Tuberculosis

Tuberculosis (TB), also known as Koch’s infection, is a contagious infectious disease caused by Mycobacterium tuberculosis. The disease usually affects the lungs causing inflammation (swelling) and gradually damaging them. Sometimes, TB spreads to the brain, spine, or sometimes the kidneys. It is a leading cause of infection-related deaths and ranks the top 10 list of all-cause mortality globally. 

Pulmonary Tuberculosis

It is the commonest variant of tuberculosis in which the lungs are affected. Lung cells are damaged by the bacteria leading to inflammation and cheese-like pus formation. Pulmonary TB presents with symptoms, such as a cough, difficulty in breathing, blood-stained sputum, fever, and weight loss. It usually spreads through the air (airborne transmission) when a person infected with TB coughs or sneezes. Poor nutritional status or a weak immune system are the risk factors for developing pulmonary tuberculosis.

Extrapulmonary Tuberculosis

A TB infection that occurs anywhere in the body outside the lungs is known as extrapulmonary tuberculosis. Based on its location, it is further classified into:

• Tuberculous Lymphadenitis
  It is the second most common form of tuberculosis, which usually affects children. It is the commonest extrapulmonary (outside the lungs/respiratory system) form of TB. It usually affects the neck and chest lymph nodes causing them to enlarge and occasionally be even visible as a swelling on the skin, or felt just under the skin. These nodes are painless, and gradually, they become matted with pus formation. This abscess may ooze out through the skin.
• Tuberculous Meningitis
  It is more common in developing countries. Malnourished children are prone to developing this infection. The bacteria, on entering the body, affects the brain covering (meninges) leading to their inflammation known as meningitis. The infection presents with symptoms such as a headache, vomiting, neck stiffness, loss of appetite, and weight loss. If not diagnosed in time or if not treated appropriately, the infection can result in death.
• Ileocaecal Tuberculosis
  It is the commonest form of gastrointestinal tuberculosis. When the bacteria enter the GI tract accidentally, they harbour at the junction of the small and the large intestine (ileocaecal junction) and narrow down the intestinal tract. It causes symptoms such as severe abdominal cramps, vomiting, fever, loss of appetite, and weight loss.
• Pott’s Spine
  It is another common variant of extrapulmonary TB, affecting the bones of the spine. The infection starts at the intervertebral discs and gradually progresses to the ligaments and the bones surrounding them. It causes chronic back pain, kyphosis (loss of spinal posture), abscess (pus) formation, and compression of the spinal cord.
• Renal TB
  It is a rare variant of TB where the bacteria harbour in the kidneys causing inflammation of the cells of the kidneys. The infection usually causes burning or painful urination, hematuria (passing blood in the urine), pyuria (passing pus cells in the urine), and increased frequency of urination. It rarely causes fever and weight loss.
  
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Tuberculosis mainly has three stages - stage of latency or inactivity or dormancy, followed by active TB where there is spread of the disease to the lungs or any other organ and then, if untreated or in immunocompromised patients, widespread TB i.e., Miliary TB.

Latent Tuberculosis

Most people from developing countries are infected with TB or are harbouring TB bacteria in their body but they do not develop an overt disease and do not show any signs or symptoms of the disease. Also, in such individuals, the results of various blood tests or the chest X-ray are normal. The only manifestation they have is a reaction to the tuberculin test (Mantoux test) or Interferon-gamma release assay (IGRA). These individuals are at the risk of developing an overt disease if their immune system is compromised or if they contract infections, which can affect their immune system (like HIV infection).

Active Tuberculosis

Active TB means that the tuberculosis bacteria are multiplying rapidly and invading the organs of the body. The commonest organs affected are the lungs and other less common ones are the lymph nodes, bones, brain among others. Active TB produces typical symptoms such as a cough, blood-stained sputum, difficulty in breathing, weight loss, weakness, and fever.

Miliary Tuberculosis

This is a rare situation, in which the disease is highly active. The TB bacteria enter the bloodstream and spread all over the body forming tiny nodules and also affect multiple organs. This is the most dangerous and fatal form of tuberculosis.

Worldwide, most people are exposed to Mycobacterium tuberculosis and many of them harbour this bacterium. An inactive or latent disease rarely produces any symptoms, however, it may only show a positive reaction to the tuberculin skin test (Mantoux test). It is unpredictable as to how long this latency period will persist, or will it develop into an active disease.

