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ORIGINAL ARTICLE
Year : 2011  |  Volume : 133  |  Issue : 3  |  Page : 308-311

Prevalence of multidrug-resistant tuberculosis among newly diagnosed cases of sputum-positive pulmonary tuberculosis


1 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Microbiology, Sanjay Gandhi Memorial Hospital, New Delhi, India
3 Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
4 New Delhi Tuberculosis Centre, New Delhi, India

Date of Submission11-Feb-2010
Date of Web Publication6-Apr-2011

Correspondence Address:
Surendra K Sharma
Chief, Division of Pulmonary, Critical Care & Sleep Medicine, Head, Department of Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029
India
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Source of Support: None, Conflict of Interest: None


PMID: 21441685

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   Abstract 

Background & objectives : The prevalence of multidrug-resistant tuberculosis (MDR-TB) is increasing throughout the world. Although previous treatment for TB is the most important risk factor for development of MDR-TB, treatment-naοve patients are also at risk due to either spontaneous mutations or transmission of drug-resistant strains. We sought to ascertain the prevalence of MDR-TB among new cases of sputum-positive pulmonary TB.
Methods: This was a prospective, observational study involving newly diagnosed cases of sputum-positive pulmonary tuberculosis diagnosed between 2008 and 2009 carried out in New Delhi, India. All sputum-positive TB cases were subjected to mycobacterial culture and first-line drug-susceptibility testing (DST). MDR-TB was defined as TB caused by bacilli showing resistance to at least isoniazid and rifampicin.
Results: A total of 218 cases of sputum-positive pulmonary tuberculosis were enrolled between 2008 and 2009. Of these, 41 cases had negative mycobacterial cultures and DST was carried out in 177 cases. The mean age of the patients was 27.8 ± 10.2 yr; 59 patients (27%) were female. All patients tested negative for HIV infection. Out of 177 cases, two cases of MDR-TB were detected. Thus, the prevalence of MDR-TB among newly diagnosed pulmonary tuberculosis patients was 1.1 per cent.
Interpretation & conclusion s: MDR-TB prevalence is low among new cases of sputum-positive pulmonary TB treated at primary care level in Delhi. Nation-wide and State-wide representative data on prevalence of MDR-TB are lacking. Efforts should be directed towards continued surveillance for MDR-TB among newly diagnosed TB cases.

Keywords: Drug resistance - India - multidrug-resistant tuberculosis (MDR-TB) - new case-pulmonary tuberculosis


How to cite this article:
Sharma SK, Kaushik G, Jha B, George N, Arora S K, Gupta D, Singh U, Hanif M, Vashisht R P. Prevalence of multidrug-resistant tuberculosis among newly diagnosed cases of sputum-positive pulmonary tuberculosis. Indian J Med Res 2011;133:308-11

How to cite this URL:
Sharma SK, Kaushik G, Jha B, George N, Arora S K, Gupta D, Singh U, Hanif M, Vashisht R P. Prevalence of multidrug-resistant tuberculosis among newly diagnosed cases of sputum-positive pulmonary tuberculosis. Indian J Med Res [serial online] 2011 [cited 2019 Nov 19];133:308-11. Available from: http://www.ijmr.org.in/text.asp?2011/133/3/308/78372

The emergence and spread of multi-drug resistant tuberculosis (MDR-TB) is threatening to destabilize global tuberculosis control. The prevalence of MDR-TB is increasing throughout the world both among new tuberculosis cases as well as among previously-treated ones [1] . Although previous treatment for TB is the strongest risk factor for development of MDR-TB [2],[3],[4] , treatment-naοve patients are also at risk due to either spontaneous mutations or transmission of resistant strains [5],[6] . The risk of transmission of resistant strains from close contacts is increasing day-by-day because of the growing burden of MDR-TB patients [1] . Therefore, in the present scenario, there is high likelihood that what initially seems to be drug-sensitive TB in a treatment-naοve patient might in fact be MDR-TB from the outset. Therefore, we sought to determine the prevalence of MDR-TB among new cases of sputum-positive pulmonary TB.


