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What Is Tuberculosis? Symptoms, Causes, and Treatment

What Is Tuberculosis? Symptoms, Causes, and Treatment

Tuberculosis (TB) is an ancient disease that has been affecting humans for thousands of years and is considered a major global health concern, causing millions of infections and thousands of deaths each year.

Thus, all international organizations and efforts are focusing more and more on healing and preventative campaigns to protect the general global health.

This blog aims to provide a full understanding of TB, including its causes, symptoms, diagnosis, treatment, prevention, and the ongoing efforts to combat this disease worldwide.

 

What Is Tuberculosis?

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that primarily spreads through the air when people with active TB disease cough, sneeze, talk, or spit.

Moreover, it mainly affects the lungs, but can also affect other parts of the body, and is a common and potentially life-threatening disease, especially in developing countries and in people with weakened immune systems.

On the other hand, TB disease can be latent, meaning that an individual is infected with the bacteria but does not show symptoms, or it can be active, leading to severe health complications and transmission to others.

 

Types of Tuberculosis Explained

Understanding the diverse types of tuberculosis is essential for accurate diagnosis, appropriate treatment selection, and effective management of this infectious disease.

Next to the main types of tuberculosis, there are also other classifications based on factors such as HIV status (TB-HIV co-infection), age (pediatric TB), and latent TB infection (where individuals have been infected with M. tuberculosis but do not have an active disease).

1.Pulmonary tuberculosis (TB)

Pulmonary tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, primarily affecting the lungs but potentially involving other organs as well. TB spreads through the air when a person with active pulmonary TB coughs, sneezes, or talks. Although tuberculosis rates have decreased significantly over the years due to effective treatment, it remains a major global health concern, especially in areas with high rates of infection, such as parts of Asia, Africa, and Eastern Europe. Understanding the key symptoms and diagnostic methods for pulmonary tuberculosis is essential for early detection and effective treatment.

Key Symptoms of Pulmonary Tuberculosis

Pulmonary TB can develop slowly, and symptoms often appear gradually. The key symptoms to watch for include:

  1. Chronic Cough: One of the hallmark symptoms of pulmonary TB is a persistent cough that lasts for more than three weeks. The cough may start as dry but can eventually become productive, producing mucus or blood (hemoptysis) as the disease progresses.
  2. Coughing Up Blood (Hemoptysis): In advanced stages of pulmonary TB, the coughing may be accompanied by blood or rust-colored sputum. This occurs due to the infection affecting the lung tissue, leading to tissue damage and bleeding.
  3. Chest Pain:People with TB often experience sharp or stabbing chest pain, which may worsen when breathing or coughing. This is caused by inflammation in the lungs and surrounding pleura (the lining of the lungs).
  4. Fever: Low-grade fever, especially in the evenings, is common in pulmonary TB. This is part of the body’s immune response to the infection.
  5. Night Sweats: Excessive sweating at night, often soaking through clothes and bedding, is another common symptom. This is typically related to the body’s response to the infection.
  6. Weight Loss: Unexplained weight loss, also known as “consumption,” is a frequent symptom of TB. As the disease progresses, the body uses energy to fight the infection, leading to loss of appetite and significant weight loss.
  7. Fatigue and Weakness : General fatigue, weakness, and malaise are common, often making it difficult for individuals to carry out normal activities.
  8. Loss of Appetite: A decreased desire to eat is common, contributing to weight loss and malnutrition, which can exacerbate the disease’s severity.
  9. Shortness of Breath: As TB affects the lungs, it can cause breathing difficulties, particularly if there is extensive damage to lung tissue.

Diagnosis Methods for Pulmonary Tuberculosis

Early detection of pulmonary tuberculosis is critical for initiating appropriate treatment and preventing its spread. Several diagnostic methods are employed to confirm the presence of Mycobacterium tuberculosis in the lungs.

