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ORIGINAL ARTICLE
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Trend of antitubercular drug sensitivity test at a multispecialty hospital in Western India


1 Col Med (Health), O/o DGAFMS, Army Hospital Research and Referral, New Delhi, India
2 Department of Microbiology, Army Hospital Research and Referral, New Delhi, India
3 Department of Pathology, Military Hospital CTC, Pune, Maharashtra, India

Date of Submission01-Oct-2019
Date of Decision02-Oct-2019
Date of Acceptance29-Jun-2020
Date of Web Publication02-Sep-2020

Correspondence Address:
Ashish Bahal,
Department of Microbiology, Army Hospital Research and Referral, Dhaula Kuan, New Delhi - 110 010
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_62_19

  Abstract 


Context: Tuberculosis (TB) infection is still a major public health burden in India. India accounts for about 25% of the global TB burden. Worldwide India is the country with highest burden of both TB and multidrug-resistant (MDR) TB. Aim: The aim of this study was to evaluate the pattern of resistance of Mycobacterium tuberculosis to first and second line antitubercular drugs among specimens from a multispecialty hospital in Western Maharashtra. Settings and Design: This record-based study was conducted from January 2018. Records of sputum from 2013 to 2017 were obtained from patients with suspected TB. Subjects and Methods: Drug-sensitivity testing was performed by the mycobacterial growth indicator tube method. Sensitivity to first line and second line antitubercular drugs was tested. Statistical Analysis Used: Trend analysis and charts using MS Excel. Results: Among 734 patients, 701 (95.5%) were male and 33 (4.5%) were female. The analysis of our study result showed that 21.7% of patients were monodrug resistant. Out of 734 isolates, 56 (7.62%) showed multi- and 39 (5.6%) out of the 734 samples showed extensive drug-resistant TB. Conclusions: Our study confirms that drug resistance, including MDR, observed against all first-line TB drugs was a real threat in the management of TB infection. The resistance pattern in this study could assist the clinicians in providing appropriate treatment regimen to TB patients and improve their clinical outcome.

Keywords: Drug resistance, first line, pulmonary tuberculosis, second line



How to cite this URL:
Jain S, Bahal A, Sidhu H S, Malik M, Singh S. Trend of antitubercular drug sensitivity test at a multispecialty hospital in Western India. J Mar Med Soc [Epub ahead of print] [cited 2020 Sep 19]. Available from: http://www.marinemedicalsociety.in/preprintarticle.asp?id=294195




  Introduction Top


India accounts for one fourth of the global tuberculosis (TB) burden. In 2018, an estimated 27 lakh cases occurred and 4.5 lakh people died due to TB. India has highest burden of both TB and multidrug-resistant (MDR) TB based on estimates reported in Global TB Report 2017. An estimated 1.3 lakh incident MDR TB patients emerge annually in India which includes 79,000 MDR-TB Patients estimates among notified pulmonary cases. India bears the second highest number of estimated HIV associated TB in the world. An estimated 1.1 lakh HIV-associated TB occurred in 2015 and 37,000 estimated number of patients died among them.[1]

MDR-TB is an important emerging public health problem of great importance across the world. A rise in the number of cases of MDR TB has recently been recognized, which is a cause of higher mortality rates than drug-sensitive TB.[2]

It is becoming increasingly important to detect the antibiotic resistance among Mycobacterium tuberculosis strains with the global recognition of drug-resistant strains and their adverse impact on clinical outcome. Globally, an estimated 10 million people suffered from TB; however, India harbors the highest number of TB cases and many of them are MDR-TB.[3]

A number of studies have described the prevalence of MDR-TB in a number of different geographical locations across the country.[4],[5],[6],[7],[8],[9],[10],[11] The emergence of mutated strains of M. tuberculosis that are resistant to the major anti-TB drugs poses a deadly threat worldwide including our country. TB is predominantly a disease of the poor with over 80% of cases occurring in Asia and Africa.[12] Although the greatest numbers of patients live in highly populous countries of Asia the highest incidence of disease is found in African region.[13]

Drug-resistance TB notably MDR-TB, was higher in patients with previously incomplete anti-TB treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community.[14] In March 2017, the Government of India (GOI) announced that the new aim for TB in India was the elimination of TB by 2025.[15]

However, as studies so far tried to emphasize the diagnosis, treatment, and care of MDR-TB, there is a lack of literature highlighting trends of resistance patterns over the years among selected populations.

The aim of this study was to document the patterns of drug resistance observed in TB patients receiving anti-TB treatment in a super-specialty hospital in India and to identify the trends and patterns in these patients over time.


