Impact of Gene Xpert on the diagnosis of pulmonary tuberculosis at a tertiary health care facility in Nigeria

Olayinka S Ilesanmi; Bamidele O Adeniyi; Ayobami Adebayo Bakare; Adesola O Kareem

doi:10.4103/jomt.jomt_38_20

ORIGINAL ARTICLE

Year : 2021 | Volume : 23 | Issue : 1 | Page : 11-16

Impact of Gene Xpert on the diagnosis of pulmonary tuberculosis at a tertiary health care facility in Nigeria

Olayinka S Ilesanmi¹, Bamidele O Adeniyi², Ayobami Adebayo Bakare³, Adesola O Kareem⁴
¹ Department of Community Medicine, College of Medicine, University of Ibadan; Department of Community Medicine, University College Hospital, Ibadan, Nigeria
² Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria
³ Department of Community Medicine, University College Hospital, Ibadan, Nigeria
⁴ Department of Community Health, Federal Medical Centre, Owo, Ondo State, Nigeria

Date of Submission	07-Jun-2020
Date of Decision	08-Sep-2020
Date of Acceptance	12-Jan-2021
Date of Web Publication	28-Apr-2021

Correspondence Address:
Ayobami Adebayo Bakare
Department of Community Medicine, University College Hospital, Ibadan
Nigeria

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jomt.jomt_38_20

Abstract

Background: Gene Xpert mycobacterium tuberculosis (MTB)/Rifampicin (RIF) was introduced for the detection of pulmonary tuberculosis (PTB) at the Federal Medical Centre, Owo, Ondo State, Nigeria in 2015. The study aimed to determine the effect of Gene Xpert MTB/RIF on diagnosis of PTB. Methods: We reviewed Gene Xpert register from January 2015 to January 2017. The agreement of Gene Xpert with acid-fast bacilli was determined using the sensitivity and positive predictive value of the Gene Xpert test. Association was assessed using chi-square test. Binary logistic regression was used to determine the predictors of positive Gene Xpert result. Results: A total of 1246 records were reviewed; the average age was 41 ± 19 years, and nearly half of the patients (48.6%) were female. While 264 (21.2%) were human immuno-deficiency virus (HIV) positive. Smear microscopy was positive in 118 (16.9%); 90 (13.6%) had tuberculosis (TB) detected on Gene Xpert. Those positive for smear microscopy and Gene Xpert were 21 (10.0%). The Gene Xpert detected 90 (8.3%) of the 653 with presumptive TB. The turnaround time for Gene Xpert was 24 hours. When compared to smear microscopy, Gene Xpert showed sensitivity of 45.7% (95% confidence interval [CI]: 31.7–60.1) and specificity of 98.2% (95% CI: 95.1–99.5) in all the cases and sensitivity of 50% (95% CI: 29.8–70.2) and specificity of 100% among HIV positives. Conclusion: Gene Xpert should be preferred to smear microscopy in evaluating HIV positive patients for TB. Nevertheless, clinicians can still rely on results from smear microscopy for clinical decision when Gene Xpert is not available.

Keywords: Acid-fast bacilli, gene xpert, hiv/aids, pulmonary tuberculosis

How to cite this article:
Ilesanmi OS, Adeniyi BO, Bakare AA, Kareem AO. Impact of Gene Xpert on the diagnosis of pulmonary tuberculosis at a tertiary health care facility in Nigeria. J Med Trop 2021;23:11-6

How to cite this URL:
Ilesanmi OS, Adeniyi BO, Bakare AA, Kareem AO. Impact of Gene Xpert on the diagnosis of pulmonary tuberculosis at a tertiary health care facility in Nigeria. J Med Trop [serial online] 2021 [cited 2023 Jun 5];23:11-6. Available from: https://www.jmedtropics.org/text.asp?2021/23/1/11/314853

Introduction

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide, affecting about 10 million people every year, and Africa is home to almost one-quarter of global TB cases.^[1],[2]

Nigeria is among the six high-burdened countries which accounted for two-third of global incidence of TB in 2018.^[1],[3] Delayed diagnosis and low case finding remain the bane to TB eradication in Nigeria. Of the estimated 586,000 cases in 2015, 90,584 cases (15%) were notified. Similarly, about one-quarter of estimated cases (418,000) were notified in 2017.^[4],[5] This underreporting is not unconnected with diagnostic dilemmas being faced by health workers in evaluating patients with suspected TB.

