Mutations in RpoB Gene and Their Association with Rifampicin-resistance Levels in Clinical Isolates of Mycobacterium Tuberculosis

Present study was aimed to identify most frequent mutations in rpoB gene region and to evaluate the association between mutations in rpoB gene and resistance levels to Rifampicin in clinical isolates of Mycobacterium tuberculosis of different geographical regions of India. A total of 100 clinical isolates of Mycobacterium tuberculosis were included in this study. Drug susceptibility testing against first line anti-tuberculosis drugs was performed on LJ medium by conventional minimal inhibitory concentration (MIC) method and the mutation(s) in rpoB gene of M. tuberculosis isolates were analyzed by sequencing method. Of the 100 M. tuberculosis isolates, 31 (31.0%) and 18 (18.0%) were found resistant and susceptible for all four first-line anti-tuberculosis drugs. The genetic mutations were observed in 96% (72/75) rifampicin-resistant M. tuberculosis isolates, while 4% (3/75) of rifampicin-resistant isolates did not have any mutation in rpoB gene. The mutation TCG531TTG (Ser531Leu) was found as most common and frequent mutation in 69.3% (52/75) of rifampicin-resistant isolates of M. tuberculosis with MIC level (≥ 512mg/l). The mutation at codon 511 was associated with low degree (128mg/l) of rifampicin-resistance, deletions at codons 514-516 or substitution at codon 516 were found to be associated with moderate degree (256mg/l) of rifampicin-resistance and mutations at codon 526, 531 were associated with the high degree (512mg/l) of rifampicin-resistance in M. tuberculosis isolates of Indian origin. The findings of this study will be useful for the development of raid and more specific indigenous molecular tools for the early diagnosis of multidrug-resistant tuberculosis in the country

Mutations in rpoB gene and their association with Rifampicin resistance levels in clinical isolates of Mycobacterium tuberculosis

Present study was aimed to identify most frequent mutations in rpoB gene region and to evaluate the association between mutations in rpoB gene and resistance levels to Rifampicin in clinical isolates of Mycobacterium tuberculosis of different geographical regions of India. A total of 100 clinical isolates of Mycobacterium tuberculosis were included in this study. Drug susceptibility testing against first line anti-tuberculosis drugs was performed on LJ medium by conventional minimal inhibitory concentration (MIC) method and the mutation(s) in rpoB gene of M. tuberculosis isolates were analyzed by sequencing method. Of the 100 M. tuberculosis isolates, 31 (31.0%) and 18 (18.0%) were found resistant and susceptible for all four first-line anti-tuberculosis drugs. The genetic mutations were observed in 96% (72/75) rifampicin-resistant M. tuberculosis isolates, while 4% (3/75) of rifampicin resistant isolates did not have any mutation in rpoB gene. The mutation TCG531TTG (Ser531Leu) was found as most common and frequent mutation in 69.3% (52/75) of rifampicin resistant isolates of M. tuberculosis with MIC level (≥ 512mg/l). The mutation at codon 511 was associated with low degree (128mg/l) of rifampicin resistance, deletions at codons 514-516 or substitution at codon 516 were found to be associated with moderate degree (256mg/l) of rifampicin resistance and mutations at codon 526, 531 were associated with the high degree (512mg/l) of rifampicin resistance in M. tuberculosis isolates of Indian origin. The findings of this study will be useful for the development of raid and more specific indigenous molecular tools for the early diagnosis of multidrug-resistant tuberculosis in the country.

Pattern of adverse drug reactions in new smear positive patients of pulmonary tuberculosis treated under directly observed treatment short course

Background: Directly observed treatment short course (DOTS), a combination therapy, drugs are administered for six to eight months in patients diagnosed with tuberculosis, increases the risk of adverse drug reactions. The objective of this study was to study the adverse drug reaction profile of new sputum smear positive (NSP) patients of pulmonary tuberculosis (PTB) treated under DOTS. A prospective observational study was carried out in Dr. RPGMC Kangra at Tanda, Himachal Pradesh, India over a period of six months.Methods: The study included 130 newly diagnosed TB patients on anti‑TB treatment under DOTS. A symptom based approach was followed for monitoring ADRs. The severity was assessed by Modified Hartwig scale and causality by WHO-UMC probability scale. Data was expressed as percentages for discrete variables using Microsoft excel.Results: Out of the total 130, 84 patients experienced ADRs with an overall incidence of 64.6%. 45 (34.6%) patients showed single ADR whereas 39 (30%) patients had two or more ADRs. Gastritis alone was present in 36 (27.8%) patients followed by itching 2 (1.5%), hypersensitivity 2 (1.5%), arthralgia 2 (1.5%), generalized weakness 2 (1.5%) and jaundice in 1 (0.8%) patients. Vomiting was present in 29 (22.2%) patients, neuropathy in 4 (3.1%) patients, arthralgia in 2(1.5%) patients, hypersensitivity, jaundice, itching and generalized weakness in 1 (0.8%) patient each. 21 (16.2%) patients experienced mild , 56 (43.1%) had moderate and only 7 (5.4%) had severe ADRs. All the ADRs were possible in nature.Conclusions: The incidence of ADRs was 64.6% and GI irritation was found to be most common ADR reported by 57.6% patients