  Subjects and Methods Top


A record-based retrospective, observational study using routinely collected laboratory data of patients visiting the Department of Respiratory Medicine at a Tertiary Care Hospital in Western Maharashtra.

Study population and setting

Epidemiological data of TB patients and data on M. tuberculosis resistance to first and second line TB drugs were retrospectively collected from January 1, 2013, to December 31, 2017. Data were collected from Master Record Register at the Department of Microbiology at a Tertiary Care Hospital in Western Maharashtra. Patients giving inadequate/inappropriate samples in the laboratory were excluded from the study.

The institution followed standard international and national guidelines on diagnosis and treatment of TB throughout the study period.

Drug resistance profiles

Drug sensitivity test (DST) to first-line and second-line antitubercular drugs were carried out using the mycobacterial growth indicator tube (MGIT) (Ms Becton Dickinson, New Jersey) as per manufacturer's instructions. DST of second-line antitubercular drugs was performed using MGIT method only in cases where resistant to first-line drugs was present especially rifampicin (RIF).

A case of MDR-TB was defined as sputum/isolate in which the positive culture of M. tuberculosis was found to havein vitro resistance to isoniazid (INH) and RIF with or without resistance to other antitubercular drugs based on additional DST.[7]

Extensively drug-resistant (XDR) TB case was defined as having an MDR-TB strain that is resistant to any fluoroquinolone (ofloxacin, levofloxacin, or moxifloxacin) and at least one second-line injectable anti-TB drug (kanamycin, amikacin, or capreomycin).[7]


  Results Top


A total of 9545 patients suspected of TB were registered in respiratory disease Centre of Western Maharashtra during the year 2013–2017. Proportion of female sputum smear positive cases was higher (8.3%) as compared to males (7.6%). Out of total sputum smear positive cases 95.5% were male and 4.5% were female [Table 1] and [Table 2].
Table 1: Gender distribution of study population

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Table 2: Gender and sputum smear positivity

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Among total suspected cases, proportion of sputum positive cases showed upward trend of TB from year 2013 to 2015 but thereafter linear downward by 2017 [Figure 1].
Figure 1: Trend of sputum smear positive cases

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Drug resistance patterns

Percentages of resistance to individual drugs are shown in [Figure 2]. The drug sensitivity profile of 13 drugs was evaluated. Of 734 isolates from sputum samples, 160 showed mono-resistance, i.e., resistance to one first-line drugs (INH, RIF, Streptomycin (SM), Pyrazinamide (PYZ), Ethambutol (EMB)]) and the remaining 574 were sensitive to all five first-line drugs.
Figure 2: Resistance to individual drugs used in this study

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Out of 734 isolates, 56 (7.62%) showed MDR (resistance to INH and RIF) whereas 39 (5.6%) out of the 734 samples showed XDR (resistance to INH and RIF, in addition to fluoroquinolones and to at least one injectable second-line drugs).

The trends in drug resistance [Figure 3] and [Figure 4] showed a spike in resistance to all first-line and second-line anti-TB drugs in 2016.
Figure 3: Trends in first-line drug resistance from 2013 to 2017

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Figure 4: Trends in second-line drug resistance from 2013 to 2017

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  Discussion Top


The present record-based evaluation study conducted in Western Maharashtra since year 2013–2017 has been shown the upward trend of sputum positivity from year 2013 to 2015 but thereafter linear downward by 2017. The difference in incidence of TB although cannot be ascertained specifically but findings reported by GOI shows that the incidence of TB has reduced from 289 per lakh per year in 2000-217 per lakh per year in 2015 and the mortality due to TB has reduced from 56 per lac per year in 2000-36 per lac per year in 2015.[16] The main contributors of increase in incidence being lack of adequate infrastructure, population explosion, and poverty. A similar study done in Maharashtra displays previous 5 years trend from year 2008 to 2012 and shows upward trend from 2008 to 2010 but linear downward trend from 2010 to 2012.[17] A similar linear downward trend is noted from year 2015 to 2016 in study done in North India.[18] The decrease in the sputum smear positive TB could be related to the success of TB control strategy.

