Publication System Publication System

Assessing the Prevalence and Seriousness of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) Detected by GeneXpert

Original Research | Open access | Published: 10 July 2022
Volume 0, article number 18, (0) Cite this article
You have full access to this open access article.
, ,
  1. Department of Pharmacology, Faculty of Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam
  2. Department of Toxicology and Drug Development, Faculty of Life Sciences, Can Tho University, Can Tho, Vietnam
118 Accesses

Abstract

According to the World Health Organization (WHO) estimates, there were 558,000 new cases of rifampicin-resistant tuberculosis, with 82% of these classified as multidrug-resistant tuberculosis (MDR-TB). This study aimed to investigate the outbreak of MDR-TB in River Nile State, Sudan, and identify the risk factors associated with its occurrence. A descriptive cross-sectional hospital-based study was conducted involving two hundred specimens from patients suspected of having MDR-TB, tested using the automated GeneXpert assay. The GeneXpert results indicated that Mycobacterium tuberculosis was detected in 81 cases (40.5%), and among these positive results, 13 (16%) were confirmed as MDR-TB. Furthermore, 7 of the MDR-TB cases had a history of previous treatment, accounting for approximately 53 percent of MDR patients. In contrast, the other 6 MDR-TB cases were new, representing 47% of the MDR-TB patients. In addition, 4 MDR-TB patients had a history of contact with other MDR-TB cases. The prevalence of MDR-TB in River Nile State, Sudan, was found to be 16%, which is higher than the WHO estimate for Sudan at 10.1%. The findings highlighted that prior contact with MDR-TB patients is the primary risk factor for developing MDR-TB, emphasizing that treatment adherence and increased social awareness about MDR-TB transmission are essential preventive measures.

Explore related subjects
Discover the latest articles in related subjects:

Introduction

The World Health Organization (WHO) estimated that over ten million individuals worldwide had tuberculosis (TB) in 2017 and 2018, although only 7 million cases were officially reported [1, 2]. TB remains one of the top 10 causes of death globally, with recent WHO studies estimating the incidence of new cases at 4.1% and 19% among previously treated cases involving multidrug-resistant tuberculosis (MDR-TB) [3].

TB is a significant public health issue in Sudan, which is classified among the countries with a high TB burden within the Eastern Mediterranean Region/World Health Organization (EMR/WHO) [4–7]. In 2017, Sudan reported 21,054 cases [8], and WHO reports indicate that the mortality rate related to tuberculosis is approximately 25 per 100,000 population [3]. Resistance to both rifampin (RIF) and isoniazid (INH) serves as a reliable indicator of MDR-TB [9]. Drug-resistant TB continues to be a global public health challenge, with nearly 580,000 cases worldwide and mortality rates exceeding those of many cancers [1, 10–13]. WHO surveillance data from 2016 estimated 600,000 MDR-TB cases and 490,000 deaths attributed to MDR-TB [3]. The incidence of MDR-TB is particularly high in sub-Saharan Africa, especially among patients with a history of prior TB treatment [14, 15].

In resource-limited countries like Sudan, MDR-TB poses a serious public health threat due to limited diagnostic facilities for MDR-TB, poor treatment adherence, and delays in initiating treatment [16]. MDR-TB is considered a significant barrier to effective TB control worldwide [17]. WHO has identified a range of risk factors associated with the development of MDR-TB [18]. Additionally, various studies have highlighted risk factors such as inadequate drug supply, poor treatment adherence, shortened treatment duration, and incorrect dosing [19].

Recent advances have improved the detection, testing, and treatment of MDR-TB, with 51% of bacteriologically confirmed TB patients diagnosed with rifampicin resistance [1]. Despite these improvements, only about one-third (32%) of the nearly 500,000 patients with MDR-TB received treatment in 2017 and 2018 [1, 2].