  1. Chest X-ray: A chest X-ray is one of the most commonly used tools in diagnosing pulmonary TB. It can reveal abnormalities in the lungs, such as cavitary lesions, infiltrates, or other signs that suggest active tuberculosis. While a chest X-ray cannot confirm the presence of TB on its own, it is essential for identifying suspected cases.
  2. Sputum Smear Microscopy: One of the most common diagnostic tests for TB involves examining sputum (mucus or phlegm) under a microscope. The sputum is stained using the Ziehl-Neelsen method to detect acid-fast bacilli (AFB), the characteristic bacteria that cause TB. This method is quick and helps identify highly infectious cases, though it may not detect all TB infections, especially in people with low bacterial loads.
  3. Sputum Culture: Sputum culture is a more sensitive method for detecting TB. In this test, sputum samples are cultured to grow Mycobacterium tuberculosis. Cultures can take several weeks, but they offer a more reliable diagnosis, especially in cases where microscopy is negative but TB is still suspected. Culture also helps in determining drug resistance patterns, which is vital for treatment.
  4. GeneXpert MTB/RIF Test: This molecular test can rapidly detect TB and resistance to rifampicin (a key TB drug) in sputum samples. The GeneXpert test is known for its speed, providing results within two hours, making it ideal for diagnosing TB in high-risk and resource-limited settings.
  5. Tuberculin Skin Test (TST): Also known as the Mantoux test, the TST involves injecting a small amount of purified protein derivative (PPD) into the skin. If the person has been exposed to TB bacteria, the skin will become raised and red at the injection site within 48 to 72 hours. While the TST is commonly used for screening, it does not distinguish between latent TB infection and active TB disease and is less commonly used for diagnosis in symptomatic individuals.
  6. Interferon-Gamma Release Assays (IGRAs): IGRAs are blood tests that measure the immune response to Mycobacterium tuberculosis antigens. They are primarily used for detecting latent TB infection and are not typically used to diagnose active TB. IGRAs have the advantage of not being affected by prior BCG vaccination, unlike the TST.
  7. Bronchoscopy: In rare or difficult-to-diagnose cases, a bronchoscopy may be performed. This procedure involves inserting a thin tube (bronchoscope) into the airways to obtain sputum or tissue samples directly from the lungs. It is typically used when sputum samples are insufficient or unavailable.
  8. Drug Sensitivity Testing: Drug sensitivity testing is essential to determine if the TB strain is resistant to first-line or second-line medications, helping guide appropriate treatment. This testing is especially crucial in cases of multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB).

2. Extrapulmonary Tuberculosis: Symptoms and Diagnostic Tools

Extrapulmonary tuberculosis (TB) occurs when Mycobacterium tuberculosis infects organs outside the lungs, including the lymph nodes, bones, kidneys, spine, brain, and other parts of the body. While pulmonary TB (which affects the lungs) is the most common form, extrapulmonary TB accounts for approximately 15-20% of all TB cases globally, and it can present challenges for diagnosis and treatment due to its diverse manifestations. Early detection is crucial to prevent complications and spread. In this article, we’ll explore the key symptoms and diagnostic tools used for identifying extrapulmonary TB.

Key Symptoms of Extrapulmonary Tuberculosis

Extrapulmonary TB presents differently depending on the affected organ or body system. Since the symptoms can mimic those of other diseases, extrapulmonary TB can often be misdiagnosed. Here are some common forms and their associated symptoms:

