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Central African Journal of Public Health

2023; 6(4): 131-136
http://www.sciencepublishinggroup.com/j/cajph
doi: 10.15648/j.cajph.20220904.15
ISSN: 2575-5773 (Print); ISSN: 2575-5781 (Online)

DRUG RESISTANT TUBERCULOSIS AND ASSOCIATED FACTORS AMONG

RESIDENTS OF PORT HARCOURT, NIGERIA.
1Ossai-Chidi L. N., 2Kinako S. E., 1Bilabou B. T.
1
School of Public Health, University of Port Harcourt, Rivers state, Nigeria.
2
Department of Anatomical Pathology, Rivers State University, Rivers state, Nigeria.

ABSTRACT
Objective: This study set out to assess the proportions of MDR tuberculosis in patients attending tuberculosis
treatment centres in Port Harcourt, Nigeria, from January 2022 to December 2022.
Methods: Five hundred and sixty participants were enrolled in this study and comprised suspected and newly
diagnosed tuberculosis cases. Sputum samples obtained from the participants were screened for the presence
of Mycobacterium tuberculosis using standard culture and phenotypic biochemical techniques, and drug
susceptibility testing was carried out using the 1% proportion conventional method.
Results: Of the 560 participants enrolled, 37 (6.6%) were confirmed as M. tuberculosis-positive cases. A high
prevalence of drug resistant tuberculosis was noted in this study (16/37, 43.2%), with 13.5% of isolates
resistant to streptomycin. MDR tuberculosis, defined as being resistant to isoniazid and rifampicin, was
detected in 5 cases (13.5%).
Conclusion: The study identifies demographic and environmental factors associated with increased drug-
resistant tuberculosis (DR-TB) risk in Nigeria. It recommends targeted interventions like improving housing
conditions, enhancing contact tracing, and tailored education campaigns. A comprehensive approach to DR-
TB control is crucial, addressing specific risk factors. High TB prevalence and substantial drug-resistant TB
in Nigeria highlight the urgent need for coordinated public health strategies focusing on early diagnosis,
effective treatment, infection control, and public education to mitigate TB's impact and reduce drug-resistant
strains in the population.

Keywords: Tuberculosis, drug resistance, multi-drug resistance, risk factors, Port Harcourt

