive’.Results: Total 220 patients were included. Among extra-pulmonary tuberculosis, there were 83.64% were pleural fluid. 65.91% patients where be <45 years of age. Mostly patients were from rural areas and illiterate. Diabetes Mellitus found as the most common co-morbidities. CB-NAAT was able to detect mycobacterium tuberculosis in 35% (77) extra-pulmonary samples, out of which 6 were rifampicin resistant. Out of 184 samples of pleural fluid, 53 were rifampicin sensitive and 4 were found rifampicin resistant.Conclusions: CB-NAAT has to be endorsed in every health care centres as the test gives rapid result and also detection of rifampicin resistance which is the major concern for every clinician.

Prevalence of primary drug resistance to rifampicin and isoniazid in newly diagnosed sputum smear positive pulmonary Tuberculosis

Background: To determine the prevalence of primary drug resistance to either rifampicin or isoniazid alone or both in newly diagnosed sputum smear positive pulmonary tuberculosis patients.Method: A prospective study 100 newly diagnosed sputum smear positive pulmonary TB patients was conducted. The patients with an age of ≥15 years and who had either not taken anti TB treatment or who had taken ATT for less than 1 month were enrolled in this study. Two sputum samples (5ml each), including one early morning sample as per the RNTCP guidelines were collected and subjected to line probe assay (LPA).Results: Out of 100 cases 6 were having resistance to both rifampicin and isoniazid, 9 has resistance to INH alone and 1 had resistance to rifampicin alone.Conclusion: The prevalence of primary drug resistance is high. For early and rapid detection of DR-TB newer modality should be used  for the detection of primary drug resistance in sputum smear positive TB patients.

To Study the Prevalence of HIV Seropositivity in Drug Resistant- Tuberculosis Patients

Drug resistance is a threat to TB control program worldwide. Patient infected with multiple drug resistant strains are less likely to become cured. Multidrug – resistant and extensively drug -resistant tuberculosis continues to emerge in high HIV prevalence settings, and their mortality in HIV co-infected patients remain high. Methods: This retrospective study was carried out at DR-TB centre, Amritsar. This study included drug resistant TB cases registered over the period of 2012 to 2018 at DR-TB centre, Amritsar. Results: A total of 1163 patients of Drug resistant tuberculosis were registered during the period of 7 years , among these 1027, 39 and 97 patients were of MDR, XDR and isoniazid monoresistance respectively. The prevalence of HIV seropositivity was 2.7%, 2.9% and 2.6% in total drug resistant cases, MDR and XDR cases respectively. No case of isoniazid mono-resistance was found positive for HIV. And only one case with primary MDR tuberculosis was HIV positive. Conclusion: In this high drug-resistant TB settings, previous TB treatment failure was strong risk factor for both MDR and XDR-TB in HIV seropositive patients. And HIV seropositivity was more prevalent in MDR-TB cases.

Socio-demographic profile of multi-drug resistant tuberculosis patients and its association with severity of adverse drug reactions in DOTS plus centre at tertiary hospital in Himachal Pradesh, India

Background: Multi-drug resistant tuberculosis has become major public health problem and obstacle to effective control of tuberculosis. Objectives was to study the socio-demographic profile of multi- drug resistant tuberculosis patients and its association with severity of ADR (adverse drug reactions) in DOTS plus centre at tertiary hospital in Himachal Pradesh.Methods: It was a prospective observational study carried out from November 2012 to October 2013 on multi-drug resistant tuberculosis (MDR-TB) patients after approved from Institutional Ethics Committee.Results: Out of 104 patients the mean age of patients was 39.9 ±14.26 years. Majority of the patients were in the economically productive age groups. Multi-drug resistant tuberculosis was more in male (76%) than female (24%) and 96% of patients were belonged to rural area. The educational status of the MDR-TB shows 24% patients were illiterate. 63.46% MDR-TB patients were underweight (BMI<18.5%) according to WHO guidelines for obesity. Severity of ADR assessed by Hart wig and Siegel’s scale showed 21% patients experienced mild ADRs, 49% patients had moderate and 17% patients had severe ADRs. Severity of ADR is seen more in male, economically productive age group, subjects on vegetarian diet, patients who were underweight (BMI<18.5%) and with lower educational status.Conclusions: MDR-TB is a rapidly increasing health problem with major socio-economic and individual consequences. Multi-drug resistant tuberculosis mainly affects middle age that is in the economically productive age group which hampers the social and economic development of individual, society and nation.