  1. Lymphatic Tuberculosis (TB Lymphadenitis):
    • Enlarged Lymph Nodes: Swelling, often in the neck, armpits, or groin. The lymph nodes may be painful, hard, or tender.
    • Localized Inflammation: Infected lymph nodes may develop abscesses or disfigure the skin.
    • Fever and Night Sweats: General systemic symptoms like low-grade fever, weight loss, and night sweats can accompany lymphatic TB.
  2. Tuberculous Meningitis:
    • Headaches: Severe, persistent headaches are common.
    • Neck Stiffness: Difficulty in flexing the neck due to inflammation of the meninges.
    • Altered Mental Status: Confusion, drowsiness, or altered consciousness, which may progress to coma if untreated.
    • Fever and Seizures: High fever and seizure activity can be a sign of severe infection.
  3. Bone and Joint Tuberculosis:
    • Pain and Swelling: Pain, particularly in the spine (Pott’s disease), hips, or knees, with swelling around the affected joints.
    • Deformity and Limited Range of Motion: In cases of spinal TB, there can be deformities like kyphosis (a rounded back). Joint tuberculosis may cause stiffness and reduced mobility.
  4. Genitourinary Tuberculosis:
    • Painful Urination (Dysuria): Difficulty or pain during urination, often with blood in the urine.
    • Frequent Urination: Increased frequency of urination, possibly with fever.
    • Flank Pain: Pain on one side of the body, typically around the kidneys or lower abdomen.
    • Urinary Retention: Difficulty in emptying the bladder or complete urinary retention in severe cases.
  5. Gastrointestinal Tuberculosis:
    • Abdominal Pain and Distension: Inflammation of the intestines can cause cramping and bloating.
    • Diarrhea and Weight Loss: Chronic diarrhea, coupled with unexplained weight loss, is common.
    • Nausea and Vomiting: Digestive issues and loss of appetite can lead to general fatigue.
  6. Cutaneous Tuberculosis:
    • Skin Lesions: Ulcerated or raised lesions on the skin, which may be painless or painful.
    • Abscess Formation: Infected areas can form abscesses that may drain pus or become fistulas.
    • Scarring: Chronic lesions may leave scars or tissue damage.
  7. Pericardial Tuberculosis:
    • Chest Pain: Sharp, pleuritic chest pain may be felt when the pericardium (the lining around the heart) becomes inflamed.
    • Shortness of Breath: Difficulty breathing due to the heart being surrounded by fluid.
    • Fever and Weakness: Systemic symptoms like fever, fatigue, and malaise may accompany the infection.

Diagnostic Tools for Extrapulmonary Tuberculosis

Diagnosing extrapulmonary TB can be more challenging than pulmonary TB because it may not show up on routine sputum tests or chest X-rays. Therefore, healthcare providers need to rely on various diagnostic tools and methods to confirm the infection.

  1. Clinical Examination:
    • A thorough physical examination is the first step in diagnosing extrapulmonary TB. The doctor will assess symptoms, such as enlarged lymph nodes, joint pain, or neurological signs, and evaluate the patient’s medical history and risk factors, such as recent exposure to someone with active TB or prior TB history.
  2. Imaging Studies:
    • X-rays: While chest X-rays are essential for pulmonary TB, imaging methods like CT scans or MRI are often used for diagnosing extrapulmonary TB, particularly in the brain, bones, and joints. CT scans can reveal lesions, abscesses, and signs of inflammation in the affected organs.
    • Ultrasound: For suspected abdominal TB or tuberculous lymphadenitis, ultrasound is a useful tool to visualize swollen lymph nodes or fluid accumulation in the abdomen or chest.
  3. Biopsy and Histopathology:
    • In cases of suspected extrapulmonary TB, biopsy of affected tissues (e.g., lymph nodes, bone tissue, or abscesses) is often performed. The tissue is examined under a microscope to identify granulomas (clusters of immune cells) and other signs typical of TB infection. PCR testing (Polymerase Chain Reaction) on biopsy samples can directly detect Mycobacterium tuberculosis.
  4. Sputum Testing (in cases of co-infection):
    • While sputum is typically used to diagnose pulmonary TB, in some cases of extrapulmonary TB, sputum tests may be done if the patient has both pulmonary and extrapulmonary TB. The detection of Mycobacterium tuberculosis in sputum samples supports the diagnosis.
  5. Culture:
    • Mycobacterial Culture: This is a highly sensitive method used to detect the presence of Mycobacterium tuberculosis in biological samples (e.g., urine, lymph nodes, pleural fluid). The samples are cultured, and growth of the bacteria confirms the diagnosis. This process can take weeks but provides a definitive result.
  6. Polymerase Chain Reaction (PCR):
    • PCR is a rapid and sensitive molecular test used to detect the genetic material of Mycobacterium tuberculosis in samples from affected tissues, fluids, or biopsies. It is particularly helpful in detecting TB in body sites where cultures are difficult or slow to grow.
  7. Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRAs):
    • While the tuberculin skin test (TST) is primarily used to detect latent TB infection, it can also help in cases of extrapulmonary TB, especially in immunocompromised patients. However, IGRAs, such as the QuantiFERON test, may be more accurate in detecting latent TB without cross-reactivity from prior BCG vaccinations.
  8. Urinary and Blood Tests:
    • In cases of genitourinary or gastrointestinal TB, urine and stool samples can be tested for the presence of Mycobacterium tuberculosis. Urinalysis may also reveal blood or signs of infection in the kidneys or bladder.
    • Blood tests can provide additional clues, such as elevated white blood cell counts, liver function abnormalities, and markers of systemic inflammation like ESR (erythrocyte sedimentation rate) or CRP (C-reactive protein).
  9. Cerebrospinal Fluid (CSF) Analysis:
    • In suspected cases of TB meningitis, cerebrospinal fluid (CSF) obtained via lumbar puncture is analyzed for the presence of Mycobacterium tuberculosis. A positive PCR test or detection of high white blood cell counts and low glucose levels in the CSF can confirm TB meningitis.

