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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 4  |  Page : 373-378

Performance of loop-mediated isothermal amplification assay for diagnosis of extrapulmonary tuberculosis and antituberculosis treatment initiation


Department of Microbiology, Seth G. S. Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India

Date of Submission24-Sep-2020
Date of Decision24-Oct-2021
Date of Acceptance30-Oct-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Gita Nataraj
Department of Microbiology, Seth G. S. Medical College and KEM Hospital, Acharya Donde Marg, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_218_21

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  Abstract 


Background: Extra-pulmonary TB(EPTB) accounts for 15-20% of total TB cases in India. Many cases remain undiagnosed due to poor sensitivity/long turn-around-time of conventional diagnostic tests. Molecular tests offer rapidity, improved sensitivity and exquisite specificity, but are expensive, require skilled manpower and enhanced laboratory infrastructure. Loop-mediated isothermal amplification (LAMP) assay is a unique, temperature-independent DNA amplification test facilitated by visual optic-readout. WHO has recommended use of LAMP for pulmonary TB diagnosis in 2016. For END-TB strategy to succeed, its necessary to capture all forms of TB. The aim of the study was to determine the sensitivity and specificity of LAMP assay against culture, Xpert MTB/RIF assay and Composite Reference Standard(CRS) for diagnosis of EPTB. Methods: In a cross-sectional study hundred consecutive EPTB specimens were processed for microscopy, culture, Xpert and LAMP assay. Standard formulae of sensitivity and specificity and McNemar chi square test of significance was applied. Results: Hundred specimens included in the study were fluids(65), pus(19) and tissue(16). TB was detected in 38 specimens by any of the four methods. Positivity of microscopy-5%, culture-28%, Xpert-25% and LAMP-32%. Sensitivity and specificity of LAMP against culture was 85.71% and 88.89%; against Xpert was 88% and 86.67%; against CRS was 80% and 88.6% respectively. LAMP detected TB in 32 patients of which 28 were put on anti-TB treatment (ATT). Of the 62 patients with negative results in all the tests, 22 were put on ATT. Conclusions: LAMP has good sensitivity for EPTB diagnosis. Further studies are required to establish utility of LAMP as EPTB diagnostic tool.

Keywords: Extrapulmonary tuberculosis, loop-mediated isothermal amplification assay, molecular assay, Mycobacterium tuberculosis, tuberculosis diagnosis


How to cite this article:
Singh P, Kanade S, Nataraj G. Performance of loop-mediated isothermal amplification assay for diagnosis of extrapulmonary tuberculosis and antituberculosis treatment initiation. Int J Mycobacteriol 2021;10:373-8

How to cite this URL:
Singh P, Kanade S, Nataraj G. Performance of loop-mediated isothermal amplification assay for diagnosis of extrapulmonary tuberculosis and antituberculosis treatment initiation. Int J Mycobacteriol [serial online] 2021 [cited 2022 Jan 23];10:373-8. Available from: https://www.ijmyco.org/text.asp?2021/10/4/373/332364




  Introduction Top


Extrapulmonary tuberculosis (EPTB) accounts for 15%–20% of the total tuberculosis (TB) cases in India.[1] Molecular tests such as Xpert mycobacterium TB (MTB)/RIF assay and genotype MTBDR (Drug resistant Mycobacterium tuberculosis) plus assay are recommended by the WHO.[2],[3] These tests offer rapidity, improved sensitivity, and specificity but are costly, need skilled workforce, and enhanced laboratory infrastructure. Loop-mediated isothermal amplification (LAMP) assay is a temperature-independent DNA amplification test, recommended by the WHO for pulmonary TB in 2016.[2] There are very few studies available regarding its applicability in the diagnosis of EPTB.[4]

The present study was aimed to determine the sensitivity and specificity of Nu-LAMP™ TB assay for diagnosis of EPTB.


  Subjects and Methods Top


Institutional ethics committee permission (approval no: EC-234-2016) was obtained before the commencement of study.

Inclusion criteria

Clinically suspected cases of EPTB of any age and gender routinely referred to the mycobacteriology division of Microbiology Department for the diagnosis of TB and those who were willing to participate in the study were included in the study. Patients already on anti-TB treatment were excluded from the study.

