Multidrug-resistant Tuberculosis Cases Research Articles

Effect of Mixed Infections with Mycobacterium tuberculosis and Nontuberculous Mycobacteria on Diagnosis of Multidrug-Resistant Tuberculosis: A Retrospective Multicentre Study in China.

BackgroundCorrect species identification is essential before initiation of TB treatment, due to substantial drug susceptibility profile differences among mycobacterial species. Given that nontuberculous mycobacteria (NTM) are frequently resistant to first-line anti-tuberculosis drugs, cases with mixed infections with Mycobacterium tuberculosis (MTB) and NTM tend to be diagnosed as multidrug-resistant tuberculosis (MDR-TB) cases. Here we report results of a retrospective multicentre study that was conducted to determine the prevalence of TB-NTM infections in previously diagnosed laboratory-confirmed multidrug-resistant tuberculosis (MDR-TB) patients using phenotypic drug susceptibility testing. The results were then used to identify risk factors associated with susceptibility to mixed infections.MethodsFrom January 2019 through December 2019, we retrospectively collected MDR-TB isolates from three TB specialised hospitals. Species identifications of isolates were performed using the MeltPro Myco assay.ResultsA total of 837 MDR-TB isolates were analysed, of which 22 isolates (2.6%) were found to contain a mixture of NTM and MTB organisms. Significant differences in prevalence rates of mixed infections across regions were observed, with prevalence rates ranging from 0.0% (0/213) in Beijing to 3.4% (12/353) in Fuzhou to 3.7% (10/271) in Guangzhou. Among the 22 patients with NTM-TB mixed infections, a total of five different mycobacterial species were identified, of which the most prevalent species was Mycobacterium intracellulare. Notably, a history of previous TB episodes correlated with higher mixed infection risk.ConclusionThe results reported here demonstrated that mixed infections with MTB and NTM occurred in approximately 3% of suspected MDR-TB patients in China. These findings raise concerns about the accuracy of molecular diagnostics-based species identification tests and draw attention to the possibility that NTM-MTB mixed infections will be misdiagnosed as MDR-TB in high TB burden settings.

Complicated Case of Multidrug-Resistant Tuberculosis with Multiple Comorbidities, Successfully Treated After Several Treatment Modifications

A 59-year-old man with relapsed pulmonary TB developed rifampin resistance. He presented with chronic untreated hepatitis B, which developed into liver cirrhosis, type 2 diabetes with diabetic retinopathy, and osteoarthritis of right knee. His initial MDR regimen included levofloxacin, cycloserine, bedaquiline, linezolid, and high-dose isoniazid. He developed episodes of linezolid-induced myelosuppression, resulting in temporary discontinuation and dose reduction, and ultimately, substitution of linezolid. On the seventh month of treatment, he developed severe depression with visual hallucination, resulting in cycloserine dose reduction. We maintained the principle of at least 4 active drugs throughout his treatment. He was considered cured after 26 months of treatment.

ЭФФЕКТИВНОСТЬ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА У ПАЦИЕНТОВ С РАЗЛИЧНЫМИ СРОКАМИ АМБУЛАТОРНОГО И СТАЦИОНАРНОГО ЭТАПОВ ЛЕЧЕНИЯ

Access to timely diagnosis and patient-friendly drug-resistant TB treatment regimens is a priority in the fight against TB. The aim of the work is to improve the efficiency of treatment of patients with tuberculosis in outpatient and inpatient settings by developing a new procedure for the provision of antituberculosis care. Materials and methods. The object of a retrospective cohort study was 15617 patients with tuberculosis who underwent treatment in the period 2015-2019. Results and discussion. Despite the annual decrease in the total number of reported cases of tuberculosis, the pattern of cases of multidrug-resistant tuberculosis has a heterogeneous trend. There has been a decrease in the proportion of MDR-TB cases among previously treated cases and an increase in new cases. There is an increase in the proportion of cases that successfully completed treatment in all patient cohorts. Conclusion. The main number of losses for follow-up is recorded at the outpatient stage of treatment, which is associated with problems in the formation of patient adherence to treatment, as well as with insufficient quality management and clinical and laboratory tracking of adverse drug events. Bed efficiency indicators for the treatment of MDR-TB patients indicate insufficient bed efficiency.