The application of gene chip in detecting the mutation of drug resistant gene in multi-drug resistant Mycobacterium tuberculosis strains / 天津医药

Objective To understand the mutation characteristics of drug resistance-associated genes rpoB, katG and inhA in Mycobacterium tuberculosis (MTB) strains using gene chip method, and evaluate its clinical application value. Methods A total of 76 MTB strains were collected from Shijiazhuang area in 2013 to 2014. Gene chip was used to detect the mutations of rpoB, katG and inhA, and the L-J proportion drug susceptibility test was used as the gold standard to evaluate the overall concordance, sensitivity and specificity of gene chip. The consistency of microarray and phenotypic resistance was evaluated by Kappa test. Results Of all the 76 strains detected, 69 harbored mutations in katG/inhA. The predominant mutation site of katG was 315 codon with the mutation rate of 89.9%(62/69), and 5.8%(4/69) carried mutations at inhA-15(C→T), and 4.3%(3/69)carried combined mutations of katG 315 and inhA-15. The rpoB mutations were detected in 73 strains, of which 64.4%(47/73)carried mutations at codon 531, 15.1%(11/73)at codon 526, 12.3%(9/73)at 516 codon, 1.4%(1/73)at 513 codon, 1.4%(1/73)at 533 codon and 5.5%(4/73)had combined mutations. Compared with results from the L-J proportion method, the sensitivity, specificity and concordance rates of gene chip for RFP were 96.1%(73/76), 100%(50/50)and 97.6%(123/126). The sensitivity, specificity and concordance rates of gene chip for INH were 90.8%(69/76), 100%(50/50)and 94.4%(119/126). The sensitivity, specificity and concordance rates of gene chip for MDR-TB were 86.8%(66/76), 100%(50/50) and 92.1%(116/126). Conclusion The predominant mutation loci of MDR strains in Shijiazhuang area are katG315 and rpoB531. Gene chip is a fast and useful tool for clinical diagnosis of MDR strains.

Clinical Analysis of Levofloxacin-included Prolonged Q-T Interval of Patients with Multi-drug Resistant Tuberculosis / 医药导报

Objective To analyze the clinical characteristics and therapy of levofloxacin-induced prolonged Q-T interval in patients with multi-drug resistant tuberculosis ( MDR-TB) . Methods Clinical materials of 6 patients with MDR-TB who developed prolonged Q-T/QTc interval caused by levofloxacin therapy were analyzed. Those cases were collected from the Tuberculosis Prevention and Control of Wuhan City form April 2010 to August 2014. Results The proportion of patients with levofloxacin-induced prolonged Q-T interval was approximately 3.0%.The condition occurred 2-8 months after the administration. The initial value of QTc interval ranged from 397 ms to 439 ms, while the average was (410.17±14.62) ms.The value of QTc interval was extended to 470-486 ms after treatment of levofloxacin, while the average was (476.33±6.16) ms.The increase of QTc interval was 47-85 ms, while the average was ( 66 ± 11. 48 ) ms. None of them developed Tdp. Conclusion The application of high dosage and long treatment course of levofloxacin in patients with MDR-TB could result in the extension of the Q-T/QTc interval, which should arouse our serious attention. In order to detect the abnormal Q-T/QTc interval in early stage, electrolyte level examination as well as ECG examination should be considered as routine tests before initiation of treatment and during the follow-up treatment.