In an active disease, a range of symptoms can be seen that help to decide the severity of the disease. Usually, the lungs are involved and show signs and symptoms of TB. The symptoms in various types of TB are:

Pulmonary Tuberculosis

• A chronic cough (a cough lasting for more than 3 weeks).
• Hemoptysis (blood-stained sputum).
• Difficulty in breathing.
• Fever (low-grade at onset and eventually, becomes high-grade).
• Night sweats.
• Weight loss.
• Fatigue.
• Loss of appetite.

TB bacteria are also known to affect other organs like the lymph nodes, bones, brain (meninges), intestines, and even kidneys; when the disease affects organs other than the lungs it is known as extrapulmonary tuberculosis. Symptoms of extrapulmonary tuberculosis include:

Tuberculous Lymphadenitis:

• Persistently swollen lymph nodes.
• Pus or abscess formation in the lymph nodes.

Intestinal TB:

• Abdominal colic (severe pain in the abdominal region).
• Vomiting.
• Fever.
• Weight loss.

Tuberculous Meningitis:

• A headache.
• Vomiting.
• Seizures (fits).
• Confusion.
• Fever.

Pott’s spine:

• Chronic back pain.
• Abscess formation.
• Kyphosis – abnormal forward curving of the spine.

Renal TB:

• Hematuria (blood in urine).
• Pyuria (pus in urine).
• Dysuria (Painful or difficult urination).
• Fever.

Miliary TB:

In some immunocompromised (those with a weakened immune system) or drug-resistant people, the bacteria enter the bloodstream and spread throughout the body causing miliary tuberculosis. Symptoms of miliary TB include:

• Fever.
• Night sweats.
• Anorexia (loss of appetite).
• Weight loss.
• A dry cough.
• A headache.
• Enlarged lymph nodes.

Miliary TB is fatal if not treated properly or in time. 

Causes 

Tuberculosis is caused by the bacteria known as Mycobacterium tuberculosis, which is also known as Koch’s bacteria. It spreads from one person to another via minute droplets that travel through the air. These droplets are released from a person suffering from active tuberculosis when he/she coughs, sneezes, spits, or talks. It’s quite easy to contract the tuberculosis bacteria, but not so easy to develop an infection. It usually causes disease when you stay in close contact with a person with active TB for a long duration.

If the immune system is active and efficient, usually it won’t allow the disease to develop, but immunocompromised patients are at a very high risk of developing tuberculosis.

Latent tuberculosis is not contagious, but on becoming active, the person suffering from it can spread the disease.

Risk Factors 

Anyone can acquire mycobacterial infection and develop tuberculosis, yet, there are certain factors, which can increase the chances of an individual developing the disease. These risk factors include:

• Poor or Weakened Immune System 
  A healthy immune system is known to fight the Mycobacterium and can prevent the disease but if the resistance is low then the risk increases by multifold. Factors that are responsible for weakening the immune system are:
  • HIV infection.
  • Uncontrolled diabetes.
  • Severe kidney disease.
  • Cancer.
  • Steroids or immunosuppressant drugs.
  • Malnutrition.
  • Old age.
• Geographical area 
  Certain countries/regions have a higher incidence of tuberculosis cases per year. Staying or travelling to these countries/regions may increase the risk of developing the disease. These countries and continents/regions include:
  • Africa
  • Asia
  • Russia
  • Eastern Europe
  • Caribbean Islands
  • Latin America
• Socioeconomic status 
  Socioeconomic status is a key factor in the development of TB, as it also defines the standard of living, nutritional status, and availability of medicines. Poor socio-economic status has a very high impact on TB development, as it can lead to an inability to afford medicines, poor nutritional status, exposure to extremes of environmental conditions, low immune status, and ultimately high exposure to TB bacteria.
• Substance Abuse 
  Use of alcohol or drugs can damage the immune system and weaken it, thus increasing the risk of developing TB.

