|Year : 2017 | Volume
| Issue : 1 | Page : 21-25
Rifampicin resistant mycobacterium tuberculosis in Nasarawa State, Nigeria
Esther S Audu1, Moses S Gambo2, Ahmed A Yakubu3
1 Special Treatment Clinic, Dalhatu Araf Special Hospital, Lafia, Nigeria
2 Laboratory Department, Dalhatu Araf Special Hospital, Lafia, Nigeria
3 Department of Surgery, Dalhatu Araf Special Hospital, Lafia, Nigeria
|Date of Web Publication||7-Apr-2017|
Esther S Audu
Special Treatment Clinic, Dalhatu Araf Special Hospital, Lafia
Source of Support: None, Conflict of Interest: None
Background: The diagnosis and treatment of drug resistant tuberculosis (TB) has presented a unique challenge to the control of TB in Nigeria. Various studies have reported the presence of drug resistant TB, and some treatment centres have been established to treat cases. This study sought to establish the prevalence of rifampicin-resistant TB in our state with a view to advocating for more commitment to efforts toward the treatment and control of drug-resistant TB, including establishment of more treatment centres in the geopolitical zone. Materials and Methods: A retrospective review of laboratory records of 1882 patients whose sputum samples were sent to the Gene Xpert Laboratory of our facility between January 2014 and April 2015 for Mycobacterium tuberculosis (MTB) and rifampicin resistance assay was done using the Gene Xpert MTB/RIF assay. The patients were presumptive TB cases, suspected TB treatment failures, and suspected drug resistant cases from various health facilities in the state. Results: Of the 1882 patients, 68.4% were females and 36.6% were males; patients were aged between 1 and 70 years. MTB was detected in 18.8% (355/1882) of the patients. Forty-three of the 355 MTB positive patients were rifampicin resistant giving a prevalence of RIF resistance of 12.1%. A total of 62.8% of the RIF resistant cases were males whereas 37.2% were females. Forty-one percent of the RIF Resistant cases were aged between 21 and 30 years, 51.2% were human immunodeficiency (HIV) positive, 44.2% were HIV negative, whereas 4.6% had unknown HIV status. A higher number (62.8%) of those with RIF resistance were referred from other facilities compared to 37.2% from the host facility. There was significant association between RIF Resistance and sex, HIV status, and the facility. Conclusion: This study has established that there is a high prevalence of rifampicin resistance in the state. There is need to increase commitment to efforts being made towards treatment and control of DRTB in this zone.
Keywords: Mycobacterium tuberculosis, Nasarawa state, rifampicin resistance
|How to cite this article:|
Audu ES, Gambo MS, Yakubu AA. Rifampicin resistant mycobacterium tuberculosis in Nasarawa State, Nigeria. Niger J Basic Clin Sci 2017;14:21-5
|How to cite this URL:|
Audu ES, Gambo MS, Yakubu AA. Rifampicin resistant mycobacterium tuberculosis in Nasarawa State, Nigeria. Niger J Basic Clin Sci [serial online] 2017 [cited 2017 Oct 21];14:21-5. Available from: http://www.njbcs.net/text.asp?2017/14/1/21/204075
| Introduction|| |
The burden of tuberculosis (TB) worldwide continues to present a public health problem, especially in developing countries. The World Health Organization (WHO) estimates that approximately 9.6 million people were infected with TB worldwide in 2014 with approximately 95% of them in low and middle income countries. Nigeria ranks third among the 22 high TB burden countries after India and Indonesia. The WHO estimates that approximately 480,000 new cases of multidrug resistant TB (MDR TB) occurred in 2014 globally.
Multidrug resistant TB (MDR TB) is said to occur if the strain of Mycobacterium tuberculosis is resistant to at least rifampicin and isoniazid. MDR TB presents a major concern to health policy because of the difficulties associated with treatment, especially in areas with high disease burden.,
The challenge to the control of TB starts with a delay in diagnosis. The conventional sputum microscopy used for diagnosis results in delay in diagnosis, and in the case of TB and human immunodeficiency virus (HIV) coinfection, the low rate of detection of TB by sputum microscopy is an even bigger challenge., Diagnostic delay due to high proportion of smear negative pulmonary TB, especially in human immunodeficiency virus (HIV)-associated TB leads to increased mortality, secondary resistance, and ongoing transmission.