Meanwhile, the use of the rapid GeneXpert MTB/RIF test has increased significantly since the WHO recommended its use in 2010. This test detects TB and potential resistance to Rifampicin within two hours. WHO now endorses GeneXpert as the primary diagnostic tool for all patients exhibiting symptoms and signs of TB [3].

This study aimed to investigate the outbreak of MDR-TB in River Nile State, Sudan, and identify the risk factors associated with its occurrence.

Materials and Methods

This descriptive cross-sectional study was conducted at a hospital in River Nile State, Sudan, between March and October 2018. River Nile State, situated in northern Sudan, consists of seven localities and has an estimated population of approximately 1.472 million. The study was centered at the diagnostic center located in Atbara locality, which is equipped with GeneXpert assay testing facilities. During the study period, 200 tuberculosis patients suspected of having MDR-TB were recruited. Data collection employed a closed-ended questionnaire administered by the principal investigators. This questionnaire gathered information on participants’ demographic characteristics, potential risk factors for MDR-TB, and the GeneXpert assay test results.

GeneXpert assay procedure

For the assay, the test reagent was combined with untreated sputum in a 2:1 ratio and with decontaminated sputum pellets in a 3:1 ratio to meet the volume requirements for the test. The sputum container was sealed and manually shaken twice for 15 minutes at room temperature before transferring 2 ml of the treated sample into the test cartridge, which corresponds to 0.7 ml of raw sputum or 0.5 ml of purified pellets. The cartridges were then inserted into the GeneXpert platform situated in the microscopy room. This fully automated system (Cepheid, Sunnyvale, CA) integrates sample preparation and heminested real-time polymerase chain reaction (PCR) to detect Mycobacterium tuberculosis and rifampicin resistance rapidly.

Data analysis

Data were analyzed using IBM SPSS Statistics version 21 (Armonk, NY, USA). Descriptive statistics were used to summarize the data distributions in terms of frequencies. Categorical data were presented as numbers and percentages. The chi-square test was utilized to assess associations, considering a P-value < 0.05 as statistically significant.

Ethical considerations

This study was conducted in accordance with the Declaration of Helsinki guidelines. Approval was obtained from the Ethical Committee of the Sudan Medical Specialization Board (SMSB) and the River Nile State Ministry of Health authorities. Written informed consent was secured from all participants before enrollment in the study.

Results and Discussion

A total of 200 patients suspected of having MDR-TB were enrolled in the study. The majority were male, accounting for 142 (71%), while females represented 58 (29%). The age group most frequently affected was 15-35 years, comprising 85 patients (42.5%). Nearly half of the participants, 96 (48%), lived in urban areas, as detailed in Table 1.

Table 1. Distribution of demographic specifications of the participants (n = 200)

Character

Frequency (%)

Age (years)

15–35

85 (42.5%)

36–55

78 (39.0%)

56–75

32 (16.0%)

> 75

5 (2.5%)

Gender

Male

142 (71.0%)

Female

58 (29.0%)

Residence

Urban

96 (48.0%)

Rural

104 (52.0%)

The GeneXpert assay detected Mycobacterium tuberculosis in 81 patients (40.5%), whereas 119 patients (59.5%) tested negative for the bacterium. Among the 81 positive cases, 13 (6.5%) were found to have Rifampicin-resistant MDR-TB, while the remaining 68 (34%) had drug-susceptible Mycobacterium tuberculosis, as shown in Table 2.

Table 2. The distribution of the study group according to GeneXpert results (n = 200)

GeneXpert

N

%

Positive

MDR-TB

13

6.5%

Non-MDR-TB

68

34%

Total positive

 

81

40.5%

Negative

119

59.5%

Total

200

100%

In this study, 132 patients (66%) had a history of previous anti-tuberculous treatment, whereas 68 (34%) were treatment-naïve. Of those previously treated, 125 (94.7%) completed their therapy, while 7 (5.3%) did not. Clinical improvement was observed in 121 (91.7%) of previously treated patients, with 11 (8.3%) showing no improvement. Signs of recovery included complete symptom resolution in 77 patients (63.6%), sputum conversion to negative in 46 (38%), and weight gain with appetite improvement in 59 (48.8%). Radiological improvement was noted in 23 patients (19%), as illustrated in Table 3.

