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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 2  |  Page : 118-125

To evaluate and quantify the Rifampicin Sensitive/Resistant tuberculosis using Xpert MTB/RIF Assay : Our Experience at the DOTS plus site


1 Additional Professor, Dept. of TB & Chest, IGIMS, Patna, Bihar, India
2 Associate Professor, Dept. of TB & Chest, IGIMS, Patna, Bihar, India
3 Assistant Professor, Dept. of Pneumnology, IGIMS, Patna, Bihar, India
4 Associate Professor, Dept. of Microbiology, IGIMS, Patna, Bihar, India
5 Associate Professor, Dept. of Community Medicine, IGIMS, Patna, Bihar, India

Date of Submission20-Jun-2019
Date of Acceptance17-Jul-2019
Date of Web Publication20-Nov-2020

Correspondence Address:
Satyadeo Choubey
Associate Professor, Dept. of TB & Chest IGIMS
India
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Source of Support: None, Conflict of Interest: None


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  Abstract 


Context: Cartridge based nucleic acid amplification test (CBNAAT) is a diagnostic tool which detects both Mycobacterium tuberculosis and its resistance to Rifampicin. Bihar has a high burden of tuberculosis but the data regarding the total and multidrug resistant TB (MDR-TB) burden is lacking.
Aims: To quantify the burden of TB and Rifampicin resistance presenting in a DOTS plus site hospital of Bihar using CBNAAT.
Setfngs and Design: A hospital based cross sectional study.
Methods and Material: All the suspected patients coming to the department of TB & chest at our institute were made to deposit there site specific samples for CBNAAT. The test result (detected/not detected, Rifampicin sensitive/ resistant) were fed into Microsoft Excel and analysis was done using Epi-info statistical software. Statistical analysis used: Descriptive statistic was used.
Results: Out of 4096 suspected patients, 958 were positive by CBNAAT between February 2016 to November 2017. 772 cases (80.58%) were sensitive while 186 (19.41%) were resistant to Rifampicin. It was pulmonary TB in 710 patients and extra pulmonary TB (EPTB) in 248 patients. Among males, 539 (20.4%) were sensitive while 124(4.7%) were resistant to Rifampicin and 233 (16.1%) and 62 (4.3%) respectively in females. 16-35 age group had the highest TB burden. Patna district has the highest TB burden.
Conclusions: Bihar harbors a significant burden of TB patients including the drug resistant cases. Utmost attention of TB control programme and prompt treatment is need of the hour.

Keywords: Xpert MTB/Rif assay, Bihar, Rifampicin resistant TB


How to cite this article:
Shankar M, Choubey S, Sharma S, Kumar R, Kumar S. To evaluate and quantify the Rifampicin Sensitive/Resistant tuberculosis using Xpert MTB/RIF Assay : Our Experience at the DOTS plus site. J Indira Gandhi Inst Med Sci 2019;5:118-25

How to cite this URL:
Shankar M, Choubey S, Sharma S, Kumar R, Kumar S. To evaluate and quantify the Rifampicin Sensitive/Resistant tuberculosis using Xpert MTB/RIF Assay : Our Experience at the DOTS plus site. J Indira Gandhi Inst Med Sci [serial online] 2019 [cited 2021 Dec 6];5:118-25. Available from: http://www.jigims.co.in/text.asp?2019/5/2/118/301094




  Introduction : Top


Multidrug resistant tuberculosis (MDR-TB) is a significant global health concern.[1],[2] As per WHO, about 50% of the world’s total burden of MDR-TB cases are in India and China[3]. India is home to highest number of both sensitive and multidrug resistant (MDR) TB cases.

Multi-drug resistant TB (MDR-TB) is defined as resistance to isoniazid and rifampicin with or without resistance to other drugs. The situation of TB is further threatened by the rapid expansion of MDR-TB which undermine the progress made by tuberculosis control program.[4] As per India TB report 2018 total TB cases notified were 96489 of which 65% were microbiologically confirmed and according to Global Tuberculosis Report 2017 the Incidence of TB (including HIV) in India is 27,90,000 that is 211/lakh whereas incidence of MDR/RR TB is 1,47,000 that is 11/lakh and mortality due to TB is 32/lakh.