Laboratory Cost Analysis of Conventional and Newer Molecular Tests for Diagnosis of Presumptive Multidrug-Resistant Tuberculosis Patients.

Introduction:Tuberculosis (TB) remains a deadliest infectious disease. Lack of rapid test with low cost is one of the important challenges to eradicate the TB. The objective of the study was to analyze the laboratory costs of conventional and newer molecular tests, for diagnosis of presumptive multidrug-resistant TB (MDR-TB) patients.Methods:A detailed laboratory cost of various conventional tests (Ziehl − Neelsen [ZN] microscopy, light-emitting diode-fluorescent microscopy [LED-FM], culture and drug susceptibility testing [DST] using solid Lowenstein–Jensen media and liquid media [BACTEC MGIT 960]) was compared with rapid methods (GenoType MTBDRplus line probe assay [LPA] and GeneXpert MTB/RIF assay). Laboratory cost was also calculated in terms of cost per TB and MDR-TB case detected by using different diagnostic scenarios.Results:Cost per test for ZN microscopy, LED-FM, LPA, GeneXpert MTB/RIF assay, solid culture plus DST, liquid culture plus DST was found as $2.5 (INR 156.8), $2.0 (INR128.9), $18.6 (INR1210), $13.8 (INR 895.2), $21.5 (INR 1396.6), and $29.1 (INR 1888.2), respectively. The laboratory cost for detecting TB and MDR-TB by diagnostic scenarios involving molecular DST was found to be less as compared to involving only conventional liquid culture-based test.Conclusions:The implementation of rapid molecular tests with selective use of liquid culture-based DST may be less in cost as compared to the use of culture-based DST alone, at high burden reference TB laboratory.

Multidrug-Resistant Tuberculosis in U.S.-Bound Immigrants and Refugees.

RationaleApproximately two-thirds of new cases of tuberculosis (TB) in the United States are among non–U.S.-born persons. Culture-based overseas TB screening in U.S.-bound immigrants and refugees has substantially reduced the importation of TB into the United States, but it is unclear to what extent this program prevents the importation of multidrug-resistant TB (MDR-TB).ObjectivesTo study the epidemiology of MDR-TB in U.S.-bound immigrants and refugees and to evaluate the effect of culture-based overseas TB screening in U.S.-bound immigrants and refugees on reducing the importation of MDR-TB into the United States.MethodsWe analyzed data of immigrants and refugees who completed overseas treatment for culture-positive TB during 2015–2019. We also compared mean annual number of MDR-TB cases in non–U.S.-born persons within 1 year of arrival in the United States between 1996–2006 (when overseas screening followed a smear-based algorithm) and 2014–2019 (after full implementation of a culture-based algorithm).ResultsOf 3,300 culture-positive TB cases identified by culture-based overseas TB screening in immigrants and refugees during 2015–2019, 122 (3.7%; 95% confidence interval [CI], 3.1–4.1) had MDR-TB, 20 (0.6%; 95% CI, 0.3–0.9) had rifampicin-resistant TB, 382 (11.6%; 95% CI, 10.5–12.7) had isoniazid-resistant TB, and 2,776 (84.1%; 95% CI, 82.9–85.4) had rifampicin- and isoniazid-susceptible TB. None were diagnosed with extensively drug-resistant TB. All 3,300 persons with culture-positive TB completed treatment overseas; of 70 and 11 persons who were treated overseas for MDR-TB and rifampicin-resistant TB, respectively, none were diagnosed with TB disease at postarrival evaluation in the United States. Culture-based overseas TB screening in U.S.-bound immigrants and refugees prevented 24.4 MDR-TB cases per year from arriving in the United States, 18.2 cases more than smear-based overseas TB screening. The mean annual number of MDR-TB cases among non–U.S.-born persons within 1 year of arrival in the United States decreased from 34.6 cases in 1996–2006 to 19.5 cases in 2014–2019 (difference of 15.1; P < 0.001).ConclusionsCulture-based overseas TB screening in U.S.-bound immigrants and refugees substantially reduced the importation of MDR-TB into the United States.