Table 3. Patient characteristics based on treatment history and clinical improvement

Item

Number (percentage)

History of previous anti-tuberculous treatment*

Yes: 132 (66%)

No: 68 (34%)

Completion of treatment course**

Yes: 125 (94.7%)

No: 7 (5.3%)

Clinical improvement**

Yes: 121 (91.7%)

No: 11 (8.3%)

Full symptom resolution***

Yes: 77 (63.6%)

No: 44 (36.4%)

Negative sputum conversion***

Yes: 46 (38%)

No: 75 (62%)

Weight gain and enhanced appetite***

Yes: 59 (48.8%)

No: 62 (51.2%)

Radiological signs of improvement***

Yes: 23 (19%)

No: 98 (81%)

* calculated from the total patient sample (n = 200); ** calculated among patients with a history of anti-tuberculous treatment (n = 132); *** calculated from patients who showed clinical improvement and were previously treated (n = 121).

Contact history emerged as the most significant risk factor associated with the development of MDR-TB (P-value = 0.000). Conversely, previous treatment history appeared to have a protective effect against MDR-TB (P-value = 0.005). No statistically significant relationship was found between MDR-TB and HIV infection status (P-value = 0.6) or diabetes mellitus (DM) (P-value = 0.4), as summarized in Table 4.

Table 4. Distribution of demographic specifications of the participants (n = 200)

Variable

MDR-TB

Non-MDR-TB

P-value

Diabetes mellitus history

Present

1 (33.3%)

2 (66.7%)

0.406

Not present

12 (15.4%)

66 (84.6%)

HIV infection history

Present

0 (0%)

1 (100%)

0.66

Not present

13 (16.2%)

67 (83.8%)

History of previous treatment

Present

7 (10.65%)

59 (89.4%)

0.005

Not present

6 (40%)

9 (60%)

History of contact

Present

4 (80%)

1 (20%)

< .001

Not present

9 (11.8%)

67 (88.2%)

 

To the best of our knowledge, no previous studies on MDR-TB have been conducted in River Nile State. This study aimed to identify the occurrence of MDR-TB among patients suspected of tuberculosis.

In this research, the majority of participants were male, accounting for nearly three-quarters of the sample, which is comparable to a similar study reporting 71% males [20]. The most affected group in our study was the younger age group, likely because they represent the working population and are therefore more exposed to pathogenic bacteria.

During the study period, the prevalence of MDR-TB in River Nile State, Sudan, was found to be 16%, which is close to the 14.7% reported in a Nigerian study [21]. This prevalence is lower than that reported in Kassala State, Sudan, where MDR-TB prevalence reached 51.7% [22], and also lower than rates from a meta-analysis in Ethiopia, which showed 2.18% in newly diagnosed cases and 21.07% in previously treated patients [23]. Conversely, the MDR-TB rate in this study is higher than a previous Sudanese study that found MDR-TB in 5% of new cases and 24% of previously treated cases [20].

The primary risk factor associated with developing MDR-TB was a history of contact with MDR-TB patients (P < 0.001). Interestingly, previous treatment history was found to be a protective factor against MDR-TB development (P = 0.005). These results align with findings from a meta-analysis in Ethiopia, which included 34 studies examining patients with prior treatment history [23]. However, our findings contrast with earlier research that identified previous treatment as a risk factor, with a risk ratio of 5.23 (95% CI: 2.30–4.60; P < 0.001) for MDR-TB [20]. Treatment default was also recognized as a contributing risk factor for MDR-TB emergence [24].

Conclusion

This section is optional and can be included if the discussion is particularly lengthy or complex.