The introduction of the Gene Xpert MTB system for rapid diagnosis of Mycobacterium tuberculosis (MTB) in sputum and detection of rifampicin resistance has revolutionized efforts at TB control, especially in countries with high TB burden such as Nigeria. Gene Xpert improves detection of MTB in smear Negative TB, especially in HIV coinfected patients. Previous studies have provided evidence that the Gene Xpert MTB/RIF system also provided sensitive detection of rifampicin resistance directly from untreated sputum in less than 2 hours with minimal hands on time, thus providing more rapid diagnosis and reducing the risk of transmission of TB. The WHO recommends the use of Gene Xpert MTB/RIF assay for the diagnosis of suspected drug resistant TB (DR TB) and as the first test in persons living with HIV (PLWHA) suspected of coinfection.
The Gene X pert MTB/RIF assay is a fully automated nested real-time polymerase chain reaction (PCR) system, which simultaneously detects MTB complex DNA in sputum and identifies mutations in the gene that are associated with rifampicin resistance.,
Tuberculosis and human immunodeficiency virus coinfection
Approximately 3.4 million Nigerians are estimated to be living with HIV (PLHIV) in 2014, with an adult prevalence of approximately 3.2%. Nigeria has the second highest burden of HIV in Africa. TB has been reported as the most common opportunistic infection in PLHIV. Reports show that as many as 50–80% of PLHIV may be coinfected with TB in sub-Saharan Africa. The treatment of MDR TB presents a unique challenge because of the complex nature of the medications and access to treatment. The challenges are even more in PLHIV because of the concurrent use of antiretroviral medications, gastrointestinal opportunistic diseases, and adherence to medications.
The treatment of MDR TB in Nigeria is centralized to special centres located in some states of the country, thus presenting a huge challenge to patients who reside in areas without treatment centres.
In many African cultures, family members do not want sick relatives to be far away from their loved ones for many reasons. Patients with MDR TB may therefore benefit from centres located closer to their homes and loved ones, especially since most of them are very ill.
Studies in Nigeria have reported the occurrence of DR TB cases, however, only few treatment centres have been established to treat these cases. This study aims to highlight the presence of DR TB cases and the need to establish more treatment centres for MDR TB in the North Central region of Nigeria and in Nasarawa state, in particular, as well as to serve as an advocacy tool to help policymakers prioritize allocation of resources in partnering with international and development partners in the treatment of DR TB.
| Materials and Methods|| |
The study was carried out in the Gene Xpert laboratory of a tertiary health facility that provides both secondary and tertiary health services. The facility receives patients from within the state as well as surrounding communities in the adjoining states.
The Gene Xpert laboratory was established in 2013 by the National TB program in conjunction with KNCV/TBCARE 1 to assist in the rapid diagnosis of TB in HIV patients and the diagnosis of drug resistant TB. The laboratory serves as a referral facility for other government facilities, and therefore samples are received from secondary and primary facilities in the state as well as private health facilities.
Samples from 1934 patients were sent to the laboratory between January 2014 and April 2015. Data from 1882 individuals were collected and analyzed for this study. Data from 52 patients were excluded because of inappropriate sample, incomplete data, and indeterminate results of MTB.
The patients were presumptive TB cases from the HIV clinic, chest clinic, suspected TB treatment failures, and suspected DR TB cases from DASH Lafia and samples sent in from other facilities. Other health facilities that sent samples are from all the three senatorial zones of the state and include:
Secondary health facilities: General Hospitals Obi, Keana, Akwanga, Nasarawa Eggon, Nasarawa, and Wamba, as well as ERCC Medical Centre Alushi and Our Lady of Apostle (OLA) Hospital Akwanga.
Primary health facilities: Primary Healthcare Clinics Doma Road, Lafia, Kwandere, Lafia East and Model Comprehensive Health Centre Shabu as well as a Non-governmental organisation (NGO) – Family Health Care Foundation.
Data collected included age (years), sex, HIV Status, results of MTB Analysis, And Rifampicin Resistance.
