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ORIGINAL ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 1  |  Page : 11-14

A study to assess the pattern of drug resistance and its causes among patients registered as retreatment cases of Tuberculosis in a tertiary care center of central India


1 Department of General Medicine, Sri Aurobindo Medical College, Indore, Madhya Pradesh, India
2 Department of Respiratory Medicine, Sri Aurobindo Medical College, Indore, Madhya Pradesh, India

Date of Web Publication29-Nov-2014

Correspondence Address:
Abhishek Singhai
Department of General Medicine, Sri Aurobindo Medical College, Indore - 453 111, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2148-7731.145797

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  Abstract 

Context: Tuberculosis is a major public health priority in the world with 8-10 million new cases added every year. Aims: To obtain information about drug resistance pattern of patients registered as re-treatment cases and its causes along with source of previous drug exposure. Settings and Design: This is a prospective study done at a tertiary care center. Materials and Methods: A total of 100 patients of re-treatment cases who gave oral informed consent were registered as subjects. Results: Drug resistance was identified as 25% mono drug and 22% multidrug resistance among retreatment cases. Isoniazid (25%) was the most common drug against which drug resistance was identified. Conclusions: Multidrug resistance is a significant health problem. Majority of these patients were drug defaulters. Our study identifies drug intolerance, ignorance about advised treatment, early symptomatic relief as the predominant causes of defaulting.

Keywords: Drug resistance, retreatment cases, tuberculosis


How to cite this article:
Singhai A, Alam A. A study to assess the pattern of drug resistance and its causes among patients registered as retreatment cases of Tuberculosis in a tertiary care center of central India . Sifa Med J 2015;2:11-4

How to cite this URL:
Singhai A, Alam A. A study to assess the pattern of drug resistance and its causes among patients registered as retreatment cases of Tuberculosis in a tertiary care center of central India . Sifa Med J [serial online] 2015 [cited 2021 Apr 20];2:11-4. Available from: https://www.imjsu.org/text.asp?2015/2/1/11/145797


  Introduction Top


Tuberculosis is one of the oldest and most prevalent diseases in our country and about 40% of the population in India is estimated to be infected with Mycobacterium tuberculosis. Tuberculosis is a major public health priority in the world with 8-10 million new cases added every year. [1]

Tuberculosis is a barrier to socio-economic development. The greatest burden of Tuberculosis incidence and mortality is seen in adults, the most productive members of the society. Tuberculosis affects males more than females and the prevalence of disease increases with age. [2]

The five countries with the largest number of tuberculosis cases in 2011 were India (2.0-2.5 million), China (0.9-1.1 million), South Africa (0.4-0.6 million), Indonesia (0.4-0.5 million) and Pakistan (0.3-0.5 million). India and China alone accounted for 26% and 12% of global cases, respectively. [3] Published literature strongly suggests that the most powerful predictor of the presence of multidrug resistant (MDR)-tuberculosis is a history of treatment of tuberculosis. [4] Tuberculosis patients in India get treatment with DOTS regimen not only through Revised National Tuberculosis Control Program (RNTCP), but also receive treatment from private medical practitioners, therefore involvement and coordination of both groups of medical practitioners is required for effective management of Tuberculosis. Irregular, incomplete and inadequate treatment is the most common means of acquiring drug resistant organism. [4] The current threat is MDR-tuberculosis due to the emergence of strains resistant to the two most potent anti-tuberculosis drugs - Isoniazid (H) and Rifampicin (R). [5] Drug resistance was observed in Mycobacterium tuberculosis isolates even in the early days of chemotherapy. The level of initial drug resistance is considered to be an epidemiological indicator to assess the success of the National Tuberculosis Program (NTP). Since current drug resistance data has a bearing on the design of the treatment regimens and policies, reliable information of these at the national level is both urgently and regularly needed.


  Materials and Methods Top


The present study was conducted in the Department of Respiratory Medicine at Sri Aurobindo Medical College and Post Graduate Institute, Indore, India.

The patients who were diagnosed as a case of sputum positive pulmonary tuberculosis with past history of tuberculosis treatment were included in the study.

A total of 100 patients of retreatment cases who gave oral informed consent were registered as subjects. Patients suffering from extra pulmonary tuberculosis, critically ill and human immunodeficiency virus (HIV) positive were excluded from the study.

Patients were instructed to collect two sputum samples in the falcon tubes. The collected samples are immediately transported to state accredited microbiology laboratory. In this laboratory, the samples were subjected to the culture in Lowenstein Jensen media followed by the drug sensitivity testing to the five first-line anti-TB drugs (rifampicin, isoniazid, ethambutol, pyrazinamide, streptomycin).