Comparative characteristics of the epidemiological situation of chemoresistant tuberculosis in Germany and Ukraine

Objective — to compare the epidemiological situation of chemoresistant tuberculosis in Germany and Ukraine, in addition analyzing the nature and features of chemoresistant tuberculosis in 192 patients treated at the Ternopil Regional TB Dispensary Ukraine during 2017—2018.&#x0D; Materials and methods. In order to study the comparative characteristics of the epidemiological situation with chemoresistant tuberculosis in Germany and Ukraine, modern literature sources were used with the search query «epidemiological situation with chemoresistant tuberculosis in Germany», «epidemiological situation with chemoresistant tuberculosis in Ukraine». Separatelly a retrospective cohort study was conducted. The nature and features of the course of chemoresistant tuberculosis in 192 patients who were treated in the Ternopil Regional TB Dispensary during 2017—2018 were analyzed. &#x0D; Results and discussion. Analysis of literature sources showed that multidrug resistant Tuberculosis (MDR-TB) is relatively seldom in Germany with around 100 cases annually. Overall, the epidemiological situation of MDR-TB has been stable since the beginning of the statistical recording of the disease in 2002. In 2013, the highest proportion of MDR TB was registered at 3.3 %. Detailed analysis of notifi cation data shows that the tuberculosis situation in Germany is mainly influenced by migratory movements and demographic changes in the population. Despite the positive overall epidemiological trend with decreasing incidence rates, however, the burden of TB in Ukraine remains significant. According to the latest WHO estimates for 2018, TB incidence in the country(new cases and relapses) is the 4th highest among 53 countries of the WHO European Region.To address the situation, reduce TB prevalence, scale up TB early detection and diagnosis, and ensure effective treatment, Ukraine adopted, in 2019, the 2020–2023 State Strategy for Development of Anti-Tuberculosis Care for the Population.The analysis performed of 192 patients of the MDR/XDR-TB Cohort from the TB-Dispensary Hospital in Ternopil (Ukraine) from 2017—2018, showed that the resistanse of mycobacteria to anti-TB drugs was dominated by cases of MDR-TB — 57.3 %. Among patients first diagnosed were 52.6 %, relapses were 46.4 %. Destruction in the lungs was detected in 71.9 %. 111 patients (57.8 %) had treatment success, and 81 (42.2 %) had poor treatment outcomes or were lost to follow-up.&#x0D; Conclusions. The epidemiological situation of tuberculosis in Germany is stable and improving. Despite the positive overall epidemiological trend, the burden of TB in Ukraine remains significant. In 2018, TB incidence in the country (new cases and relapses) was 80 per 100 thousands population. In Ukraine during the period (2015—2018), the proportion of «pre-XDR» and XDR cases increased from 47.4 to 51.3 %. Among patients with chemoresistant tuberculosis, MR TB predominates (57.3 %), with destruction in the lungs and only 57.8% are effectively treated.

Challenges and perceptions of depression amongst multi drug resistant TB cases: qualitative study among medical officers of tuberculosis units across the Ahmedabad city, India

Background: Drug resistant tuberculosis (DR-TB), is usually associated with adverse socioeconomic and psychological outcomes. Such patients with co-morbid depression have lower treatment adherence and poor outcomes. Programmatic management of drug resistant tuberculosis (PMDT) guidelines recommend screening of DR-TB patients for mental illnesses at baseline and Follow-up (FU). The objectives were to explore perceptions and experiences of service providers about depression amongst MDR TB cases, review current strategies for screening for depression at Tuberculosis units (TUs) and recommend measures to address depression among MDR TB cases.Methods:This qualitative study was conducted across all TUs of Ahmedabad Municipal Corporation wherein 26 Key informant interviews (KIIs) were conducted using thematic guidelines and subsequently categorized in to subtheme for thematic analysis.Results: MOs had mixed experiences about encountering depression among MDR-TB cases, ranging from 1%-50%. Long duration and side effects of treatment, financial burden due to unemployment and societal stigma were contributory factors. Ensuring compliance was a major challenge. Counselling is an effective intervention for this but lack of counsellors in the program was another challenge. MOs stated that pre-treatment screening for depression is done at DR TB centre, but there is no structured, process. However, most of them don’t do subsequent follow up for depression.Conclusions:More counsellors need to be included in the program and a structured method needs to be devised for screening of depression among MDR TB patients. Both MO TUs and Counsellors need to be sensitized and trained for screening and monitoring depression amongst MDR TB in a systematic way.

