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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 35-39

Prevalence and determinants of latent tuberculosis infection among healthcare personnel in India: A scoping review


1 Department: School of Public Health, Indian Council of Medical Research -National Institute of Epidemiology (ICMR-NIE), Chennai, India
2 Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
3 Department of Pulmonary Medicine, Government Medical College, Thrissur, Kerala, India

Date of Submission30-Jul-2021
Date of Decision22-Nov-2021
Date of Acceptance23-Nov-2021
Date of Web Publication1-Feb-2022

Correspondence Address:
Dr. Mathew J Valamparampil
Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpsic.jpsic_19_21

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  Abstract 


Introduction: Health personnel in high-burden countries are at a greater risk of tuberculosis (TB) infection, due to continuous exposure to diagnosed and undiagnosed pulmonary TB cases. A scoping review is done to ascertain the prevalence and risk factors for latent TB infection (LTBI) among India's healthcare personnel.
Materials and Methods: A review of literature was done from Medline, CINAHL, Global Health and PubMed. Full-text review of 30 articles was done, and three were found to be eligible for final analysis.
Results: The prevalence of LTBI was found to range from a quarter to one-third of the study participants. Available evidence has revealed the role of increased time being spent in the healthcare profession as an essential risk factor for the development of LTBI. The study participants were of younger age in all studies. There was a lack of representation of different categories of health workers.
Discussion: Higher prevalence in younger participants poses significant threats to the well-being of healthcare professionals. The absence of proper guidelines for treating LTBI in high-prevalent settings and the lack of awareness among healthcare professionals regarding LTBI are significant challenges for preventing TB infection among healthcare professionals.

Keywords: Health personnel, India, latent tuberculosis, occupational medicine, review, tuberculosis


How to cite this article:
Vaman RS, Valamparampil MJ, Nair S. Prevalence and determinants of latent tuberculosis infection among healthcare personnel in India: A scoping review. J Patient Saf Infect Control 2021;9:35-9

How to cite this URL:
Vaman RS, Valamparampil MJ, Nair S. Prevalence and determinants of latent tuberculosis infection among healthcare personnel in India: A scoping review. J Patient Saf Infect Control [serial online] 2021 [cited 2022 May 29];9:35-9. Available from: https://www.jpsiconline.com/text.asp?2021/9/2/35/337091




  Introduction Top


Tuberculosis (TB) caused by Mycobacterium tuberculosis is a significant killer disease worldwide, with approximately 10 million cases and 1.4 million deaths in 2019, with India contributing to 26% of the global TB burden.[1] The infected persons can be classified into either latent TB infection (LTBI) or active TB disease. The WHO defines LTBI as “a state of the persistent immune response to M. tuberculosis antigens with no evidence of clinically manifest active TB.”[2] The global burden of LTBI is estimated to be around a quarter of the world population.[3],[4] Health personnel in high-burden countries are at a greater risk of tuberculosis (TB) infection due to continuous exposure to diagnosed or undiagnosed pulmonary TB cases and also due to inadequate implementation of TB infection prevention and control practises. Countires with hig TB burden of TB are low resource settings as well. A systematic review across 16 countries has estimated a significantly higher risk (odds ratio [OR] 2.27; 95% confidence interval [CI] 1.61–3.20) to healthcare workers (HCWs) for LTBI compared to the general population.[5] Another systematic review of studies from 26 low- and middle-income countries estimates the mean prevalence of positive tuberculin skin test (TST) as 49% and interferon-gamma release assay (IGRA) as 39% and the mean annual risk as 18% to HCWs.[6] The WHO has advocated drugs such as isoniazid, rifampicin, rifabutin and their combinations to prevent and treat LTBI in high- and low-burden settings. However, comprehensive guidelines for the management of LTBI in HCWs, especially in high-burden settings, are lacking.[7] This is of concern due to the increased exposure risk in healthcare settings, similar to those of TB patients' household contacts. The burden of LTBI among HCWs in a highly prevalent environment like India needs to be ascertained to develop policies for safeguarding scarce and valuable human resource in low- and middle-income setting. This review aims to determine the prevalence and risk factors for LTBI among healthcare personnel in India.