3. Managing Drug-Resistant Tuberculosis: Causes and Treatment Options

Drug-resistant tuberculosis (DR-TB) represents one of the most significant challenges in the fight against tuberculosis (TB). Unlike drug-sensitive TB, which can be effectively treated with a standard combination of antibiotics, drug-resistant TB does not respond to one or more of the first-line TB drugs. This type of TB requires specialized treatment regimens, which are often more expensive, take longer, and may have more severe side effects. The emergence of drug-resistant strains of Mycobacterium tuberculosis threatens global TB control efforts, making early detection, effective treatment, and prevention strategies essential.

Causes of Drug-Resistant Tuberculosis

Drug resistance in tuberculosis occurs when Mycobacterium tuberculosis undergoes mutations that allow it to survive despite the presence of drugs that would normally kill or inhibit its growth. The causes of drug-resistant TB are multifactorial and can be attributed to a variety of factors:

  1. Incomplete or Inadequate Treatment:
    • Improper or incomplete drug regimens: Patients who do not complete the full course of TB treatment or who receive inadequate doses may allow the bacteria to survive and mutate. This can occur if patients stop taking their medication early due to feeling better or due to the side effects of the drugs.
    • Non-adherence to prescribed treatment: In some cases, patients may miss doses or fail to follow the prescribed treatment regimen, giving the bacteria an opportunity to develop resistance.
  2. Inadequate Healthcare Infrastructure:
    • Access to healthcare and medications: In resource-limited settings, patients may not have access to the full range of first-line drugs, leading to partial treatment. Poor quality or counterfeit medications can also contribute to drug resistance.
    • Lack of trained healthcare professionals: Inadequate healthcare training can lead to mismanagement of TB treatment, resulting in insufficient drug regimens and increased risk of resistance.
  3. Transmission of Resistant Strains:
    • Person-to-person transmission: Drug-resistant TB can spread from one person to another. A person with drug-resistant TB can infect others, passing on resistant strains, particularly in crowded living conditions, healthcare settings, or areas with high TB prevalence.
    • Co-infection with HIV: People living with HIV are more susceptible to TB, and HIV-positive individuals with weakened immune systems are at higher risk of developing drug-resistant TB due to inadequate immune response and longer treatment times.
  4. Incorrect Diagnosis:
    • Misdiagnosis or delayed diagnosis: If drug-resistant TB is not diagnosed early, patients may continue taking ineffective medications, which can promote resistance. Inaccurate testing methods can delay the identification of resistant strains, allowing the bacteria to further adapt to the drugs.
  5. Use of Second-Line Drugs:
    • Improper use of second-line drugs: Second-line TB drugs, used to treat drug-resistant TB, can also contribute to resistance if they are not used properly or if they are introduced too early in treatment for non-resistant cases. Overuse or misuse of these drugs can encourage the development of further resistance.

Types of Drug-Resistant Tuberculosis

  1. Multidrug-Resistant Tuberculosis (MDR-TB):
    • MDR-TB occurs when Mycobacterium tuberculosis is resistant to at least two of the most effective first-line anti-TB drugs: isoniazid and rifampicin. MDR-TB requires treatment with second-line drugs, which are typically more expensive, harder to obtain, and come with more severe side effects.
  2. Extensively Drug-Resistant Tuberculosis (XDR-TB):
    • XDR-TB is an even more severe form of drug-resistant TB. It is resistant to isoniazid and rifampicin, plus at least one of the three second-line injectable drugs (kanamycin, amikacin, or capreomycin) and at least one of the fluoroquinolones. XDR-TB is more difficult to treat and has a much higher mortality rate.
  3. Totally Drug-Resistant Tuberculosis (TDR-TB):
    • TDR-TB is a rare but extremely concerning form of TB where the strain is resistant to all available TB drugs, including both first-line and second-line medications. The treatment options for TDR-TB are very limited and often result in poor outcomes.

