Abstract
Diagnosing EPTB is difficult as various clinical presentations are seen with paucibacillary nature of the disease. Maurya AK et al. (J Postgrad Med 58(3):185–189) AFB smear hasn’t been much effective in diagnosing of EPTB. Tuberculosis of head and neck diagnosis can be missed due to large number of smear negative cases, leading false negative cases increase. CBNAAT is cartridge-based nucleic acid amplification test which detects the presence of TB bacilli this study we have examined the effectiveness of CBNAAT for diagnosing EPTB with cervical lymphadenitis and compared with Sputum AFB Microscopy smear. Aims and objective 1.To study the role of cartridge-based nucleic acid amplification test (CBNAAT) in early diagnosis of extra pulmonary tuberculosis. 2 Comparative analysis of CBNAAT with AFB smears in EPTB. Type of Study Descriptive retrospective observational study was done at the department of ENT and Head & surgery, A.B.V. Govt medical college, Vidisha, M.P, India. Result Out of 184 patients 43 samples were AFB smear positive and 141 were negative. In CBNAAT 88 out of 184 and 96 were found to be negative.32 patients were negative on Sputum microscopy AFB analysis but found to be positive on CBNAAT. Sensitivity of CBNAAT was 86% AFB 64%, Specificity of CBNAAT, AFB is 91% and 89% respectively. Our study finds that CBNAAT is much more effective in diagnosis of EPTB with cervical lymphadenitis when compared to AFB smear microscopy alone.
Keywords: CBNAAT, Lymph node TB, AFB direct smear, Cytology, AFB culture, Extrapulmonary tuberculosis (EPTB)
Introduction
Tuberculosis is an ancient disease known to mankind, found in human remains dating from at least 5000 BCE; still tuberculosis (TB) remains one of the leading cause of morbidity and mortality in the world [1]. World Health Organization (WHO) report in 2015 stated that the global annual incidence of tuberculosis was 9.6 million cases, and out of which 2.2 million cases are reported in India, making it highest TB burden country in the world with one fourth of the global burden of tuberculosis [2]. 23% of global annual TB incidents occurs in India [3] tuberculosis is still one the leading causes of childhood mortality and morbidity in almost all developing nations [4]. Diagnosing EPTB is difficult as various clinical presentations are seen with paucibacillary nature of the disease [5]. AFB smear hasn’t been much effective in diagnosing of EPTB. Cervical lymphadenitis is one of the common modes of presentation in extra pulmonary tuberculosis. Patients have usually no major clinical symptoms or signs except nodal enlargement. Patients suffering from Tuberculosis of head and neck diagnosis can be missed due to large number of smear negative cases, which leads to missing out the positive cases increasing the burden of TB. CBNAAT is cartridge-based nucleic acid amplification test which detects the presence of TB bacilli and tests for resistance to Rifampicin also. It has made the diagnosis and treatment of EPTB easy and effective, as it is a very rapid test with high sensitivity. Hence, in our study we have studied the effectiveness of CBNAAT for diagnosing EPTB with cervical lymphadenitis and compared with Sputum AFB Microscopy smear. Our study is a Descriptive retrospective observational study and conducted as an Institutional Research project by the Department of ENT and Head & Neck Surgery, A.B.V Govt Medical College, Vidisha, MP, India.
Aims and Objective
To Study the role of cartridge-based nucleic acid amplification test (CBNAAT) in early diagnosis of extra pulmonary tuberculosis.
Comparative analysis of CBNAAT with AFB smears in EPTB.
Materials and Method
Type of Study Descriptive retrospective observational study
The study was conducted as an Institutional Research project done by the department of ENT and Head & surgery at Atal Bihari Government medical college, Vidisha, M.P, India along with RNTCP lab associated with district hospital, Vidisha, M.P India. In our study 184 patient samples were collected visiting the ENT OPD at Atal Bihari Government medical college, Vidisha, M.P, India having suspected extrapulmonary tuberculosis with cervical lymphadenitis.
Duration of the Study Study was conducted for a period of 1 year during January 2019 to January 2020.
Inclusion criteria All Patients were included in the study visiting the ENT OPD having suspected extrapulmonary tuberculosis with cervical lymphadenitis.
Exclusion Criteria
Patients who already have pulmonary tuberculosis.
Defaulter cases of tuberculosis.
Patients not willing for any samples for CBNAAT were also excluded from the study.
Patients suspected to have extrapulmonary tuberculosis with cervical lymphadenitis both sputum AFB microscopy smear and CBNAAT were taken. Pus was aspirated from the cervical abscess and sent for CBNAAT to the RNTCB lab in the associated district hospital, Vidisha. Sputum smear microscopy was also done by light emitting diode (LED) fluorescent microscopy and the results of both the AFB smear and CBNAAT of the samples of all the suspected extrapulmonary tuberculosis patients were compared in the study. CBNAAT is cartridge-based nucleic acid amplification test and it detects TB bacilli presence and Rifampicin resistance. CBNAAT can take up to 2 h to gives accurate results and it is rapid, cost effective simple as well as simple test which doesn’t not require much technical expertise.