  Materials and Methods Top


A systematic literature search was conducted across various databases for articles discussing LTBI in India. The period of publication was determined as between 2010 and 2020. This was because the tools for better identifying LTBI were available only in the last decade and other publications before this period contained inaccurate measurement tools. The articles were searched from databases including Medline, CINAHL, Global Health and PubMed using MeSH terms and keywords. The search strategy is described in [Table 1].
Table 1: Search Strategy

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Following the full-text review of 30 manuscripts, a total of three articles were finally found to be suitable for data extraction. The criteria and processes for excluding the rest of the manuscripts are described in [Figure 1].
Figure 1: Article selection process for review

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  1. Kinikar et al., 2019 - High risk for LTBI among medical residents and nursing students in India
  2. Christopher et al., 2010 - TB infection among young nursing trainees in South India
  3. Janagond et al. 2019 - Screening of HCWs for LTBI in a tertiary care hospital.



  Results Top


The selected articles were critically appraised using the Critical Appraisal Skills Programme checklist for prospective cohort studies.[8] The major findings from the reviewed articles are included in [Table 2]. The study by Kinikar et al.[9] targeted 200 postgraduate medical residents and nursing students at a public sector teaching hospital in Western India and aimed at assessing the incidence, prevalence and risk factors for LTBI among the study cohort. The study included both the medical residents and nursing students who are the central clinical workforce in teaching hospitals, providing a differential risk pattern in Indian settings. The median (interquartile range [IQR]) age of the study group was 25 (17–27) years. The study utilised both TST and IGRA for estimating the risk of LTBI. IGRA is considered as a replacement for non-standardised TST due to its improved diagnostic accuracy in Bacille Calmette–Guérin-vaccinated populations.[10] Interrestingly, a few of the participants who had tested positive on both the tests turned out to have clinical disease during follow-up. A repeat TST was performed at 12 months, eliminating the baseline TST boosting effect, leading to overestimation of LTBI incidence. The baseline data were summarised using proportions and medians with IQR; incidence and prevalence were calculated with 95% CI. Univariable or multivariable logistic regression and Poisson regression were performed for risk factors and were appropriate. Similar proportions of participants turning out to be positive on both TST and IGRA offer valuable information, pointing to a better LTBI prevalence assessment. Even though “being a medical resident” has emerged as a risk factor, the closeness of the lower limit of CI of its risk ratio points to the challenges in obtaining such information from a high-risk setting. Even though efforts have been made to capture the exposures in the past year, the overall total exposure may vary between residents and nursing students. The authors have additionally mentioned regarding the chances of recall bias during the self-reporting of TB exposure. However, this has limited bearing on the estimation of prevalent LTBI. The comparatively younger study population restricts the conclusion that could be drawn from the study regarding prevalent LTBI.
Table 2: Major characteristics and findings of reviewed manuscripts

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The study by Christopher et al.[11] was done at a large tertiary care institution in South India to assess the LTBI prevalence and association between LTBI prevalence and TB exposure and risk factors among nursing students. More than 80% of the study participants were aged less than 22 years. The researchers approached all the enrolled students for consent to participate in the study, and participants with a negative TST underwent repeat testing at 7–14 days to determine boosting. The study focussed on nursing personnel who have considerable contact time with TB patients and are at high risk of getting TB infection. To minimise the confounding effect of age from the effect of time spent in healthcare, the age of entry into healthcare was used for analysis. Use of hospital logbooks for ascertaining exposure with TB patients minimised the recall bias. The LTBI prevalence was estimated using Bayesian latent class analysis (LCA) that allowed adjusting the observed TST results, with the prior knowledge of TST sensitivity and specificity. This offers a more realistic picture regarding the LTBI prevalence due to the inherent deficits associated with TST. The study's weakness included predominant inclusion of female gender and the inclusion of only young individuals, thereby offering limited insight in LTBI prevalence with increasing age and exposures. Use of standardised TST provides a comparative result similar to IGRA in this study.

The study by Janagond et al.[12] was conducted to assess TB infection risk among HCWs who directly engage in medical duties. Similar to the other two studies, a younger mean age of 27 years of study participants and the absence of different occupational groups of HCWs are also present in this study. The prevalence of LTBI was determined based on TST alone with a single high dose (10 tuberculin units [TU]). The rationale for using such a high dose in a highly prevalent setting like India is not mentioned as the WHO's recommendation is 5 TU.[13]

In addition, the type of protein used for testing seems to be different from those accepted for use for TST by the WHO. The average of the measurements of the induration made by two investigators was taken as the final value. Instead of averaging measurements made by a ruler in millimetres in direct vision, taking the maximum value of induration could have been a better strategy. The higher prevalence of LTBI seen in this study could very well be due to the higher dose used for TST and the lack of adjustment for the inherent deficits of TST as a diagnostic test.