Study design

A cross-sectional study was carried out on all clinically suspected cases of EPTB (as mentioned in the inclusion criteria), who were willing to participate in the study by giving written informed consent. Results of microscopy and Xpert for which patient had been referred routinely were recorded. Culture and Nu-LAMP™ TB assay (RAS Lifesciences Pvt. Ltd., a bioMérieux group company, Telangana, India) were performed and results recorded.

Statistics and analysis

Sample size was calculated using the formula:

n = t2 × p (1 − p)/m2

Description:

n = Required sample size

t = Confidence level at 95% (standard value of 1.96)

p = Estimated prevalence of EPTB in India (13%)[5]

m = margin of error at 5% (standard value of 0.05)

On putting these values in the above formula, we get:

n = 173.72 or, n = 174

However, due to cost constraints, only 100 samples were tested.

Sensitivity and specificity were calculated using standard formulae. McNemar Chi-square test was applied as the test of significance using IBM SPSS Statistics software for Windows, Version 20.0. (Armonk, New York, U.S.A.: IBM Corp) and P < 0.05 was considered as statistically significant.

Reference standard

Detection of mycobacterium TB complex (MTBC) by culture (LJ medium and/or MGIT) and/or Xpert assay was considered as composite reference standard (CRS). Specimen detected positive by any one of the above methods was considered as positive for TB. Sensitivity and specificity of LAMP assay were calculated in comparison with culture, Xpert assay, and CRS.

Study procedure

All processing was carried out in certified Biosafety Cabinets (BSCs) Class II-A2.

Hundred extrapulmonary samples were processed for each of the following:

  1. Acid-fast stain
  2. Light-emitting diode fluorescent microscopy
  3. Culture on Lowenstein–Jensen (LJ) medium (solid medium)
  4. Culture on mycobacteria Growth Indicator Tube (MGIT) (liquid medium)
  5. Xpert MTB/RIF assay
  6. Nu-LAMP™ TB assay (RAS Lifesciences Pvt. Ltd., a bioMérieux group company, Telangana, India).


Each sample received in TB laboratory was divided into three equal portions. One was used for microscopy and culture, one for Xpert assay, and one for LAMP assay. Microscopy, Xpert assay, and culture were done as per the WHO/National program guidelines.[6],[7],[8],[9],[10],[11],[12] LAMP procedure was carried out as per the kit literature and amplification was done in a heating block set at 65°C.[13],[14] The results were analyzed after 60 min using an ultraviolet light reader [Table 1].[14]
Table 1: Interpretation of loop-mediated isothermal amplification assay result

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  Results Top


Of the 100 patients enrolled, 52 were male and 48 were female patients. MTB was detected in 17 male patients and 21 female patients. The majority of the patients were in the age group of 31–45 years. MTB was detected in 38 specimens by any of the four methods as mentioned in [Table 2]. MTB detection was maximum in pus specimens (78.94%) followed by tissue/fine-needle aspiration cytology (FNAC) specimens (37.5%) and pleural fluid (34.28%). No MTB was detected in pericardial fluid by any test.
Table 2: Mycobacterium tuberculosis detection in different specimens (n=100)

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Sensitivity of LAMP assay was 85.71% and specificity was 88.89% when compared with culture. Eighty-eight samples showed concordance between the results of culture and LAMP assay [Table 3]. Four samples were culture positive and LAMP negative. Eight samples were culture negative and LAMP positive.
Table 3: Comparison of Nu-loop-mediated isothermal amplification tuberculosis and culture results (n=100)

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Eighty-seven samples showed concordance between the results of Xpert and LAMP assay [Table 4]. Three samples were Xpert positive and LAMP negative. Ten samples were Xpert negative and LAMP positive. Sensitivity of LAMP assay was 88% and specificity was 86.67% when compared with Xpert assay.
Table 4: Comparison of Nu-loop-mediated isothermal amplification tuberculosis and Xpert assay results (n=100)

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When compared with CRS, sensitivity of LAMP was 80% and specificity was 88.6% [Table 5].
Table 5: Comparison of Nu-loop-mediated isothermal amplification tuberculosis with composite reference standard (n=100)

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Test results were also compared with decision to start anti-TB treatment (ATT) [Table 6]. Total of 56 patients were given ATT. All culture-positive (28) and Xpert-positive (25) patients were put on ATT. Of the 32 LAMP-positive patients, 28 were put on ATT. Of the 62 patients with negative results in all the tests, 22 were put on ATT.
Table 6: Comparison of antituberculosis treatment with test result