Results
| Test | CBNAAT Pus aspirate analysis | AFB sputum analysis |
|---|---|---|
| Positive test | 88 | 43 |
| Negative test | 96 | 141 |
| Total patients | 184 | 184 |
Out of 184 patients suspected extrapulmonary tuberculosis cases with cervical lymphadenitis, 43 samples were AFB smear positive and 141 were negative for AFB smear. Where as in CBNAAT results, 88 out of 184 suspected extrapulmonary tuberculosis with cervical lymphadenitis cases were positive for TB bacilli and 96 were found to be negative. When we analyzed and compared the results of 184 samples of AFB smear and CBNAAT we have observed that 32 patients were negative on Sputum AFB analysis were as they were found to be positive on TB bacilli in CBNAAT, hence 32 patients were found to be false negative in AFB sputum analysis. In only 14 samples were positive of AFB sputum analysis and negative on TB bacilli on CBNAAT. And 18 patients were both positive on AFB and CBNAAT. In our study we have found that the sensitivity of CBNAAT for extrapulmonary tuberculosis was found out to be around 86% when compared to AFB sputum smears which was 64%, Specificity of CBNAAT is 91 and 89% for sputum AFB microscopy in EPTB cases with cervical lymphadenitis.
Discussion
Diagnosing EPTB has always been difficult as it has various clinical and subclinical presentations with paucibacillary nature of disease leading to further delay in the diagnosis. This delay in diagnosis of TB is responsible for a large burden of disease in the population. Culture DST is still the gold standard for diagnosis for tuberculosis but it is time consuming and also requires skilled trained workers. Most common presentation of extrapulmonary Tuberculosis is tuberculous cervical lymphadenitis. Early diagnosis and early initiating of anti-tubercular treatment plays a very crucial role in control and spread of the disease and further limits the mortality and morbidity of disease. The introduction of the CBNAAT assay has significantly revolutionized the diagnostics of tuberculosis. In our study we have taken from 184 patient’s suspected extrapulmonary tuberculosis with cervical lymphadenitis. 43 samples were AFB smear positive and 141 were negative for AFB smear. Where as in CBNAAT, 88 out of 184 suspected extrapulmonary tuberculosis with cervical lymphadenitis cases were positive for TB bacilli and 96 were found to be negative. Sputum microscopy for AFB is a simple, economical, and easy to perform test in diagnosing pulmonary tuberculosis. But at least 10,000 bacilli per ml should be present to give a positive result and it is subjective test as it depends a lot on the examiner. This sensitivity of sputum AFB is further decreased in PLHIV due to lower rates of caseous necrosis and sputum production [6]. On the other hand CBNAAT is a semi-quantitative nested nucleic acid amplification test which is based on the molecular detection of mutated gene. It is simple, rapid, and cost effective and doesn’t require much technical expertise. Diagnosis can be made within 2 h with accurate result another advantage is that it has a disposable closed cartridges which further prevents cross contamination of disease [7]. A study conducted by Denkinger et al. states that the sensitivity of CBNAAT for TB bacilli detection in pleural fluid was 46% and sensitivity among lymph node specimens was 83% [8]. where as in an a another study conducted by Sharma et al. regarding the utility of GeneXpert in diagnosing EPTB has shown an overall sensitivity of 71% and PPV ranging from 98 to 100%. [9] In a study conducted by Armand et al. the sensitivity of CBNAAT in extrapulmonary samples, the sensitivity was highest among lymph nodes (94.74%) [10]. In our study we have found that the sensitivity of CBNAAT for extrapulmonary tuberculosis was found out to be around 86% when compared to AFB sputum smears which was 64%, Specificity of CBNAAT is 91 and 89% for sputum AFB microscopy in EPTB cases with cervical lymphadenitis. Hence our study finds that CBNAAT is much more effective as compared to Sputum AFB smear microscopy in the diagnosis of EPTB with cervical lymphadenitis and it should be routinely used in diagnosis of EPTB with other tests such as AFB smear examination and culture DST.
Conclusion
This delays in starting anti-tubercular medication tuberculosis patients, amplifies the risk of transmission of drug-resistant TB in the surrounding community and further increases the risk of spread to extrapulmonary sites within the patient itself [11]. Tuberculous lymphadenitis is the most common form of extrapulmonary Tuberculosis. CBNAAT assay which is a rapid, cost effective, rapid test which can identify the presence of Mycobacterium tuberculosis in EPTB with high sensitivity; it can identify the resistance to rifampicin associated with mutation of rpoB gene in a single test. This helps in early diagnosis and detection of EPTB with further reduces the mortality and morbidity associated with the disease, proper diagnosis also reduces the number of false negative and false positive cases which helps avoiding injudicious use of anti-tuberculosis drugs. Our study finds that CBNAAT is much more effective as compared to AFB smear microscopy alone in the diagnosis in cases of EPTB with cervical lymphadenitis particularly in places with high burden and limited availability of resources (Figs. 1, 2).
Fig. 1.
Suspected EPTB patient with Cervical abscess
Fig. 2.
Aspiration of Pus and sent for CBNAAT
Funding
No funds were taken from any source as all investigations were done free of Cost in Govt Medical College, Vidisha, M.P, India.
Declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Informed Consent
Written consent was taken from all the patients prior to their participation In the study.
Footnotes
Vote of thanks: Respected Prof. Dr Sunil Nandeshwar sir, Dean A.B.V Govt medical college, Dr Shivkumar Raghuwanshi sir Assoc Prof, & HOD Department of ENT and Head & Neck Surgery, A.B.V Govt Medical college, Dr D. Paramhans sir Medical Superintendent A.B.V Govt Medical college, Dr Sanjay Khare sir Civil Surgeon, District Hospital, Vidisha, Dr Puneet Maheshwari sir Nodal officer TB control program, District Hospital, Vidisha thank you for your Guidance and encouragement.
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