Antibiotic Resistance in Tuberculosis: A Re-Emerging Disease and Public Health Problem

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Tuberculosis (TB) is the ninth global cause of mortality and the leading cause of morbidity from a single infectious agent, with the disease burden higher in low and medium-income countries especially in Africa, such as Kenya. Although the existing tuberculosis treatment strategies have averted an estimated 44 million deaths between 2000 and 2015; drug-resistant tuberculosis is a major threat to the disease control strategies as 490,000 cases of multidrug-resistant TB (MDR-TB) emerged in 2016 with an additional 110,000 cases susceptible to isoniazid but resistant to rifampicin (RR-TB) - the most effective first-line anti-TB drug. Tuberculosis not only interferes with the quality of life and the economic productivity of the individual community members but morbidity and mortality associated with it increases the cost of treatment and reduction in the population respectively. This study aimed to review literature on prevalence of tuberculosis in Kenya and globally, the current treatment combinations in tuberculosis treatment and the molecular basis of tuberculosis drug resistance. Kenya is among the top twenty countries with the highest tuberculosis burden both among adults and children. The incidence of tuberculosis among males was found to be higher than females both in Kenya and globally. The current tuberculosis treatment combinations include Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide. However, a patient can resist rifampicin alone (RR-TB) or more than a single antituberculosis agent (multi-drug resistant tuberculosis –MDR TB). The molecular basis of anti-tuberculous drug resistance may involve either blocking the drug target such as mutations in rpoB prevent binding of rifampicin to RNA polymerase, blocking activation of a prodrug such as mutations in katG lead to loss of the ability of catalase to activate isoniazid to its active form; or producing an activity that binds or inactivates the drug through mutations in the inhA promoter increase the amount of InhA product that binds sufficient isoniazid to reduce its effective intracellular concentration to below an inhibitory level. Laboratory diagnosis of tuberculosis involves the use of conventional culture methods, rapid molecular techniques, line probe assays, GeneXpert for rifampicin and multi-drug resistant tuberculosis and new techniques adopting whole genome sequencing (WGS). The current review summarized global incidence of tuberculosis as 2, 590 (2,310-2,900) per 100,000 populations and 348 (213-516) per 100,000 populations in Kenya and both multi-drug and rifampicin resistant tuberculosis. Some of the existing treatment combinations used in tuberculosis treatment include Isoniazid, Rifampin, Ethambutol and Pyrazinamide (RHZE).  The review identified several genes associated with drug resistant and multidrug resistant tuberculosis to include rpoB, katG and inhA. Some of the common diagnostic techniques used in detection of drug resistance include conventional culture methods, rapid molecular tests, line probe assays and GeneXpert MTB/RIF. Future studies may consider highlighting information on the clinical outcomes to ensure the clinical relevance of results obtained using in vitro in diagnostic tests.