|Year : 2019 | Volume
| Issue : 2 | Page : 126-130
Role of Xpert MTB/RIF assay (Gene Xpert) in diagnosing tuberculosis in elderly patients - A hospital based study
Raj Kishor Sharma1, Namrata Kumari2, Rakesh Kumar3, Pallavi Priya4, Shailesh Kumar5, Shivendra Kumar Shahi6
1 Junior Resident, Dept. of Microbiology, IGIMS, Patna, Bihar, India
2 Professor, Dept. of Microbiology, IGIMS, Patna, Bihar, India
3 Associate Professor, Dept. of Microbiology, IGIMS, Patna, Bihar, India
4 Senior Resident, Dept. of Microbiology, IGIMS, Patna, Bihar, India
5 Additional Professor, Dept. of Microbiology, IGIMS, Patna, Bihar, India
6 Professor & Head, Dept. of Microbiology, IGIMS, Patna, Bihar, India
|Date of Submission||27-Jan-2019|
|Date of Acceptance||19-Jun-2019|
|Date of Web Publication||20-Nov-2020|
Associate Professor, Dept. of Microbiology, IGIMS, Patna
Source of Support: None, Conflict of Interest: None
Background: Tuberculosis is a major public health problem throughout the world. Tuberculosis has long been known as a disease of young people but many elderly (? 60 years of age) are now falling ill with TB. Several factors associated with aging result in delayed diagnosis and initiation of treatment.
Aim of the Study:
- To detect the prevalence of tuberculosis (TB) and drug resistant TB (DR-TB) among elderly.
- To compare the role of molecular methods with conventional tests in diagnosis of tuberculosis in elderly patients.
Materials and Methods: Clinical samples received from patients were subjected to-
- Smear microscopy using Zeihl Neelsen (ZN) & Fluorescent staining
- Xpert MTB/RIF assay (GeneXpert test)
Results: Acid fast bacilli (AFB) were detected in 17.80% (73/410) of samples. Elderly contributed to 11.40% (73/640) of total TB cases. Gene Xpert detected M tb in 34 smear negative samples also which constituted 46.57% (34/73) of total positive. AFB detection by Gene Xpert test was the highest followed by Fluorescent & ZN staining. Majority of the samples were sensitive to rifampicin.
Conclusion: Elderly TB patients have high smear negativity. Gene Xpert test allows early detection of smear negative and drug resistant cases. It may be offered as the first choice investigating modality. Early diagnosis and initiation of specific anti tubercular therapy will have a major impact in reducing the disease burden and achieving our goal of “TB Free India”.
Keywords: Elderly patients, Smear microscopy, Tuberculosis, Xpert MTB/RIF assay
|How to cite this article:|
Sharma RK, Kumari N, Kumar R, Priya P, Kumar S, Shahi SK. Role of Xpert MTB/RIF assay (Gene Xpert) in diagnosing tuberculosis in elderly patients - A hospital based study. J Indira Gandhi Inst Med Sci 2019;5:126-30
|How to cite this URL:|
Sharma RK, Kumari N, Kumar R, Priya P, Kumar S, Shahi SK. Role of Xpert MTB/RIF assay (Gene Xpert) in diagnosing tuberculosis in elderly patients - A hospital based study. J Indira Gandhi Inst Med Sci [serial online] 2019 [cited 2022 Jan 25];5:126-30. Available from: http://www.jigims.co.in/text.asp?2019/5/2/126/301095
| Introduction|| |
Tuberculosis (TB) is a major public health problem. In 2016, there were 10.4 million new estimated TB cases globally and 2.8 million in India. Tuberculosis, disease of young people is increasing among elderly (aged 60 years or above).,,
Sputum smear microscopy is specific but insensitive diagnostic method., Smear negative TB is diagnosed clinically and/or radiologically. These tests cannot detect drug resistant tuberculosis (DR-TB). Culture of bacilli is gold standard method for TB & DR-TB cases but cumbersome. Xpert MTB/RIF assay is a rapid test for diagnosis of both TB and Rifampicin resistant/ Multi-drug resistant TB (RR/ MDR-TB).