Clinical Observation of Levofloxacin and Capreomycin Combined with Chemotherapy Regimen in the Treat-ment of Multi-drug Resistant Tuberculosis / 中国药房

OBJECTIVE:To observe the efficacy and safety of levofloxacin and capreomycin combined with chemotherapy regi-men in the treatment of multi-drug resistant tuberculosis(MDR-TB). METHODS:84 MDR-TB patients were randomly divided in-to observation group (42 cases) and control group (42 cases). Observation group received 0.75 g Capreomycin sulfate for injec-tion,addint into 100 ml 0.9% Sodium chloride injection,intravenous infusion,once a day+0.4 g Levofloxacin hydrochloride tab-let,orally,once a day+0.2 g Protionamide tablet,orally,3 times a day+0.3 g Pasiniazid tablet,orally,3 times a day+0.5 g Pyra-zinamide tablet,orally,4 times a day. Control group received 0.4 g Amikacin sulfate injection,adding into 100 ml 0.9% Sodium chloride injection,once a day,intravenous infusion+0.3 g Ofloxacin tablet,orally,twice a day+Protionamide tablet (the same dose with observation group)+Pasiniazid tablet (the same dose with observation group)+Pyrazinamide tablet (the same dose with observation group). All patient were given 0.1 g Glucuronolactone tablet,orally,3 times a day. The treatment course for both group was 12 months. Sputum negative conversion rate,negative conversion time,symptom improvement time,lesion absorption and lung cavity closing,and cell immune indexes (CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+),IL-17 level before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The sputum negative conversion rate,ab-sorption rate,lung cavity closing and narrowing cases in research group after 3,6,9,12,18 months treatment were significantly higher than control group,sputum negative conversion time,symptom improvement time in observation group were significantly lower than control group,the differences were statistically significant(P0.05). After treatment,CD4+CD25+/CD4+,CD4+CD25+CD127low/CD4+ in 2 groups were significantly lower than before,and observation group was lower than control group,IL-17 level was significantly higher than before,and observation group was higher than control group,the differences were statistically significant (P0.05). CON-CLUSIONS:Levofloxacin and capreomycin combined with chemotherapy in the treatment of MDR-TB,it can reduce T regulatory cells,increase IL-17 level,do not increase the incidence of adverse reactions.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB).</p><p><b>METHODS</b>A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains.</p><p><b>RESULTS</b>Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation.</p><p><b>CONCLUSION</b>This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.</p>

Nuevas perspectivas terapéuticas en tuberculosis / New perspectives in tuberculosis treatment

To advance in the control and elimination of tuberculosis (TB) we must achieve a high level of effectiveness in the prevention of TB in populations infected by Mycobacterium tuberculosis. Latent TB prevention success with current therapies (single isoniazid or in combination with rifampicin) is close to 60%. We also must offer a high level of treatment success in first-line drugs sensitive TB patients. With currently available drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) treatment success should reach at least 95%. Drug side reactions together with the lengthen treatment of infection and disease (6 months) decrease the compliance to these therapies. In Multi-Drug-Resistant TB (MDR-TB), therapies are even longer (20 months according to WHO's recommendation) and much less tolerated, with rates of success under 50%. New trials for latent TB using rifapentin and isoniacid; combined fixed-dose offirst-line drugs in sensible TB, and the addition of new drugs (fluorquinolones, bedaquiline, delamanid and linezolid) in multi-drug resistant TB, together with shorter regimens of 12 months duration which include Clofazimine (experience in Cameroon with modification of a 9 months trial previously used in Bangladesh showing 89% cure) are discussed in this article.

