European Journal of Cardiovascular Medicine

Tuberculosis (TB) remains one of the most widespread infectious diseases globally, with approximately 10.6 million cases reported in 2022, according to the WHO. However, only about 7 million of these cases reach TB care centres, while the remainder go undiagnosed. TB continues to be the leading cause of death from a single infectious agent [WHO 2022¹]. India accounted for 27% of new TB cases, the highest among the 30 high-burden countries, and also reported the second-highest number of multidrug-resistant TB (MDR-TB) cases globally, with around 110,000 cases annually. MDR-TB, defined as resistance to at least rifampicin and isoniazid, arises due to various factors such as poor compliance, inappropriate treatment regimens, and substandard medications^2,3. Unfortunately, only 20% of MDR-TB cases are diagnosed, largely due to the unavailability of specialized testing facilities. The Revised National Tuberculosis Control Programme (RNTCP) has introduced measures such as Drug Susceptibility Testing (DST)⁴, improved culture techniques, and the Directly Observed Treatment Short Course (DOTS) to manage MDR-TB. However, several challenges still hamper TB control, including delayed diagnosis, lack of trained personnel, inaccessible healthcare services, and treatment noncompliance. Traditional diagnostic methods such as smear microscopy and solid culture have significant limitations. Smear microscopy has low sensitivity and is prone to quality control issues, while culture techniques are slow, with a turnaround time of up to 21 days⁵. Though liquid culture techniques offer faster results, they are still too slow to significantly reduce transmission risk. In response to these limitations, nucleic acid amplification tests (NAATs), such as conventional polymerase chain reaction (PCR) and line probe assays, were developed to detect TB and drug resistance more rapidly. However, conventional NAATs require skilled personnel, expensive equipment, and are vulnerable to contamination due to multiple manual steps^6,7. The cartridge-based nucleic acid amplification test (CBNAAT) addresses many of these issues. It is an automated, PCR-based test that detects Mycobacterium tuberculosis and Rifampicin resistance by targeting the rpoB gene. CBNAAT delivers results in approximately 100 minutes and has demonstrated high accuracy, with a sensitivity of 92.2% for culture-positive cases and a specificity of 99%, outperforming direct sputum smear microscopy^8,9. Due to its speed and reliability, CBNAAT represents a valuable tool in the early diagnosis and effective management of drug-resistant pulmonary tuberculosis.

AIM

Study of Initial Drug Resistance in Newly Detected Cases of Pulmonary TB by CBNAAT in Tertiary Care Hospital.

This hospital-based observational study was conducted at Mahatma Gandhi Medical College & Hospital, Jaipur, over a period extending from March 2023 to August 2024. Prior to the commencement of the study, ethical clearance was obtained from the Institute Ethics Committee. Additionally, written and informed consent was collected from all participants before their enrolment. The study included a total of 100 patients who were newly diagnosed with pulmonary tuberculosis. The inclusion criteria comprised patients admitted to Mahatma Gandhi Hospital, Jaipur, who were identified as newly detected cases of pulmonary TB. Both male and female patients aged between 18 and 65 years were considered eligible. Patients were excluded from the study if they had a history of prior anti-tubercular treatment (ATT), were diagnosed with extrapulmonary tuberculosis, were pregnant women, or were co-infected with HIV. The study aimed to assess drug resistance patterns among new pulmonary TB cases and evaluate diagnostic tools and clinical outcomes within the defined cohort.

Table 1: Mean Age of the Study Group

Above table shows that the mean age of study group was 44.54 ± 10.61 years.

Table 2: Distribution of clinical symptoms in Study Group

Above table shows that in present study the most common symptom in patients was Cough, followed by Fever. Expectoration was present in 48% cases, Shortness of Breath was present in 34% cases, loss of appetite was present in 70% cases, Hemoptysis was present in 24% cases, Weight loss was present in 74% cases, Generalised Weakness was present in 50% cases.

Table 3: Distribution of clinical signs in Study Group

Above table shows that Pallor was present in 54% cases, Tachycardia was seen in 16% cases, Tachypnea was seen in 42% cases, Wheeze was present in 16% cases and Crepitation was present in 30% cases.

Table 4: Residential profile of cases as per MDR

Above table shows that group of pulmonary TB patients without MDR and group of pulmonary TB patients with MDR was comparable on parameter of residential status.

Table 5: Chest-X ray finding and Lung Zone Involvement profile of cases as per MDR

Above table shows that group of pulmonary TB patients without MDR and group of pulmonary TB patients with MDR were comparable on parameters of distribution of Chest-X ray finding but on basis of Lung Zone Involvement we found that all 4 patients with MDR TB have Midzone involvement whereas group of TB patients without MDR involvement maximum patients have involvement of Upper Zone.