Sputum culture for Mycobacterium tuberculosis remains the gold standard for diagnosis of TB, but it is relatively slow, complex, and requires skilled workers.^[6] Sputum smear for acid-fast bacilli however is cheap, easy to perform, and relatively common in low-resource settings like Nigeria, but its sensitivity is low, especially in human immuno-deficiency virus (HIV) positive patients.^[7],[8] However, people with HIV/AIDS are 15 to 22 times more likely to develop TB.^[9]

In 2010, World Health Organization (WHO) adopted Gene Xpert and recommended its rapid implementation.^[10],[11] Gene Xpert (Cepheid, Sunnyvale, CA) mycobacterium tuberculosis (MTB)/Rifampicin (RIF) is an automated, user-friendly, real-time polymerase chain reaction (PCR) assay designed for the rapid and simultaneous detection of M. tuberculosis and rifampicin resistance.^[12],[13] By 2016, it was adopted as first diagnostic tool for TB in Nigeria.^[14] Currently, there are Gene Xpert machines in each of the 36 states of the federation.^[5],[14] Previous reports on Gene Xpert in Nigeria focused on challenges with its implementation.^[15] However, there is a need for local assessment of Gene Xpert use for TB diagnosis among people with or without HIV/AIDS given the burden of HIV/AIDS in Nigeria.^[16] The study therefore aimed to assess the effect of Gene Xpert MTB/RIF on diagnosis of TB at a tertiary hospital in Owo, Ondo State, Nigeria.

Methods

Study design/Setting

We conducted a cross-sectional retrospective study, involving the review of patients’ medical charts at the Tuberculosis and Leprosy (TBL) Clinic of the Federal Medical Centre (FMC), Owo, Ondo State, Nigeria.

Using a case report form, we extracted details of patients who had attended TBL Clinic from January 2015 to January 2017. The TBL Clinic is in the Department of Community Health of the FMC, Owo which is the only tertiary hospital in Ondo State. Owo is situated in southwestern Nigeria and is predominantly inhabited by the Yoruba ethnic group. Yoruba and English are the main languages of communication.

The TBL Clinic carries out activities in line with the National Tuberculosis and Leprosy Control Program (NTBLCP) and is supported by doctors, nurses, and Community Health Extension Workers. The activities in the unit include screening of patients with suspected TB by collecting sputum samples for acid and alcohol-fast bacilli and Gene Xpert. Further screening is done at the end of the second and fifth months, and at the end of therapy (sixth month). The unit also oversees directly observed therapy for patients who are diagnosed with TB and conduct counseling and follow-up of patients who are on treatment for TB. Furthermore, the activities include stocking of TB diagnosis and treatment commodities; conduct tracing of contacts of TB patients to reduce the burden of TB at the community level. Review of records is done on a monthly, quarterly, and yearly basis.

The anti-TB drugs are supplied free of charge by the Federal Ministry of Health in conjunction with the Ondo State Ministry of Health. The TB Clinic is opened from 8 a.m. to 4 p.m. on weekdays and closes for weekends. However, staff of the clinic are available to provide services during weekends.

Analysis

Data entry and analysis was done using SPSS version 16 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp). Frequencies of sociodemographic characteristics; age group, sex, and health facility utilized were generated. Proportions were analyzed for the results of Gene Xpert, smear microscopy, reasons for examination, and HIV status. Bivariate analysis was done to determine the association between sociodemographic characteristics, clinical variables, and Gene Xpert result. The association between sociodemographic characteristics, clinical characteristics, and HIV status were assessed using chi-square test. Binary logistic regression was used to determine the predictors of Gene Xpert result. The level of statistical significance was P<0.05.

Results

We identified total number of 1,246 patients who were investigated for TB at FMC, Owo, Ondo State, Nigeria, of which 51.18% were female. The average age of the patients was 41.5 ± 19.6 years. More than half of the cases reviewed 770(66.7%) were referred from within FMC, Owo while the remaining were referred from primary/basic health centers 385 (33.3%) surrounding the tertiary hospital. Throughout the period under review (January 2015–January 2017), Gene Xpert and smear microscopy were the screening tests being requested for evaluation of TB patients. At the time under consideration, only sputum samples were being collected for evaluation. Gene Xpert was done on almost half of the patients. The reasons for investigation were either for initial diagnosis 868 (81.6%) or for follow-up 196 (18.4%).The Gene Xpert detection rate for M. tuberculosis was 13.6% (90/664), whereas 16.9% (118/700) samples were positive for smear microscopy. Among the 1246 cases reviewed, 264 patients (21.2%) were HIV positive while 195 patients (15.7%) had their status unknown [Table 1].

Table 1: Sociodemographic characteristics, laboratory test, and reasons for examination of tuberculosis patients seen at Federal Medical Centre, Owo, Ondo State, Nigeria from 2015–2016

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We found that 54 (18.2%) males had M. tuberculosis detection with Gene Xpert compared to the females 36 (10.1%) (P = 0.003). Also, 27 (20.8%) cases which were within the age group of 35 to 44 years had Gene Xpert detected compared to other age groups (P = 0.011). Gene Xpert detection was in 70 (12.4%) patients who had initial diagnosis compared to 8 (29.6%) for follow-up (P = 0.010). Among patients that had positive smear microscopy, 21 (87.5%) had Gene Xpert detected compared to 25 (13.4%) of those with negative smear microscopy who were more likely to have MTB detected on Gene Xpert (P = 0.001). Among cases with smear positive result, 23 (20.5%) of them were living with HIV compared to 154 (29.8%) who were smear negative (P = 0.048) [Table 2].

