Mycobacterium tuberculosis: Introduction, Morphology, Pathogen

Introduction

Table of Contents

Mycobacterium tuberculosis is a bacterium that causes tuberculosis (TB), a contagious infectious disease primarily affecting the lungs but can also affect other parts of the body. TB has been a significant public health concern worldwide, causing illness and death for thousands of years.

Key features of Mycobacterium tuberculosis:

Morphology: M. tuberculosis is a rod-shaped bacterium, classified as an acid-fast bacillus due to its ability to retain certain dyes even after being washed with acid-alcohol. This characteristic is vital in its laboratory identification.
Transmission: TB is primarily transmitted through the air when an infected person with active TB coughs, sneezes, or talks. Inhalation of these infectious droplets by a susceptible individual can lead to infection.
Latent vs. Active TB: When Mycobacterium tuberculosis infects a person, the immune system may not always eliminate the bacterium completely. In some cases, the bacteria can enter a dormant or latent state, where they remain in the body without causing active disease. Latent TB is not contagious, but it can progress to active TB if the immune system weakens, leading to symptoms and potential transmission to others.
Symptoms: Active TB typically presents with symptoms such as persistent cough, chest pain, coughing up blood, fatigue, weight loss, fever, and night sweats. TB can also affect other organs, leading to extrapulmonary TB, which involves the bones, lymph nodes, kidneys, and other parts of the body.
Diagnosis: Diagnosing TB involves a combination of clinical evaluation, imaging (such as chest X-rays), and laboratory tests, including sputum smears and cultures to identify the bacterium.
Treatment: TB can be treated with a combination of antibiotics for an extended period, typically lasting several months. The treatment must be completed as prescribed to prevent drug resistance and ensure complete eradication of the bacteria.
Global Impact: TB remains a significant global health challenge, especially in developing countries with limited resources and high population density. Efforts to control TB include early detection, proper treatment, infection control measures, and vaccination (using the Bacille Calmette-Guérin vaccine in some areas).
Drug Resistance: One of the major concerns in TB control is the emergence of drug-resistant strains, such as multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). These strains are more challenging to treat and pose a serious public health threat.

Morphology

Mycobacterium tuberculosis is a unique bacterium with distinctive morphology, which plays a crucial role in its identification and differentiation from other bacteria. Here are the key morphological features of M. tuberculosis:

Fig. Acid fast bacilli (AFB) in Ziehl-Neelsen staining of sputum microscopy-Mag. 3000X

Shape: Mycobacterium tuberculosis is a rod-shaped bacterium, meaning it has a cylindrical or elongated shape. The cells typically have a straight or slightly curved appearance.
Size: The size of individual M. tuberculosis cells can vary, but they are generally considered to be larger compared to many other bacteria. The average length of these rod-shaped cells is around 2 to 4 micrometers (μm), and their width is approximately 0.2 to 0.6 μm.
Acid-Fast Staining: One of the most distinctive characteristics of Mycobacterium tuberculosis is its ability to retain certain dyes even after being treated with acid-alcohol during staining. This property is known as “acid-fastness” or “acid-fast staining.” The primary stain used for this purpose is the red dye carbol fuchsin. The acid-fast property is due to the unique composition of the bacterial cell wall, which contains a high concentration of mycolic acids. These waxy substances make the cell wall impermeable to conventional stains, resulting in the retention of the carbol fuchsin dye. Following staining, M. tuberculosis appears red under a microscope.
Cell Wall Composition: The cell wall of Mycobacterium tuberculosis is particularly thick and complex compared to many other bacteria. It consists of several layers, with the outermost layer containing mycolic acids, which contribute to the acid-fast property. This robust cell wall is essential for the bacterium’s survival in various environmental conditions and also plays a role in its resistance to certain drugs and the host immune response.
Aerobic and Slow-Growing: M. tuberculosis is an aerobic bacterium, meaning it requires oxygen for growth. However, it is considered a slow-growing organism compared to many other bacteria. Its slow growth rate is one of the reasons why laboratory cultures and diagnostic tests for tuberculosis may take several weeks to yield results.