Data from studies conducted by Tuberculosis research Centre, Chennai (TRC) and National tuberculosis institute, Bangalore (NTI), have found MDR-TB levels of less than 1% to 3% in new cases and around 12% in re-treatment cases.[5] The high prevalence of drug resistance TB is an important epidemiological indicator of transmission of the disease as well as measure of how effective is the implementation of health care services.[6] That’s why, effective surveillance is the need of the hour for DR-TB to ensure continuous recording and reporting of the epidemiological profile of DR TB. In India and especially in Bihar there is limited resources and data available and lack of quality laboratories which are capable of doing microscopic and DST testing leading to underreporting and underestimation of exact magnitude of the DR-TB incidence and prevalence.[7],[8]

World Health Partners (WHP) is the implementer of Public Private Interface Agency (PPIA), a project supported by BMGF (Bill & Melinda Gates Foundation), covering a population of 6.4 million in the district of Patna, Bihar.

Key achievement of the Patna Project is that they covered total population in Patna 6.4 million of which number of TB case notifications were 19,467, pulmonary cases microbiologically confirmed were 34%, Proportion of pulmonary cases receiving a DST (CBNAAT) 56% and number of DR-TB cases notified were 383.[9]

As per global TB report 2018, TB patients notified from Public sector in Bihar is 54995 out of the population of 1178 lakhs among which pulmonary TB is 93% and EPTB is 7%,microbiologically confirmed is 65%,Paediatric TB population is 8%.

Number of presumptive DR-TB patient subjected to DST in 2017 is 35850 of which 1848 were notified in Bihar. Although there is comprehensive district wise data available of TB but there is no systematic data available about DR-TB.

This study was carried out to appraise the prevalence of rifampicin sensitive and rifampicin resistance in Mycobacterium Tuberculosis (MTB) and its patterns among different types of TB patients from different settngs in Bihar. The Xpert MTB/RIF assay, which is based on realtime polymerase chain reaction (PCR) analysis of the rpo Bgene, is a molecular diagnostic test for detection of mycobacterium tuberculosis(MTB) and rifampicin (RIF) resistance directly from clinical specimens[10]. The assay has got high sensitivity and specificity and capable of diagnosing in less than 2 hours.[11],[12],[13] Sensitivity of Xpert MTB/RIF ranged from 70% to 100% in culture-positive patients to around 60% in patients with smear-negative disease. The specificity ranged from 91% to 100%.

Additionally, the Xpert MTB/RIF assay can rapidly identify possible multidrug-resistant TB (MDR TB). Rifampicin (RIF) resistance is a suggestive of MDR TB because resistance to RIF, in most cases, occurs with resistance to INH (Isoniazide). For patients who are found to not have TB disease, rapid results from the Xpert MTB/RIF assay may help in cost savings by avoiding unnecessary hospitalization and treatment.


  Materials and Methods: Top


OBJECTIVES:

  1. To assess the epidemiology and geographical profile of MDR-TB in patients with clinical suspicion of pulmonary and extra pulmonary TB (EPTB) in patients attending IGIMS (Indira Gandhi Institute of Medical Sciences) Patna DOTS Plus site, a tertiary health care centre of Bihar.
  2. To evaluate the present status of tuberculosis control programs in Bihar.
  3. To study the difference in the distribution of MDR TB in different social strata of Bihar.
  4. To emphasize the importance of continuing the systemic surveillance of mycobacterium tuberculosis isolates to monitor the trends of drug resistance in different patient categories in different region of Bihar to timely modify and strengthen the national programs in order to prevent the emergence of MDR-TB and avert the threat of XDR-TB


Study design: It is a Hospital based cross-sectional study.