Patients

During the study, MDR-TB prevalence was 6.5% across all participants and approximately 16% among those testing positive for M. tuberculosis by GeneXpert assay. The WHO estimated Sudan’s MDR-TB prevalence at 10.1% in 2002, making our findings higher than the WHO estimate. Key risk factors identified were previous treatment history and contact with MDR-TB patients.

Recommendations

We advocate for early diagnosis and appropriate management of TB cases to reduce transmission risk. It is recommended to provide health services equipped with modern diagnostic tests for resistant strains at the state level, to monitor all MDR-TB cases, and to report new cases to the Sudan Federal Ministry of Health. Additionally, increasing public awareness about the risks of MDR-TB spread and promoting efforts to control it are essential to curb the rising number of MDR-TB patients.

Acknowledgements

None

Conflict of interest

None

Financial support

None

Ethics statement

This study was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board of the Sudan Medical Specialization Board (SMSB), the Ethical Committee, and the health authorities at the Ministry of Health in River Nile State, Sudan.

References

WHO. Global tuberculosis report executive summary 2019. [cited 2019 Oct 28]. Available from: URL:https://www.who.int/tb/publications/global_report/tb19_Exec_Sum_15October2019.pdf?ua=1.
WHO. Global tuberculosis report (full). 2019. [cited 2019 Oct 28]. Available from: URL:https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1
World Health Organization WHO website https://www.who.int/immunization/diseases/tuberculosis/en/
Abdallah TM, Ali AAA. Epidemiology of tuberculosis in Eastern Sudan. Asian Pac J Trop Biomed. 2012;2(12):999-1001.
Hassanain SA, Edwards JK, Venables E, Ali E, Adam K, Hussien H, et al. Conflict and tuberculosis in Sudan: a 10-year review of the National Tuberculosis Programme, 2004-2014. Confl Health. 2018;12(1):1-9.
https://doi.org/10.1186/s13031-018-0154-0
Faller EM, Hernandez MT, Hernandez AM, Gabriel JR. Emerging roles of pharmacists in global health: an exploratory study on their knowledge, perception, and competency. Arch Pharm Pract. 2020;11(1):40-6.
Soep S, Agussalim A. The impact of health education about Diabetes mellitus on patient knowledge to control their Blood Sugar. J Adv Pharm Educ Res. 2020;10(3):141-5.
World Health Organization. Global Tuberculosis Report; World Health Organization: Geneva, Switzerland, 2018; Available online: http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?ua=1 (accessed on Jun 12, 2019).
Chen X, Wang B, Yang W, Kong F, Li C, Sun Z, et al. Rolling circle amplification for direct detection of rpoB gene mutations in Mycobacterium tuberculosis isolates from clinical specimens. J Clin Microbiol. 2014;52(5):1540-8.
https://doi.org/10.1128/JCM.00065-14
Seaworth BJ, Griffith DE. Therapy of multidrug-resistant and extensively drug-resistant tuberculosis. Microbiol Spectr. 2017;5(2):1-16.
https://doi.org/10.1128/microbiolspec.MTSY-0031-2017
Dheda K, Chang KC, Guglielmetti L, Furin J, Schaaf HS, Chesov D, et al. Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Microbiol Infect. 2017;23(3):131-40.
Kapata N, Grobusch MP, Chongwe G, Chanda-Kapata P, Ngosa W, Tembo M, et al. Outcomes of multidrug-resistant tuberculosis in Zambia: a cohort analysis. Infection. 2017;45(6):831-9.
WHO. Global Tuberculosis Report. 2016. [cited 2019 Jun 1]. Available from URL:http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1
Berhan A, Berhan Y, Yizengaw D. A meta-analysis of drug resistant tuberculosis in Sub-Saharan Africa: how strongly associated with previous treatment and HIV co-infection? Ethiop J Health Sci. 2013;23(3):271-82.
Musa BM, Adamu AL, Galadanci NA, Zubayr B, Odoh CN, Aliyu MH. Trends in prevalence of multi drug resistant tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. PLoS One. 2017;12(9):e0185105.
World Health Organization (WHO), Multidrug and extensively drug-resistant TB (M/XDR-TB): Global report on surveillance and response. Geneva, Switzerland; WHO Press; 2010. Available from: http://www.who.int/tb/publications/global_report/en/
Goble M, Iseman MD, Madsen LA, Waite D, Ackerson L, Horsburgh Jr CR. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med. 1993;328(8):527-32.
World Health Organization. Companion handbook to the WHO guidelines for the pro-grammatic management of drug-resistant tuberculosis; 2014 [cited 2018 Sep 26]. Available from: https://www.who.int/tb/publications/pmdt_companionhandbook/en/.
Günther G, Van Leth F, Alexandru S, Altet N, Avsar K, Bang D, et al. Multidrug-resistant tuberculosis in Europe, 2010–2011. Emerg Infect Dis. 2015;21(3):409.
Stosic M, Vukovic D, Babic D, Antonijevic G, Foley KL, Vujcic I, et al. Risk factors for multidrug-resistant tuberculosis among tuberculosis patients in Serbia: a case-control study. BMC Public Health. 2018;18(1):1-8.
Girum T, Muktar E, Lentiro K, Wondiye H, Shewangizaw M. Epidemiology of multidrug-resistant tuberculosis (MDR-TB) in Ethiopia: a systematic review and meta-analysis of the prevalence, determinants and treatment outcome. Trop Dis Travel Med Vaccines. 2018;4(1):1-12.
Eldin GS, Fadl-Elmula I, Ali MS, Ali AB, Salih AL, Mallard K, et al. Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs. BMC Infect Dis. 2011;11(1):1-8.
Abdul-Aziz AA, Elhassan MM, Abdulsalam SA, Mohammed EO, Hamid ME. Multi-drug resistance tuberculosis (MDR-TB) in Kassala state, eastern Sudan. Trop Doct. 2013;43(2):66-70.
Egail A, Ibrahim Mohamed NY, Mohamed Nour EO, Hoffner S, Haile M. Molecular charac-terization of Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Khartoum, Sudan. Int J Mycobact. 2018;7(3):236-41.
https://doi.org/10.4103/ijmy.ijmy_82_18

