Tuberculosis is a ubiquitous, contagious infectious disease caused by the Mycobacterium tuberculosis complex (MTC), characterized by slow multiplication and resistance to acid and alcohol decolorizing agents, hence their designation as Acid Fast Bacilli (AFB) [1].

This disease affects all age groups, and any organ can be af fected. It constitutes a major public health problem both na t ionally and internationally. However, it remains a disease that can be prevented and treated. Unfortunately, what has made the disease even more challenging to manage is the develop ment of resistance to various first-line antitubercular drugs, which is due to different mutations in the MTC genome. In re cent years, the emergence of resistance to Tuberculosis (TB) treatments, particularly multidrug-resistant TB (MDR-TB), char acterized by resistance to at least rifampicin and isoniazid, has become a major public health challenge in many countries and a barrier to successful global TB control efforts [2]. Some strains have developed resistance to second-line antitubercular drugs, leading to what is known as extensively Drug-Resistant (XDR) tuberculosis. XDR-TB occurs when tuberculosis-causing bacte ria become resistant not only to isoniazid and rifampicin (the drugs that define multidrug-resistant TB) but also to all fluoro quinolones and at least one of the second-line injectable drugs, such as amikacin, kanamycin, or capreomycin. This form of TB can emerge when second-line treatments are misused or poorly managed, ultimately rendering them ineffective [3].

According to 2022 international epidemiological data, tu berculosis is one of the leading causes of death worldwide. The number of people affected by tuberculosis disease was estimated at 10.6 million, equivalent to 133 cases per 100,000 inhabitants. Among bacteriologically confirmed pulmonary tu berculosis cases, 175,650 cases of Multidrug-Resistant Tuber culosis (MDR-TB) were diagnosed and treated [1]. In Morocco according to the ministerial report from 2021, a total of 29,327 TB cases were recorded., translating to an incidence of 80 per 100,000 inhabitants. Of these, 51% were pulmonary forms. Among these cases, 295 developed multidrug-resistant tuber culosis, representing 1% of the cases [4,5].

The main objective of this study is to describe the epidemio logical profile of multidrug-resistant pulmonary tuberculosis in the Meknes prefecture, Fes-Meknes region.

Study design

This is a cross-sectional study of pulmonary tuberculosis cases monitored at the Tuberculosis and Respiratory Disease Diagnostic Center (CDTMR) in the city of Meknes, Fez-Meknes region. Data collection was conducted over a period spanning from January 2017 to December 2022 (6 years).

Study population

Inclusion criteria: All cases diagnosed and treated as pul monary tuberculosis (including all forms of resistance) at the CDTMR in the city of Meknes during the study period were in cluded.

Exclusion criteria: All cases of extrapulmonary tuberculosis (including all forms of resistance) and pulmonary tuberculosis cases diagnosed outside the study period were excluded.

Ethical considerations

Authorization from the provincial delegation and the head physician of the CDTMR was obtained, along with strict adher ence to patient anonymity and confidentiality of their informa t ion.

Data collection

Data collection was carried out through the computerized da tabase of the CDTMR in the city of Meknes, with additional data gathered from medical records for certain variables. The main variables collected and analyzed include: sociodemographic data (age, gender, origin, and occupation), bacteriological and therapeutic data, culture results and antibiogram or molecular biology results at the time of multidrug-resistant tuberculosis diagnosis, the prescribed treatment regimen, recorded adverse effects, and patient outcomes during treatment.

Outcome’s definitions:

Based on the results of the microscopic examination, we have two categories of cases: Pulmonary tuberculosis with negative microscopy TPM (0) and pulmonary tuberculosis with positive microscopy TPM (+). In our study, the confirmation of drug-resistant tuberculosis is carried out using molecular biol ogy methods: the gene amplification technique coupled with automated extraction (Xpert MTB/RIF). If resistance to rifam picin is detected, it is further confirmed with the reverse hy bridization technique on a strip (the Genotype MTBDR Plus test and the Genotype MTBDR sl test). Based on the results of these techniques, we classify cases into five categories: Isoniazid-re sistant Tuberculosis (TB-Hr): tuberculosis caused by MTC strains that are resistant to isoniazid but remain sensitive to rifampi cin, Rifampicin-Resistant Tuberculosis (TB-RR): tuberculosis caused by MTC strains that are resistant to rifampicin. These strains may be either sensitive to isoniazid or resistant to it (in which case it is classified as MDR-TB), or they may be resistant to other first- or second-line antitubercular drugs. Multidrug resistant tuberculosis (MDR-TB): tuberculosis caused by MTC strains resistant to at least isoniazid and rifampicin. Extensively drug-resistant tuberculosis (XDR-TB): tuberculosis resistant to rifampicin, a fluoroquinolone, and at least one of the group A drugs, bedaquiline or linezolid et Pre-extensively drug-resistant tuberculosis (pre-XDR TB): multidrug-resistant tuberculosis with additional resistance to fluoroquinolones [6].