Cost-effectiveness of incorporating Mycobacterium indicus pranii vaccine to multidrug therapy in newly diagnosed leprosy cases for better treatment outcomes & immunoprophylaxis in contacts as leprosy control measures for National Leprosy Eradication Programme in India

BACKGROUND & OBJECTIVES: The elimination goal for leprosy as a public health problem at the national level was achieved in 2005 in India. However, the number of new cases reporting annually remained nearly the same during the last 10-15 years. Moreover, a substantial number of these new cases reported disabilities for the first time. Therefore, besides multidrug therapy (MDT), newer strategies with focus on effectively decreasing the number of new cases, optimizing the treatment of detected cases, averting disabilities and arresting the transmission of the disease are required. So the objective of this study was to assess the cost-effectiveness of Mycobacterium indicus pranii (MIP) vaccine implementation in National Leprosy Eradication Programme (NLEP) for newly diagnosed leprosy patients as well as their contacts to arrest/decrease the transmission and occurrence of new cases. METHODS: This was a model-based estimation of incremental costs, total quality-adjusted life years (QALYs) gained, new cases averted, deaths averted, incremental cost-effectiveness ratio (ICER) and budget impact of the vaccination intervention. This model included the addition of MIP treatment intervention to the newly detected leprosy patients as well as vaccination with MIP to their contacts. RESULTS: Using the societal perspective, discounted ICER was estimated to be ₹73,790 per QALY gained over a five-year time period. Probabilistic sensitivity analysis (PSA) was assessed by varying the values of input parameters. Majority (96%) of simulations fell in North East quadrant of cost-effectiveness plane, which were all below the willingness to pay threshold. INTERPRETATION & CONCLUSIONS: Introduction of MIP vaccination in the NLEP appears to be a cost-effective strategy for India. Significant health gains were reduction in the number of new leprosy cases, decreased incidence and severity of reactions during treatment, and after release from treatment, prevention of disabilities, thus reducing the cost as well as stigma of the disease

A Toolbox for Tuberculosis Diagnosis: An Indian Multicentric Study (2006-2008): Microbiological Results

BACKGROUND: The aim of this multicentric prospective study in India was to assess the value of several microbiological tools that contribute to the diagnosis of tuberculosis (TB) according to HIV status. METHODS: Standard microbiological tools on individual specimens were analyzed. RESULTS: Among the 807 patients with active TB, 131 were HIV-infected, 316 HIV-uninfected and 360 had HIV-unknown status. Among the 980 non-active TB subjects, 559 were at low risk and 421 were at high risk of M. tuberculosis (Mtb) exposure. Sensitivity of smear microscopy (SM) was significantly lower in HIV-infected (42.2%) than HIV-uninfected (75.9%) (p = 0.0001) and HIV-unknown pulmonary TB patients (61.4%) (p = 0.004). Specificity was 94.5% in non-TB patients and 100% in health care workers (HCW) and healthy family contacts. Automated liquid culture has significantly higher diagnostic performances than solid culture, measured by sensitivity (74.7% vs. 55.9%) (p = 0.0001) and shorter median time to detection (TTD) (12.0 vs. 34.0 days) (p = 0.0001). Specificity was 100% in HCW and cured-TB patients, but was lower in non-TB patients (89%) due to isolation of Mycobacteria other than tuberculosis (MOTT). TTD by both methods was related to AFB score. Contamination rate was low (1.4%). AccuProbe hybridization technique detected Mtb in almost all culture-positive specimens, but MOTT were found in 4.7% with a significantly higher frequency in HIV-infected (15%) than HIV-uninfected TB patients (0.5%) (p = 0.0007). Pre-test classification significantly increased the diagnostic value of all microbiological tests in pulmonary TB patients (p<0.0001) but to a lesser degree in extrapulmonary TB patients. CONCLUSIONS: Conventional microbiological tools led to results similar to those already described in India special features for HIV-infected TB patients included lower detection by SM and culture. New microbiological assays, such as the automated liquid culture system, showed increased accuracy and speed of detection

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Remaining Challenges to Further Reduce the Leprosy Burden in Rajasthan Kiran Katoch

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Challenges in Leprosy: Suggestions on the Way Forward

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HIV and HBV co-infections among patients with active TB disease attending a primary health care centre in a rural area of north India

This prospective cross-sectional hospital based study was carried out in order to assess the prevalence of HIV and HBV co-infections among patients with active TB disease attending an OPD at the Model Rural Health Research Unit (MRHRU) in Ghatampur, a rural village in Kanpur district of UP. This is a field unit of National JALMA Institute for Leprosy & other Mycobacterial Diseases at Agra. The socio-demographic features and clinical profile of the TB patients were analysed in the context of symptoms at the time of testing. The HIV and HBV status were determined and correlated with clinical features at the time of testing. In our study, seroprevalence of HIV infection among TB patients is 1.48% (18/1215) and that of HBsAg reactivity was found to be 2.96% (36/1215). During 2007–2010, the HIV-positivity varied between 1.5% and 1.45% whereas HBV reactivity ranged between 2.4% and 3.63%. A substantial percentage of the TB patients attending the OPD in Ghatampur harbour HIV and HBV co-infections, which otherwise would remain undiagnosed without serological screening. There is an urgent need to perform population based surveys of HIV and Hepatitis infections among TB patients to assess the true extent of the problem