   Material and Methods Top


This was a prospective, observational study involving newly diagnosed cases of sputum-positive pulmonary tuberculosis. These are preliminary results from an ongoing double-blind, placebo-controlled trial. The cases were recruited through a dedicated chest clinic functioning at primary care level at Sanjay Gandhi Memorial Hospital in Mongolpuri, New Delhi. All suspected cases of TB attending the clinic were subjected to sputum smear examination and mycobacterial culture and drug-susceptibility testing (DST) at the New Delhi Tuberculosis (NDTB) Centre laboratory, New Delhi. The NDTB centre was accredited as the intermediate reference laboratory (IRL) during the study period. Sputum-positive pulmonary TB was defined as TB in a patient with at least 2 initial sputum smear examinations positive for acid-fast bacilli (AFB) or one sputum smear examination positive for AFB and radiographic abnormalities consistent with active pulmonary TB or one sputum smear specimen positive for AFB and culture positive for Mycobacterium tuberculosis[7] . New case was defined as a TB patient who has never had treatment for tuberculosis or has taken anti-tuberculosis drugs for less than one month [7] . Cultures were done on Lowenstein-Jensen (L-J) slopes by modified Petroff's method [8] . All the isolates were identified as M. tuberculosis by their slow growth rate, colony morphology, inability to grow on L-J media containing p-nitrobenzoic acid (PNB), niacin test and catalase test. DST was carried out by the economic variant of 1 per cent proportion method for all drugs except pyrazinamide which was tested by the resistance-ratio method. The tested drugs and their critical concentrations (in μg/ml) were as follows: isoniazid (H)- 0.2, rifampicin (R)- 40, pyrazinamide (Z) - 100, ethambutol (E) - 2 and streptomycin (S) - 4. MDR-TB was defined as TB caused by bacilli showing resistance to at least isoniazid and rifampicin. Human immunodeficiency virus (HIV) testing was carried out routinely in all patients and HIV positive patients were excluded from the study. Written informed consent was obtained from all patients. The Ethical Committee of AIIMS hospital, New d0 elhi approved the study protocol.


   Results Top


We prospectively enrolled 218 cases of newly diagnosed sputum-positive pulmonary tuberculosis between February 2008 and December 2009. Of the 218 cases, 41 patients had negative mycobacterial cultures and hence DST was carried out in 177 cases. The mean age of the patients was 27.8 ± 10.2 yr; 59 (27%) were female. The mean body mass index (BMI) was 17.33 ± 1.99 kg/m 2 . Out of 177 cases, two cases of MDR-TB were detected. Both were male, HIV negative, aged 20 and 25 yr with BMI 17.1 and 19.7 kg/m 2 , and resistance pattern was H, R, S and H, R, E, S, respectively. Thus, the prevalence of MDR-TB among new sputum positive pulmonary TB patients was 1.1 per cent. The resistance rates (%) observed to various first-line drugs were isoniazid 6.2, rifampicin 1.1, pyrazinamide 0, ethambutol 3.4, and streptomycin 2.3. The rates of mono- and poly-drug resistance rates are shown in [Table 1].
Table 1: Mono- and poly-drug resistance rates in patients


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   Discussion Top


We found a low prevalence of MDR-TB among new cases of pulmonary TB in Delhi. The reported prevalence of MDR-TB among new TB cases has varied from 0.14 to 5.3 per cent in previous studies from different parts of India [8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] and our findings are in consonance with such observations [Table 2]. But there are a few studies which have reported a high prevalence of MDR-TB among new TB cases [20],[21] . Bias in patient selection and differences in methodology may account for such high prevalence of MDR-TB noted in these studies.
Table 2: Prevalence of MDR-TB among new cases of pulmonary TB in India reported in previous studies


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Our findings carry some important implications. Firstly, the prevalence of MDR-TB has not risen over the years, which reflects the success of DOTS in effective treatment of drug-susceptible TB and preventing the emergence of MDR-TB. Secondly, since MDR-TB is rare among new TB cases, all new cases of pulmonary tuberculosis can be treated with empirical category I regimen without the risk of treatment failures or aggravation of drug-resistance.

The major limitation of the present study is the small sample size and therefore, it is not representative of the population at large. In fact, this limitation was observed in most previous studies on MDR-TB. Nation-wide and State-wide representative data on the prevalence of MDR-TB are an urgent need of the hour to design effective empirical regimens, to monitor functioning and progress of the national TB control programme and for continued surveillance of MDR-TB among category I TB patients. In conclusion, our findings are quite reassuring in that MDR-TB prevalence has not risen over the years and still continues to be low among new cases of pulmonary TB.

Conflicts of interest: We declare that we have no conflict of interest.


   Acknowledgment Top


Authors thank the Department of Biotechnology, Ministry of Science and Technology, Govt. of India (BT/PR7894/Med/14/1175/2006) for financial assistance.

