June 30th 2021
Mycobacterium tuberculosis (M. tuberculosis), a non-motile, obligately aerobic, intracellular bacterium known to cause Tuberculosis (TB), was discovered by Robert Koch in 1882 . TB primarily affects the lungs along with the abdomen, bones, nervous system, reproductive system, liver, and lymph glands .
Global Burden of Tuberculosis
The World Health Organization (WHO) has reported a 22% decrease in TB-related mortality between 2000-2015, with a gradual 1.5% decrease in the annual rate. However, despite this trend and successful control of disease transmission, TB continues to have a significantly higher rate of morbidity. In 2015, six countries (China, India, Nigeria, Pakistan, Indonesia, and South Africa) accounted for 60% of TB-related deaths .
Global cases of Tuberculosis between 1965-2019
Pathogenicity of Mycobacterium tuberculosis
Mycobacterium tuberculosis is transmitted in the form of droplet nuclei exhaled by individuals affected with laryngeal/pulmonary TB. It enters the body via the nasal cavity/mouth and travels to the alveoli of the lungs, where it recruits macrophages to the lung surface, in turn transporting the bacteria to the deeper tissues . Another round of macrophage recruitment to the originally infected locus forms an organized aggregate of differentiated macrophages and immune cells called a granuloma. The infected granuloma undergoes necrosis, promoting bacterial growth and transmission to the next host .
Diagnosis of TB
Some patients with TB may present with non-specific findings such as anemia, weight loss, fever of unknown origin, and fatigue; while others may be asymptomatic and show no abnormalities on physical examination . Thus, the physician should collect body fluids/tissues for Acid-Fast bacilli (AFB) smear and culture. Only a positive culture can confirm the diagnosis of TB.
Confirmatory and diagnostic tests for TB:
– Culture, followed by Ziehl-Neelsen (AFB) staining
– A Chest X-ray to confirm the diagnosis in case of positive culture, indicating active disease
– Gene-based tests and nuclear amplification to identify the bacterial strains using DNA-based molecular techniques, such as GeneXpert .
AFB staining is the traditional method of TB diagnosis, as it is inexpensive and provides rapid results . Mycobacterium species retain dyes when heated and treated with acidified organic compounds. The most common acid-fast staining method for M. tuberculosis is the Ziehl-Neelsen stain method, in which a specimen is fixed, stained with carbol-fuchsin dye, and decolorized with an acid-alcohol mixture. After counter-staining the smear with methylene blue or a similar dye, AFB appear red against a contrasting blue background . In general, a sputum sample must contain at least 10,000 organisms/mL to visualize these bacteria at 100x magnification.
Latent TB vs. Active TB
Latent TB represents the condition where the body’s immune system restricts the growth of M. tuberculosis bacterium, making the individual appear asymptomatic .
An individual with latent TB infection shows
– no symptoms.
– is not infectious (cannot spread TB).
– tests positive for TB blood/skin tests.
– may eventually develop active TB if the immune system weakens.
Active TB represents a condition where the body’s immune system is unable to restrict the growth of M. tuberculosis, rendering patients both ill and contagious.
The symptoms of TB depend on the affected area.
a. General symptoms include:
- Night sweats
- Weight loss
- Prolonged fever
- Loss of appetite
b. Symptoms of Pulmonary TB (infected lungs):
- Shortness of breath, which progressively worsens
- A persistent cough that produces phlegm and sometimes blood, persisting > 3 weeks.
c. Symptoms in the case when other areas of the body are infected:
- Swellings in the neck or other regions
- Pain in a joint or affected bone
- Abdominal pain
According to the World Health Organization (WHO), first-line treatment for TB may include combinations of five essential drugs: Rifampicin (R), Isoniazid (H), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S) . Patients with TB undergo a standardized treatment for 6 to 9 months, including an initial two-month course of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol, followed by another 4-month course of Isoniazid and Rifampicin .
For patients with Multi Drug-Resistant Tuberculosis (MDR-TB), directly-observed therapy (DOT) is used. In DOT, drugs are administered at least six days/week under the direct observation of the physician [13, 14]
Bacillus Calmette-Guerin (BCG), a vaccine for TB, was introduced in 1921 to control tuberculosis in humans. It is administered at birth, primarily in regions with a high disease burden, such as India, South Africa, and Pakistan . Widespread immunization using BCG vaccine has facilitated a reduction in TB cases globally .
Five-to-ten percent of people with latent TB who do not receive appropriate treatment will eventually develop active TB disease 
Individuals at a higher risk of contracting TB include:
– Those who have traveled to or are living in a country with a high prevalence of TB.
– Those living in crowded conditions
– Those who have been in close contact with a person infected with TB
– Children ages <= 5 years who have tested positive for TB
– People who reside or work with persons at high risk for TB, such as those in hospitals, correctional facilities, homeless shelters, residential homes for HIV-infected individuals, and nursing homes
Additionally, immune dysfunction associated with diabetes mellitus, HIV infection, cancer chemotherapy, malnutrition, and advanced age is associated with an increased risk of contracting TB.
Additional conditions associated with high risk for tuberculosis include silicosis, substance abuse, malignancy, organ transplantation, corticosteroid therapy, Crohn’s disease, and rheumatoid arthritis.
Tuberculosis and HIV
Co-infection by TB and HIV places a diagnostic and therapeutic burden on the health care system. HIV infection has been shown to increase the risk of reactivation of latent TB by 20-fold. .
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