Data analysis

Statistical analysis was performed using SPSS software ver sion 26.0. A descriptive analysis was conducted for all variables, with the results presented as percentages for qualitative vari ables and as mean ± Standard Deviation for quantitative vari ables. We used a Chi-square test (or Fisher’s exact test when conditions were not met) for the comparison of percentages, and Student’s t-test for the comparison of means, to identify potential associations between antitubercular drug resistance and various factors.

The study included 28 cases of Multidrug-Resistant Tuber culosis (MDR-TB) in Meknes Prefecture. The mean age of the participants was 17.32 years (±6.86 years), indicating a predom inantly young population. The majority of the cases were male (85.7%), and most resided in urban areas (85.7%), with only 14.3% coming from rural settings. Regarding diagnostic status, nearly all patients (99%) were smear-positive (TPM+), with only one smear-negative (TPM−) case. The duration of treatment varied, with 50% of the cases undergoing a 24-month regi men, 46.4% completing 11 months, and only 3.6% treated for six months. The study observed a mortality rate of 10.7%, with three deaths recorded, while 89.3% of the patients survived. Relapse was reported in 32.1% of cases, whereas 67.9% did not experience a recurrence of the disease. Risk factors were prevalent in the sample, with 75% of the participants present ing at least one risk factor and 25% reporting none. Smoking was identified in more than half of the cases (53.6%), highlight ing its potential role in disease progression, while 46.4% were non-smokers. Table 1 represent the results.

Adverse events related to treatment were documented in a minority of cases. Neurological and sensory side effects each occurred in 7.1% of patients, while digestive complications were also observed in 7.1%. Hematological effects were slightly more common, affecting 10.7% of cases, whereas renal complications were rare, appearing in only 3.6% of patients. Despite these challenges, treatment adherence was generally good, with 82.1% of patients demonstrating proper compliance, though 17.9% were classified as having poor adherence. The results are represented in Table 1.

The bivariate analysis explored factors associated with mor tality in individuals with multidrug-resistant tuberculosis (MDR TB). The overall mortality rate was 10.7%, with three deaths recorded among the 28 cases. Gender did not show a signifi cant association with mortality (p=1.000). Residence also did not show a significant relationship with mortality, although a higher proportion of deaths occurred among urban residents (66.7%) compared to rural residents (33.3%) (p=0.382). Regard ing smear status, all deaths occurred in smear-positive (TPM+) patients, with no mortality recorded among smear-negative (TPM−) cases (p=1.000). Relapse history also did not significant ly affect mortality; the proportion of deaths among those with out relapse (33.3%) was similar to the proportion of non-deaths without relapse (p=1.000). Risk factors were present in all pa t ients who died (100%), compared to 72% in the non-mortality group (p=0.551) (Table 2).

Diabetes and HIV status were assessed, with mortality ob served in 33.3% of those with diabetes or HIV, compared to 4% among those without these conditions. However, these differ ences were not statistically significant (p = 0.206 for both fac tors). The presence of treatment side effects showed a higher, though not statistically significant, proportion of deaths (66.7%) compared to those without side effects (33.3%) (p=0.188) (Ta ble 2).

Table 1

Table 1: Socio-demographic, clinical and epidemiological characteristics of individuals (N=28).

Abbreviations: SD: Standard deviation; TPM: Tuberculin positive Man toux; HIV: Human immunodeficiency virus; SE: Side effects.

Table 2

Table 2: Bivariate analysis researching factors associated with the mortality in individuals with TBK-MR.

Abbreviations: TPM: Tuberculin positive mantoux; HIV: Human immu nodeficiency virus, SE: Side effects.

Notably, sensory side effects were significantly associated with mortality (p=0.008). All deaths occurred in patients who experienced sensory side effects (66.7%), whereas no deaths were recorded among those without these side effects. Hema tological and renal side effects also showed higher mortality proportions (33.3%) compared to those without these com plications but were not statistically significant (p=0.298 and p=0.107, respectively) (Table 2).