1.0 INTRODUCTION
Tuberculosis (TB) is a disease that holds significant public health importance, causing approximately 10 million
new infections and resulting in 1.5 million deaths in 2019[1]. Nigeria is among the 30 countries with the highest
burden of TB, including TB/HIV and drug-resistant TB (DR-TB)[2, 3]. In terms of reported TB cases, Nigeria
ranks fourth worldwide and first in Africa. The effectiveness of TB programs is measured by the success of TB
treatments and the ability to prevent the emergence of DR-TB strains through early detection and timely treatment
with quality-assured drugs[3, 4]. DR-TB refers to laboratory-confirmed resistance to one or more of the primary
TB medications [5]. It can be categorized as mono-resistant tuberculosis (MR-TB) when resistance is observed to
one of the primary anti-TB drugs, polyresistant TB (PDR-TB) when resistance is observed to more than one
primary anti-TB drug except rifampicin and isoniazid, and multi-drug-resistant tuberculosis (MDR-TB) when
resistance is observed to both rifampicin and isoniazid [6, 7].
Several factors contribute to the development of DR-TB, including the absence of Directly Observed Therapy
Short Course (DOTS), poor drug quality, interrupted supply of TB drugs, lack of standardized regimens in non-
NTBLCP (National Tuberculosis, Buruli Ulcer and Leprosy Control Program) facilities, inappropriate
prescription or underuse of genuine anti-TB medications, and low socioeconomic status [7, 8]. Non-adherence to
TB medications often leads to the emergence of DR-TB. In 2017, it was estimated that 558,000 individuals
developed rifampicin-resistant TB, and 82% of them had MDR-TB [9]. In Nigeria, DR-TB was estimated to occur
in 4.3% of new cases and 25% of previously treated cases in 2018 [1]. In Nigeria, the incidence, prevalence, and
death rate of DR-TB are reported as 140/100,000, 200/100,000, and 20/100,000 population, respectively [4, 10].
Accurate diagnosis is crucial for successful DR-TB treatment, yet the World Health Organization (WHO) states
that only 16% of MDR-TB patients receive a correct diagnosis [6, 11]. With the transition from standardized to
more personalized TB treatment approaches, understanding drug resistance patterns at the population level
becomes crucial. Rifampicin resistance, which coincides with isoniazid resistance in 85-90% of cases, has been
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used as a surrogate marker for MDR-TB [12, 13]. However, controversies exist regarding the suitability of
rifampicin resistance as a surrogate marker due to inconsistencies found in some studies, where patients with
rifampicin-resistant TB did not exhibit isoniazid resistance [1, 14]. Additional tests, such as Drug Susceptibility
Test (DST) for isoniazid, are strongly recommended to avoid overdiagnosis and overtreatment of DR-TB[15].
Delayed laboratory results of the DST pose a significant problem and act as a barrier to DR-TB treatment since
obtaining DST results typically takes 2-3 months. In certain areas, routine DST is lacking, resulting in many TB
patients being assumed to have Drug-Sensitive TB (DS-TB) and only a small number being referred for DR-TB
evaluation. Despite these limitations, DST remains the most reliable laboratory test to determine the appropriate
treatment regimen for patients[16]. However, it is recommended to cautiously consider adding isoniazid to MDR-
TB treatment when DST results confirm rifampicin resistance in the context of Xpert-confirmed RR-TB [17].
Accurate information on DR-TB patterns is crucial for informing the selection and use of various resistance
diagnostic tools. Limited data exist in Nigeria regarding the drug resistance patterns of DR-TB. Therefore, this
study aims to investigate the patterns of TB and DR-TB in Port Harcourt, Rivers state, Nigeria.
2.0 METHODS
2.1 Ethical considerations
This study was approved by the Ethic and Research Committee of the University of Port Harcourt Teaching
Hospital, Port Harcourt, Rivers State, Nigeria. Written informed verbal consent was obtained from all participants
and names were omitted to protect participants’ privacy.
2.2 Study population
Participants between the ages of 18 and 75 years attending six randomly selected directly observed treatment
short-course clinics and centres in Port Harcourt, Rivers State, Nigeria, were enrolled in this study from January
2022 to October November 2022. These participants comprised people with suspected or presumptive tuberculosis
and those recently diagnosed with less than one month duration of tuberculosis therapy. Known tuberculosis
patients on therapy for more than one month were excluded from this study.
2.3 Sample collection and processing
Three sputum samples of 5 mL volume were obtained from each participant. These samples were screened for the
presence of M. tuberculosis using standard microscopic, culture and phenotypic biochemical techniques.
Preliminary detection for acid fast bacilli was carried out by direct microscopic examination following Ziehl-
Neelsen staining using a standard protocol. Next, sputum samples were processed for culture using the Petroff’s
method[17] and culture was carried out on Lowenstein-Jensen agar slants. The set-up was incubated at 37 °C and
inspected for characteristic growth weekly, for up to six weeks. Phenotypic biochemical identification was then
carried out based on catalase enzyme production, nitrate reductase and niacin production.
2.4 Drug susceptibility testing
Drug susceptibility testing was carried out using the Lowenstein-Jensen proportion method[18, 19]. This involved
the use of critical drug concentrations of 0.2 µg/mL for isoniazid, 40 µg/mL for rifampicin, 2 µg/mL for
ethambutol and 4 µg/mL for streptomycin. Following a 28-day incubation, isolates were documented as resistant
if a growth rate exceeding 1% of the control was observed. Multi-drug resistance was defined as resistance to
isoniazid and rifampicin.