Para el control y eliminación de la tuberculosis se debe lograr un alto grado de eficacia en la prevención del desarrollo de tuberculosis en la población infectada por Mycobacterium tuberculosis. Esta prevención, con las terapias actuales de la tuberculosis latente (isoniazida sola o combinada con rifampicina), es cercana al 60%. También debemos alcanzar una alta tasa de curación para los enfermos con tuberculosis sensible a los fármacos de primera línea (vírgenes a tratamiento). Con los fármacos actualmente disponibles (isoniazida, rifampicina, etambutol y pirazinamida) esta curación debería alcanzar a no menos del 95%. La regular tolerancia y reacciones colaterales de los fármacos y el largo tiempo que demandan las terapias de la infección y de la enfermedad (6 meses) atenta contra su adherencia. En el caso de la Tuberculosis Multi-Drogo-Resistente (TB-MDR), los tratamientos son aún más prolongados (20 meses según recomienda la OMS actualmente) y menos tolerados, siendo sus tasas de curación inferiores a 50%. Se analizan nuevos esquemas para el tratamiento de la tuberculosis latente usando rifapentina asociada a isoniacida; dosis fijas combinadas de fármacos de primera línea para tuberculosis sensibles, y asociación de fármacos antiguos y nuevos (fluoroquinolonas, bedaquilina, delamanid y linezolid) para el tratamiento de las tuberculosis multirresistentes. También se presentan nuevos esquemas acortados, de 12 meses de duración, que incluyen clofazimina (experiencia en Camerún con modificación del esquema de 9 meses usado previamente en Bangladesh, con tasas de curación de 89%).

Effect of Rifabutin Combined with Multi-drugs in the Treatment of Multi-drug Resistant Tuberculosis with Long-term Therapy / 中国药师

Objective:To evaluate the effect and safety of rifabutin combined with multi-drugs in the treatment of multi-drug resist-ant tuberculosis with long-term therapy. Methods:Totally 86 cases of patients with multi-drug resistant tuberculosis were divided into the control group and the treatment group with 43 ones in each according to a random number table method. The two groups were trea-ted with levofloxacin, pasiniazid, ethambutol, protionamide and amikacin etc. The control group was treated with rifapentine, and the treatment group was treated with rifabutin additionally. After 18-month treatment, the negative conversion ratio of sputum smear and sputum mycobacterium tuberculosis culture, lesion absorption rate and cavity closure rate of X-ray chest radiograph and adverse reac-tions in the two groups were compared. Results:The negative conversion ratio of sputum smear and sputum mycobacterium tuberculosis culture in the treatment group was 41. 86% and 32. 56%, respectively, which were similar with those in the control group ( P >0. 05). There were no significant differences in lesion absorption rate and cavity closure rate of X-ray chest radiograph and adverse re-actions between the two groups (P>0. 05). Conclusion:Rifapentine or rifabutin combined with multi-drugs in the treatment of multi-drug resistant tuberculosis can improve the negative conversion rate of sputum mycobacterium and lesion absorption and cavity closure with high safety.

DRUG USE SURVEY RESULTS OF MULTI-DRUG RESISTANT TUBERCULOSIS / Монголын эм зүй, эм судлал

Tuberculosis disease is directly proportional to a country’s socio-economic situation and standard of living. Studies have shown that in Mongolia the inflation, unemployment, poverty and migration that have emerged as a consequence of the socio-economic changes in 1990s have influenced the spread of the disease.The Global Fund to Fight AIDS and Tuberculosis Project was initiated by the UN and launched in our country in 2003. In relation to an expected completion of the project in 2016, the need has been determined to include the funds required for AIDS and tuberculosis (TB) treatment into the state budget and, therefore, the necessity to conduct a detailed study of TB drug usage to validate this need has become the basis of this research.[3,5,6] Materials and methods: Patient history of 200 inpatients in (NCCD). Registration of drug expenditure of pulmonary tuberculosis and multi-drug resistant tuberculosis (MDRTb) and statistic survey data.As WHO recommended determining drug consumption by disease and mathematic statistic method. Purpose:Multi-drug resistant drugs tuberculosis used in the treatment of estimated needs, and to be determined by the main anti-tuberculosis drug spending.Results: 1. 50 patients diagnosed as MDRtb by the NCCD used 9 main types of drugs, Out of these 5 were most widely used. 2. 1,211,700,0±546,008,9million was spent on treatment of MDRtb in inpatient facilitiesКey words:Multi-drug resistant tuberculosis

Declining trend of resistance to first-line anti-tubercular drugs in clinical isolates of Mycobacterium tuberculosis in a tertiary care north Indian hospital after implementation of revised national Tuberculosis control programme.