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  Discussion Top


Timely and accurate diagnosis of all forms of TB is important for effective management of the disease and prevention of infection in the community, particularly in countries like India which have the highest burden of the disease. The present study was conducted to evaluate LAMP assay for diagnosis of EPTB by comparing its performance with culture using LJ medium and MGIT 960 system and molecular assay (Xpert MTB/RIF assay). LAMP assay is an innovative rapid diagnostic technique with increased specificity, speed, and low cost.[15],[16] It is a simple technique wherein the template DNA is amplified under isothermal conditions (~65°C) by Bst DNA polymerase enzyme which has high strand displacement activity. The target gene of Nu-LAMP™ TB assay is rpoB gene (same as that of Xpert assay) which is highly specific for MTBC.[13],[14] To the best of our knowledge, this is the first study to determine the sensitivity and specificity of LAMP assay detecting rpoB gene and comparing it with Xpert assay which also detects the same target gene.

Sensitivity and specificity of loop-mediated isothermal amplification assay

LAMP assay results were compared to that of culture, Xpert assay, a CRS, i.e., CRS (culture and/or Xpert assay), and initiation of ATT. The sensitivity and specificity of LAMP when compared to culture were 85.71% and 88.89%, respectively, with 88% concordance. The difference in the detection rates of LAMP and culture was not found to be statistically significant (P = 0.388) [Table 3]. The sensitivity and specificity of LAMP when compared to Xpert were 88% and 86.67%, respectively, with 87% concordance. The difference in the detection rates of these two tests was again not found to be statistically significant (P = 0.092) [Table 4] and when LAMP was compared to CRS, sensitivity was 80% and specificity was 88.6% with 86% concordance and with similar detection rates and the difference again was not statistically significant (P = 0.791) [Table 5].

Data on detection of MTB in various EPTB specimens are variable and also limited with various in-house and commercial LAMP assays targeting different genes with variable incubation time (ranging from 35 min to 90 min).[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28] The most common target genes used in LAMP studies for EPTB diagnosis were IS6110 followed by mpb64. The pooled sensitivity and specificity of MPB64-LAMP were 86% (95% confidence interval [CI]; 86 ± 86) and 100% (95% CI: 100 ± 100), respectively, and those of IS6110-LAMP were 75% (95% CI: 64 ± 84) and 99% (95% CI: 90 ± 100), respectively, when compared with CRS.[29] Studies such as Modi et al., 2016, Sharma et al., 2016, and Sharma et al., 2017 show that LAMP using a combination of targets (IS6110 + mpb64) improved the sensitivity of the assay.[18],[19],[20] Thus, the diagnostic efficacy of the present study could be improved with a combination of targets such as rpoB + IS6110 or rpoB + mpb64.

A systematic review and meta-analysis by Yu et al., 2018 on performance of LAMP for extrapulmonary specimens showed a pooled sensitivity of 77% (95% CI: 68 ± 85) and specificity of 99% (95% CI: 96 ± 100) against a CRS of culture and PCR.[29] It showed a pooled sensitivity of 93% (95% CI: 88 ± 96) and specificity of 77% (95% CI: 64 ± 86) against culture.[29] However, of all the studies included in Yu et al. meta-analysis, only one study, i.e. Ghosh et al., 2017, had rpoB gene as the target gene of LAMP assay.[22],[29]

For extrapulmonary samples, the sensitivity of Xpert MTB/RIF assay varies with sample type. In the present study, Xpert assay had a better sensitivity (87.5%) for pleural fluid. Sensitivity of Xpert assay is highest for lymph node biopsies/aspirates and CSF but poor for pleural fluid as per systematic review and meta-analysis by Denkinger et al., 2014.[30] Another meta-analysis by Penz et al., 2015 showed pooled sensitivity and specificity of Xpert for EPTB detection, respectively, as 77% (95% CI: 66–85) and 97% (95% CI: 94–98) against culture.[31] In the present study, LAMP missed three cases which were Xpert positive and detected 10 cases which were Xpert negative. Furthermore, in this study, LAMP has showed good sensitivity for pus and pleural fluid specimens. Compared with Xpert MTB/RIF, LAMP has shortcomings, such as its inability to determine bacillary load and rifampicin resistance.