Key factors influencing multidrug-resistant tuberculosis in patients under anti-tuberculosis treatment in two centres in Burundi: a mixed effect modelling study

BackgroundDespite the World Health Organization efforts to expand access to the tuberculosis treatment, multidrug resistant tuberculosis (MDR-TB) remains a major threat. MDR-TB represents a challenge for clinicians and staff operating in national tuberculosis (TB) programmes/centres. In sub-Saharan African countries including Burundi, MDR-TB coexists with high burden of other communicable and non-communicable diseases, creating a complex public health situation which is difficult to address. Tackling this will require targeted public health intervention based on evidence which well defines the at-risk population. In this study, using data from two referral anti-tuberculosis in Burundi, we model the key factors associated with MDR-TB in Burundi.MethodsA case-control study was conducted from 1stAugust 2019 to 15th January 2020 in Kibumbu Sanatorium and Bujumbura anti-tuberculosis centres for cases and controls respectively. In all, 180 TB patients were selected, comprising of 60 cases and 120 controls using incidence density selection method. The associated factors were carried out by mixed effect logistic regression. Model performance was assessed by the Area under Curve (AUC). Model was internally validated via bootstrapping with 2000 replications. All analysis were done using R Statistical 3.5.0.ResultsMDR-TB was more identified among patients who lived in rural areas (51.3%), in patients’ residence (69.2%) and among those with a household size of six or more family members (59.5%).Most of the MDR-TB cases had already been under TB treatment (86.4%), had previous contact with an MDR-TR case (85.0%), consumed tobacco (55.5%) and were diabetic (66.6 %). HIV prevalence was 32.3 % in controls and 67.7 % among cases. After modelling using mixed effects, Residence of patients (aOR= 1.31, 95%C: 1.12-1.80), living in houses with more than 6 family members (aOR= 4.15, 95% C: 3.06-5.39), previous close contact with MDR-TB (aOR= 6.03, 95% C: 4.01-8.12), history of TB treatment (aOR= 2.16, 95% C: 1.06-3.42), tobacco consumption (aOR = 3.17 ,95% C: 2.06-5.45) and underlying diabetes’ ( aOR= 4.09,95% CI = 2.01-16.79) were significantly associated with MDR-TB. With 2000 stratified bootstrap replicates, the model had an excellent predictive performance, accurately predicting 88.15% (95% C: 82.06%-92.8%) of all observations. The coexistence of risk factors to the same patients increases the risk of MDR-TB occurrence. TB patients with no any risk factors had 17.6% of risk to become MDR-TB. That probability was respectively three times and five times higher among diabetic and close contact MDR-TB patients.ConclusionThe relatively high TB’s prevalence and MDR-TB occurrence in Burundi raises a cause for concern especially in this context where there exist an equally high burden of chronic diseases including malnutrition. Targeting interventions based on these identified risk factors will allow judicious channel of resources and effective public health planning.

The pncA gene mutations of Mycobacterium tuberculosis in multidrug-resistant tuberculosis.

The pncA gene encodes pyrazinamidase enzyme which converts drug pyrazinamide to active form pyrazinoic acid, but mutations in this gene can prevent enzyme activity which leads to pyrazinamide resistance. The cross-sectional study was carried out during 2016-2017 for 12 months. The purpose of the study was to detect mutation at codon 12 and codon 85 in the pncA gene in local multidrug-resistant tuberculosis (MDR-TB) patients by developing a simple molecular test so that disease could be detected timely in the local population. DNA extracted from sputum-cultured samples from MDR-TB patients and subjected to semi-multiplex allele-specific PCR by using self-designed primers against the pncA gene. Among 75 samples, 53 samples were subjected to molecular analysis based on purified DNA quantity and quality. The primers produced 250 and 480 bp fragments, indicating the mutations at codon 12 (aspartate to alanine) and codon 85 (leucine to proline) respectively. MDR-TB was more common in the age group 21-40 years. Fifty-seven percent of samples (n = 30) were found positive for pncA mutations, whereas 43% of samples (n = 23) showed negative results. Thirteen percent of samples (n = 4) had mutations at codon 12 in which aspartate was converted to alanine, and they produced an amplified product of 480 bp. Eighty-seven percent of samples (n = 26) had mutations at codon 85 in which leucine was converted to proline and amplified product size was 250 bp. The mutations were simple nucleotide substitutions. The prevalence of mutations in which leucine was substituted by proline was higher than the mutations in which aspartate was substituted by alanine. A high prevalence of substitution mutation (CTG → CCG; leucine to proline) was detected in MDR-TB cases. Earlier detection of MDR-TB via an effective molecular diagnostic method can control the MDR tuberculosis spread in the population.