TB prevention has many aspects ranging from coughing etiquette to vaccination with very high success rates. Here are certain preventive measures:

• General precautions
  Avoid contact with TB patients or use a face mask when in contact with a person suffering from TB. Use a handkerchief or cover the nostrils and mouth if someone is coughing nearby, as it prevents the entry of germs and infection.
• Coughing etiquette
  Keep a tissue or cover your mouth and nose while coughing or sneezing to avoid the spread of germs.
• Medication for latent infection
  If the test for latent infection turns out to be positive, it is better to start with TB medication immediately under your doctor’s guidance. Staying at home, ventilating the room, and following cough etiquette can help to prevent the spread of TB bacteria.
• For people with HIV infection  
  Maintaining good nutritional status is important. Regularly check for CD4 cell count, as well as take anti-retroviral therapy for HIV infection.
• For frequent travellers
  Travelling to endemic areas (where the TB infection occurs regularly) may expose you to TB bacteria. Therefore, in such regions, it is better to avoid staying in extremely crowded or closed environment. Regular evaluation for Mycobacterium is another effective way to detect TB infection at an early stage or during the latency period.
• Vaccination
  BCG (Bacille Calmette-Guerin) vaccine is used commonly against TB. In endemic countries, it is given at birth, while in developed countries, where TB incidence is low, it is given to children after testing them for Tuberculin skin test; if the test result is negative, then they are vaccinated with BCG. BCG vaccine has a Bovine (a bacterial strain that causes TB in cows) strain of Mycobacterium and it is a live-diluted (attenuated) vaccine. The vaccine is known to have a good success rate.

In most cases, a careful clinical history and a thorough physical examination of the patient gives an idea to make the diagnosis of tuberculosis. Yet, for confirmation, certain tests are used, which help to determine the severity of the infection and guide in planning the therapeutic approach.

• Physical Examination
  A complete medical history along with a thorough examination of the chest or the airways suggest the presence of an abnormal-breathing sound. Other signs that may be present include raised body temperature, pallor (due to anaemia), and sometimes reduced oxygen saturation levels. In the case of extrapulmonary TB, there can be other symptoms, such as neck-stiffness and enlarged lymph nodes.
• Blood test  
  Tuberculin skin test or Mantoux test is helpful in diagnosing TB, but it can be falsely positive in patients who were either exposed previously to TB bacteria or were vaccinated with BCG vaccine. Other tests include:
  • Quantiferon TB Gold
  • T- spot test

These tests evaluate the immune response towards TB bacteria and a positive test indicates an infection with Mycobacterium tuberculosis.

• Sputum Test
  Apart from a blood test, sputum or the mucus that comes up while coughing is evaluated for TB bacteria. Sputum test not only helps in confirming the presence of the Mycobacterium but also helps to select the right and effective medicines that can be used to treat this infection. Sputum test is much more important if the person is suffering from drug-resistance TB.
• Imaging  
  Usually, an X-ray of the chest is helpful in confirming the diagnosis. However, sometimes CT scan of the chest is also used for diagnosing tuberculosis.
• Biopsy or FNAC (Fine Needle Aspiration Cytology)  
  In certain cases, like extra-pulmonary TB, a small needle is inserted in the enlarged lymph node or in the spinal cord (meninges) to obtain a sample, which is then tested for the presence of TB bacteria. Positive reports confirm extra-pulmonary tuberculosis.

Tuberculosis is the most studied disease and has a wide variety of drugs available for treatment. These drugs are classified as bactericidal (the drugs that kill the bacteria) and bacteriostatic drugs (stop the growth of the bacteria, so that our immune cells can kill them). The selection of medication, dosage, and duration of the treatment is decided by the type of infection and severity of the infection.

• Latent Infection
  It is usually treated with a single drug, which is taken for six months.
• Active Pulmonary infection
  Usually, a combination therapy is employed to treat pulmonary TB and the treatment goes on for six to nine months.
• Extra-pulmonary infection
  It is considered as a relatively severe form of the disease and here, multiple combinations are used for the initial 6-9 months, followed by a short course of a single drug for the next three months.
• Drug-resistant infection
  In a drug-resistant infection, the bacteria develop certain mechanisms to counteract the effect of medicines and become resistant to them. Thus at first, the sensitivity test is performed to find out which drugs can be used to kill the bacteria and that drug, along with other drugs, are given as a combination therapy and depending upon the type of resistance i.e. multi-drug resistance (MDR- TB) or extreme drug resistance (XDR-TB), the therapy and the duration of therapy is decided, which ranges from 18 months to 3 years.

 The drugs that are commonly used to treat tuberculosis include:

• Rifampin
• Isoniazid
• Ethambutol
• Pyrazinamide

In the case of a drug-resistant TB, injectable medicines are used, like fluoroquinolones and amikacin, kanamycin or capreomycin. These medicines are given in combination with oral medications.