Each patient submitted a sputum sample, which was collected on the spot on a dry, clean, transparent, leak proof, and open-mouthed container with cover.
Patients were instructed on appropriate sample collection as follows: patients were asked to rinse mouth with clean water; take 3–4 deep breaths holding for 3–5 seconds after each inhalation; cough after the last inhalation, emptying the sputum produced into the sputum container provided, taking care not to contaminate the outside cup. The sputum cup/container was then closed tightly with the appropriate cover.
Samples collected from other health facilities were collected in the same manner and transported to the laboratory in a cold box accompanied by appropriate patient data on the appropriate laboratory request order form. Samples that were not immediately transported to the laboratory were refrigerated at 4°C before transport to the laboratory.
The sputum samples were then prepared and processed in the laboratory according to the standard operating procedures for Gene Xpert MTB/RIF assay. The processed samples were analyzed for MTB and rifampicin resistance using the automated Gene Xpert MTB/RIF assay machine.
At least 1 ml of sputum was required. The sample was inspected for quality, and if appropriate, sample reagent was added to the sample in a ratio of 2:1 and the lid was closed. Sample was then shaken for 10–20 times and incubated for approximately 10 min. Sample was then shaken again and incubated for a further 5 min.
The liquefied sample was then transferred into the Gene Xpert cartridge in the Gene Xpert MTB/RIF assay system. The computerized system was then operated according to the standard operating procedures to carry out the analysis.
Results were automatically generated indicating if MTB was detected or not detected. Where MTB was detected, the Gene Xpert automatically generated result indicating if the MTB was rifampicin resistant or not resistant.
The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 16.0). P value less than 0.05 was considered significant.
Ethical approval for the study was obtained from the Research Ethics committee of the Dalhatu Araf Specialist Hospital (DASH) before commencement of data collection. Exclusion criteria were inappropriate sample, incomplete data, and indeterminate MTB result.
| Results|| |
A total of 1882 patients had their samples analyzed; 689 (36.6%) were males and 1193 (63.4%) were females. The patients were aged between 1 and 70 years. A total of 1469 (78%) were HIV positive, 346 (18.4%) were HIV negative, and 67 (3.6%) had unknown HIV status. A total of 1199 (63.7%) were from the host facility where the laboratory was located, whereas 683 (36.3%) were from other health facilities in the state.
A total of 355 (18.9%) patients had MTB in their samples; 189 of them were females and 166 were males. A total of 1527 (81.1%) samples were negative for MTB.
Forty-three (12.1%) out of the 355 who had MTB were rifampicin resistant whereas 312 (87.9%) had no RIF Resistance. The prevalence of RIF resistance in this study was 12.1%.
A total of 62.8% of those who were rifampicin resistant were males compared to only 37.2% females [Table 1]. The association with gender was statistically significant (P > 0.05).
|Table 1: Distribution of Mycobacterium tuberculosis and Rifampicin Resistance by Gender|
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Forty-one percent of those who were rifampicin resistant were aged between 21 and 30 years, and over 80% were aged between 11 and 40 years [Table 2]. Overall, there was no significant statistical association with age.
|Table 2: Distribution of Mycobacterium tuberculosis and Rifampicin Resistance by Age|
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A total of 51.2% of those who were rifampicin resistant were HIV Positive, 44.2% were HIV negative, whereas 4.6% had unknown HIV status [Table 3]. HIV status had significant association with rifampicin resistance.
|Table 3: Distribution of Mycobacterium tuberculosis and Rifampicin Resistance by Human Immunodeficiency Status|
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A total of 62.8% of the patients who were RIF resistant were from other facilities compared to 37.2% of who were from the host facility [Table 4]. There was significant association with facility in this study.
| Discussion|| |
The overall prevalence of rifampicin resistance in this study was 12.1% among the MTB positive patients who constituted 18.8% of the total analyzed data. This prevalence is similar to other reports from different studies carried out in Nigeria with rifampicin resistance prevalence reported between 7.1% and 18.8%.,,, Studies on culture isolates in Nigeria show that between 16% and 31% of MTB isolates show resistance to at least one first-line drug whereas approximately 3.6% were multidrug resistant.,
Reports from other parts of the world show various prevalence rates. In South Africa, rifampicin resistance ranged between 7.3% and 10%, and from Indonesia, studies showed that 20.5 to 22% culture isolates showed resistance to at least one first-line drug.,,
Other reports indicate that rifampicin resistance occurs worldwide with studies showing varying prevalence ranging from 1.7% in Uruguay to 36.9% in Estonia.