In elderly, chronic diseases and atypical presentation of tuberculosis delays its diagnosis., Hence, we conducted a study on the comparative evaluation of diagnostic methods of tuberculosis in elderly population.
| Objectives:|| |
- To detect the prevalence of tuberculosis (TB) and drug resistant TB (DR-TB) among elderly people.
- To compare the role of molecular methods with conventional tests in diagnosis of tuberculosis in elderly patients.
| Materials and Methods|| |
In this cross sectional study, samples were received from patient clinically suspected of multi-drug resistant (MDR) pulmonary or extra pulmonary tuberculosis (PTB or EPTB) and aged 60 years or above in routine laboratory of Microbiology department of a tertiary care hospital during January 2017 to December 2017. Various clinical samples received from different patients were -sputum, pleural fluid, pus, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) fluid, and ascitic fluid. Repeat sample and hematological or radiological investigations were not included in the study. All the samples were subjected to following tests:
- Smear microscopy using Zeihl Neelsen (ZN) staining
- Smear microscopy using Fluorescent staining
- Xpert MTB/RIF assay: Cartridge based nucleic acid amplification test (CBNAAT)
For smear microscopy, all samples were stained using standard methods of ZN and Fluorescent staining as per RNTCP guidelines.
XPERT MTB/RIF ASSAY
All the samples were subjected to Xpert MTB/RIF assay, following manufacturer’s instructions. (Xpert MTB/RIF assay, Xpert®; Cepheid; Sunnyvale, CA).  Institutional ethical clearance was taken for the study.
| Results :|| |
A total of 2751 samples were received in the routine laboratory for Gene Xpert tests during the study period of 1 year. Acid fast bacilli (AFB) were detected in 640 samples. Out of 2751 samples, 410 samples were received from elderly patients (aged 60 years and above). In elderly, suspected pulmonary and extra pulmonary samples contributed to 76.82% (315/410) and 23.17% (95/410) of samples respectively. Males formed the majority (78%) of the patients while female contributed to 22% [Figure 1]. Most of the suspected patients (79%) were living in rural areas and 21% belonged to urban area [Figure 2].
AFB was detected in 17.80% (73/410) of samples received from elderly by Gene Xpert [Figure 3]. AFB detection by Gene Xpert test was the highest followed by fluorescent & ZN staining [Table 1]. M tb detection by Gene Xpert was almost 2 and 5 times in comparison to smear microscopy in case of pulmonary and extra pulmonary samples respectively. Gene Xpert also detected MTB in 34 smear negative samples which constituted 46.57% (34/73) of total positive. Elderly contributed to 11.40% (73/640) of total TB cases [Figure 4].
Majority of the samples were sensitive to rifampicin [Table 2].
| Discussion :|| |
India is also being affected by demographic transition. The population share of elderly (aged 60 years or above) in India has increased from 5.6 percent in 1961 to 8.6 per cent in 2011. So, the number of tuberculosis cases in elderly is expected to rise in near future. Tuberculosis in elderly is a significant problem, owing to the atypical presentation, diagnostic challenges and adverse events associated with treatment.
Decreased immunity in elderly due to acute or chronic diseases, impaired microbial clearance mechanisms, and biological changes associated with aging puts them at a greater risk of acquiring infection or reactivation of infection. Tuberculosis in elderly occurs mainly due to the reactivation of endogenous infection. With the increasing age, there is a decrease in T lymphocytes, proliferative responses and synthesis of gamma interferon.,,, Malnutrition, social neglect and poverty common among elderly in underdeveloped and developing countries further increase the risk of tuberculosis in this vulnerable age group.
In this study, prevalence of tuberculosis in suspected elderly was 73/410 (17.80%).Elderly contributed to 11.40% (73/640) of total tuberculosis patients. It is in conformity with study by Ananthakrishnan R et al from Tamil Nadu who reported elderly patients with tuberculosis to be 14%. It is slightly higher than that reported by Pardeshi G et al (10%) from Maharashtra.