Mathematical model with fractional order derivatives for Tuberculosis taking into account its relationship with HIV/AIDS and Diabetes

In this paper, we present a mathematical model for the study of resistance to tuberculosis treatment using fractional derivatives in the Caputo sense. This model takes into account the relationship between Tuberculosis, HIV/AIDS, and diabetes and differentiates resistance cases into MDR-TB (multidrug-resistant tuberculosis) and XDR-TB (extensively drug-resistant tuberculosis). We present the basic results associated with the model and study the behavior of the disease-free equilibrium points in the different sub-populations, TB-Only, TB-HIV/AIDS, and TB-Diabetes. We performed computational simulations for different fractional orders (α-values) using an Adams-Bashforth-Moulton type predictor-corrector PECE method. Among the results obtained, we have that the MDR-TB cases in all sub-populations decrease at the beginning of the study for the different α-values. In XDR-TB cases in the TB-Only sub-population, there is a decrease in the number of cases. XDR-TB cases in the TB-HIV/AIDS sub-population have differentiated behavior depending on α. This knowledge helps to design an effective control strategy. The XDR-TB cases in diabetics increased throughout the study period and outperformed all resistant compartments for the different α-values. We recommend special attention to the control of this compartment due to this growth.

Identification of Serum Cytokine Biomarkers Associated with Multidrug Resistant Tuberculosis (MDR-TB)

Existing tools (including GeneXpert) for diagnosis of multidrug resistant TB (MDR-TB) have limited utility when sputum samples for microbiological analyses cannot be obtained. There is the need for immunological biomarkers which could serve as putative diagnostic markers of MDR-TB. We measured and compared the serum cytokine levels of inflammatory cytokines (IFN-γ, TNF-α, IL12p70, IL-17A, granzyme B) and anti-inflammatory cytokines (IL-10, IL-6, IL-4) among MDR-TB, drug-susceptible (DS)-TB and healthy controls (no-TB) using the Human Magnetic Luminex Multiplex Immunoassay. Levels of IFN-γ and IL-4 were respectively 1.5 log lower and 1.9 log higher in MDR-TB compared to DS-TB cases. Moreover, IFN-γ, TNF-α, IL-10, IL-6, and IL-4 levels were significantly higher in individuals with MDR-TB and DS-TB cases compared to healthy controls. Pairs of cytokines, IL-4 and IFN-γ (p = 0.019), IL-4 and TNF (p = 0.019), and Granzyme B and TNF-α (p = 0.019), showed significant positive correlation in MDR-TB. Serum cytokine profiles can be exploited for immunodiagnostics, as made evident by the Interferon Gamma Release Assays (IGRAs) for TB infection. Using area under the curve values, no single or multiple cytokine combinations could discriminate between DS- and MDR-TB in this study. Studies with a larger sample size and more cytokines could better address the issue.

Culture conversion and six months interim outcomes in retreatment cases of pulmonary MDRTB - a six month interim analysis.

To estimate the time to culture conversion and factors associated with failure to culture conversion, six-month interim outcomes and associated risk factors with poor interim outcomes in multi-drug resistant tuberculosis patients previously treated with second-line drugs. The prospective clinical case series study was conducted from March 2016 to January 2017 at the Indus Hospital Tuberculosis Clinic and seven other sites that are part of the hospital's Programmatic Management of Drug Resistant Tuberculosis initiative. All bacteriologically confirmed multi-drug resistant tuberculosis retreatment patients were enrolled. Data was collected on age, gender, site of enrollment, detailed history of previous treatment with anti-tuberculosis drugs, medical history, history of first-line drugs, history of second-line drugs, treatment outcomes, baseline sputum smear microscopy and monthly follow-up sputum smear microscopy and culture results. Data was subjected to univariate and multiple logistic regression analyses, and risk factors for failure to culture conversion were assessed using Cox Proportional Hazards Model. Out of 266 patients, 143(53.8%) were males, the overall largest age group was 5-24 years 97(36.5%), and 250 (94%) patients had previous history of treatment with first-line drugs. Overall, 101(40.1%) patients experienced poor interim outcome. Poor interim outcomes were significantly associated with higher number of drugs on the regimen, (odds ratio: 1.27; 95% confidence interval: 1.03-1.58) and high sputum smear grading (odds ratio: 4.56; 95% confidence interval: 3.30-18.71). Besides, 186(70.3%) patients experienced culture conversion within the initial six months of treatment. The success rate of re-treatment of multi-drug resistant tuberculosis with conventional regimen was found to be unacceptably low.

