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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 11
| Issue : 1 | Page : 88-93 |
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A study of rifampicin and isoniazid resistance in pulmonary tuberculosis patients with various radiological presentations at a designated microscopy center
Roshan Lal1, Chandra Shekhar2, Neeraj Kumar3, Kajal Chandrakar4
1 Department of TB and Chest, Government Medical College, Mahasamund, Chattishgarh, India
2 Department of TB and Chest, The Neurocity Hospital, Varanasi, Uttar Pradesh, India
3 Department of Pulmonary Medicine, GSVM Medical College, Kanpur, Uttar Pradesh, India
4 Department of Pathology, Government Medical College, Mahasamund, Chattishgarh, India
| Date of Submission | 06-Jul-2022 |
| Date of Decision | 01-Sep-2022 |
| Date of Acceptance | 06-Sep-2022 |
| Date of Web Publication | 02-Feb-2023 |
Correspondence Address:
Roshan Lal
Department of TB and Chest, Government Medical College, Mahasamund, Chattishgarh
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/mjhs.mjhs_44_22
Background: Correlation between chest X-ray findings and drug resistance can provide valuable guide for physicians working at low-resource settings.
Objective: To study tuberculosis (TB) drug sensitivity pattern as per the radiological presentation.
Materials and Methods: A hospital-based prospective study was conducted among 67 newly diagnosed sputum-positive pulmonary TB patients who never took anti-TB treatment. They were subjected to history, systemic examination, radiology, and sputum smear examination. Ten patterns of chest X-ray were studied in the present study, which was not studied before. Chest X-ray radiology pattern was correlated with the drug resistance.
Results: Isoniazid (INH) monoresistance was present in 11.9% of patients. 1.5% had rifampicin (RIF) resistance but no INH resistance. RIF and INH both resistance (multidrug-resistant [MDR]) was present in 7.5% of cases. Pattern Four was the most common radiological presentation in our patients being present in 20 (29.9%) patients. In this pattern, bacteria of 5.0% were RIF resistant. 15.0% were INH resistant, and 5.0% were both RIF and INH resistant (MDR). RIF resistance was most common in chest X-ray PA view with “Pattern Two” being present in bacteria of 21.42% of patients.
Conclusion: Radiological patterns 2, 3, and 4 were highly correlated with the multidrug resistance, but it was not statistically significant. Patients' chest X-ray showing these patterns can be suspected to have MDR-TB and sent for further evaluation for early diagnosis and treatment of MDR-TB, which will give us good outcome. Further studies on this hypothesis should be conducted with bigger sample size to throw more light in this field.
Keywords: Directly observed treatment short course chemotherapy (DOTS), lung disease, resistance, sensitivity, tuberculosis
How to cite this article:
Lal R, Shekhar C, Kumar N, Chandrakar K. A study of rifampicin and isoniazid resistance in pulmonary tuberculosis patients with various radiological presentations at a designated microscopy center. MRIMS J Health Sci 2023;11:88-93 |
How to cite this URL:
Lal R, Shekhar C, Kumar N, Chandrakar K. A study of rifampicin and isoniazid resistance in pulmonary tuberculosis patients with various radiological presentations at a designated microscopy center. MRIMS J Health Sci [serial online] 2023 [cited 2023 Mar 30];11:88-93. Available from: http://www.mrimsjournal.com/text.asp?2023/11/1/88/369043 |
| Introduction | |  |
Tuberculosis (TB) is an ancient infectious disease, caused by Mycobacterium tuberculosis that remains a threat for public health around the world. TB appeared to be a disease that could be easily eradicated, with the discovery of effective antitubercular drugs, but as the antitubercular drugs evolved, the M. tuberculosis bacteria also evolved, developing resistance to the antitubercular drugs in a gradual manner, predominantly due to inadequate or inappropriate treatment of TB. These drug-resistant strains were moderately less virulent due to the metabolic compromises made to enable drug resistance.[1]
The emergence of resistance to drugs used to treat TB, and particularly multidrug-resistant TB (MDR-TB), has become a significant public health problem in a number of countries and an obstacle to effective TB control. In India, the available information from the several drug resistance surveillance studies conducted in the past suggest that the rate of MDR-TB is relatively low in India. Under the National Tuberculosis Elimination Program, measures are taken to control MDR-TB. This is done by regular treatment of MDR-TB patients and preventive measures for the same.[2]
It has been estimated that about 37% of new cases go missing every year globally. The cases detection and treatment rate for MDR-TB has been estimated to be very low at 25%. Even for HIV-TB cases, the rate of detection and treatment increased; it has been estimated to be only one-third of the actual.[3]
The prevalence of MDR-TB worldwide is around 3.3% among the new cases of TB, while it is about 20% in the previously treated cases. With the more and more use of molecular tests, the case detection rate is improving year on year. Around more than 50% of the global MDR-TB cases are supposed to be from India, China, and Russia. Western Pacific Region of the World Health Organization shows that the detection rates are poor. Globally, about 90% of the enrolled cases start treatment. The success rate of treatment for MDR-TB is only 50%. Some countries are demonstrating more than 75% of the success rates. The prevalence of extensively drug-resistant TB is 9.7% among MDR-TB cases.[4]
A study of rifampicin (RIF) and isoniazid (INH) drug sensitivity patterns with correlation to chest X-ray finding can help physicians to suspect the level of drug resistance at an early stage. Chest X-ray is easily available and can guide early detection of drug resistance, thereby preventing the chances of treatment failure.