3.0 RESULTS
Table 1 shows the demographic distribution of the study participants.
Table 1: Demographic Information of Participants

Variable Frequency (n=560) Percent (%)

Gender
Female 210 37.5
Male 350 62.5
Age Groups
20 - 29 115 20.5
30 - 39 211 37.7
40 - 49 146 26.1
50 and above 88 15.7

Figure 1 shows a 6.6% MTB prevalence among the study participants. Figure 2 shows that 43.2% of persons with
MTB had drug-resistant tuberculosis.
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37, 6.6%
Positive MTB
Negative MTB

523,
93.4%

Figure 1: MTB Prevalence

Drug resistant TB
16,
Drug sensitive TB
43.2%
21,
56.8%

Figure 2: DR-TB Prevalence in MTB isolates

Table 2 shows the pattern of drug susceptibility among the MTB isolates. It was observed that 56.8% were drug
susceptible, 13.5% were resistant to Streptomycin, also, 13.5% were multidrug resistant 8.1% were resistant to
Ethambutol, 5.4% were resistant to Isoniazid and 2.7% were resistant to Rifampicin.

Table 2: Drug Susceptibility pattern of MTB Isolates

Drug Susceptibility pattern Frequency (n=37) Percent (%)

Mono-resistant
EMB 3 8.1
INH 2 5.4
RIF 1 2.7
STR 5 13.5
Multidrug resistant (n=5) 5 13.5%
EMB-INH-STR 2 5.4
EMB-RIF-STR 2 5.4
INH-RIF-STR 1 2.7
Drug Susceptible 21 56.8
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Table 3: Factors associated with drug resistance in participants.

DR-TB SS-TB Total Chi-square (p-

Variables n (%) n (%) n (%) value) OR (95% C.I)
Gender
Male 8(44.4) 10(55.6) 18(100.0) 0.02 (0.885) 1.1 (0.2 – 4.3)

Female 8(42.1) 11(57.9) 19(100.0)

Age group
<40 years 9(45.0) 11(55.0) 20(100.0) 0.05 (0.8150) 1.1 (0.3 – 4.3)

>= 40 years 7(41.2) 10(58.8) 17(100.0)

Contact with confirmed Tb cases (~2wks)
Yes 10(52.6) 9(47.4) 19(100.0) 1.40 (0.236) 2.2 (0.5 – 7.5)

No 6(33.3) 12(66.7) 18(100.0)

Previous TB Treatment
Yes 9(52.9) 8(47.1) 17(100.0) 1.20 (0.272) 2.1 (0.5 – 6.9)

No 7(35.0) 13(65.0) 20(100.0)

Sharing room with>2 persons
Yes 10(47.6) 11(52.4) 21(100.0) 0.37 (0.538) 1.5 (0.3 – 5.0)

No 6(37.5) 10(62.5) 16(100.0)

Table 3 shows no significant differences in the distribution of selected risk factors associated with drug resistant
tuberculosis. However, it was observed that Males and Persons aged <40 years old were 1.1 times more likely to
have DR-TB. Also, sharing the room with more than 2 persons increased the likelihood of DR-TB by 1.5 times,
while persons with previous TB treatment were 2.1 times likely to have DR-TB and persons that have had contact
with confirmed TB cases within 14 days were 2.2 times more likely to have DR-TB