 
   References Top

1.The WHO / IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance. Anti-Tuberculosis Drug Resistance in the World. Report No.4. Geneva, Switzerland: WHO; WHO/HTM/TB/2008.394.  Back to cited text no. 1
    
2.Sharma SK, Mohan A. Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control. Chest 2006; 130 : 261-72.  Back to cited text no. 2
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3.Espinal MA, Laserson K, Camacho M, Fusheng Z, Kim SJ, Tlali RE, et al. Determinants of drug-resistant tuberculosis: analysis of 11 countries. Int J Tuberc Lung Dis 2001; 5 : 887-93.  Back to cited text no. 3
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4.Casal M, Vaquero M, Rinder H, Tortoli E, Grosset J, Rüsch-Gerdes S, et al. A case-control study for multidrug-resistant tuberculosis: risk factors in four European countries. Microb Drug Resist 2005; 11 : 62-7.  Back to cited text no. 4
    
5.Paramasivan CN, Venkataraman P. Drug resistance in tuberculosis in India. Indian J Med Res 2004; 120 : 377-86.   Back to cited text no. 5
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6.Snider DE Jr, Kelly GD, Cauthen GM, Thompson NJ, Kilburn JO. Infection and disease among contacts of tuberculosis cases with drug resistant and drug susceptible bacilli. Am Rev Respir Dis 1985; 132 : 125-32.  Back to cited text no. 6
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7.Revised National Tuberculosis Control Programme (RNTCP). RNTCP at a glance. Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare, New Delhi, Government of India. Available from: http://uttarkashi.nic.in/Dept/Health/ RNTCP/ RNTCP.pdf, accessed on January 26, 2010.  Back to cited text no. 7
    
8.Chandrasekaran S, Chauhan MM, Rajalakshmi R, Chaudhuri K, Mahadev B. Initial drug resistance to anti-tuberculosis drugs in patients attending an urban district tuberculosis centre. Indian J Tuberc 1990; 37 : 215-6.  Back to cited text no. 8
    
9.Narang P, Nayar S, Mendiratta DK, Tyagi NK, Jajoo U. Smear and culture positive cases of pulmonary tuberculosis found among symptomatics surveyed in Wardha district. Indian J Tuberc 1992; 39 : 159-63.  Back to cited text no. 9
    
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11.Chandrasekaran S, Jagota P, Chaudhuri K. Initial drug resistance to antituberculosis drugs in urban and rural district tuberculosis programme. Indian J Tuberc 1992; 39 : 171-5.  Back to cited text no. 11
    
12.Gupta PR, Singhal B, Sharma TN, Gupta RB. Prevalence of initial drug resistance in tuberculosis patients attending a chest hospital. Indian J Med Res 1993; 97 : 102-3.  Back to cited text no. 12
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13.Jain NK, Chopra KK, Prasad G. Initial and acquired isoniazid and rifampicin resistance to Mycobacterium tuberculosis and its implication for treatment. Indian J Tuberc 1992; 39 : 12-4.  Back to cited text no. 13
    
14.Jena J, Panda BN, Nema SK, Ohri VC, Pahwa RS. Drug resistance pattern of Mycobacterium tuberculosis in a chest diseases hospital of armed forces. Lung India 1995; 13 : 56-9.  Back to cited text no. 14
    
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16.Paramasivan CN, Venkataraman P, Chandrasekaran V, Bhat S, Narayanan PR. Surveillance of drug resistance in tuberculosis in two districts of south India. Int J Tuberc Lung Dis 2002; 6 : 479-84.  Back to cited text no. 16
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17.Anuradha B, Aparna S, Hari Sai Priya V, Vijaya Lakshmi V, Akbar Y, Suman Latha G, et al. Prevalence of drug resistance under the DOTS strategy in Hyderabad, South India, 2001-2003. Int J Tuberc Lung Dis 2006; 10 : 58-62.  Back to cited text no. 17
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19.Ramachandran R, Nalini S, Chandrasekar V, Dave PV, Sanghvi AS, Wares F, et al. Surveillance of drug-resistant tuberculosis in the state of Gujarat, India. Int J Tuberc Lung Dis 2009; 13 : 1154-60.  Back to cited text no. 19
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20.Jain A, Mondal R, Prasad R, Singh K, Ahuja RC. Prevalence of multidrug resistant Mycobacterium tuberculosis in Lucknow, Uttar Pradesh. Indian J Med Res 2008; 128 : 300-6.  Back to cited text no. 20
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21.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; 211 : 1-9.  Back to cited text no. 21
    



 
 
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