Trends showing drug‑resistance pattern are needed to understand direction of tuberculosis (TB) control programme. The drug‑resistance pattern in state of Uttar Pradesh, India, is not documented. Here we are reporting the prevalence of multi‑drug‑resistant (MDR) and drug‑resistant TB in previously treated cases of pulmonary tuberculosis following launch of revised national TB control programme (RNTCP) in whole of Uttar Pradesh. Isolates of Mycobacterium tuberculosis, from patients of pulmonary tuberculosis, who were treated with antitubercular drugs for more than 4 weeks, were tested for resistance to first‑line drugs; streptomycin (S), Ethambutol (E), Rifampicin (R) and isoniazid (H) over a period of 4 years, 2009‑2012. Total 2496 isolates of M. tuberculosis were tested, of which 1139 isolates (45.6%) were pan‑sensitive and 370 (14.8%) were pan‑resistant. Total 695 isolates (27.8%) were MDR. Maximum resistance was with Isoniazid (n = 1069, 42.8%) followed by streptomycin (n = 840, 33.7%), rifampicin (n = 742, 29.7%), and ethambutol (n = 613, 24.6%). A decline in number of MDR strains and individual drug resistance was seen. Total MDR strains in the year 2009, 2010, 2011 and 2012 were 35.6%, 30.8%, 26.7% and 22.8% respectively. The drug resistance pattern reported from time to time may vary substantially. The decline in drug resistance visible over last four years, after implementation of DOTS, appears promising.

Vulnerabilidade e tuberculose no Rio de Janeiro / Vulnerability and tuberculosis in Rio de Janeiro

This paper aims at understanding social causality of Tuberculosis in Rio de Janeiro. This is one of the Brazilian states with the highest incidence of this disease. We follow the story of Paulo, a patient who received care at the outpatient clinic for multi-drug resistant Tuberculosis, in Rio de Janeiro. To make sense of his story, we will look at it through the concept of vulnerability in life conditions. Along with Sabroza (2006), we argue that this vulnerability is a collective expression of the economic insertion of a growing segment of Rio’s population in the current technical-scientific-informational capitalism (Santos, 2002 [1979]). Limitations in the health services add directly to vulnerability in life conditions of patients making treatment a hard endeavour. We propose to think and act on Tuberculosis at the collective level of reality, through intersectoral actions. We aim at contributing to the current debates on the social determination of Tuberculosis, to inform actions that can significantly reduce the suffering associated to this and other similarly caused diseases...

Este artigo pretende compreender a causalidade social da tuberculose no Rio de Janeiro. Este é um dos Estados brasileiros com maior incidência da doença. Seguimos a história de Paulo, um paciente que recebeu cuidados no ambulatório de referência para a tuberculose multirresistente. Para fazer sentido da sua história, pensaremos nela por meio do conceito de vulnerabilidade das condições de vida. Junto com Sabroza (2006), argumentamos que essa vulnerabilidade é a expressão coletiva da inserção econômica de um segmento populacional crescente no Rio de Janeiro no atual sistema capitalista técnico-científico-informacional (Santos, 2002). Os limites dos serviços de saúde agravam a vulnerabilidade das condições de vida, tornando o tratamento difícil. Propomos pensar e agir sobre a tuberculose no nível coletivo, através de ações intersetoriais. Pretendemos, assim, contribuir para os debates atuais sobre a determinação social da tuberculose, e informar ações que possam reduzir significativamente o sofrimento associado a esta e outras doenças com causas semelhantes...