The present study was carried out to correlate chest X-ray PA view presentations in new sputum-positive pulmonary TB patients with RIF and INH drug sensitivity patterns in patients attending the Department of Tuberculosis and Respiratory Diseases, G. S. V. M. Medical College, Kanpur.
| Materials and Methods | | |
This was a hospital-based prospective study conducted in the Department of Tuberculosis and Respiratory Diseases, G. S. V. M. Medical College, Kanpur, and the Department of Microbiology, K. G. M. U, Lucknow, from January 2014 to August 2016.
Inclusion criteria
Newly diagnosed sputum-positive pulmonary TB patients who never taken anti-TB treatment.
Exclusion criteria
- Diabetic
- HIV positive.
Sixty-seven pulmonary TB patients who were sputum smear positive and had never taken anti-TB treatment from the outpatient department and ward were included in the study. All patients were subjected to detailed clinical history, systemic examination, radiological examination, and sputum smear examination for acid-fast bacilli staining (fluorescent staining). Patients were also investigated for complete blood count, blood sugar (fasting and postprandial) to screen diabetes mellitus, serum creatinine, serum urea, serum bilirubin, serum glutamic-pyruvic transaminase, and serum glutamic-oxaloacetic transaminase and referred to ICTC center to know HIV infection status.
Patients were advised to collect morning sputum samples in falcon tube. Sputum samples were packed and transported to intermediate reference laboratory (IRL) KGMU, Lucknow.
At laboratory, the sputum sample was processed by NaOH-NALC method. Then, the DNA extracted from pretreated sputum sample was subjected to amplification of genes with biotinylated primers. Then, the amplified DNA was hybridized to the probes and the bands visually detected by means of a color-forming enzymatic reaction involving streptavidin adhering to biotinylated primers. Line probe assay results were noted.
Radiological presentations were classified in 10 patterns in our observation, which was not previously published in any literature. It was recorded as Site of lesion (unilateral/bilateral), Extent of lesion (restricted/unrestricted to zones), and type of lesion like Nodular shadows, One or more cavity (present/absent), tension cavities, (lobar/segmental/subsegmental) atelectasis or overinflation favoring endobronchial tuberculosis, miliary shadows, pneumo/hydropneumothorax, and whole lung consolidation. The investigator who did the radiological reporting was unaware of drug sensitivity testing (DST) results [Table 1].
Statistical analysis
The data were entered into the Microsoft Excel worksheet and analyzed using proportions. Chi-square test was applied for comparison data and P < 0.05 was taken as statistically significant.
| Results | | |
[Table 2] shows the distribution of study subjects as per the sociodemographic variables. Majority of the patients were in the age group of 20–39 years (43.3%). Males were slightly more than females. People from rural area were more affected compared to urban area. Majority of the cases were farmers and students. 37.3% chewed tobacco and 22.3% were smokers. | Table 2: Distribution of study subjects as per the sociodemographic variables
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[Table 3] shows the distribution as per the clinical features. Cough was universal and fever was seen in 85.1% of the cases. Hemoptysis was seen in 14.9% of the cases. Pallor was the most common clinical finding.
[Table 4] shows the drug sensitivity pattern among cases. The prevalence of drug resistance was 20.9% in the present study. 1.5% had resistance to only RIF and 11.9% had resistance to INH only. 7.5% had resistance to both the drugs.