Mycobacterium tuberculosis colony morphology on LJ medium — Fig. *Mycobacterium tuberculosis* colony morphology on LJ medium

Pathogenicity

The pathogenicity of Mycobacterium tuberculosis refers to its ability to cause disease, particularly tuberculosis (TB), in humans and some other animals. M. tuberculosis is a highly successful pathogen, and its pathogenicity is influenced by several factors:

Transmission: Mycobacterium tuberculosis primarily spreads through the air when an infected person with active TB coughs, sneezes, or talks, releasing infectious droplets. When inhaled by a susceptible individual, the bacteria can enter the respiratory tract and initiate an infection.
Entry and Survival in the Host: Once inhaled, the bacteria are phagocytosed by immune cells called macrophages. Instead of being killed, Mycobacterium tuberculosis can evade the host’s immune response and survive and replicate within these macrophages. The bacterium has developed various mechanisms to resist being destroyed by the host’s immune system.
Granuloma Formation: The body’s immune response to Mycobacterium tuberculosis infection involves the formation of granulomas, which are organized collections of immune cells, mainly macrophages, surrounding the bacteria. Granulomas help contain the infection and prevent its spread, but they also contribute to the persistence of the bacteria, leading to latent TB infections.
Latency and Reactivation: M. tuberculosis has the ability to enter a dormant or latent state in the host. In this latent form, the bacteria remain viable but do not cause active disease. However, under certain conditions, such as a weakened immune system, the bacteria can reactivate, leading to active TB disease.
Host Immune Response: The host’s immune response plays a crucial role in determining the outcome of the infection. In many cases, the immune system can control the bacteria’s growth, leading to latent infection. However, in individuals with compromised or weakened immune systems, the bacteria can overcome the immune defenses and cause active TB disease.
Drug Resistance: Some strains of Mycobacterium tuberculosis have developed resistance to the drugs commonly used to treat TB. Drug-resistant strains, such as multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), pose significant challenges for treatment and control.
Extrapulmonary TB: While the lungs are the primary site of infection, M. tuberculosis can also affect other organs, leading to extrapulmonary TB. The bacterium can disseminate through the bloodstream or lymphatic system and cause infections in the bones, lymph nodes, central nervous system, kidneys, and other parts of the body.

Acid fast bacilli (AFB) of Mycobacterium tuberculosis in Auramine phenol staining of sputum fluorescence microscopy — Fig. Acid fast bacilli (AFB) of *Mycobacterium tuberculosis* in Auramine phenol staining of sputum fluorescence microscopy

Lab Diagnosis

The laboratory diagnosis of Mycobacterium tuberculosis involves a series of tests and techniques to identify and confirm the presence of the bacterium in clinical specimens. Timely and accurate diagnosis is crucial for initiating appropriate treatment and controlling the spread of TB. Some of the common laboratory methods used for the diagnosis of M. tuberculosis include:

Urease test positive Mycobacterium tuberculosis — Fig. Urease test positive *Mycobacterium tuberculosis*

Sputum Smear Microscopy: Sputum samples are collected from individuals suspected of having TB and examined under a microscope after staining with a special dye (e.g., Ziehl-Neelsen stain or auramine-rhodamine stain). Acid-fast bacilli, including Mycobacterium tuberculosis, retain the stain and appear as red rods against a blue background. Sputum smear microscopy is a rapid and cost-effective method, but it has limitations, especially in cases of low bacterial load or extrapulmonary TB.
Culture: The gold standard for diagnosing M. tuberculosis is the isolation of the bacterium in culture. Sputum or other clinical specimens are inoculated into specific culture media, such as Lowenstein-Jensen or Middlebrook 7H10/7H11 agar, and incubated for several weeks. If M. tuberculosis is present, colonies will grow, allowing for subsequent identification and drug susceptibility testing.
Nucleic Acid Amplification Tests (NAATs): NAATs, such as the polymerase chain reaction (PCR), are highly sensitive and specific tests that detect the genetic material (DNA or RNA) of Mycobacterium tuberculosis in clinical samples. These tests can provide rapid results, especially when the presence of drug-resistant strains needs to be confirmed.
GeneXpert MTB/RIF: This is a type of NAAT that simultaneously detects Mycobacterium tuberculosis and assesses its resistance to the drug rifampicin, which is a key indicator for multidrug-resistant TB (MDR-TB). GeneXpert is a widely used and point-of-care test that offers rapid results and helps in early detection of drug resistance.