These studies highlight the high and significant prevalence of rifampicin resistance and the need for adherence to TB treatment to reduce the development of drug resistance.
This study also found a high number of rifampicin resistance cases among males compared to females. While 27 out of 166 MTB positive males (62.8%) were rifampicin resistant, only 16 out of 189 MTB positive females (37.2%) were rifampicin resistant. This association was statistically significant (P < 0.05). The findings of male preponderance in this study are similar to other reports from Nigeria and other parts of the world, which found that the male gender has a strong association with development of drug resistance.,, In contrast, the report from Benue state, Central Nigeria, found no significant association between Rifampicin resistance and gender.
The high association of rifampicin resistance with the male gender could be due to factors such as the high risk and poor health seeking behavior of males compared to females. The age group with the highest occurrence of rifampicin resistance in this study was between 21 and 30 years accounting for over approximately 40% of the cases. Similar findings were reported in a study from South Africa where patients between 21 and 25 years had higher prevalence of rifampicin Rresistance. Over 80% of those who are MTB positive and rifampicin resistance were aged between 11 and 40 years. This is similar to the report from kwara and Benue, North Central Nigeria., This age range corresponds with the age most at risk for HIV infection, with high prevalence of coinfection with TB. However, there was no statistically significant association with age. This finding is similar to the report by Daniel and Eltayah who found no association with age.
A total of 51.2% of those who had rifampicin resistance were HIV positive whereas 44.2% were HIV negative. The association between rifampicin resistance and HIV status was significant. The findings are in contrast to the reports from Jos and Kwara, Central Nigeria and Calabar, south-south Nigeria.,, However, other studies have found significant association between HIV and drug resistant TB. The association of HIV and TB has long been established. The complex nature of both diseases and their treatment using drug cocktails presents unique challenges that can lead to treatment failure and development of drug resistance. The reduced immunity and malabsorption due to other gastrointestinal opportunistic infections may also lead to reduced absorption of anti-TB medications, which may further contribute to the development of resistance, especially to rifampicin.
This study found a high prevalence of rifampicin resistance among patients from other facilities. A total of 62.8% of the rifampicin resistance cases were from other health facilities whereas only 37.2% were from the host facility. This may be due to the fact that the host facility serves as a referral centre, and hence only cases suspected to be drug resistant are referred to the Gene Xpert laboratory. A report from India showed that patients referred from facilities outside the facility hosting the laboratory carrying out the diagnosis may have higher prevalence due to selective referrals. The report also observed that antiretroviral treatment (ART) clinics refer patients more readily, and hence the lower prevalence in the host facility.
| Conclusion|| |
This study has established that there is a high prevalence of rifampicin resistance in the state. The presence of drug resistant TB is a real threat in the management of TB infection, especially when the treatment is not easily accessible to the patients. Therefore, this underscores the need to scale up intervention that will improve the treatment of DR TB cases and to make such treatment available closer to the patients. Early treatment, adherence to medication, and adequate follow up is needed to reduce the development and spread of drug resistance as well as early detection of MDR TB.
National TB Program in conjunction with KNCV/TBCARE 1 provided the Gene Xpert equipment and technical support to the laboratory. Their support is hereby acknowledged.
We also acknowledge Mrs. Josephine Marcus who helped with data analysis
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Espinal MA, Laszlo A, Simonsen L, Boulahbal F, Kim SJ, Reniero A, et al
. Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N Eng J Med 2001;344:1294-303.
Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al
. Rapid Molecular detection of Tuberculosis and rifampicin Resistance. N Eng J Med 2010;363:1005-15.