Opposite trend was reported from a study done in Ghana showing increase in sputum smear positive pulmonary TB from 2013 to 2016.[19] This could be due to ineffective strategies and TB control program. TB was declared as an emergency in Africa in 2005 when the annual incidence increased four time in African countries from the 1990 incidence and continues to rise, killing more than half a million every year.[20] Gender is an important variable in infectious disease epidemiology. A 1998 review[1] on gender differences in TB suggested that women in low-income countries were probably under notified. Proportion of female sputum smear positive cases was higher (8.3%) as compared to males (7.6%). Out of total sputum smear positive cases 95.5% were male and 4.5% were female and same trend was reported in earlier study in Maharashtra.[17] Studies done in India shows similar gender distribution pattern having a wide sex gap with male patients outnumbering female patients.[21],[22]

This retrospective study regarding drug resistance patterns among TB cases has generated valuable information in the context of the drug-resistant TB situation in India. The development of drug resistance TB, including MDR, is attributed to poor patient compliance, inappropriate TB drug regimen, inadequate laboratory facilities for drug-susceptibility testing, and acceleration of HIV epidemic.[23]

Resistance to INH and INH plus RIF in India was 6.2% and 13.1%, respectively[10] whereas Shah et al.[24] studied 482 previously treated pulmonary TB patients and reported that resistance to INH and INH plus RIF was 12.86% and 15.77%, respectively. In our study, resistance to INH and INH plus RIF was 17.6% and 7.6%, respectively. Although INH resistance was higher than in the study by Shah et al. (2002), INH plus RIF resistance was lesser.

Kadam et al. reported that resistance to INH, either alone or in combination with another drug, was highest, at 27.4%. SM resistance India was 6.8% which was lower than the 16% observed in their study and corroborated with this meta-analysis.[25] Resistance against RIF in India was found to be 5.1% whereas it was 14.28% in the present study but was lower than the RIF resistance (15.5%) reported in a previous study.[24]

Noncompliance among patients is an important factor in this regard. Second, we found the highest of resistance (78.51%) against cycloserine among the second-line drugs. Although the reason for this resistance may be attributed to the cross-resistance among drugs, for example, cross-resistance of ethionamide with INH. This study shows a low resistance to fluoroquinolones among the strains tested in this study. This study underlines the necessity of direct observed therapy in Indian patients.

Globally, India has one of the highest burdens of MDR-TB, with an estimated 63,000 patients having MDR strains among pulmonary TB cases in 2013, which accounts for more than 20 percent of the estimated global burden of drug-resistant TB.[26]

In India, the incidence of MDR TB is 3.4%. A high degree (7.62%) of MDR-TB was observed among patients in this study. However, 462 (63%) isolates were sensitive to all four first-line drugs (INH, RIF, SM, and EMB) that were tested. Although noncompliance is a major factor for poor outcome of therapy, this study underscores the presence of MDR-TB strains among these patients.


  Conclusions Top


Data in this study show that TB is a great challenge and there is a need to intensify the awareness program about TB, involvement of public private partnership, early case detection and adherence with treatment to control the burden of TB. Efforts to increase the gender sensitivity of health services and to promote community awareness of TB are of utmost importance.

The study also confirms that drug resistance, including MDR, observed against all first-line TB drugs was a real threat in the management of TB infection. The resistance patterns observed in this study may give an insight to the clinician for early suspicion of MDR-TB at early stage and improve their clinical outcome in TB patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
RNTCP Annual Report- TB India. Central TB Division, DGHS, Government of India. 2017. Available from https://tbcindia.gov.in/WriteReadData/TB%20India%202017.pdf. [Last accessed 2020 Jan 20].  Back to cited text no. 1
    
2.
The World Health Organization. Global Tuberculosis Control: Surveillance, Planning, Financing. Geneva: WHO Report; 2008.  Back to cited text no. 2
    
3.
Udwadia Z. Totally drug resistant-tuberculosis in India: The bad just got worse. J Assoc Chest Phys 2016;4:41.  Back to cited text no. 3
    
4.
Paramasivan CN, Rehman F, Wares F, Sundar Mohan N, Sundar S, Devi S, et al. First- and second-line drug resistance patterns among previously treated tuberculosis patients in India. Int J Tuberc Lung Dis 2010;14:243-6.  Back to cited text no. 4
    
5.
D'souza DT, Mistry NF, Vira TS, Dholakia Y, Hoffner S, Pasvol G, et al. High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Programme in an urban metropolis (Mumbai) in Western India. BMC Public Health 2009;9:211.  Back to cited text no. 5
    
6.
Nagaraja C, Shashibhushan BL, Sagar C, Asif M, Manjunath PH. Resistance pattern in drug-resistant pulmonary tuberculosis. J Postgrad Med 2011;57:181-3.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
James P, Gupta R, Christopher DJ, Thankagunam B, Veeraraghavan B. MDR- and XDR-TB among suspected drug-resistant TB patients in a tertiary care hospital in India. Clin Respir J 2011;5:19-25.  Back to cited text no. 7
    
8.
Nagaraja C, Shashibhushan BL, Asif M, Manjunath PH, Sagar C. Pattern of drug-resistance and treatment outcome in multidrug-resistant pulmonary tuberculosis. Indian J Chest Dis Allied Sci 2012;54:23-6.  Back to cited text no. 8
    