4.0 DISCUSSION
The 6.6% MTB (Mycobacterium tuberculosis) prevalence rate among the study participants indicates that a
considerable portion of the population in of persons resident in Port Harcourt is infected with TB. This prevalence
of TB observed is consistent with reports of similar studies reporting TB prevalence ranging from 4.5 – 10.1%
around different locations in southern Nigeria[2, 5, 11]. The high TB prevalence suggests that TB transmission is
ongoing in the community, making it a significant public health concern. This finding highlights the need for
intensified efforts in TB prevention, diagnosis, and treatment to reduce the burden of the disease.
The majority of MTB isolates (56.8%) were found to be drug-susceptible, meaning they could be effectively
treated with standard TB medications. This is a positive finding and suggests that many TB cases in Nigeria can
be successfully managed with the existing treatment regimens. Drug-resistant TB was found to be considerably
high among persons diagnosed with TB exceeding 20% reported in other parts of Nigeria[2, 15]. This is a more
challenging and dangerous form of the disease because it doesn't respond well to standard TB treatments. The
high prevalence of drug-resistant TB is a cause for serious concern, posing public health challenges. Drug-resistant
TB requires longer and more complicated treatment regimens, often involving more expensive and less accessible
drugs. This increases the strain on healthcare systems[18, 20–22]. Drug-resistant TB strains can be more
contagious than drug-susceptible TB, increasing the potential for further transmission within communities. Cure
rates for drug-resistant TB are lower than for drug-susceptible TB, which can result in more severe health
outcomes and increased mortality. It was observed that 13.5% of MTB isolates were found to be multidrug-
resistant, meaning they were resistant to both Isoniazid and Rifampicin, the two most powerful and commonly
used TB drugs. MDR-TB is a severe form of TB that is more challenging to treat and has lower cure rates
compared to drug-susceptible TB[22–24]. Controlling the spread of MDR-TB is critical to prevent further
transmission. Continuous monitoring of drug susceptibility patterns is crucial to identify emerging resistance
trends and tailor treatment protocols accordingly[23, 25]. Also, enhancing diagnostic facilities and access to drug
susceptibility testing is vital for early detection of drug-resistant TB. These findings underscore the importance of
early detection, proper treatment, and comprehensive TB control programs in the country. Addressing drug-
resistant TB requires a concerted effort from the healthcare system, policymakers, and public health authorities to
prevent its spread and improve treatment outcomes.
Males and persons aged under 40 years old were found to be 1.1 times more likely to have DR-TB. This suggests
that there might be gender and age-related differences in the prevalence of DR-TB[2, 3]. Understanding these
demographic differences can help tailor TB control strategies to target at-risk populations. For example, specific
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outreach and educational programs can be designed to reach younger individuals and males to promote early TB
detection and treatment.
The findings of the current study showed that sharing a room with more than two persons increased the likelihood
of DR-TB by 1.5 times. Overcrowding in living spaces is a known risk factor for TB transmission. Overcrowded
living conditions can facilitate the spread of TB. Public health efforts should prioritize improving housing
conditions and implementing effective infection control measures, especially in densely populated areas[3, 10,
12].

Persons with a history of previous TB treatment were 2.1 times more likely to have DR-TB. This finding highlights
the importance of monitoring and managing patients who have previously been treated for TB[26, 27]. Patients
with a history of TB treatment should be closely monitored to detect and manage any drug resistance that may
develop during or after treatment. This underscores the significance of adherence to treatment regimens and the
need for robust follow-up. It was observed that persons who had contact with confirmed TB cases within 14 days
were 2.2 times more likely to have DR-TB[3, 10]. This suggests that close contact with infectious TB cases is a
significant risk factor for drug resistance. Contact tracing and early screening of individuals who have been in
close contact with confirmed TB cases are essential to identify cases of DR-TB promptly. This finding emphasizes
the need for a strong contact investigation system.
5.0 CONCLUSION
The results suggest that certain demographic and environmental factors are associated with an increased likelihood
of DR-TB in Nigeria. These findings should inform targeted public health interventions to address these risk
factors, including improved housing conditions, enhanced contact tracing, and tailored educational campaigns.
Controlling DR-TB requires a multifaceted approach that considers the specific risk factors present in the
population. In conclusion, the findings of high TB prevalence and a substantial proportion of drug-resistant TB in
Nigeria underscore the urgent need for comprehensive and well-coordinated public health strategies. These
strategies should focus on early diagnosis, effective treatment, infection control, and public education to mitigate
the impact of TB and reduce the prevalence of drug-resistant strains in the population.
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