[Table 5] shows the drug sensitivity pattern among cases as per the radiological presentation. Drug resistance was 26.7% among those with patterns 2, 3, and 4 compared to only 9.1% among those with patterns 5-10. Even though the difference was more, on applying the Chi-square test, the difference was not found to be statistically significant.{Table 4}
[Table 6] shows the comparison of drug sensitivity pattern for endobronchial lesion versus nonendobronchial lesion. The prevalence of drug resistance was more in those without endobronchial lesions compared to those with endobronchial lesions. However, this difference was not found to be statistically significant (P > 0.05). | Table 6: Comparison of drug sensitivity pattern for endobronchial lesion versus nonendobronchial lesion
Click here to view |
[Table 7] shows the comparison of drug sensitivity pattern for bilateral lesions versus unilateral lesions. The prevalence of drug resistance in those with bilateral lesions on radiology was 25.9% compared to only 20.6% among those with unilateral lesions. This difference was not found to be statistically significant. | Table 7: Comparison of drug sensitivity pattern for bilateral lesions versus unilateral lesions
Click here to view |
| Discussion | | |
The present study was conducted in the Department of Tuberculosis and Respiratory Diseases, Dr. Murari Lal Chest Hospital, G. S. V. M Medical College, Kanpur, from January 2015 to August 2016. Line probe assay of the specimens was done at RNTCP IRL, Department of Microbiology, KG Medical University, Lucknow.
A total 67 patients were registered: 56.71% were male and 43.28% were female. Most of the patients (43.28%) were in the 21–40 years of age group, and the mean age of patients was 34.46 ± 15.61 years. Majority of our study patients were from rural background (64.17%).
The predominant symptoms in our cases were cough (100%), followed by expectoration (88.05%), fever (85.07%), and breathlessness (49.25%). 14.92% of patients presented with hemoptysis as a complaint.
Total 50.74% of patients had a history of contact; 26.86% of the patients were “Close Contacts” with Pulmonary Tuberculosis whose sputum status was unknown and 23.88% were Close Contacts of known Sputum Positive Pulmonary Tuberculosis patients. None of our patients were close contact of MDR tuberculosis patients. Kumar et al.[5] studied the prevalence of TB among 1810 contacts of 50 cases and found that the prevalence was 5.4% among the household contacts and 2.6% among the neighborhood contacts. The prevalence was more among sputum-positive contacts than the sputum-negative contacts. Gupta et al.[6] noted that the prevalence symptoms suggestive of TB among the contacts were 3.5%. The yield of secondary cases was 4.5%.
In the present study patients, 37.31% were tobacco-chewing addicts, 22.3% were smokers, and 19.4% were alcohol addicts. Agarwal and Agrawal[7] observed that the prevalence of TB among smokers was 23.6%. The odds of having TB were 4.8 times more among smokers compared to the nonsmokers. Dyspnea was the most common symptom in their study. Smokers had more proportion of cavitations and fibrosis in 98%. Among heavy smokers, high positivity rate was noted.
Pallor was the most common finding in general examination present in 71.64% of our patients. Sputum smears of all our patients were positive. Sputum positivity grading of our patients were 47.76% had 3+, 19.40% had 2+, 19.40% had 1+ and 13.43% were scanty positives. The grading was done as per the guidelines of RNTCP. Line probe assay was done in all sputum smears with a view to know RIF and INH drug resistance. It was discovered that 79.10% of patients were sensitive to both RIF and INH, 11.9% were resistant to INH monoresistance, 1.5% were resistant to RIF only, and 7.5% were resistant to both RIF and INH. Elahi et al.[8] in Lahore, Pakistan, in a study of INH resistance among 169 new cases of sputum smear-positive pulmonary tuberculosis found that frequency of resistance to INH came out to be about 20.1%, while 79.9% of persons were found sensitive to INH. 13 (7.7%) patients had RIF resistance alone, while multidrug resistance (INH and RIF) was found in 7.1% of patients. They determined drug resistance by 'proportion method'. Saugat et al.[9] in Bikaner, Rajasthan, India, studied RIF and INH resistance among the 100 new sputum smear-positive patients. They found MDR TB (RIF and INH resistance) was present in 1%, INH monoresistance in 12% and nil monoresistance to RIF. Though 79.10% of patients were also drug sensitive INH and RIF, there were 10.44% were. The total INH resistance in our study was 19.4% and the total RIF resistance as 9.0%. Dhingra et al.[10] in their study found that a total of 94.77% of samples were sensitive to the four first line essential drugs and IDR to any drug was 5.22%.
