Tuberculosis: A Leading Cause of Adult Mortality Worldwide
Tuberculosis is one of the leading causes of adult mortality worldwide. Based on research using the tuberculin skin test, it has been determined that approximately one-fourth of the world’s population is infected. And out of the infected population, 15 million individuals can progress to active disease at any given time. According to the World Health Organization (WHO), each untreated patient can infect up to 15 people per year.
Tuberculosis is a chronic progressive infection that primarily affects the lungs and has a prolonged asymptomatic latent period following initial infection. The main symptoms include productive cough, fever, weight loss, and increased fatigue. Diagnosis is often confirmed through smear microscopy and culture of sputum samples, and if available, nucleic acid amplification tests.
The Causative Agents and Transmission
The disease is caused by the bacteria Mycobacterium tuberculosis, which enters the body through inhalation of airborne particles (droplet nuclei) with a diameter of less than 5 micrometers. Transmission occurs when individuals with active pulmonary or laryngeal tuberculosis cough, sing, or perform other respiratory activities, releasing large quantities of the pathogenic bacteria in their sputum. Infection is intensified through frequent or prolonged contact with untreated patients, especially in crowded, poorly ventilated enclosed spaces. Healthcare workers who have close contact with patients with open forms of the disease are also at an increased risk of infection.
Progression and Treatment
M. tuberculosis bacteria initially cause primary infection, a small fraction of which later progresses to clinical disease of varying severity. However, the majority (approximately 95%) of primary infections remain asymptomatic. An unknown portion of primary infections resolves spontaneously, but in most cases, a latent (dormant) phase ensues. Subsequently, in a varying proportion of cases (5-10%) of latent infection, reactivation occurs with symptoms and signs of the disease.
For patients with normal immunity and drug-susceptible pulmonary tuberculosis, even in severe cases with extensive cavitation, appropriate therapy guided by drug susceptibility testing for rifampicin, isoniazid, and fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) usually leads to cure if initiated promptly and completed fully (Nardell E.A., 2022).
Nanocarrier-Based Drug Delivery for Tuberculosis Treatment
An intriguing approach to improving tuberculosis therapy involves drug delivery systems based on nanocarriers, which can transport new antibiotics directly to the source of infection and infected cells.
Researchers from the Karlsruhe Institute of Technology in Germany have developed special nanoparticles that deliver antibiotics directly to the lungs. Initial trials have demonstrated high effectiveness and good compatibility between nanocarriers and antibiotics. Specifically, lipophilic antibiotics of the new generation, bedaquiline, and BTZ-043, effective against multi-drug-resistant tuberculosis bacteria, have been studied. Surface-active nanoparticles facilitate the dispersion of highly lipophilic antibiotics in water and help overcome various biological barriers during transport to the lungs.
In the future, this nanomedical approach may help reduce the development of bacterial resistance (Rudolph D. et al., 2023).