MTB was detected by all 3 tests (Culture, Xpert, and LAMP) in 22 patients. Two patients' samples were culture positive, LAMP positive but Xpert negative. One patient's sample was culture positive, Xpert positive but LAMP negative. Three patients' samples were only culture positive; two patients' samples were only Xpert assay positive and eight patients' samples were only LAMP assay positive. False-negative results by Xpert/LAMP assay in culture-positive specimens may be explained by several factors: the presence of inhibitors in DNA extracted from various clinical specimens (applicable to only Xpert as LAMP is an inhibitor-resistant assay); availability of only a small volume of the sample after distribution for various investigations (microbiological, pathological, and biochemical); paucibacillary nature with uneven distribution of mycobacteria in specimens due to its tendency to form clumps.[21],[22],[32] It is also important to emphasize upon the role of quantity of DNA template in limit of detection of LAMP assay (which has not been established/standardized yet) considering that some clinical specimens may yield very small quantities of bacterial DNA.[24] Culture can yield false-negative results when sample contains dormant bacilli, <10–100 bacilli/ml or due to over decontamination process or if patients are under treatment.[25]

False-positive LAMP results can occur due to high rate of possible contamination or nonspecific reactions by complicated primers.[33] Exposure of reaction tubes to humidity can also lead to false-positive reaction.[4] The biggest limitation of molecular tests is that they cannot differentiate between dead and live target organisms.[25] These are also the possible reasons for low specificity of LAMP in the present study.

Specimen-wise Mycobacterium tuberculosis detection and anti-tuberculosis treatment

In extrapulmonary specimens, LAMP assay has variable sensitivity and specificity depending on the type of specimen, target gene, and the composite reference or gold standard method used for confirmation.[29] [Table 7] shows the comparison of anti-TB treatment with specimen type. Nineteen (19) of 35 patients, from whom pleural fluid was received, were put on ATT; only 11 of these 19 were positive by one or more of the four tests. Ten (10) of 21 patients, from whom ascitic fluid was received, were put on ATT; only four of these 10 were positive for MTBC by the tests. Twelve (12) of 19 patients, from whom pus specimen was received, were put on ATT. All 12 were positive by one or more of the four tests. LAMP detected all these 12 patients but in addition, it also detected three patients (false positive). Thus, Nu-LAMP™ TB assay has shown excellent results with pus specimens which were also reported by Ghosh et al., 2017.[22] Ten (10) of 16 FNAC/Biopsy/Tissue specimen patients were put on ATT; only six of these were positive. Three (3) of five patients, from whom CSF was received, were put on ATT; however, only one of these patients was MTBC positive and all the four tests were positive.
Table 7: Comparison of antituberculosis treatment with specimen type

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Mycobacterium tuberculosis detection and anti-tuberculosis treatment

Overall, 56 of 100 patients were started on ATT. All culture-positive and Xpert-positive patients were put on ATT. Of the 32 LAMP-positive patients, 28 were put on ATT. Four patients with LAMP-positive results were not started on ATT. Of them, one patient with pleural effusion was finally diagnosed as a case of lung cancer; whereas, the other three were pus specimens from pediatric patients who were diagnosed with infections other than TB and received treatment for the same and got cured. Of 62 patients with negative results in all the four tests, 22 were put on ATT based on clinical and radiological findings. The laboratory diagnostic modalities available today do not detect all TB cases, underscoring the need for better tests.

Limitations

The limitation of the study was small sample size due to cost constraints. A study with larger sample size would be desirable for more realistic results.


  Conclusions Top


LAMP has good sensitivity for the diagnosis of EPTB but does not detect bacillary load or TB drug resistance. Further specimen-specific studies need to be done with larger sample size before generalizing the results to establish the utility of LAMP assay as an EPTB diagnostic tool.

Ethical clearance

Institutional ethics committee permission (approval no: EC-234-2016) was obtained prior to the commencement of study.