Walusimbi S, Bwanga F, De Costa A, Haile M, Joloba M, Hoffner S. Meta-analysis to compare the accuracy of Gene Xpert, MODS and the WHO 2007 algorithm for diagnosis of smear negative pulmonary tuberculosis. BMC Infect Dis 2013;13:507.
Chemhuru M, Duka M, Joseph K, Nana-n'zeth B, Simons S, Van Den Broucke S, et al
. Implementation of Xpert MTB/RIF Assay in Buhera District, Zimbabwe: Lessons learned. www.msf.org.za/download/file/fid/4653.
Cepheid Gene X pert GXMTB/RIF-10. Operator Manual; September 2010. p. 300.
GeffenN. Gene Xpert demonstrates good sensitivity and specificity but at a high cost. HIV Treatment Bulletin. www.i-base.info/htb/1443
. [Last accessed on 2015 Nov 08].
Luetkemeyer A. Tuberculosis and HIV. HIV In site knowledge base chapter, January 2013. www.hivinsite.ucsf.edu/Insite
. [Last accessed on 2016 Apr 17].
WHO Nigeria support for Rapid Scaling-Up of Programmatic Management of Drug-Resistant Tuberculosis in Nigeria. www.afro.int/en/n
. [Last accessed on 2016 Aug 11].
Cultural traditions and beliefs of older adults. Barbara Dixon, Manager, Diversity and Immigrant Student Support, Red River College, 2009. Information assembled from a variety of sources. www.virtualhospice.ca/assets/culturaltraditionsandbeliefsofolderadults
Nwadioha SI, Nwokedi EO, Ezema GC, Eronini NC, Anikwe A, AuduI F, et al
. Drug Resistant Mycobacterium Tuberculosis in Benue, Nigeria. Br Microbiol Res J 2014;4:988-95.
Daniel O, Osman E. Prevalence and risk factors associated with drug resistant Tuberculosis in South West Nigeria. Asian Pac J Trop Med 2011;4:148-51.
Rasaki SO, AJibola AI, Musa SA, Moradeyo AK, Odeigah LO, Abdullateef SG, et al
. Rifampicin Resistant Tuberculosis in a secondary Health institution in Nigeria, West Africa. J infect Dis Ther 2014;2014.
Bello LA, Shittu MO, Shittu BT, Oluremi AS, Akinnuroju ON, Adekola SA. Rifampicin monoresistant mycobacterium tuberculosis among patients visiting chest clinic, State Specialist Hospital, Akure Nigeria. Int J Res Med Sci 2014;2:1134-7.
Lawson L, Habib AG, Okobi MI, Idiong D, Olajide I, Emenyonu N, et al
. Pilot study on multidrug resistant tuberculosis in Nigeria. Ann Afr Med 2010;9:184-7.
] [Full text]
Ani AE, Idoko J, Dalyop YB, Pitmang SL. Drug Resistant profile of Mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Jos, Nigeria. Trans R Soc Trop Med Hyg 2009;103:67-71.
Coovadia YM, Mahomed S, Pillay M, Werner L, Mlisana K. Rifampicin Mono-Resistance in Mycobacterium tuberculosis in Kwazulu-Natal, South Africa: A significant phenomenon in high prevalence Tb/HIV Region. PLos One 2013;8:e77712.
Wiwing V, Widysanto A, Lugito NP. Mycobacterium Tuberculosis Resistance pattern against first-line drugs in patients from urban areas. Int J Mycobacteriol 2015;4:302-5. [Full text]
Otu A, Umoh V, Habib A, Ameh S, Lawson L, Ansa V. Drug Resistance among Pulmonary Tuberculosis patients in Calabar, Nigeria. Pulmonary Med 2013;2013.
Mesfin YM, Hailemariam D, Biadglign S, Kibret KT. Association between HIV/AIDS and Multidrug Resistance Tuberculosis: A systemic Review and Meta-analysis. PLos One 2014;9:e82235.
Nair SA, Raizada N, Sachdeva KS, Denkinger S, Schumacher S, Dewan P, et al
. Factors associated with Tuberculosis and Rifampicin- Resistant Tuberculosis amongst Symptomatic patients in India: A retrospective analysis. PLos One 2016;11:e0150054.
[Table 1], [Table 2], [Table 3], [Table 4]