  Discussion Top


This scoping review tried to bring out the evidence on the burden of LTBI among healthcare professionals in India. A comprehensive search of various databases proved that much more research needs to be undertaken for understanding the risk of LTBI in the high-risk category of people. Different challenges plagued the few available studies conducted in Indian population. All studies have restricted occupational groups as the study participants. Doctors and several other staff personnel in constant contact with patients have not been included in the studies. The recruitment of the study participants is more toward younger age groups, which initially helps estimate the risk of LTBI in the community and later due to the exposures from the healthcare institutions.

The studies mention the TU present in the TST preparations used in the respective studies. This is relevant due to experts' varying opinions regarding the dose to be used for TST in high-prevalent settings. TST is considered by the WHO as a gold standard test in resource-poor settings.[2] As standardised and non-standardised preparations of TST are available, it is imperative that the investigators use specified TST preparations for drawing robust conclusions. The study by Kinikar et al. used 5 TU. In contrast, Christopher et al. used 2 TU of standard preparation of RT23 PPD (Staten Serum Institute, Copenhagen). Hence, the usage of TST itself is varying even if the test seems to be the same.

The prevalence of LTBI ranged from 30% to 48% between the three studies. The study with a lower TU dose for TST and with the better documentation of TB exposure showed the highest prevalence of 48%. The study with the TST validation using advanced IGRA showed the lowest at 30% and the one with less rigorous methodology gave the prevalence as 36%. With most of the study participants in all studies falling into the 20–40-year-old age group and with at least one-third prevalence being reported, the risks of the increasing occurrence of LTBI and active TB later are genuine causes for concern. In the study with the highest prevalence, the use of LCA for accounting for TST deficits as a screening test was an essential step for accounting for the deficiencies of TST as a screening test. However, simultaneous testing with TST and IGRA by Kinikar et al. in the very recent study showed lower prevalence. Hence, this could be considered as a more accurate estimation of the prevalence of LTBI in HCWs. Given the unavailability of WHO-recommended standard preparations of TST in India for the past several years, appropriate screening tests need to be adopted to screen LTBI.

All three studies have revealed the role of increasing the time being spent in the healthcare profession as an essential risk factor for the development of LTBI. This is very pertinent due to the constant pool of TB patients that could emerge with advancing time. With most of the other sociodemographic variables falling short of being significant risk factors for the development of LTBI, the most critical risk factor that should be of concern for policymakers should be the increased risk to HCW with advancing years of healthcare-related activities.

Healthcare professionals in high-prevalent settings are at increased risk of LTBI and subsequent active TB with increasing exposure years. With almost a quarter of the study participants turning out to have LTBI and the age of the study participants being in the younger group, the risk of TB in healthcare professions is a frightening reality. The absence of proper guidelines for treating LTBI in high-prevalent settings and the lack of awareness among healthcare professionals regarding LTBI are major challenges. Nosocomial TB is also a significant threat which needs to be addressed along with other nosocomial infections. Contrasting evidence exists regarding the cost-effectiveness of IGRA over TST for LTBI screening.[13],[14] Guidelines need to be put in place for serial testing of HCWs using TST or IGRA or upcoming C-Tb for tackling the challenge of LTBI.[15] The current focus on providing treatment for LTBI in India should be supplemented by increased awareness among HCWs to test and treat LTBI. However, the issues associated with repeated infection in those treated for LTBI are even more challenging.

However, the studies conducted in these settings have very few doctors and other healthcare staff as participants. This lack of evidence among various other groups will pose challenges during the development of policies for managing LTBI in high-prevalent settings. Moreover, the prevalence of LTBI is estimated to be around 50% in the community and in household contacts of TB patients.[16],[17] With the national average estimated to be around double that of the global average, high-burden countries like India need to tackle LTBI with more vigour.[18] With the prevalence of LTBI in young HCWs being around 30% ,the need for LTBI treatment for older HCW with more years of exposure need to be discussed urgently. With the increased risk of development of LTBI with more years of work, policies for risk stratification for various groups/categories of HCW need to be developed for bringing out useful risk reduction strategies. More comprehensive research across multiple settings needs to be undertaken to assess the risk of LTBI in all categories of HCWs. Hence, urgent policies for tackling the challenges for diagnosis and management of LTBI among HCWs are the need of the hour.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
WHO | Global Tuberculosis Report 2020. Geneva: WHO; 2021. Available from: http://www.who.int/tb/publications/global_report/en/. [Lastaccessed on 2020 Oct 28].  Back to cited text no. 1
    
