Egypt had 12,000 cases of tuberculosis (TB) in 2019. TB incidence in Egypt decreased from 35 to 12 per 100,000 individuals between 1990 and 2019 [11] . The mortality rate due to TB also reduced from 3.5 to 0.43 per 100,000 people. In 2018, the treatment success rate for TB patients was 86%. Additionally, 100% of TB patients diagnosed with HIV received antiretroviral therapy (ART) in 2019. However, only 23% of children under five years old who lived in households with confirmed cases of TB received TB-preventative therapy [12]. In 2019, it was estimated that 1.4% of new TB cases and 23% of previously treated TB cases were multidrug-resistant TB (MDR-TB) or rifampicin-resistant TB (RR-TB) [13]. Egypt had 264 cases of laboratory-confirmed MDR-TB/RR-TB in 2019, but only 98 of them received treatment [14].
The current study examined 121 MDR-TB patients, confirmed via sputum smear microscopy, culture, sensitivity tests, and GeneXpert.Mean age was 40 years, consistent with prior research (39.04 ± 13.06 years) [15]. Similar findings were noted in previous studies (mean age: 39.35 years) and in the frequency of tuberculosis among 35 to 49-year-olds [16,17]. Moreover, we found that 75.21% of MDR-TB patients were male, consistent with Ibrahim et al. [15], who reported 75.9%. This gender skew aligns with global trends, reflected in WHO data showing a higher TB burden among men (55%) compared to women (33%) and children (12%) [18], additionally, previous studies show consistent gender distributions in MDR-TB patients, with males comprising 66% to 76% and females 24% to 34% [19,20]. This trend extends globally, including regions like southeast Turkey [21]. However, exceptions exist; Khan et al. found a majority of female MDR-TB patients in the economically active age group (25-54 years) in Peshawar, Pakistan, emphasizing the influence of regional and socioeconomic factors [22].
In our study, 61.16% of patients were from rural areas. In contrast, findings were noted by ElBouhy et al with 61.11% patients live in urban areas, while 38.89% patients live in rural areas. This reflects an increase in the percentage of TB in urban places against the past prevalence which was the highest in rural areas [23].
Our results showed that 96.69% subjects belonged to the working social class. Similar findings were noted by Ibrahim et al., with 55.5% of patients employed, possibly due to increased physical stress [15]. However, another study found 51.8% of MDR-TB cases among the unemployed, possibly linked to socioeconomic status or illness-induced debilitation [24].
The prevalent risk factors in this work included a history of TB medication and current smoking (40.5%), consistent with Ibrahim et al. [15] and other literature [25–27]. Drug resistance was high, with over 90% resistant to Cycloserin, Ethionamide, Pyrazinamide, and levofloxacin, and approximately 71.9% resistant to Amoxicillin. However, less than a third showed resistance to INH, PAS, and Kanamycin, differing from previous findings [15] where the most common pattern was resistance to rifampicin, isoniazid, ethambutol, and streptomycin (RHES), possibly due to prior TB treatment history [28].
The medication success was recorded in 84.3% of our patients, in line with WHO targets [22], and higher than rates in South Africa (49%) [29], Shanghai (54.9%) [30], New York (64%) [31], and South Korea (48.2%) [32]. Contrastingly, in Brazilian study, a 13% favorable outcome had been reported, and 9% defaulters [33], while Indian report found that a 19.4% success rate and 13.4% defaulters [34], possibly due to smaller sample sizes. Munsiff et al [35] noted a less favorable outcome, with successful treatment in only 40% of cases and a higher mortality rate of 47%. Egypt's successful outcomes were attributed to its National TB control program, tailored drug regimens, and strict Directly Observed Therapy (DOT). Poor prognosis was 5.7%, comparable to similar studies. Mortality rate was 2.48%, lower than rates reported in other studies (19% to 36%), [22,36,37]. Contrastingly, mortality rates varied widely across studies, ranging from 5% to 67% [38–41]. Demographic factors didn't significantly impact treatment outcomes, but rural residence has been associated with poorer prognosis due to healthcare access challenges [22]. Improving patient education and counseling is crucial for enhancing MDR-TB treatment outcomes in rural settings.