Fig. TB PCR or GeneXpert MTB-RIF Assay showing MTB dtected low and Rifampicin resistance also detected

Chest X-rays: Although not a direct method for diagnosing Mycobacterium tuberculosis, chest X-rays can reveal characteristic patterns of TB infection in the lungs, such as nodules, cavities, and infiltrates. Radiological findings can support the clinical suspicion of TB and prompt further testing.
Serological Tests: Serological tests that detect antibodies against M. tuberculosis have been developed, but their diagnostic accuracy is limited, and they are not recommended for routine use in TB diagnosis.
Interferon-Gamma Release Assays (IGRAs): IGRAs are blood tests that measure the release of interferon-gamma by T cells in response to specific TB antigens. These tests help diagnose latent TB infection and are useful in individuals who have received the Bacille Calmette-Guérin (BCG) vaccine or have conditions that may cause false-positive reactions in the tuberculin skin test (TST).

Treatment

The treatment of Mycobacterium tuberculosis infection, commonly known as tuberculosis (TB), involves the use of specific antibiotics called anti-tuberculosis drugs. The treatment aims to eliminate the bacteria, cure the disease, and prevent the development of drug-resistant strains. The World Health Organization (WHO) recommends a standardized treatment regimen known as Directly Observed Treatment Short-Course (DOTS), which typically consists of two phases:

Intensive Phase: The intensive phase aims to rapidly kill the actively multiplying bacteria. It usually lasts for two months and involves the administration of four drugs: isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB). This four-drug combination helps to prevent the emergence of drug resistance. During the intensive phase, patients are usually closely monitored, and the treatment is directly observed by a healthcare worker or a designated person to ensure adherence.
Continuation Phase: After completing the intensive phase, the continuation phase follows for a duration of four to six months. In the continuation phase, two of the four drugs (isoniazid and rifampicin) are continued, while pyrazinamide and ethambutol are stopped. This phase aims to eliminate the remaining bacteria and prevent relapse. Like the intensive phase, patients are typically monitored, and treatment adherence is ensured during the continuation phase as well.

It is important to note that the duration of treatment and the choice of drugs can vary based on several factors, such as the patient’s age, drug susceptibility test results, the presence of drug resistance, and whether the patient has received prior TB treatment. For example, in cases of drug-resistant TB (MDR-TB or XDR-TB), more extended and more complex treatment regimens are required, often involving second-line anti-tuberculosis drugs with potentially more significant side effects.

Adherence to the prescribed treatment is crucial to ensure successful outcomes and prevent the development of drug resistance. Interrupting or discontinuing treatment prematurely can lead to treatment failure and the emergence of drug-resistant TB strains, making the disease much more difficult to treat.

Mycobacterium tuberculosis acid fast bacilli in Acid fast staining of sputum microscopy used alachite green as a counter stain — Fig. *Mycobacterium tuberculosis* acid fast bacilli in Acid fast staining of sputum microscopy used alachite green as a counter stain

In addition to drug treatment, supportive care, nutrition, and management of potential side effects of the medications are essential components of TB management. Patients are advised to maintain good nutrition and adhere to infection control measures to prevent the spread of TB to others.