Treatment Options for Drug-Resistant Tuberculosis

Managing drug-resistant tuberculosis requires an intensive, tailored treatment regimen, often involving second-line drugs and longer treatment periods. The treatment process for MDR-TB and XDR-TB differs significantly from that of drug-sensitive TB.

  1. Diagnosis and Drug Sensitivity Testing:
    • Before starting treatment, accurate diagnosis through drug susceptibility testing (DST) is crucial. DST identifies which drugs the strain of TB is resistant to, guiding healthcare providers in selecting the most effective treatment regimen. Testing methods include sputum smear microscopy, culture, PCR-based tests, and GeneXpert MTB/RIF.
  2. Second-Line Drugs:
    • Fluoroquinolones: These are a group of antibiotics (e.g., levofloxacin, moxifloxacin) that are commonly used to treat MDR-TB. Fluoroquinolones are powerful drugs that target bacterial DNA synthesis.
    • Injectable Drugs: For XDR-TB, second-line injectable drugs, such as amikacin, kanamycin, or capreomycin, may be required. These drugs are used in more severe cases but come with a risk of side effects like kidney damage or hearing loss.
    • Linezolid: This antibiotic is effective against a wide range of bacteria, including TB, and may be used for MDR-TB or XDR-TB. However, it can cause serious side effects such as bone marrow suppression and peripheral neuropathy.
    • Bedaquiline: A newer drug specifically designed to treat drug-resistant TB, particularly MDR-TB and XDR-TB. Bedaquiline is used in combination with other second-line drugs and has shown promising results.
    • Delamanid: Another newer drug approved for MDR-TB. Like bedaquiline, it is used in combination with other drugs to treat resistant forms of TB.
  3. Longer Treatment Duration:
    • The treatment for drug-resistant TB typically lasts much longer than the standard six-month regimen for drug-sensitive TB. The duration of treatment for MDR-TB is usually 18-24 months, and for XDR-TB, it can extend even further. Adherence to the treatment plan is critical to prevent further resistance and relapse.
  4. Directly Observed Treatment Short-course (DOTS):
    • DOTS is a strategy that ensures patients adhere to their treatment regimen by having a healthcare provider directly observe them taking their medications. This is particularly important for drug-resistant TB, where non-compliance can lead to treatment failure and further resistance.
  5. Supportive Care:
    • Supportive care plays a crucial role in managing side effects, which can be severe in drug-resistant TB. Regular monitoring of liver function, kidney function, and hearing is essential when patients are on second-line drugs.
    • Nutritional support and psychological counseling can also improve outcomes by ensuring patients are physically strong and mentally prepared to manage the lengthy and challenging treatment process.
  6. Surgical Intervention:
    • In certain cases, particularly with localized drug-resistant TB, surgery may be considered as part of the treatment strategy. Surgery can help remove infected tissue or abscesses, making it easier for antibiotics to work effectively.
  7. Contact Tracing and Infection Control:
    • Patients with drug-resistant TB need to be isolated to prevent transmission, especially in healthcare settings. Contact tracing and screening of individuals who have been in close contact with the patient are essential in preventing the spread of the resistant strain.

Challenges in Treating Drug-Resistant Tuberculosis

  1. Cost of Treatment:
    • Treating drug-resistant TB is significantly more expensive than treating drug-sensitive TB. The cost of second-line drugs, diagnostic tests, and extended treatment durations can be prohibitive, particularly in low-resource settings.
  2. Side Effects:
    • Second-line drugs often come with serious side effects, including toxicity to the liver, kidneys, and nervous system. These side effects require careful monitoring and may necessitate changes in the treatment regimen.
  3. Limited Drug Options:
    • The emergence of extensively drug-resistant and totally drug-resistant TB has led to a shortage of effective treatment options. New drugs like bedaquiline and delamanid are promising, but their availability and cost remain barriers in many regions.
  4. Adherence and Resistance Management:
    • Ensuring that patients complete their long, challenging treatment regimens is crucial. Non-adherence is a significant contributor to treatment failure and the development of further drug resistance.