2.
Global Tuberculosis Programme. Latent Tuberculosis Infection: Updated and Consolidated Guidelines for Programmatic Management. Geneva: Global Tuberculosis Programme; 2018. Available from: http://www.ncbi.nlm.nih.gov/books/NBK531235/. [Last accessedon 2020 Oct 28].  Back to cited text no. 2
    
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Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: A re-estimation using mathematical modelling. PLoS Med 2016;13:e1002152.  Back to cited text no. 3
    
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Cohen A, Mathiasen VD, Schön T, Wejse C. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2019 Sep 12;54(3):1900655. doi: 10.1183/13993003.00655-2019. PMID: 31221810.  Back to cited text no. 4
    
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Uden L, Barber E, Ford N, Cooke GS. Risk of tuberculosis infection and disease for health care workers: An updated meta-analysis. Open Forum Infect Dis 2017;4:ofx137.  Back to cited text no. 5
    
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Apriani L, McAllister S, Sharples K, Alisjahbana B, Ruslami R, Hill PC, et al. Latent tuberculosis infection in healthcare workers in low- and middle-income countries: an updated systematic review. Eur Respir J. 2019 Apr 18;53(4):1801789. doi: 10.1183/13993003.01789-2018. PMID: 30792341.  Back to cited text no. 6
    
7.
Global Tuberculosis Programme. Latent Tuberculosis Infection: Updated and Consolidated Guidelines for Programmatic Management. Geneva: Global Tuberculosis Programme; 2018. Available from: http://www.ncbi.nlm.nih.gov/books/NBK531235/. [Last accessed on 2020 Nov 06].  Back to cited text no. 7
    
8.
Brice R. CASP – Critical Appraisal Skills Programme. Oxford: CASP Checklists; 2020. https://casp-uk.net/casp-tools-checklists/. [Last accessed on 2020 Nov 07].  Back to cited text no. 8
    
9.
Kinikar A, Chandanwale A, Kadam D, Joshi S, Basavaraj A, Pardeshi G, et al. High risk for latent tuberculosis infection among medical residents and nursing students in India. PLoS One 2019;14:e0219131.  Back to cited text no. 9
    
10.
Haas MK, Belknap RW. Diagnostic tests for latent tuberculosis infection. Clin Chest Med 2019;40:829-37.  Back to cited text no. 10
    
11.
Christopher DJ, Daley P, Armstrong L, James P, Gupta R, Premkumar B, et al. Tuberculosis infection among young nursing trainees in South India. PLoS One 2010;5:e10408.  Back to cited text no. 11
    
12.
Janagond AB, Ganesan V, Vijay Kumar GS, Ramesh A, Anand P, Mariappan M. Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital. Int J Mycobacteriol 2017;6:253-7.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Nayak S, Acharjya B. Mantoux test and its interpretation. Indian Dermatol Online J 2012;3:2-6.  Back to cited text no. 13
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14.
Greenaway C, Pareek M, Abou Chakra CN, Walji M, Makarenko I, Alabdulkarim B, et al. The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review. Euro Surveill. 2018 Apr;23(14):17-00543. doi: 10.2807/1560-7917.ES.2018.23.14.17-00543. PMID: 29637889; PMCID: PMC5894253.  Back to cited text no. 14
    
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Aggerbeck H, Ruhwald M, Hoff ST, Borregaard B, Hellstrom E, Malahleha M, et al. C-Tb skin test to diagnose Mycobacterium tuberculosis infection in children and HIV-infected adults: A phase 3 trial. PLoS One 2018;13:e0204554.  Back to cited text no. 16
    
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Chandrasekaran P, Mave V, Thiruvengadam K, Gupte N, Shivakumar SV, Hanna LE, et al. Tuberculin skin test and QuantiFERON-Gold in Tube assay for diagnosis of latent TB infection among household contacts of pulmonary TB patients in high TB burden setting. PLoS One 2018;13:e0199360.  Back to cited text no. 18
    


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