We classified chest X-ray PA view in ten patterns which were commonly seen in patients attending our hospital. It was being observed in the last 4–5 year in our department that some X-ray patterns were associated with INH resistance and resistance to RIF and INH both. On the basis of these scattered observations, the present study was undertaken. We did not find much in the literature about such observations in other centers.
In our study, maximum 29.9% of patients had “Pattern Four” which had predominantly/only one-sided lesions, restricted to one or contiguous zones, tension cavity/cavities, lobar/segmental/subsegmental atelectasis or over inflation favoring endobronchial tuberculosis. In this pattern, out of 20 patients, 3 (15%) were having bacteria resistant to INH and 2 (10%) patients had bacteria resistant to RIF, Out of them 1 (5%) had bacteria resistant to both RIF and INH.
The second most common presentation was “Pattern Two” present in 14 (20.89%) patients in which there are Bilateral lesions, nodular shadows, one or more cavities. RIF and INH resistance was most common and being present in bacteria of 3 out of 14 (21.42%) patients and one (7.1%) had resistant to INH.
In Pattern Three had 11 (16.42%) patients, in which bacteria resistant to INH had 2 (18.2%) and one patient's bacteria (9.1%) were resistance to both RIF and INH.
The lone patient in “Pattern Nine” findings in chest X-ray PA view consisting of Lobar/Whole Lung Consolidation, had bacteria resistant to INH. There were four patients in chest X-ray PA view “Pattern Six” consisting of predominantly/only unilateral lesions, not restricted to one or more contiguous zones, no tension cavity/cavities, no lobar/segmental/subsegmental atelectasis or over inflation. One (25%) of these patients had bacteria resistant to INH and none had RIF resistance.
Zahirifard et al.[11] observed that MDR-TB is characterized by multiple bilateral cavities along with the pleural effusion. These findings are usually absent in those patients who have drug sensitive TB. Unlike our study, they included both previously untreated and treated cases.
Dholakia et al.[12] observed a statistically significant association between MDR-TB and lung cavitation on X-ray. Bilateral cavities were more common in MDR-TB cases and among the males.
When endobronchial Disease with two characteristics (a) “Nodular shadows, no/one or more cavities, but no tension cavity, atelectasis or obstructive inflation favoring endobronchial lesion” verses (b) “tension cavity/cavities, lobar/segmental/subsegmental atelectasis vs over inflation favoring endobronchial lesions” were compared with non endobronchial Disease it was found that drug resistance was present in bacteria of 25.8% in former and 18.5% in latter.
When X-ray pattern having bilateral lesions were compared with those having unilateral lesions, INH monoresistance was present in bacteria of 12% patients in bilateral lesions versus 14.7% Unilateral Lesions. RIF and INH combined resistance was present in 16% of former verses 3.0% in latter. (Patterns 1 + 2 + 3 vs. 4 + 5 + 6 + 9).
When X-ray Chest PA View Unilateral (or Predominantly unilateral) restricted to one or more contiguous zones or not restricted to one or more contiguous zones were compared on two variables namely: (a) Presence of Tension cavity/cavities, or lobar/segmental/subsegmental atelectasis or over inflation favoring endobronchial tuberculosis verses (b) No Tension cavity/cavities, or lobar/segmental/subsegmental atelectasis or over inflation favoring endobronchial tuberculosis it was found that RIF resistance was 10% in former than nil in latter. (Patterns 4 vs. 5 + 6).
When two variables namely all lesions suggestive of endobronchial lesions Verses all lesions not suggestive of endobronchial lesions were compared then it was found that INH monoresistance was less in patients having lesions which are not in favor of endobronchial type. It was 7.4% as compared to 16.12% in the endobronchial group (3 + 4 vs. 1 + 2 + 5 + 6).
Finally, the chest X-ray pattern was not found to be significantly associated with the drug resistance. However, it showed that drug resistance was more in those with bilateral lesions compared to unilateral lesions. Further studies may be required with large sample size to establish this association.
| Conclusion | | |
Radiological patterns 2, 3, and 4 were highly correlated with the multidrug resistance, but it was not significant statistically. Patients' chest X-ray showing these patterns can be suspected to have MDR-TB and sent for further evaluation for early diagnosis and treatment of MDR-TB which will give us good outcome. Further studies on this hypothesis should be conducted with bigger sample size to throw more light in this field.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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