The aim of this study is the define the epidemiological char acteristics and factors associated with mortality in Multidrug Resistant Tuberculosis (MDR-TB) which can provide critical in sights for improving management and outcomes.

As observed in our study, MDR-TB is predominantly associ ated with younger populations, with a mean age of 17.32 ± 6.86 years. This finding aligns with those of other studies conducted in Brazil and South Africa, which reported a median age of 38 years in Brazil and a mean age of 37.7 years in South Africa, respectively [7,8]. Men often represent a larger proportion of cases, with a proportion of 85.7% in our study and 64.4% in Brazil [7]; which may be attributed to higher exposure in occupational settings or behavioral risk factors like smoking and substance abuse [9].

The presence of comorbid conditions and risk factors is clearly noticed in several studies [7,10], ours showed that risk factors were prevalent with 75% of the participants presenting at least one risk factor and 25% reporting none and smoking was identified in more than half of the cases (53.6%).

In the present study, 10.7% of MDR-TB cases resulted in death. This outcome aligns with the results of several studies conducted in various countries, such as Brazil, Peru, and Malay sia, which reported mortality rates of 14.3%, 18.6%, and 19.2%, respectively [7,9,11]. Factors associated with mortality in MDR TB were assessed, with key findings highlighting smear status, diabetes, and HIV status. All deaths occurred in smear-posi t ive (TPM+) patients, while no mortality was recorded among smear-negative (TPM−) cases (p = 1.000). Additionally, mortality was observed in 33.3% of patients with diabetes or HIV, com pared to 4% among those without these conditions (p=0.206). Another study conducted in South Africa found that MDR-TB/ HIV co-infected patients had a 50% higher mortality rate com pared to non-HIV patients [12].

Diabetes has been independently associated with increased mortality in MDR-TB patients. Research indicates that individu als with both diabetes and MDR-TB have a higher risk of death compared to non-diabetic MDR-TB patients [7]. Diabetes can impair the immune response, making it more difficult for the body to fight TB infections. Moreover, diabetes may affect the pharmacokinetics of TB medications, potentially reducing their effectiveness [11].

For HIV, it compromises the immune system by depleting CD4+ T cells, which play a critical role in fighting TB infections. This immunosuppression makes it harder for the body to con trol MDR-TB, leading to faster disease progression and a higher risk of mortality that’s why studies have shown that MDR-TB patients with HIV co-infection have a mortality rate up to 4-10 t imes higher than those without HIV [13].

Adverse events, such as medication side effects, have been linked to higher mortality. Our study showed that sensory side effects were associated with a higher mortality rate (p=0.008). These side effects often reduce treatment adherence and wors en patient outcomes.

It is true that our study provides new insights and perspec t ives that can inform policy and practice. However, it also has some limitations, such as the small sample size, which reduces statistical power and generalizability. This limitation was be yond our control, as only 28 well-documented cases of MDR-TB were available over a six-year period, The study was conducted in a single institution that represents only the prefecture of Me knes city, which limits its external validity.

The interplay of demographic, clinical, and behavioral factors highlight the complexity of managing MDR-TB. Addressing co morbidities, mitigating side effects, and improving adherence through comprehensive and equitable healthcare interventions are essential for reducing mortality. Future studies should ex plore tailored strategies to bridge gaps in rural access and ad dress behavioral determinants of health.

These findings reinforce the need for targeted interventions, such as early detection and management of comorbidities and exposures, robust patient support systems to ensure adher ence, and mitigation of adverse effects through personalized treatment approaches. Strengthening public health infrastruc ture, especially in high-burden urban areas, and addressing be havioral risk factors are crucial for reducing mortality.

Conflicts of interest: The authors declare no conflicts of in terest related to this article. No external funding influenced the design, analysis, or interpretation of the results of this study.

Acknowledgements: I would like to express my sincere grati tude to the officials of the Directorate of Epidemiology and Disease Control (CDT) in Meknès for their valuable support and collaboration. Their commitment and dedication have been in strumental in facilitating this work, and their contributions are deeply appreciated.

Author Contributions: Conceptualization: all authors; Meth odology: all authors; Formal analysis: all authors; Data curation: Zouggar H; Software: Bartal FZ and Zouggar H; Validation: all authors; Investigation: Zouggar H; Writing - original draft prepa ration: Bartal FZ; Writing - review and editing: Sbiti M, EL Fakir S; Approval of final manuscript: all authors.