Table 2: Relationship between sociodemographic characteristics, clinical data, Gene Xpert result, and HIV status at FMC, Owo, Ondo State, Nigeria from 2015–2016

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The performance of Xpert MTB/RIF compared with sputum smear microscopy in all cases showed an overall sensitivity of 45.7% (95% confidence interval [CI], 31.7–60.1). In patients living with HIV, the Gene Xpert MTB/RIF revealed a sensitivity of 50% (95% CI: 29.8–70.2) and specificity of 100% compared to sputum smear microscopy [Table 3].

Table 3: Performance outcomes of Xpert MTB/RIF for the detection of Mycobacterium tuberculosis compared to smear microscopy

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Detection of MTB was significantly associated with follow-up as a reason for sample analysis, those who were tested as follow-up had four times odds of detection of MTB/RIF compared with those having initial diagnosis [Odds Ratio (OR): 4.07; 95% CI: 1.15–14.40]. The cases that were tested positive by using smear microscopy had 92 times odds of MTB/RIF detection (OR: 92.85; 95% CI: 18.83–457.85) [Table 4].

Table 4: Determinants of detection of MTB/RIF (Gene Xpert)

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Discussion

This study has provided insight into Gene Xpert use in a typical low-resourced setting area. We found prospects in the use of Gene Xpert as a diagnostic test for TB. Greater proportion of HIV positive patients had MTB detected through Gene Xpert compared to HIV negative patients who were positive on Gene Xpert. Our study thus underscores the relevance of Gene Xpert in evaluation of HIV patients for TB. While these findings support use of Gene Xpert in evaluation of HIV patients,^[17] proportion of HIV patients with MTB detected through Gene Xpert is low compared to other studies.^[18],[19] In a prospective study by Akanbi et al., 73.7% of HIV patients had pulmonary tuberculosis (PTB) detected via Gene Xpert. Similarly, Carriquiry et al. in another study reported 97.8% of HIV positive patients with PTB detected from Gene Xpert.^[18],[19] We found lower proportion of HIV patients with PTB detected from Gene Xpert. This may be due to differences in the study design, given that we conducted a retrospective study whereas prospective data collection was done in the other studies.^[18],[19]

Gene Xpert was requested in almost half of the patients, making it the most frequently requested screening test for evaluation of patients with confirmed or suspected TB. This differs from other studies which showed minimal use of the technology in evaluation of presumptive TB cases.^[20] While this represents progress toward achieving WHO recommendation on rapid uptake of Gene Xpert,^[10] there is need for continuing and sustained efforts on scale up. About a third of the subjects were referred from primary health centers and neighboring facilities for Gene Xpert testing. There is greater possibility that significant number of people who were referred from neighboring facilities might have defaulted. Nonadherence to referral advice may undermine the fight against TB in Nigeria. Thus, there is a need for continuing efforts on scale up of Gene Xpert up to secondary health facilities and comprehensive health centers.

Among cases with HIV/AIDS, greater proportion were smear negative for TB compared to proportion that were smear negative among HIV negative cases. This is in keeping with the documented challenges of TB diagnosis in the setting of HIV/AIDS.^[21] Our study found that smear microscopy is still useful in evaluation of TB patients in a resource-constrained setting. Cases that were positive on smear microscopy were more likely to be detected by Gene Xpert technology. The performance of Gene Xpert for the detection of M. tuberculosis compared to sputum smear microscopy was better. Thus, Gene Xpert should be preferred to smear microscopy in evaluating HIV positive patients for TB. Nevertheless, clinicians can still rely on results from smear microscopy for clinical decision in management of TB cases, particularly, in places where Gene Xpert is not available.

We observed poor documentation of relevant clinical data on subjects that were tested. Complete and accurate data is crucial for evaluation of National TB Control program; hence, this aspect needs further strengthening. We recommend health system strengthening interventions such as supportive supervision for healthcare workers, infrastructural support, and effective leadership.

This study has some limitations. Apart from being a retrospective study flawed with substantial data quality issues, we could not ascertain how results of Gene Xpert influenced patient management, particularly regarding commencement or discontinuing of anti-TB drugs. Also, we do not know the clinical stages of patients with positive HIV results. However, our study still provided insight into current use of Gene Xpert technology in a resource-constrained setting and underscored its usefulness in evaluation of HIV positive patients for TB. We recommend further prospective study to be carried out to know impact of Gene Xpert use in management of HIV positive people.

Acknowledgements

We would like to thank all the staff of FMC, Owo, Ondo State, Nigeria who were involved in the diagnosis, care, and other management of patients having tuberculosis.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors report no conflicts of interest.

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