Primary Bedaquiline Resistance Among Cases of Drug-Resistant Tuberculosis in Taiwan.

Bedaquiline (BDQ), which is recommended for the treatment of drug-resistant tuberculosis (DR-TB), was introduced in Taiwan in 2014. Due to the alarming emergence of BDQ resistance, we conducted BDQ resistance analyses to strengthen our DR-TB management program. This retrospective population-based study included initial Mycobacterium tuberculosis isolates from 898 rifampicin-resistant (RR) or multidrug-resistant (MDR) TB cases never exposed to BDQ during 2008–2019. We randomly selected 65 isolates and identified 28 isolates with BDQ MIC<0.25μg/ml and MIC≥0.25μg/ml as the control and study groups, respectively. BDQ drug susceptibility testing (DST) using the MGIT960 system and Sanger sequencing of the atpE, Rv0678, and pepQ genes was conducted. Notably, 18 isolates with BDQ MIC=0.25μg/ml, 38.9% (7/18), and 61.1% (11/18) isolates were MGIT-BDQ resistant and susceptible, respectively. Consequently, we recommended redefining MIC=0.25μg/ml as an intermediate-susceptible category to resolve discordance between different DST methods. Of the 93 isolates, 22 isolates were MGIT-BDQ-resistant and 77.3% (17/22) of MGIT-BDQ-resistant isolates harbored Rv0678 mutations. After excluding 2 MGIT-BDQ-resistant isolates with borderline resistance (GU400growth control-GU100BDQ≤1day), 100% (15/15) harbored Rv0678 gene mutations, including seven novel mutations [g-14a, Ile80Ser (N=2), Phe100Tyr, Ala102Val, Ins g 181–182 frameshift mutation (N=2), Del 11–63 frameshift mutation, and whole gene deletion (N=2)]. Since the other 22.7% (5/22) MGIT-BDQ-resistant isolates with borderline resistance (GU400growth control-GU100BDQ≤1day) had no mutation in three analyzed genes. For isolates with phenotypic MGIT-BDQ borderline resistance, checking for GU differences or conducting genotypic analyses are suggested for ruling out BDQ resistance. In addition, we observed favorable outcomes among patients with BDQ-resistant isolates who received BDQ-containing regimens regardless of Rv0678 mutations. We concluded that based on MIC≥0.25μg/ml, 3.1% (28/898) of drug-resistant TB cases without BDQ exposure showed BDQ resistance, Rv0678 was not a robust marker of BDQ resistance, and its mutations were not associated with treatment outcomes.

Survival Status and Predictors of Mortality among Multidrug-Resistant Tuberculosis Patients in Saint Peter's Specialized Hospital, Addis Ababa, Ethiopia.