9.
Maurya AK, Kant S, Nag VL, Kushwaha RA, Dhole TN. Trends of anti-tuberculosis drug resistance pattern in new cases and previously treated cases of extrapulmonary tuberculosis cases in referral hospitals in northern India. J Postgrad Med 2012;58:185-9.  Back to cited text no. 9
  [Full text]  
10.
Gupta H, Kant S, Jain A, Natu SM, Ahluwalia S. Initial drug resistance pattern among pulmonary tuberculosis patients. Indian J Tuberc 2013;60:154-61.  Back to cited text no. 10
    
11.
Sagar T, Singh NP, Kashyap B, Kaur IR. Current status of multidrug resistant tuberculosis in a tertiary care hospital of East Delhi. J Postgrad Med 2013;59:173-6.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
Zager EM, McNerney R. Multidrug-resistant tuberculosis. BMC Infect Dis 2008;8:10.  Back to cited text no. 12
    
13.
Corbett EL, Marston B, Churchyard GJ, de Cock KM. Tuberculosis in sub-Saharan Africa: Opportunities, challenges, and change in the era of antiretroviral treatment. Lancet 2006;367:926-37.  Back to cited text no. 13
    
14.
Banu S, Rahman MT, Uddin MK, Khatun R, Ahmed T, Rahman MM, et al. Epidemiology of tuberculosis in an urban slum of Dhaka City, Bangladesh. PLoS One 2013;8:e77721.  Back to cited text no. 14
    
15.
TB in India Elimination, Private Care, TB burden, NSPs. Available from: https://www.tbfacts.org/tb-india/. [Last accessed on 2018 May 15].  Back to cited text no. 15
    
16.
TB India 2017: Central TB Division. Available from: Ttps://tbcindia.gov.in/index1.php?lang=1&level=2&sublinkid= 4728&lid=3275. [Last accessed on 2018 May 15].  Back to cited text no. 16
    
17.
Mohite RV, Mohite VR, Ganganhalli PG, Lele SV. Trend of tuberculosis and performance evaluation of new sputum positive tuberculosis from Satara district. Asian J Med Sci 2015;6:2-7.  Back to cited text no. 17
    
18.
Rohit. Knowledge on directly observed treatment short course (DOTS) among tuberculosis patients of selected DOTS centres of Ludhiana, Punjab. Int J Adv Res 2017;5:540-3.  Back to cited text no. 18
    
19.
Osei FA, Enimil A, Ansong D, Laryea DO, Mensah NK, Amuzu EX, et al. Review of organism density and bacteriologic conversion of sputum among tuberculosis patients. Int Sch Res Not 2017;2017:1-5.  Back to cited text no. 19
    
20.
WHO WHO Declares TB an emergency in Africa. World Health Organization; 2010. Available from: WHO: WHO Declares TB an emergency in Africa. World Health Organization; 2005. Available from: https://www.who.int/mediacentre/news/releases/2005/africa_emergency/en/. [Last accessed 2020 Jan 20].  Back to cited text no. 20
    
21.
Prakasha SR, Suresh G, D'sa IP, Kumar SG, Rao RS. A study of clinical characteristics and trend of different types of tuberculosis in coastal South India. Ann Trop Med Public Heal 2012;5:489-94.  Back to cited text no. 21
    
22.
Mukherjee A, Saha I, Sarkar A, Chowdhury R. Gender differences in notification rates, clinical forms and treatment outcome of tuberculosis patients under the RNTCP. Lung India 2012;29:120-2.  Back to cited text no. 22
  [Full text]  
23.
Cucunawangsih, Wiwing V, Widysanto A, Lugito NP. Mycobacterium tuberculosis resistance pattern against first-line drugs in patients from urban area. Int J Mycobacteriol 2015;4:302-5.  Back to cited text no. 23
    
24.
Shah AR, Agarwal SK, Shah KV. Study of drug resistance in previously treated tuberculosis patients in Gujarat, India. Int J Tuberc Lung Dis 2002;6:1098-101.  Back to cited text no. 24
    
25.
Goyal V, Kadam V, Narang P, Singh V. Prevalence of drug-resistant pulmonary tuberculosis in India: Systematic review and meta-analysis. BMC Public Health 2017;17:817.  Back to cited text no. 25
    
26.
Dalal A, Pawaskar A, Das M, Desai R, Prabhudesai P, Chhajed P, et al. Resistance patterns among multidrug-resistant tuberculosis patients in greater metropolitan Mumbai: Trends over time. PLoS One 2015;10:e0116798.  Back to cited text no. 26
    


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