Higher proportion of males observed in this study is similar to previous reports by Sood R, Lee JH et al, & Khan M et al where the proportion of male patients ranged from 61-67.6 %.,,
Sputum smear microscopy is still the most commonly used method of TB diagnosis especially in peripheral health centers as it is economical and can be done by paramedical staff with minimal training. Smear microscopy is highly specific but an insensitive diagnostic method. The requirement of higher load of bacilli (10,000 bacilli/ml) along with other factors like quality of the specimen and the training and motivation of laboratory personnel leads to a variable sensitivity from 20% to 80%. It detects only about 50% of all the active cases of TB. As per Revised National Tuberculosis Control Programme (RNTCP) guideline, smear negative TB cases are diagnosed on the basis of persistence of respiratory symptoms and/or radiological abnormality even after a course of antibiotics. Apart from these limitations both smear microscopy and radiological investigations further cannot detect resistance pattern.
In this study smear negativity was observed in 37/73 (50.68%) of samples. Higher sputum smear negativity observed is in conformity with other studies done in India and abroad by Pardeshi G et al, Gaur SN et al, and Hauer B et al.,, Delayed diagnosis due to higher smear negativity in elderly is a major obstacle in tuberculosis control programme .
Due to being cumbersome, time consuming and requirement of highly trained staff, Culture and DST even after being the gold standard method of diagnosis cannot be used routinely in most of the resource limited centres. Therefore, the proportion of smear negative patients who could have been diagnosed positive by culture, is not known.
The problem is further aggravated in peripheral areas where modern diagnostic methods are still not available. In our country 71% of elderly population resides in rural areas. In this study population 79% patients were from rural areas.
Xpert® MTB/RIF assay (Cepheid, USA) is the only rapid test recommended by WHO for diagnosis of TB. Xpert MTB/RIF assay (GeneXpert test) is an automated Cartridge based nucleic acid amplification test (CBNAAT) that can identify Mycobacterium tuberculosis (MTB) and resistance to rifampicin (RIF) within 2 hours.
In this study, case detection by modern diagnostic method like GeneXpert was almost double in pulmonary and five times in extra pulmonary of those diagnosed by smear microscopy. At the same time Gene Xpert also detected resistance to rifampicin, which was very less here, as tuberculosis in elderly occurs mainly due to the reactivation of endogenous infection. Hence, the ability of Gene Xpert to rapidly confirm TB in smear-negative cases offers the possibility of improving early TB case detection and control of the disease. Several other authors have also reported higher rate of case detection by Gene xpert compared to microscopy especially in smear negative cases., It is fortunate that the facility of Gene Xpert is readily available in all districts of our country in comparison to Culture & DST. Therefore, Gene xpert may be used as initial test in diagnostic algorithm of suspected elderly patients. Several other authors have also recommended use of Gene Xpert as initial diagnostic method for tuberculosis in elderly. In 2013, WHO also recommended that Xpert MTB/RIF assay to be used as the initial diagnostic test in all persons with signs and symptoms of TB. Additionally, diagnosis of DR-TB by Gene Xpert will help in curbing the menace of rising multi drug resistant tuberculosis (MDR-TB).
In rural areas the use of Gene Xpert could be a boon for the people and health care service provider allowing early and accurate diagnosis of tuberculosis as well as drug resistant tuberculosis.
| Conclusion :|| |
Elderly TB patients have high smear negativity. Gene Xpert test allows early detection of smear negative and drug resistant cases which limits the spread of disease in community and health care providers. Gene Xpert test should be offered as the first choice investigating modality rather than conventional microscopy, culture and DST in elderly suspected of TB. This study could be a guiding tool for physicians and public health expert for advocating the preferred use of Gene Xpert over conventional methods of TB diagnosis. Early diagnosis with Gene Xpert and initiation of specific anti tubercular therapy will have a major impact in reducing the disease burden and achieving our goal of “TB free India”.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sood R.The problem of geriatric tuberculosis. J Acad Clin Med 2000;5:156-62.
Davies PD. Tuberculosis in the elderly: an international perspective, Clin Geriatr 1997;5:15-26.
Elderly in India-Profile and Programmes 2016. New Delhi: Ministry of Statistics and Programme Implementation.Government of India; 2016.page 9.