Tuberculosis Pulmonar: reto actual para la Salud Pública cubana / Pulmonary tuberculosis: a current challenge to the Cuban Public Health System

Se realizó una actualización sobre la tuberculosis pulmonar, con el objetivo de elevar el nivel de información de los médicos y demás personas relacionadas con el control de esta enfermedad, acerca de la situación de esta a nivel mundial y en nuestro país. Se expusieron los criterios de diversos expertos sobre las causas que han propiciado la reemergencia de la tuberculosis y los factores que han dado al traste con los programas de control, siendo las fundamentales: La deficiente búsqueda activa de los casos considerados reservorios y la multirresistencia del Mycobacterium tuberculosis a los medicamentos, debido a la aplicación de tratamientos inadecuados.

An update about pulmonary tuberculosis aimed at increasing the level of information of medical doctors and the personnel who are in charge of the control of this disease was conducted analyzing the worldwide and Cuban situation. Criteria of diverse experts about the causes that have favored the emergence of tuberculosis and the factors falling through the control programs, where among the most important are: the deficient active searching of cases who are considered reservoirs and the multi-drug resistance to Mycobacterium tuberculosis, due to the application of inadequate treatments.

An analysis on 200 randomized clinical isolates of Mycobacterium in Sichuan / 中华微生物学和免疫学杂志

Objective To find out the resistant situation and drug of Mycobacteria patients in Sichuan and offer foundation for clinical.Methods Two hundred randomized clinical isolates of Mycobacterium were determined by Roche drug sensitivity and minimum inhibitory concentration (MIC) method.Results Of the 200 clinical isolates,192 stains were Mycobacterium tuberculosis(MTB) (96.0％),8 strains (4.0％) were non-tuberculosis mycobacterium(NTM).Of the 192 MTB strains,108( 57.3％ ) sensitive strains and 84 (43.7％)stains were resistant to one or more than one drugs.Among these 84 resistant strains 23 were multi-drug resistant ( MDR,12.0％ ),4 were extensively drug resistant( XDR,2.1％ ).The anti-TB drug resistance rates were:SM(16.7％),INH(20.8％),RFP(17.2％),EMB(10.9％),PI(16.1％),LFX(8.8％),AMK ( 16.7％ ),CPM ( 6.2％ ),PTA ( 33.3％ ),respectively.Conclusion The resistance rate of tuberculosis keeps at a high level in Sichuan,especially the resistance rate of multiple (≥4) drug,we should oar attention.

Nuevos desafíos en tuberculosis / New challenges in tuberculosis

Tuberculosis (TB) is a main cause of disease and death in many countries of the world. The efforts to control this scourge have not been very successful. Even in Chile where we are near to reach the advanced stage of elimination of TB as a public health problem, five persons each week die of this disease. The main challenges for the control of TB and the most recent advances to counteract them are reviewed. A series of modern methods of diagnosis based on the techniques of molecular biology are reviewed. There is a need to develop procedures that can be applied in the so called "point of diagnosis", like the Xpert MTB/RIF test. There are new techniques for the diagnosis of latent TB infection (IGRA's), in order to identify infected subjects of high risk to develop disease to subject them to chemo-profilaxis. We need to develop shorter treatments for new cases and better drugs for multi-resistant patients. Ten new drugs have progressed into the clinical development pipeline for TB. New vaccines against tuberculosis are being investigated. Some of them are already being tried in the field. In the last years two new challenges have appeared: the association TB-AIDS, and the new epidemics of Multi Drug Resistant Tuberculosis (TB MDR and TB XDR). New techniques of diagnosis are described. Our main challenge is to make all this advances available for everybody. In Chile only the private sector has some of these techniques.