Moreover, in this work, sputum conversion occurred in 95.04% of patients within one to six months, averaging 1.59 ± 1 month. Patients with bad prognosis had a lower conversion rate (68.42%) and longer conversion time (2.21 ± 1.44 months, p=0.001). Medication side effects weren't linked to poor prognosis; 50% of the successful group reported side effects compared to 21.05% in the poor prognosis group (p=0.02). Sputum conversion, crucial for monitoring MDR-TB treatment, typically occurs around the second month, indicating effective treatment regimens and adherence [42]. However, conversion times vary, with Turkish reports averaging 1.9 months [43], and Indonesian studies noting a 50% conversion rate over three months [44]. Early conversion increases treatment success likelihood, consistent with WHO recommendations and findings in various studies [45,46].
Considering the medication side effects, we found that it affected 45.45% of patients, with hyperuricemia being most common (28.1%), followed by ototoxicity and gastritis (11.57% each). In contrast, Ibrahim and coworkers noted gastrointestinal disorders, peripheral neuritis, depression, sleep disturbances, arthritis, and hypothyroidism [15]. Tag El Din et al. found that gastrointestinal manifestations were the most frequent adverse reaction, followed by PN, hypokalemia, Ototoxicity, Hypothyroidism, Skin manifestations, Hepatotoxicity then nephrotoxicity. Hyponatremia and dizziness were the least encountered adverse reactions [27]. A Pakistani study reported hepatobiliary system effects in 57.1% of cases, with gastrointestinal, skeletal, skin, renal, and CNS, ear, and ocular effects in smaller percentages [47]. Törün et al. found higher rates of ototoxicity (41.8%) and psychological effects (21.3%), possibly due to prolonged drug exposure [48].
In this study, comorbidities such as diabetes (DM), hypertension (HTN), ischemic heart disease (IHD), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) were assessed. DM was most prevalent 24.79%, followed by HCV 10.74%. This aligns with Tag El Din et al. who concluded that DM was the most frequent co-morbidity, which affected about one third of cases followed by chronic liver disease then chronic pulmonary disease (COPD) while the majority of cases in the studied group had no co-morbid diseases [27]. Khalil and coworkers found that about 16% of patients had different comorbidities, the most common were diabetes mellitus (DM) and liver disease by 8% for both, then ischemic heart disease in 4% [49]. Also, Ibrahim et al. [15]and other studies, highlight diabetes as a common comorbidity in MDR-TB cases [23,50,51]. However, chronic chest disease was reported as the most common comorbidity in another study [16], possibly due to increased infection risk from hospitalization. We reported that hypertension (HTN) and ischemic heart disease (IHD) were significantly associated with poor prognosis (p=0.05, 0.01, respectively), while HIV and HCV had no impact. Only 0.3% of patients had HIV, contrasting with other studies reporting 9.2% HIV-infected patients among MDR-TB cases [52], possibly due to a diverse patient population from different countries.
Radiological characteristics of our MDR-TB patients weren't significantly linked to poor prognosis (p > 0.05), differing from findings associating lung cavitation with worse outcomes [22]. Cavitation may hinder drug penetration, but radiological response within three months strongly predicted success. Ibrahim et al. [15] observed far advanced lesions initially, with minimal lesions indicating success later, suggesting cavitation might impede drug penetration. While pulmonary infiltrations followed by cavitations were common in one study [53], another study found cavitary lesions significantly correlated with MDR-TB, highlighting the complexity of radiological findings and their implications for treatment response [54,55]
Furthermore, we found that resistance to Kanamycin and levofloxacin significantly correlated with poor prognosis (p=0.05), while Ofloxacin resistance showed no impact (p > 0.05), contrary to findings emphasizing its importance in poor MDR-TB outcomes. Khan et al. [22] reported high Ofloxacin resistance (55.3%), possibly due to its widespread use for respiratory infections, raising concerns about preserving drug effectiveness. Conversely, in Bulgaria, streptomycin and ethambutol resistance was prevalent in 48% of cases [56], while in India, isoniazid and rifampicin resistance were common [57].
In our study, ischemic heart disease (IHD) significantly increased the risk of poor prognosis (OR=15.34, p=0.02), along with longer sputum conversion time and medication side effects (OR=1.63, p=0.03 and OR=0.31, p=0.04, respectively). Gender, weight, previous TB treatment, and resistance to first-line drugs did not significantly influence outcomes. Previous Egyptian studies identified predictors of unsuccessful outcomes, including male sex, smoking, alcohol and illicit drug use, diabetes history, previous second-line TB drug use, lung lesions, and delayed sputum conversion [46]. Multivariate analysis identified diabetes history, lung lesions, and delayed conversion as independent factors [46]. In contrast to our study, older age was found to predict poor outcomes in MDR-TB, attributed to comorbidities and slower drug response [58].