  Aims and Objectives Top


  1. To obtain information about sources of previous drug exposure for patients registered as retreatment cases in RNTCP Program at Sri Aurobindo Medical College & Post Graduate Institute, Indore.
  2. To find out major reasons for defaulting treatment of Tuberculosis.
  3. To measure the incidence of drug resistance in retreatment cases and analyze their pattern.



  Results Top


This study dealt with 100 cases of retreatment tuberculosis. Among these cases, 68.0% of the subjects received previous anti-tubercular treatment (ATT) from DOTS centers (Government run centers under RNTCP) and 32.0% of the subjects received from Non-RNTCP group (treatment from private practitioners). The mean age for the subjects chosen from RNTCP group was 45.31 ± 17.06 years. The mean age for the subjects chosen from private ATT group was 39.81 ± 14.02 years. The maximum numbers of subjects in this study (25.0%) were from the age group between 28-37 years. Literacy rate was 36.7% among retreatment cases. 76.5% of retreatment cases had monthly income less than 5000 rupees [Table 1].
Table 1: Category of subjects for retreatment

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The groups registered under the RNTCP program showed a lower average body mass index (BMI) in comparison with the patients enrolled in the Non RNTCP. Deranged liver functions were noted in 30.8% in RNTCP group and 16.7% in Non-RNTCP group. Highest incidence (57%) of alcoholism was seen in male population of RNTCP group. Highest incidence (38%) of smoking was seen in male population of RNTCP group. Drug intolerance was observed as the most common cause for defaulting treatment. It is seen in 20% patients of RNTCP group and 6% in Non-RNTCP group. Vomiting was most common symptom leading to drug defaulter.

Isoniazid was determined as the most common drug having resistance. It is observed in a total of 25 subjects, out of which 11 subjects were defaulters, 10 were relapse cases and 4 were treatment failure cases. Out of the total 25 subjects, 22 subjects showed resistance to rifampicin. Among these 8 subjects were defaulters, 9 subjects were relapse and 5 cases were failure. Pyrazinamide and Ethambutol had showed equal drug resistance identified in 20 patients for each. The drug resistance for streptomycin was found in 19 subjects, most of them were defaulters. Total of 22 subjects showed multidrug resistant tuberculosis.

Among the subjects showing drug resistance, 6 patients were resistant to isoniazid, rifampicin, ethambutol and streptomycin and 5 patients were resistant to isoniazid, rifampicin and streptomycin. Of these, 10 patients were resistant to isoniazid and rifampicin alone. Only 1 patient was resistant to isoniazid, rifampicin and pyrazinamide.


  Discussion Top


In our study, 68% of patients had taken ATT from RNTCP who had registered for retreatment. The data was comparable to the findings of Jha et al., [6] who recorded 73% of his cases to be derived from RNTCP. While in a other study by Sachdeva et al., higher proportion of patients registered as defaulters (64%) and 'retreatment others' (59%) were likely to be treated outside the National Program, when compared to the proportion among 'relapse' (22%) or 'failure' (6%). [7] Our study reveals 63.3% of illiteracy in the study population as compared with 57.43% by Chatterjee et al., [8] and 37.53% in a study conducted by Balu et al.[9] Illiteracy therefore was recognized to be an important cause of defaulting in ATT as there is usually low level of health awareness and understanding of disease.

Reasons for defaulting were analyzed for every patient in detail based on clinical history taken at the time of presentation. The reasons determined in this study revealed drug intolerance as a major cause of drug defaulting, identified in both male and female population. This drug intolerance was related to the cumulative side effects of these drugs in the form of gastritis and abdominal discomfort. The reason usually attributed for the same was drug induced gastritis, drug induced hepatitis and the relatively poor adjustment of dosage of the drug as per subject's lean body weight. In similar studies carried out by Chatterjee et al., and Jha et al., drug intolerance could not be identified as an important reason of drug defaulting. Chatterjee et al., and Jha et al., determined distance from the DOTS center as the primary cause of defaulting but we could not identify it as a major cause in our study. It may be due to even and wide spread distribution of DOTS center in our region.

The rate of resistance in previously treated cases are invariably higher than in newly diagnosed cases, though data on resistance in previously treated patients are limited. The longitudinal trend of drug resistance in Gujarat between 1980 and 1986 shows that in treatment failure or relapsed patient, resistance to rifampicin increased from 2.8% in 1980 to 37.3 % in1986 and to isoniazid from 34.5% to 55.8%. [10] It was presumed that high level of rifampicin resistance was almost entirely acquired.