Table 6: Sputum AFB positivity profile of cases as per MDR

Above table shows that group of pulmonary TB patients without MDR and group of pulmonary TB patients with MDR have significant differences in terms of Sputum AFB positivity index. Out of 4 patients of pulmonary TB with MDR are 3 are Sputum AFB 3+ Positive, and 1 is Sputum AFB 2+.  

Table 7: Resistance to Rifampicin profile of cases as per MDR

Above table shows that group of pulmonary TB patients without MDR and group of pulmonary TB patients with MDR have significant differences in terms of Resistance to Rifampicin. All 4 patients of pulmonary TB with MDR have Resistance to Rifampicin, whereas out of 96 patients of pulmonary TB without MDR only 6 have Resistance to Rifampicin.

The incidence of drug-resistant tuberculosis varied throughout the nation based on number of confounding factors, such as a lack of laboratory services and a reporting system, different criteria for choosing the patients for study, the degree of drug abuse, and different questionnaires used to learn about past treatment history. Furthermore, data on drug-resistant and MDR-TB that had previously been published from India were from institutions and referral centers and did not accurately represent the country's overall drug resistance burden ¹¹.

Few studies have been conducted in the past to assess the prevalence of early medication resistance in newly diagnosed tuberculosis cases. The current investigation was conducted on 100 patients with pulmonary tuberculosis at the Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan.

Out of 100 study subjects of pulmonary TB number of males outnumbered females (60% males versus 40% females). 

Previous investigations have found higher incidence of tuberculosis infection in males¹². Sociological issues can be the cause of this¹³. Ray D et al¹⁴in their study found that incidence of pulmonary tuberculosis was higher in males as compared to females which is consistent with results of present study.

In present study the mean age of study population of pulmonary TB was 44.54±10.61 years. Sriram Selvaraju et al. in their study found that individuals aged > 30 years were more likely to have TB infection which is consistent with results of present study¹².

People living in urban location have higher chances of developing TB infection as per present analysis. 2.2% urban and 1.3% rural people have annual risk of getting TB infection as per earlier study¹³. Overcrowding, slums and migrant population play important role for the same

In present study the symptoms of pulmonary TB in patients were fever, cough, expectoration, shortness of breath, hemoptysis, weight loss, generalised weakness, and loss of appetite.  V.K. Chadha et al. in their study found that symptoms of TB in patients were fever, cough, expectoration, shortness of breath, hemoptysis, weight loss, generalised weakness and loss of appetite which is consistent with results of present study ¹⁵.

In present study the signs of pulmonary TB in patients were pallor, tachypnea, tachycardia, wheeze, and crepitations. Similarly Ray D et al. in their study found that most common signs of Pulmonary TB in patients were  pallor and  tachypnea which is consistent with results of present study¹⁴.

In present study the most common Chest-X ray finding in Pulmonary TB was Infiltration followed by Infiltration with cavity. The most common Lung Zone involvement in present study was Upper Zone followed by Middle zone involvement. Similarly Ray D et al and V.K. Chadha et al. in their study found that the most common Chest-X ray finding in Pulmonary TB was Infiltration followed by Infiltration with cavity and the most common Lung Zone Involvement was Upper Zone which is consistent with results of present study^14,15.

The upper lobes of the lungs have a higher concentration of oxygen, which can promote bacillary growth, and slower lymphatic drainage, allowing for prolonged bacterial presence¹⁶.

Resistance to Rifampicin, INH and MDR positivity in Study Group in present study the prevalence of resistance to Rifampicin was 10%, the prevalence of resistance to INH was 4% and the prevalence of MDR TB was 4%.

The prevalence of initial medication resistance in several Indian research was found to be approximately 18.8% (7.9% - 27.1%).¹⁷ These studies were carried out in various tertiary care facilities and institutions. Although these studies do not actually reflect the broader aspect of the drug resistance problem in India, the message from these research is clear: there is considerable drug resistance seen with Mycobacterium Tuberculosis. Since Rifampicin is a strong bactericidal and sterilizing agent, it is the most essential medication in the DOTS protocol. Resistance to rifampicin could cause the DOTS program to fail.¹⁸

MDR has drawn increasing attention as a potential threat to TB control. According to current estimates, the prevalence of primary and acquired MDR in India is 3.4% and 25%, respectively.¹⁹ Multidrug resistance that mostly happens because of inadequate treatment services could cause XDR-TB to appear if MDR-TB is not handled properly.

One of the biggest barriers preventing humanity from advancing in the medical system is still tuberculosis. Despite continuous efforts, TB cannot be eradicated until the NTEP's guidelines for the diagnosis and treatment of TB are followed.  The prevalence of drug-resistant tuberculosis has been rising recently.

This study emphasizes the necessity of identifying treatment resistance in all TB cases at the earliest in order to treat this new epidemic and reduce transmission. The NTEP guidelines stress the use of CBNAAT in every suspected or confirmed TB patient and to search for treatment resistance and improve patient outcomes. 

CBNAAT is a crucial diagnostic tool for sputum-negative patients' early identification and care.

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