Financial support and sponsorship

This study was financially supported by the Research Society of Seth G. S. Medical College and KEM Hospital, Mumbai.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120:316-53.  Back to cited text no. 1
    
2.
World health Organization. The Use of Loop-Mediated Isothermal Amplification (TBLAMP) for the Diagnosis of Pulmonary Tuberculosis: Policy Guidance. Geneva: World Health Organization; 2016. p. 1-52. Available from: http://www.who.int/iris/handle/10665/249154. [Last accessed on 2021 Oct 20]  Back to cited text no. 2
    
3.
Country Office for India; World Health Organization. Standards for TB Care in India. New Delhi: WHO Country Office for India; 2014. p. 1-84. http://www.who.int/iris/handle/10665/208894. [Last accessed on 2021 Oct 20]  Back to cited text no. 3
    
4.
World Health Organization. The Use of a Commercial Loop-Mediated Isothermal Amplification Assay (TB-LAMP) for the Detection of Tuberculosis: Expert Group Meeting Report. Geneva: World Health Organization; 2013. p. 1-50. Available from: http://www.who.int/iris/handle/10665/83142. [Last accessed on 2021 Oct 20]  Back to cited text no. 4
    
5.
Arora VK, Chopra KK. Extrapulmonary tuberculosis. Indian J Tuberc 2007;54:165-7.  Back to cited text no. 5
    
6.
Central TB Division. Revised National Tuberculosis Control Programme. RNTCP at a Glance. New Delhi: Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare; 2017. p. 1-153.  Back to cited text no. 6
    
7.
Central TB Division. Revised National TB Control Programme. Manual for Sputum Smear Fluorescence Microscopy. New Delhi: Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare (Govt. of India);2013. p. 1-16.  Back to cited text no. 7
    
8.
Central TB Division. Revised National TB Control Programme. Manual of Standard Operating Procedures (SOPs): Culture of Mycobacterium Tuberculosis and Drug Susceptibility Testing on Solid Medium. New Delhi: Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare; 2009. p. 1-142.  Back to cited text no. 8
    
9.
Central TB Division. Revised National TB Control Programme. Training Manual for Mycobacterium Tuberculosis Culture and Drug Susceptibility Testing. New Delhi: Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare (Govt. of India); 2009. p. 1-76.  Back to cited text no. 9
    
10.
Siddiqi SH, Rush-Gerdes S. MGITTM Procedure Manual for BACTECTM MGIT 960TM TB System (Also applicable for Manual MGIT): Mycobacteria Growth Indicator Tube (MGIT) Culture and Drug Susceptibility Demonstration Projects. Geneva, Switzerland: Foundation for Innovative New Diagnostics (FIND); 2006. p. 1-89.  Back to cited text no. 10
    
11.
Cepheid. GeneXpert Xpert MTB/RIF®. Sunnyvale, California: Cepheid; 2015. p. 1-48, 91.  Back to cited text no. 11
    
12.
Cepheid. GeneXpert Dx System: Operator Manual (Software Version 4). Sunnyvale, California: Cepheid; 2012. p. 1-220.  Back to cited text no. 12
    
13.
RAS Lifesciences Pvt. Ltd. RAS DNA Extraction Kit: Product Insert. Hyderabad (India): RAS Lifesciences Pvt. Ltd; 2012. p. 1-13.  Back to cited text no. 13
    
14.
RAS Lifesciences Pvt. Ltd. Nu-LAMPTM TB Kit (Loop Mediated Isothermal Amplification TB Test Kit Based on Real Time PCR/Visual Detection): Product Insert. Hyderabad (India): RAS Lifesciences Pvt. Ltd; 2012. p. 1-15.  Back to cited text no. 14
    
15.
Njiru ZK. Loop-mediated isothermal amplification technology: Towards point of care diagnostics. PLoS Negl Trop Dis 2012;6:e1572.  Back to cited text no. 15
    
16.
García-Basteiro AL, DiNardo A, Saavedra B, Silva DR, Palmero D, Gegia M, et al. Point of care diagnostics for tuberculosis. Pulmonology 2018;24:73-85.  Back to cited text no. 16
    
17.
Sethi S, Dhaliwal L, Dey P, Kaur H, Yadav R, Sethi S. Loop-mediated isothermal amplification assay for detection of Mycobacterium tuberculosis complex in infertile women. Indian J Med Microbiol 2016;34:322-7.  Back to cited text no. 17
[PUBMED]  [Full text]  
18.
Sharma M, Sharma K, Sharma A, Gupta N, Rajwanshi A. Loop-mediated isothermal amplification (LAMP) assay for speedy diagnosis of tubercular lymphadenitis: The multitargeted 60-minute approach. Tuberculosis (Edinb) 2016;100:114-7.  Back to cited text no. 18
    