A study conducted by the Institute of Thoracic Medicine, Chennai [11] aimed at finding out the prevalence of Tuberculosis resistance in four Districts. The Tuberculosis Centers in Tamil Nadu, showed that acquired resistance was 63%, out of which 23.5% were resistance to single drug and 39.5% resistant to more than one drug. In a recently conducted study in Bengaluru, [12] the MDR in previously treated cases was found to be 12.8% and ranged from 8.4-17.2%. The proportion of 12% MDR-tuberculosis in previously treated patient appears to be similar in other DOTS implemented areas, such as Hong Kong. [13]

Kandi S et al., showed 28% MDR among previously treated patient in a tertiary care hospital of Hyderabad. [14] In another study conducted by Paramasivan et al., [15] showed that 20.3% MDR-Tuberculosis in previous treated patient and mono drug resistance was 23.5% as compared with 22% MDR-Tuberculosis and 25% mono drug resistance in our study. The overall rates of resistance in previously treated patients to isoniazid ranged from 34.5-67%, for streptomycin from 26.0-26.9% and for rifampicin from 2.8-37.3%. But in our study finding, rates of drug resistance in previously treated patient to isoniazid was 25%, rifampicin 22%, ethambutol and pyrazinamide 20% and streptomycin to 19%, which are lower in comparison to previous study.


  Conclusion Top


Our study identifies drug intolerance, ignorance about advised treatment, and early symptomatic relief as the predominant causes of defaulting. Drug resistance was identified as 25% mono drug and 22% MDR among retreatment cases. Isoniazid (25%) was the most common drug against which drug resistance was identified. Addiction to tobacco and alcohol was seen in a very significant proportion of all the study subjects. High prevalence rate of drug resistance was observed in retreatment cases and so we conclude that in all freshly diagnosed cases of pulmonary tuberculosis, the ATT as recommended by RNTCP should be started immediately but before starting the treatment sputum for AFB Culture and Sensitivity should be sent to identify primary drug resistance.

 
  References Top

1.
Mitter B, Schieffelbein C. Tuberculosis. Bull World Health Organ 1998;76 Suppl 2:141-3.  Back to cited text no. 1
    
2.
Sivaraman S. Tuberculosis in India: The prospects. Indian J Tuberc 1999;46:81.  Back to cited text no. 2
    
3.
Available from: http://www.who.int/tb/publications/global_report/gtbr12_main.pdf page no11 [Last assessed on 2014 Feb 10].  Back to cited text no. 3
    
4.
Sharma SK. Multi drug resistant tuberculosis. Indian J Med Res 2004;4:76.  Back to cited text no. 4
    
5.
Paramasivan CN, Bhaskaran K, Venkataraman P, Chandrasekaran V, Narayanan PR. Surveillance of drug resistance in tuberculosis in the state of Tamil Nadu. Indian J Tuberc 2000;47:27-33.  Back to cited text no. 5
    
6.
Jha UM, Satyanaryanan S, Dewan PK, Chatham S, Wartes F, Sahu S, et al. Risk factors for treatment default among re- treatment tuberculosis patients in India, 2006. PLoS One 2010;5:e8873.  Back to cited text no. 6
    
7.
Sachdeva KS, Satyanarayana S, Dewan PK, Nair SA, Reddy R, Kundu D, et al. Source of previous treatment for re-treatment TB cases registered under the National TB control Programme, India, 2010. PLoS One 2011;6:e22061.  Back to cited text no. 7
    
8.
Chatterjee P, Banarjee B, Dutt D, Pati RR. A comparative evaluation of factors and reasons for defaulting in tuberculosis treatment in the states of West Bengal and Jharkand and Arunachal Pradesh. Indian J Tuberc 2003;50:17.  Back to cited text no. 8
    
9.
Balu, Jha PK, Murleedhar. A study of defaulters of dots in Warangal district of Andhara Pradesh. J Eval Med Dent Sci 2013;2:7234-9.  Back to cited text no. 9
    
10.
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. 10
    
11.
Vasanthakumari R, Jagannath K. Multi drug resistance tuberculosis- A Tamil Nadu Study. Lung India 1997;15:178-80.  Back to cited text no. 11
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12.
Sophia V, Balasangameshwara VH, Jagannath PS, Saroj VN, Shiva Shankar B, Jagota P. Retreatment outcome of smear positive Tuberculosis under DOTS in Bangalore city. Indian J Tuberc 2002;49:195-204.  Back to cited text no. 12
    
13.
Kam KM, Yip CW. Surveillance of mycobacterium tuberculosis drug resistance in Hong Kong, 1986-1999, after the implementation of directly observed treatment. Int J Tuberc Lung Dis 2001;5:815-23.  Back to cited text no. 13
    
14.
Kandi S, Prasad SV, Sagar Reddy PN, Reddy VC, Laxmi R, Koppu D, et al. Prevalance of multidrug resistance among retreatment pulmonary cases in a tertiary care hospital, Hyderabad, India. Lung India 2013;30:277-9.   Back to cited text no. 14
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Paramasivan CN. An overview of drug resistant tuberculosis in India. Indian J Tuberc 1998;45:73-81.  Back to cited text no. 15
    



 
 
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Abstract
Introduction
Materials and Me...
Aims and Objectives
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