Since the TB treatment goes on for a longer duration and the medicines used have a relatively higher drug strength; these medicines are known to have serious side effects. Most of these are toxic to the liver. If you experience any of the following symptoms, it’s important to report it to your doctor immediately:

• Persistent nausea and vomiting.
• Yellow discolouration of the skin (jaundice).
• Loss of appetite.
• Persistent fever.

Lifestyle management

Tuberculosis has a significant impact on a person’s normal lifestyle, as the treatment of TB is complicated as well as prolonged. The best way to get along is to stick to the treatment and regular follow-ups with your doctor. Sometimes, one may require the help of a psychologist, as there are possibilities of developing mental illnesses, such as frustration, anxiety, stress, depression or even denial. Proper nutrition and positive coping strategies are crucial in dealing with tuberculosis.

Apart from these, certain other lifestyle modifications include:

• Isolation
  It is better to stay at home during the active phase of the disease as the infection can spread to others. Even at home, follow coughing etiquettes like covering the mouth while coughing or sneezing, collecting sputum in a disposable bag or tissue and discarding it on collection. After a few weeks of treatment, once you are no longer infectious, you can resume your normal activities.
• Personal Hygiene
  Personal hygiene plays a vital role in preventing the spread of the disease. These measures include keeping the room ventilated, using masks to cover the nose and the mouth, and cleaning personal items regularly among others.
• Proper Treatment
  Taking adequate rest and following the medication schedule are the key factors. If you stop taking medicines mid-way or change the dosage of the medicines, there are chances of developing drug resistance, which is difficult to treat and may require even longer therapy. Drug overuse can also cause troubles as most of these medicines are toxic to the liver.
• Regular follow-up & evaluation of blood parameters 
  Apart from taking medicines regularly, it is important to visit your doctor regularly for a check-up and as these medicines have some harmful effects on the liver, blood parameters like complete blood count (CBC), creatinine, and liver function tests are (LFT) estimated and evaluated to confirm that these medicines are not causing any side-effects.
• Nutritional status
  A good nutritional status or positive nitrogen balance is equally important to maintain and hasten recovery and for reducing the convalescence phase. A good diet, rich in protein and carbohydrates, forms the foundation of a healthy weight gain, which is important to compensate for the weight loss that occurs during the infection.

Prognosis

Tuberculosis is a curable infection. If diagnosed early with adequate effective therapy, it can be cured completely. But, if the treatment is left mid-way or is inadequate, it can result in drug resistance (MDR – multiple drug resistance & XDR – extreme drug resistance). In drug resistance cases, the therapy goes on for a longer duration; for MDR it is 18 months and for XDR it is 36 months. While MDR has a relatively better prognosis than XDR. There are certain factors that adversely affect the prognosis, apart from drug resistance, which include:

• Chronic kidney disease.
• HIV infection.
• COPD ( a type of chronic lung disease).
• Malnutrition.
• Alcoholism.

Complications 

If left untreated or poorly treated, tuberculosis may be fatal. Mycobacterium can enter the bloodstream and travel anywhere in the body and infect any organ or organ system. Some of the commonly seen complications include:

• Drug resistance
  It is the most common complication seen in people with poor socioeconomic status and a poor compliance with the medication schedule. It results from an inadequate or incomplete treatment. It can result in MDR (Multiple drug resistance) or XDR (Extreme drug resistance). MDR has a better prognosis, but XDR is invariably fatal.
• Spine Damage
  TB bacteria can enter the bones of the spinal cord and affect the vertebral column causing back pain, stiffness, sciatica, and sometimes cold-abscess.
• Joint pain
  Rarely, this bacteria may affect the joints, causing tuberculous arthritis, which commonly affects the hips and knees.
• Meningitis
  It is also one of the most common complications seen in younger children in which the bacteria reach the brain and meninges. It can cause symptoms, such as a headache, vomiting, neck stiffness, and sometimes confusion or brain damage. It can also be fatal.
• Pericarditis
  In very rare cases, Mycobacterium may affect the covering of the heart (pericardium) and cause its inflammation. This can cause accumulation of fluid around the heart and can reduce it’s pumping efficiency. Again, this can also be life-threatening.
• Miliary TB
  Miliary TB is a rare condition in which the TB bacteria enter the bloodstream and infect multiple organs at the same time, resulting in a fatal condition. If treatment is delayed, it invariably causes death.