19.
Sharma K, Sharma M, Batra N, Sharma A, Dhillon MS. Diagnostic potential of multi-targeted LAMP (loop-mediated isothermal amplification) for osteoarticular tuberculosis. J Orthop Res 2017;35:361-5.  Back to cited text no. 19
    
20.
Modi M, Sharma K, Sharma M, Sharma A, Sharma N, Sharma S, et al. Multitargeted loop-mediated isothermal amplification for rapid diagnosis of tuberculous meningitis. Int J Tuberc Lung Dis 2016;20:625-30.  Back to cited text no. 20
    
21.
Balne PK, Barik MR, Sharma S, Basu S. Development of a loop-mediated isothermal amplification assay targeting the mpb64 gene for diagnosis of intraocular tuberculosis. J Clin Microbiol 2013;51:3839-40.  Back to cited text no. 21
    
22.
Ghosh PK, Chakraborty B, Maiti PK, Ray R. Comparative evaluation of loop-mediated isothermal amplification and conventional methods to diagnose extrapulmonary tuberculosis. Ann Trop Med Public Health 2017;10:160-4.  Back to cited text no. 22
  [Full text]  
23.
Joon D, Nimesh M, Saluja D. Loop-mediated isothermal amplification as alternative to PCR for the diagnosis of extra-pulmonary tuberculosis. Int J Tuberc Lung Dis 2015;19:986-91.  Back to cited text no. 23
    
24.
Joon D, Nimesh M, Varma-Basil M, Saluja D. Evaluation of improved IS6110 LAMP assay for diagnosis of pulmonary and extra pulmonary tuberculosis. J Microbiol Methods 2017;139:87-91.  Back to cited text no. 24
    
25.
Kumar P, Pandya D, Singh N, Behera D, Aggarwal P, Singh S. Loop-mediated isothermal amplification assay for rapid and sensitive diagnosis of tuberculosis. J Infect 2014;69:607-15.  Back to cited text no. 25
    
26.
Nagdev KJ, Kashyap RS, Parida MM, Kapgate RC, Purohit HJ, Taori GM, et al. Loop-mediated isothermal amplification for rapid and reliable diagnosis of tuberculous meningitis. J Clin Microbiol 2011;49:1861-5.  Back to cited text no. 26
    
27.
Yang B, Wang X, Li H, Li G, Cao Z, Cheng X. Comparison of loop-mediated isothermal amplification and real-time PCR for the diagnosis of tuberculous pleurisy. Lett Appl Microbiol 2011;53:525-31.  Back to cited text no. 27
    
28.
Mishra B, Hallur V, Behera B, Preetam C, Mishra PN, Turuk J, et al. Evaluation of loop mediated isothermal amplification (LAMP) assay in the diagnosis of tubercular lymphadenitis: A pilot study. Indian J Tuberc 2018;65:76-9.  Back to cited text no. 28
    
29.
Yu G, Shen Y, Zhong F, Ye B, Yang J, Chen G. Diagnostic accuracy of the loop-mediated isothermal amplification assay for extrapulmonary tuberculosis: A meta-analysis. PLoS One 2018;13:e0199290.  Back to cited text no. 29
    
30.
Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: A systematic review and meta-analysis. Eur Respir J 2014;44:435-46.  Back to cited text no. 30
    
31.
Penz E, Boffa J, Roberts DJ, Fisher D, Cooper R, Ronksley PE, et al. Diagnostic accuracy of the Xpert® MTB/RIF assay for extra-pulmonary tuberculosis: A meta-analysis. Int J Tuberc Lung Dis 2015;19:278-84, i-iii.  Back to cited text no. 31
    
32.
Chakravorty S, Tyagi JS. Novel multipurpose methodology for detection of mycobacteria in pulmonary and extrapulmonary specimens by smear microscopy, culture, and PCR. J Clin Microbiol 2005;43:2697-702.  Back to cited text no. 32
    
33.
Bi A, Nakajima C, Fukushima Y, Tamaru A, Sugawara I, Kimura A, et al. A rapid loop-mediated isothermal amplification assay targeting hspX for the detection of Mycobacterium tuberculosis complex. Jpn J Infect Dis 2012;65:247-51.  Back to cited text no. 33
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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