Background Multidrug-Resistant Tuberculosis (MDR-TB) is tuberculosis that is resistant to at least both rifampicin and isoniazid. The World Health Organization as reported in 2019 revealed that Ethiopia is among the 20 countries with the highest estimated numbers of incident MDR-TB cases. However, supporting evidence is limited in the study area after the Ethiopian national strategic plan for tuberculosis prevention and control is started. Objective To determine survival status and predictors of mortality among multidrug-resistant tuberculosis patients treated in Saint Peter's Specialized Hospital at Addis Ababa, Ethiopia, 2020. Methods An institutional retrospective cohort study was conducted using all MDR-TB patients who were enrolled in Saint. Peter's Specialized Hospital from January 01, 2015, to December 31, 2017. A pretested data extraction form that had 5 items for sociodemographic and 15 items for the measurement of clinical characteristics of 484 MDR-TB patients was used. STATA software version 14.2 was used for data cleaning and analysis. A variable that fitted in the bivariable Cox proportional hazard model at p value <0.25 was used in the final multivariable Cox proportional hazard model, and independent predictors of time to event were determined at a p value of 0.05. Result A total of 484 patients were followed up for 5,078 person-months. Among the total patients, nearly half, 238 (48.8%), were males. The median age of patients was 30 years (interquartile range (IQR), 24–39), and 56 (11.6%) were aged between 1 and 19 years. During the follow-up period, 315 (65.1%) patients were cured, 125 (25.8%) completed treatment, 24 (5%) died, and 20 (4.1%) were lost to follow-up. The overall cumulative probability survival of the patients at the end of treatment was 94.85% (95% confidence interval (CI): 92.38%–96.53%). The independent predictors of time to death were being anemic (AHR = 3.65; 95% CI: 1.36, 9.79), having clinical complication (AHR = 3; 95% CI: 1.2, 7.5), and being HIV infected (AHR = 5.8; 95% CI: 2.2, 15.7). Conclusions MDR-TB patients' survival rate was high in St Peter's Specialized Hospital. MDR-TB patients with anemia, HIV coinfection, and clinical complications had higher risk of mortality. So, prevention and controlling of anemia, HIV/AIDS, and clinical complications will reduce the mortality of MDR-TB patients.

MANAGEMENT OF ANTIBIOTIC RESISTANCE BY AYURVEDA – A LITERARY REVIEW

Background – Antibiotic resistance is rising to dangerously high levels worldwide. WHO’s new Global Antimi- crobial Surveillance System (GLASS) reveals widespread occurrence of Antibiotic resistance among 500000 people with suspected bacterial infections across 22 countries. India is no different from it, facing the problem of rising cases of multidrug-resistant TB which adds to the burden of infectious disease in India. Aim – In this literary review problem, current scenario, causes and solution on Antibiotic Resistance from an Ayurvedic perspective will be assessed. Methodology - Articles on Antibiotic Resistance from research papers, journals, and various sites and basic principles from Samhitas and various Ayurvedic Journals, Articles and Research papers on this perspective will be reviewed. Conclusion – Conclusion will be drawn after a thorough literature review on the above subject. Keywords- Antibiotic Resistance, Panchkarma, Rasayana

Analysis on trend of drug resistance tuberculosis, Liuzhou, Guangxi

Objective To understand the spread trend of drug resistant tuberculosis (DR TB) over time in Liuzhou City, Guangxi Zhuang Autonomous Region, and provide evidences to contain the spread and transmission of DR-TB. Methods Data from the DR TB surveillance network in Liuzhou were analyzed. The percentage of DR-TB cases among the newly registered TB cases and the average annual percentage change (APC) were calculated. The regression model was constructed with linear and binomial regression. The hypothesis testing of the average APC was conducted by using line/curve fitting approach. Results A total of 571 DR-TB cases were detected through the DR surveillance network in Liuzhou from 2014 to 2019, accounting for 2.14% (571/26691) of new registered TB cases. The number of DR-TB cases increased from 50 in 2014 to 189 in 2019, an increase of 2.60 times. Of those with drug resistant TB, 30.30% (173/571) were isoniazid resistant, 19.26% (110/571) were rifampin resistant, 29.25% (167/571) were multi-drug resistant (MDR), and 7.01% (40/571) were extensive drug resistant (XDR). In MDR TB cases, XDR TB cases accounted for 23.95%. From 2014 to 2019, the proportion of XDR-TB cases among newly registered TB cases increased from 0.15% to 0.17%. After 2016, the result of APC testing indicated that the total number of DR TB, isoniazid resistant TB cases and rifampin resistant TB were significant increased among new tuberculosis cases (P=0.031, P=0.018, P=0.043). Although the increasing trends of MDR TB and XDR TB cases were observed among new tuberculosis cases, the differences were not significant (PMDR TB=0.098, PXDR TB=0.484). Conclusion The average APCs of DR TB, isoniazid resistant TB and rifampin resistant TB cases significantly increased in Liuzhou overtime, but the difference in case increase over time between MDR TB and XDR TB had no significance. It is necessary to conduct consecutive surveillance to facilitate the development of evidence based prevention and control measures for DR TB and improve the prevention and control of TB and the spread of DR TB.

Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however those visited public HCF diagnosed earlier as compared to others. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

Microbiome in sputum as a potential biomarker of chronicity in pulmonary resistant to rifampicin-tuberculosis and multidrug-resistant-tuberculosis patients.

Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB. Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (P = 0.003). Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM. Actinobacteria found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM. Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of Actinobacteria could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice.

Programmatic Challenges in Managing Multidrug-Resistant Tuberculosis in Malawi

Background:Multidrug-resistant tuberculosis (MDR-TB) is one of the most urgent challenges that Malawi tends to take a firm public health action. A recent increase in multidrug MDR-TB cases, a decrease in treatment success rate, and a double increase of lost-to-follow-up call into question the country’s programmatic management of MDR-TB (PMDT). As such, the study aimed at exploring programmatic challenges in managing MDR-TB in Malawi.Methods:A comprehensive and nonsystematic search was made in PubMed and Google Scholar using mainly the keywords “MDR-TB” “extensively drug-resistant TB,” Malawi. The study reviewed existing guidelines and gray literature and reviewed data obtained from the national TB program (NTP) as well.Results:The study found the following challenges affecting PMDT: decrease in funding, partial access to GeneXpert, delay in diagnosis, long treatment duration, lack of adequate personal protective equipment, the long turnaround time of culture results, failure to initiate all diagnosed patients on treatment, absence of alternative second-line medicines, and lack of transport from health facilities to patient homes.Conclusion:If the Malawi NTP is to achieve a vision of a “TB-free Malawi,” rigorous efforts at all levels must be made, including mobilizing domestic resources for improved MDR-TB program performance. Developing partners should continue providing the much-needed funding to the Malawi government to stand in the wake of the MDR-TB crisis.

Phenotypic and molecular characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Ningbo, China

BackgroundDetection of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis (TB) patients is critical, especially in dealing with multidrug-resistant Mycobacterium tuberculosis (MDR-TB) case. Up to date, PZA drug susceptibility testing (DST) has not been regularly performed in China. The prevalence and molecular characteristics of PZA resistance in M.tuberculosis isolates, especially MDR-TB have not been studied in Ningbo, China. This study aimed to analyze the phenotypic and molecular characterization of PZA resistance among MDR-TB isolates in Ningbo.MethodsA total of 110 MDR-TB isolates were collected from the TB patients who were recorded at local TB dispensaries in Ningbo. All clinical isolates were examined by drug susceptibility testing and genotyping. DNA sequencing was used to detect mutations in the pncA gene associated with PZA resistance.ResultsThe prevalence of PZA resistance among MDR-TB strains in Ningbo was 59.1%. With regard to the history and the outcome of treatments among MDR-TB cases, the percentages of re-treated MDR-TB patients in the PZA-resistant group and of successful patients in PZA-susceptible group were significantly higher than the ones in the PZA-susceptible group and in the PZA-resistant group, respectively (P = 0.027, P = 0.020). The results showed that the resistance of streptomycin (67.7% vs 46.7%, P = 0.027), ethambutol (56.9% vs 33.3%, P = 0.015), ofloxacin (43.1% vs 11.1%, P = 0.000), levofloxacin (43.1% vs 11.1%, P = 0.000), pre-XDR (pre-Xtensively Drug Resistance) (38.5% vs 15.6%, P = 0.009), were more frequently adverted among PZA-resistant isolates compared with PZA-susceptible isolates. In addition, 110 MDR-TB was composed of 87 (PZA resistant, 78.5%) Beijing strains and 23 (PZA resistant, 21.5%) non-Beijing strains. Fifty-four out of 65 (83.1%) PZA-resistant MDR strains harbored a mutation located in the pncA gene and the majority (90.7%) were point mutations. Compared with the phenotypic characterization, DNA sequencing of pncA has sensitivity and specificity of 83.1 and 95.6%.ConclusionThe mutations within pncA gene was the primary mechanism of PZA resistance among MDR-TB and DNA sequencing of pncA gene could provide a rapid detection evidence in PZA drug resistance of MDR-TB in Ningbo.