Prevention

Prevention of Mycobacterium tuberculosis infection, or tuberculosis (TB), is a critical component of efforts to control the spread of the disease. Preventive strategies aim to reduce the transmission of TB, identify and treat latent TB infections, and protect vulnerable populations. Some key prevention measures include:

Vaccination: The Bacille Calmette-Guérin (BCG) vaccine is the only licensed vaccine for the prevention of TB. While it does not provide complete protection against all forms of TB, BCG vaccination can offer some level of protection, particularly against severe forms of TB in children. It is often administered in countries with a high burden of TB, especially to infants and young children.
Early Diagnosis and Treatment: Prompt detection and treatment of active TB cases are crucial for preventing the spread of the disease. Timely identification of TB cases, especially through active case-finding efforts, can help reduce transmission in the community. Access to quality healthcare services and improved diagnostic tools are vital in this regard.
Contact Tracing: Contact tracing involves identifying and evaluating individuals who have been in close contact with active TB patients. It helps identify latent TB infections and provides an opportunity for preventive treatment in those at risk of developing active TB.
Preventive Therapy for Latent TB: Individuals with latent TB infections are asymptomatic and not contagious, but they have the potential to develop active TB in the future. Preventive therapy involves giving anti-tuberculosis drugs to people with latent TB to reduce their risk of progressing to active disease. The most commonly used drugs for this purpose are isoniazid (INH) and rifampicin (RIF), often prescribed for several months.
Infection Control Measures: In healthcare settings, implementing proper infection control measures is essential to prevent the transmission of TB to healthcare workers and other patients. These measures include ensuring good ventilation, the use of respiratory protection, and appropriate isolation procedures for patients with active TB.
Addressing Social Determinants: Poverty, overcrowded living conditions, malnutrition, and lack of access to healthcare are factors that increase the risk of TB transmission and disease progression. Addressing social determinants of health can contribute to TB prevention efforts.
Targeted Interventions for High-Risk Groups: Identifying and targeting high-risk populations, such as those living with HIV, healthcare workers, prisoners, and people in congregate settings, is important for TB prevention. These groups may require additional preventive measures and screening.
Drug-Resistant TB Control: Preventing the emergence and transmission of drug-resistant TB is crucial. Proper treatment of drug-susceptible TB, adherence to treatment regimens, and careful monitoring of drug resistance are essential components of this effort.

Keynotes

Keynotes on Mycobacterium tuberculosis:

Bacterium:It s is a rod-shaped bacterium responsible for causing tuberculosis (TB) in humans and some animals.
Acid-Fast Bacillus: It is an acid-fast bacillus due to its ability to retain certain dyes even after acid-alcohol treatment during staining.
Transmission: TB primarily spreads through the air when infected individuals cough, sneeze, or talk, releasing infectious droplets that others may inhale.
Latent TB vs. Active TB: After infection, the bacterium may enter a dormant or latent state in some individuals, leading to asymptomatic infection. It can reactivate to cause active TB if the immune system weakens.
Symptoms: Active TB commonly presents with symptoms like a persistent cough, chest pain, coughing up blood, fatigue, weight loss, fever, and night sweats.
Diagnosis: Diagnosis involves sputum smear microscopy, culture, nucleic acid amplification tests (NAATs), chest X-rays, and interferon-gamma release assays (IGRAs).
Treatment: TB is treated with a combination of antibiotics during an intensive phase (usually two months) and a continuation phase (four to six months).
Drug Resistance: Drug-resistant strains of M. tuberculosis, such as MDR-TB and XDR-TB, are a significant concern and require more complex treatment regimens.
Prevention: Prevention includes BCG vaccination, early diagnosis, contact tracing, preventive therapy for latent TB, infection control measures, and addressing social determinants of health.
Global Health Challenge: TB remains a significant global health issue, particularly in areas with high prevalence rates and limited healthcare resources.
Public Health Measures: Control efforts involve a combination of early detection, proper treatment, infection control, and research for improved drugs and vaccines.
Treatment Adherence: Adherence to the prescribed treatment is crucial to prevent treatment failure and the development of drug resistance.

Mycobacterium tuberculosis: Introduction, Morphology, Pathogenicity, Lab Diagnosis, Treatment, Prevention, and Keynotes