La tuberculosis (TBC) sigue siendo una de las principales causas de morbi-mortalidad en el mundo y los esfuerzos para controlarla han demostrado ser insuficientes. Aun en Chile, donde estamos cerca de alcanzar la etapa avanzada de su eliminación como problema de salud pública, fallecen 5 personas por semana de TBC. Este artículo presenta los principales desafíos de los Programas de Control de la TBC y los avances más recientes para enfrentarlos. Se analiza una serie de métodos de diagnóstico basados en técnicas de biología molecular. Se necesitan técnicas más sensibles que la baciloscopia que puedan ser empleadas en la periferia, en el llamado "punto del diagnóstico", como el test Xpert MTB/RIF. Están en estudio nuevos métodos de diagnóstico de la infección tuberculosa latente -los IGRA's - para identificar con mayor especificidad que con el PPD, a los infectados con alto riesgo de progresar a TBC para someterlos a quimioprofilaxis. Necesitamos tratamientos más breves para los casos nuevos, y drogas más eficaces para los enfermos de TBC multi-resistentes. Está en desarrollo la introducción de 10 nuevos medicamentos anti-TBC. Se necesitan vacunas más eficaces que la BCG, capaces no sólo de prevenir la infección, sino también de reforzar la inmunidad de los infectados y aún de los enfermos. Varias de estas vacunas se están ensayando en África. En los últimos decenios han aparecido dos nuevos desafíos: la asociación TBC-SIDA y las epidemias de TBC multi-resistentes (TB MDR y XDR). Se han desarrollado técnicas para identificar polimorfismos del gen rpo B, principal causa de resistencia a la rifampicina, considerada marcador de TB MDR. El principal desafío actual es poner todos estos avances al alcance de los que más los necesitan. En Chile sólo disponemos de algunas de estas nuevas técnicas, en su mayoría en clínicas privadas.

Results of molecular genetic study of m. Tuberculosis strains isolated from specimens of mdr-tb suspects in Ulaanbaatar, Mongolia in 2009-2010 / Монголын Анагаах Ухаан

Bacground: DST by conventional methods takes several weeks, while early diagnosis of the disease and the rapid identification of resistant strains are essential for efficient treatment and control of the MDR strains. Rapid molecular testing of detecting MDR-TB is needed.Objective: The aim of this study was to assess performance of molecular line probe assay, Genotype16 MTBDRp/us, for rapid detection of RIF and INH resistance for M.Tuberculosis in Mongolia. The sensitivity and specificity of Genotype® MTBDRp/us to detect RIF and INH resistance-associated mutations in culture specimens and directly in smear-positive clinical specimens was examined and compared with conventional culture and drug susceptibility testing on solid medium.Material and Methods: The subjects of this study were 218 MDR-TB suspects aged 14-75 years from 8 districts in Ulaanbaatar city. The study was conducted from July 2009 to May 2010. The Genotype M. Tuberculosis drug resistance first line (MTBDR plus) assay (Hain Life-science, Nehren, Germany) was tested on directly on 41 sputum specimens and 109 clinical isolates.Results: The high correlation of the results from Genotype® MTBDRp/us and conventional drug susceptibility testing was obtained from this study. The results clearly show high performance of Genotype® MTBDRp/us with almost 100% accuracy for all the important indicators, such as sensitivity, specificity, positive and negative predictive values of detection of RIF and INH resistance. Some minor discrepancies were obtained in comparison with DNA sequencing results.Our study found that among high proportion for detection of RIF resistance, S531L mutation (MUT3 band) occurred the most commonly, with 80.0% of all RIF-resistant strains (83.6% of MDR) having the mutation. Other mutation in the 530-533 regions was common, as detected by the lack of binding to the WT8 probe in the absence of S531L mutation.In this study we observed that mutations in the promoter region of inhA gene played a major role (67.6 % (63.9% of MDR strains and 90% of INH-mono-resistant strains) had a mutation in the inhA.Conclusion: The Genotype® MTBDRp/us assay was demonstrated as a rapid, reliable and highly accurate tool for early detection of MDR-TB through examining smear positive cases enabling early start of appropriate therapeutic and public health measures to control of the spread of drug resistant M.tuberculosis in the population.