 

Recognizing Common Symptoms of Tuberculosis

The tuberculosis symptoms can vary depending on which part of the body is affected.

In pulmonary tuberculosis symptoms  in lungs may include:

  • A persistent cough that lasts for more than three weeks, coughing up blood or sputum.
  • Chest pain.
  • Weakness or fatigue.
  • Weight loss.
  • Fever.
  • Night sweats.

In extrapulmonary tuberculosis (affecting other parts of the body), symptoms can include:

  • Pain in the affected area.
  • Swelling.
  • Neurological symptoms if the brain is affected.

 

Understanding the Causes of Tuberculosis

Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex, that could spread from one person to another through tiny droplets released into the air via coughs and sneezes of an infected individual.

Moreover, factors that increase the risk of developing active TB include weakened immune systems due to conditions such as HIV/AIDS, malnutrition, diabetes, or certain medications.

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Tuberculosis Diagnosis: Techniques and Best Practices

Early tuberculosis tests and diagnosis are vital for effective treatment and to prevent its spread to others, there are several methods and techniques used for diagnosing tuberculosis, each with its own advantages and limitations.

  • Clinical Evaluation.
  • Tuberculin Skin Test (TST).
  • Interferon-Gamma Release Assays (IGRAs).
  • Chest X-ray.
  • Sputum Smear Microscopy.
  • Nucleic Acid Amplification Tests (NAATs).
  • Culture Testing.
  • Biopsy.

 

Treatment Options for Tuberculosis

The treatment of tuberculosis typically involves a combination of antibiotics to effectively kill the bacteria and prevent the development of antibiotic resistance.

Moreover, the treatment routine for tuberculosis can be complex and long, often lasting several months to over a year, depending on the type and severity of the infection, as well as the patient’s overall health condition.

However, while tuberculosis medications are essential for curing the infection, they can also cause many side effects such as liver toxicity, peripheral neuropathy, gastrointestinal disturbances, and others. Thus, regular monitoring of patients undergoing TB treatment is required to detect and manage any potential side effects promptly.

1. First-Line Drugs: Key Components of Tuberculosis Treatment

The standard treatment for tuberculosis involves a combination of several first-line drugs, that are highly effective in treating TB and are recommended by health organizations such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC).

The first-line drugs commonly used in tuberculosis treatment include:

  • Isoniazid (INH):

Isoniazid is a key component of tuberculosis treatment regimens, as it is highly effective in killing the bacteria that cause TB.

  • Rifampin (RIF):

Rifampin is another essential drug used in the treatment of tuberculosis, it works by inhibiting the growth of Mycobacterium tuberculosis.

  • Pyrazinamide (PZA):

Pyrazinamide is often included in the initial phase of tuberculosis treatment to effectively eliminate the bacteria.

  • Ethambutol (EMB):

Ethambutol is another first-line drug that is used in combination with other medications to treat TB.

These first-line drugs are typically used in combination to form a multidrug regimen, which is vital for preventing the development of drug-resistant strains of Mycobacterium tuberculosis.

2. Managing Drug-Resistant Tuberculosis

In cases where Mycobacterium tuberculosis shows resistance to first-line drugs, second-line medications are used.

As drug-resistant TB requires longer and more complex treatment regimens, often involving multiple antibiotics that are less effective and may have more severe side effects than first-line drugs.

3. Ensuring Adherence to Tuberculosis Treatment

To ensure treatment adherence and reduce the risk of medication non-compliance, healthcare providers often implement directly observed therapy (DOT) for patients undergoing tuberculosis treatment.

This approach involves healthcare workers directly observing patients as they take their medications to ensure proper adherence to the prescribed regimen.

 

Finally,

Tuberculosis is a serious infectious disease that requires effective diagnosis and appropriate treatment to prevent its spread and complications, thus, understanding its causes, diagnostic methods, and treatment options is important in managing this global health concern.

Get in touch with us to know more about our in vitro diagnostic for tuberculosis.

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