Author information

Nguyen Thi Lan, Tran Minh Duc & Pham Hoang Anh contributed to this work.

Authors and affiliations

Department of Pharmacology, Faculty of Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam
Nguyen Thi Lan & Tran Minh Duc

Department of Toxicology and Drug Development, Faculty of Life Sciences, Can Tho University, Can Tho, Vietnam
Pham Hoang Anh

Corresponding author

Correspondence to Tran Minh Duc

Rights and permissions

Open Access The author(s) retain copyright. This article is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It may be shared and adapted for non-commercial purposes with appropriate attribution, an indication of changes, and distribution of adaptations under the same license. Third-party material may be subject to separate terms identified in its credit line. View the license at https://creativecommons.org/licenses/by-nc-sa/4.0/.

About this article

Cite this article

Vancouver
Lan NT, Duc TM, Anh PH. Assessing the Prevalence and Seriousness of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) Detected by GeneXpert. . 0;0:18.
APA
Lan, N. T., Duc, T. M., & Anh, P. H. (0). Assessing the Prevalence and Seriousness of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) Detected by GeneXpert. EAMD 3, 0, 18.
Received
20 January 2022
Revised
26 April 2022
Accepted
26 June 2022
Published
10 July 2022
Version of record
10 July 2022

Share this article

Easily share this article with others using the link below:

Assessing the Prevalence and Seriousness of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) Detected by GeneXpert
Scan to access
this article

Ready to submit?
Start a new submission or continue a submission in progress:
Submission Portal Author Guidelines

Follow this journal
Get notified of new updates and articles.