Parsons LM, Somoskövi A, Gutierrez C, Lee E, Paramasivan CN, Abimiku A, et al. Laboratory diagnosis of tuberculosis in resource-poor countries: Challenges and opportunities. Clin Microbiol Rev 2011;24(2):314- 50.
Behr MA, Warren SA, Salamon H, Hopewell PC, Ponce de Leon A , Daley CL , et al . Transmission of Mycobacterium tuberculosis from patients smear- negative for acid-fast bacilli. Lancet 1999;353:444-9.
Revised National Tuberculosis Control Programme (RNTCP). Technical and Operational Guidelines 2016 Central TB Division (CTD), Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India.New Delhi: CTD.
Lee JH, Han DH, Song JW, Chung HS. Diagnostic and therapeutic problems of pulmonary tuberculosis in elderly patients. J Korean Med Sci 2005;20:784-9.
Khan MA, Kovnat DM, Bachus B, Whitcomb ME, Brody JS, Snider GL. Clinical and roentgenographic spectrum of pulmonary tuberculosis in the adult. Am J Med 1977;62:31-8.
Xpert MTB/RIF assay, Xpert; Cepheid; Sunnyvale, CA available at www.cepheid.com/us/
Stead WW. Pathogenesis of first episode of chronic pulmonary tuberculosis in man: Recrudescence of residuals of primary infection of exogenous re-infection. Ann Intern Med 1968; 68:731-45.
Davies PD. The effects of poverty and ageing on the increase in tuberculosis. Monaldi Arch Chest Dis 1999;54:168-71.
Lesourd B, Mazari L. Nutrition and immunity in the elderly. Proc Nut Soc 1999;58:685-95.
Ben-Yehuda A, Weksler ME. Host resistance and the immune system. Clin Geriatr Med 1994;8:701-11.
Pedrazzini T, Hug K, Louis J A. Importance of L3T4+ nd Lyt2+ cells in the immunologic control of infection with Mycobacterium bovis strain bacillus Calmette Guerin in mice. Assessment by elimination of T cells subsets in vivo. J Immunnol 1987;139:2032-37.
Ananthakrishnan R, Kumar K, Ganesh M, Kumar AMV, Krishnan N, et al. The Profile and Treatment Outcomes of the Older (Aged 60 Years and Above) Tuberculosis Patients in Tamilnadu, South India.PLoS ONE 2013; 8(7): e67288. doi:10.1371/journal.pone.0067288
Pardeshi G,Deshmukh D. Disease characteristics and treatment outcome in elderly tuberculosis patients on DOTS. Indian J CommunityMed 2007;32:292-4.
Gaur SN, Dhingra VK, Rajpal S, Aggarwal JK, Meghna. Tuberculosis in the elderly and their treatment outcome under DOTS. Indian J Tuberc 2004;51:83-87.
Hauer B, Brodhun B, Altmann D, Fiebig L, Loddenkemper R, et al.Tuberculosis in the elderly in Germany. Eur Respir J 2011;38(2):467-70.
Lombardi G, Di Gregori V, Giromett N, Tadolini M, Bisognin F, Dal Monte P. Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF. F e r n a n d e z - R e y e s D, ed. PLoS ONE 2017;12(4):e0176186. doi:10.1371/journal. pone.0176186
Ondimu TO, Grace MO, Samson AO, Asito SA. Comparative Study of Smear Microscopy, Gene Xpert and Culture and Sensitivity Assays in Detection of Mycobacterium tuberculosis on Sputum Samples among Tuberculosis Suspected Cases in Nyamira County Referral Hospital. Mycobact Dis 2017; 7:249. doi:10.4172/2161-1068.1000249
India TB report 2018 , Revised national TB Control Programme, Annual Status Report. Central TB Division , Directorate General of Health Services, Ministry of Health and Family Welfare, Nirman Bhawan, New Delhi 110108.Available at http://www.tbcindia.gov.in
Velayutham BRV, Nair D, Chandrasekaran V, Raman B, Sekar G, Watson B, et al. Profile and Response to Anti-Tuberculosis Treatment among Elderly Tuberculosis Patients Treated under the TB Control Programme in South India 2014. PLoS ONE 9(3): e88045. https://doi.org/10.1371/journal.pone.0088045
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]