Inclusion criteria: -

  1. Clinical signs and symptoms suggestive of pulmonary (cough, fever, weight loss, breathlessness, chest pain, hemoptysis) and Extra pulmonary tuberculosis (Lymph node, Pleural effusion, Pott’s spine) with/without
  2. Radiological evidences (exudation, infiltration, caviatation, calcification, pleural effusion)
  3. Family history of pulmonary tuberculosis/Extra pulmonary TB
  4. RNTCP category I failure
  5. Category II sputum positive at 4 months or latter
  6. MDR TB Contact
  7. Retreatment Smear positive at diagnosis
  8. Any follow up smear positive
  9. Retreatment smear negative
  10. Patients having HIV


Exclusion criteria: -

  • People who were considered physically or mentally unfit to give any sample


A total of 4096 pulmonary (sputum, BAL) and extra pulmonary specimen (pus and pleural fluid)were taken from patients with suspected MDR TB coming to our institute from different districts of Bihar. Our Institute is a nodal DR-TB centre linked to 6 districts of Bihar namely Patna, Buxar, Begusarai, Bhojpur, Jehanabad & Lakhisarai but patients are coming from all districts of Bihar and also from adjoining states and neighboring country Nepal since this is a tertiary care centre. The samples were subjected to Xpert MTB/RIF assay. Samples were collected from patients attending the TB & Chest outpatient and inpatient department between February 2016 and November 2017 in IGIMS, a tertiary care centre in Patna, Bihar. Gene Xpert test were done in our centre. The Xpert MTB/RIF assay is a nucleic acid amplification (NAA) test that uses a disposable cartridge with the Gene Xpert Instrument System. Pulmonary/Extra pulmonary (EP) sample were collected from the patient with suspected TB. The sample were processed and then mixed with the reagent that was provided with the assay, and a cartridge containing this mixture was placed in the Gene Xpert machine. All processing from this point on is fully automated. Blood sample were taken for routine blood testing including HIV.

  1. Results from the Xpert MTB/RIF assay indicated whether or not MTB was detected in the sample. In some instances, the result was “invalid,” whereby the test were repeated. If MTB was detected, the results also state whether resistance to RIF was Detected,
  2. Not detected, or
  3. Indeterminate
  4. In Inderminate result the test were repeated.


Following tests were done:

  1. Sputum smear for AFB 2 samples, Morning and spot
  2. Sputum for Gene Xpert examination
  3. Blood sample for HIV testing
  4. Chest X-Ray
  5. Complete blood count, Liver function test, Blood urea, Serum creatinine, Blood sugar fasting and post prandial.


Survey Methodology:

Systematic sampling method was used for data collection.

Statistical analysis

Data were collected on the pre-structured, pre-tested and pre-coded Performa. A closed-ended questionnaire with some open-ended responses. The information collected using the above mentioned tools were converted into a computer based spreadsheet using Microsoft Excel. All analysis was done using the statistical software Epi-info on computer.


  Result: Top


A total of 4096 patients were tested for tuberculosis including both pulmonary(sputum, BAL) and extra pulmonary samples within a period of 21 months i.e. between February 2016 to November 2017 among which 958 cases detected MTB(23.38%). Out of 958 cases 772 cases were Rifampicin sensitive i.e. 80.58% and 186 (19.41%) were Rifampicin resistant. Among them 539(20.4%) males had Rifampicin sensitive TB and 124(4.7%) were having Rifampicin resistant TB. Among females 233(16.1%) were having Rifampicin sensitive TB whereas 62(4.3%) Rifampicin resistant.3137(79.7%) samples were tested negative on CBNAAT.[Figure 1].
Figure: 1

Click here to view


If we compare site of disease pulmonary TB was detected in 710 patients out of which males were 504(70.98%) and females were 206(29.01%) and extra pulmonary TB (EPTB) in 248 patients, males were 159(64.11%) and females were 89(35.88%).Among males 4% of PTB and 0.6% of EPTB was Rifampicin resistant whereas among females 3.7% of pulmonary TB (PTB) and 0.6% of EPTB was Rifampicin resistant out of the total samples(4096) tested. [Table 1].
Table 1: Sex and site of disease cross tabula

Click here to view


On comparing the age group, it is the 16-35 year age group in both males and females which has the highest burden of TB i.e. 12.4% in males and 12.1% in females out of the total patients tested. This age group also has the highest burden of RRTB i.e. 3% in males and 2.6% in females. More than 75 years age group had the lowest incidence of TB in both males and females i.e. 0.3% and 0.1% respectively with none of them were diagnosed RRTB. [Figure 2].
Figure 2:

Click here to view


Although IGIMS is a Nodal DR-TB centre of six linked districts of Bihar, we received TB cases from all the districts of Bihar(Total 38 districts) as this is a tertiary health care centre. If we look at the district wise distribution of the disease in our study, Patna has the highest incidence of TB i.e. 5% of the total tested(4096) followed by Samastipur 1.3%.Patna also tops the list of highest incidence of RRTB i.e. 0.9% of the total. Domicile records of 820 CBNAAT reports could not be traced. [Table 2] [Figure 3].
Table 2:

Click here to view
Figure 3:

Click here to view


We also received patients from adjoining states like Jharkhand, West Bengal, Uttar Pradesh, Some cases from Delhi and Haryana (these patients were migrants of Bihar origin) and few cases from neighboring country Nepal. Jharkhand tops the list with 10 cases of TB out of which 4 were RRTB. [Table 2] [Figure 3].


  Discussion: Top


As of now, India has the highest burden of TB out of the 22 countries, but any comprehensive information on the magnitude of MDR-TB is largely unavailable.[14] India is estimated to have a significant absolute burden of 25% MDR-TB.[15] In India, new cases with MDR-TB is 2.1% and estimated figure in previously treated cases is 15%.[16] As per RNTCP drug-resistant surveys, it indicated MDR-TB in >3% among new cases and 12-17% in previously treated cases in Andhra Pradesh , Maharashtra and Gujarat.[17]

This is also true for Bihar .In fact the Geographical data of TB & MDR-TB is scarce from Bihar. We used CBNAAT as a surrogate marker of MDR-TB in this study. As our institute is a tertiary care centre we receive cases of TB from all across Bihar.

We studied the epidemiology and geographical distribution of 4096 suspected cases of TB in patients presenting to our institute during 21 months (between February 2016 to November 2017) and found 23.38% microbiologically confirmed TB cases of which 19.41% were Rifampicin resistant. This is in agreement with national data.

Among different age groups, maximum number of cases in the present study were in 16-35 years age group. Other Indian studies have also reported the same figure.[18]

In our study incidence and prevalence of disease in males predominated over females and majority of them were from a rural background. This corroborates with the findings of Gupta etal.[19] High MDR-TB in young adult males has several socioeconomic implications as they are economically productive member of the society.

Our observed RIF resistance was also similar to other studies from different tertiary care centers in India.[20] Most of the suspected TB cases (20.6%) were microbiologically confirmed from Patna including both Rifampicin sensitive (4.1% of the total) and resistant one (0.9% of the total) followed by Samastipur (5% of the total were suspected of TB),Rif sensitive (1.1% of the total), Rif resistant (0.2% of the total). According to India TB report 2018 out of the total 21237 cases notified of Rifampicin sensitive TB, 55% were microbiologically confirmed. The present study appears to be first to investigate the demographic and geographical prevalence of DR-TB in Bihar. However, it should be emphasized that the prevalence rates reflected in our study only reflects the status among suspected patients referred for MTB diagnosis and resistance testing in our institute and may not be supposed to be the actual reflection of prevalence rates of Rifampicin resistance in Bihar. Highest incidence of MTB & RR-TB occurrence in Patna in comparison to other districts of Bihar in our study may be due to overpopulation, workforce migration, overcrowding leading to increased risk of transmission, poor socioeconomic condition, poor TB control programme and lack of uniform regimen of ATT among different practioners which are potential region of its upsurge.[21] In states like Bihar there is a need of comprehensive and robust implementation of RNTCP programme to combat the high incidence and prevalence of TB including both sensitive and resistant one as reflected in our study. Another area of concern is discordant recording and reporting of patient and their clinical isolate data, which establishes the requirement of standardized diagnosis, collection and reporting so that adequate health care implementation and policy decision can be taken. There exists a need of utmost importance of comprehensive epidemiological study and data collection of TB cases in Bihar in collaboration with RNTCP and private stake holders.


  Conclusion: Top


DR-TB is a rapidly emerging threat in India and especially in Bihar where health care resources are suboptimal. High incidence of DR-TB in this part of the world as reflected in our study needs utmost attention of the TB control programme where rapid diagnosis with CBNAAT tool and prompt treatment with the help of all stakeholders is the need of the hour. Besides this social support, poverty upliftment and medical security is required to prevent the transmission of this dreaded disease. Also district wise installation of CBNAAT machine is implemented by RNTCP for the rapid diagnosis which is a commendable step taken.



 
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[PUBMED]  [Full text]  
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