Tuberculosis

According to the World Health Organization [WHO], Tuberculosis [TB] is the number one cause of death in the world. Approximately 1.7 billion people i.e. one third of the whole world’s population are infected with TB bacteria is not suffering from the active disease itself. Each year 8 million of people develop TB and 3 million die. Someone in the world is newly infected with TB every second and one person dies from TB every 10 second.

TB is a bacterial infection that mainly affects the lungs [Pulmonary TB] but can also spread to other organs of the body [Extrapulmonary TB]. The bacteria can invade all proportion of body from skin to any of the internal organs usually by spreading from the lung infection. People of all ages are susceptible to TB; however the elderly, HIV patients and people suffering from malnutrition are at greater risk.

TB can be both Inactive & Active

• Inactive TB

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  [Often referred as Primary Infection] The TB causing bacteria is present in the body, but the patient is not affected by it in anyway and hence unaware of their condition. Primary infection is a state in the development of Tuberculosis but does not always lead to the disease. Only 5 to 10% of the individuals with tuberculosis infection progress to the active TB disease at some stage of their life. A person TB infected cannot spread the infection to others.

• Active TB

  [Often referred as Tuberculosis Disease] Tuberculosis disease develops if the TB causing bacteria becomes active. This may occur immediately after the primary infection in infants, elderly and people with weak immune system. However in most case tuberculosis develops, if does so, long after the person have been infected. A patient with Tuberculosis can spread the infection to others around them.

Causing Agent

Rod-shaped bacteria called tubercle bacilli cause tuberculosis. These bacilli belong to a group of bacteria called Mycobacterium tuberculosis. M. Tuberculosis complex includes 3 other mycobacteria that can cause TB

1. M. Bovis
2. M. Aficanum
3. M. Microti

It is a slow growing, anaerobic [i.e. must intake oxygen to live] bacteria that thrives in areas of the body that are rich in blood and oxygen e.g. lungs.

Transmission

Airborne droplets nuclei expelled when active TB patients cough, sneeze, spit or speak transmit tuberculosis causing bacteria Mycobacterium tuberculosis. Each droplets [5 µm in diameter] containing 1 to 3 tubercle bacilli stays in the air long enough for people around the patient to inhale and become TB infected. Infection may also result from consuming contaminated food or from drinking milk from cattle infected with Mycobacterium bovis bacteria.

Only Pulmonary TB is contagious and can be transmitted when a person with active disease produces aerosol droplets containing Mycobacterium tuberculosis and an otherwise healthy person inhales this air containing bacteria. A person with untreated, active Tuberculosis may infect up to 20 people each year. People with latent/ inactive TB cannot spread the disease.

Extrapulmonary TB cannot be spread easily to others.

The probability of transmission depends upon the following:

1. Infectiousness of the patients with TB
2. Quantity of bacilli expelled
3. Environment of exposure
4. Duration of exposure
5. Virulence of the patient

At High Risk

People at high risk of TB are those that have:

• HIV
• AIDS
• Malnutrition
• Silicosis
• Diabetes
• End-stage renal disease
• Hematologic disease
• Immunosuppressive therapy
• Intravenous/ illicite drug users
• Alcoholic

Otherwise healthy people under the following condition are also at high risk of acquiring TB:

• Long term care facilities e.g. prison, nursing homes
• Close contact with infectious tubercular individuals
• Health care workers
• Medically underserved
• Low-income population
• High risk racial/ethnic minority population

Host Response

Even though tuberculosis has been one of the leading causes of death for centuries, the understanding of human host response to this infection is in the shadow. However extensive researches show that host immunity plays an important role in the clinical manifestation of tuberculosis and the ultimate outcome of patients.

Once Mycobacterium tuberculosis from the air droplet has reached the lung, there are 4 possible outcomes.

1. Initial host response can be completely effect and kill the bacilli successfully and hence the patient has no chance of developing TB at any point their life
2. Organism can enter cell can being to grow and reproduce and immediately after infection and hence causing TB disease
3. Bacilli may become dormant under the influence of tough scar tissues i.e. become latent TB infection and not harm the patient.
4. Latent TB infection at some point can eventually become active hence grows and reproduce resulting in the clinical disease

As a person inhales the bacilli from the air from of them settle into the layer of mucus that lines of the nasal passages and the tracheobronchial tree of respiratory system. These bacilli trapped in the mucus may be moved up the airways towards throat, mouth, and nose and subsequently expelled as sneeze, spit, cough etc. They can also be swallowed and pass through the digestion.

However some tubercle bacilli penetrate beyond the airways into the alveolar sacs of the lungs. Once there the bacilli are usually engulfed by alveolar macrophages cells, which are able digest bacterium. This is known as the process of phagocytosis.

Once inside the macrophages bacilli are subjected destruction via a number of responses.

• Phagosome-lysosome fusion
• Generation of reactive intermediates and nitrogen intermediates

However the tubercle bacilli resist this digestion and start multiplying inside the phagocytes. Some of these phagocytic cells may eventually migrate to the mucus layer where the bacilli are carried out of the body but other carry them to various parts of the lung, lymph of a nearby lymph nodes or even into the blood stream to other site e.g. lung apices, bone marrow, kidney, meninges.

Within several weeks of the initial exposure to infection, tubercle, a hard swelling, is formed in the alveolar sac, as macrophages containing the tubercle bacilli clump together. As these macrophages are joined by other white blood cells, the clump grows larger and destroys surrounding lung tissues. If cells inside the tubercle die, they form caseous, which supports the growth of tubercle bacilli. At the same time the tough scar tissue surround the tubercle and decrease the amount of oxygen and prevents further growth of the bacilli. These bacilli however remain alive but inactive.

In recent studies cytokines have, addition to activation of macrophages, proved to be able to kill Mycobacteria directly through cytotoxic T-lymphocyte activity.

Symptoms

Neither pulmonary nor extrapulmonary tuberculosis display any definite symptoms. In the past TB was called “consumption” because the sufferers appear as if they are “consumed” from within.

The following symptoms may be the only indication to the patient of the progression of Tuberculosis.

• Prolonged cough [more than 3 weeks]
• Cough sputum containing mucus, pus and/or blood
• Fatigue
• Weight loss
• Loss of appetite
• Night sweats
• Chills
• Fever
• Acute influenza like illness
• Rapid heart beat
• shortness of breath
• chest pain
• Erythema nodosum
• Swelling in the neck {when lymph nodes in the neck are infected}

Burning on urination

• Blood and white cells in the urine

Acute or chronic fever

• Headache
• Irritability
• Malaise

Diagnosis

As tuberculosis does not display any specific symptom it is quite hard for physicians to diagnose patients with the disease. Initial medical history of the patient is taken to find any suspected TB symptoms e.g. prolonged cough, loss of appetite, fatigue etc. Following medical history, upon physical examination of the lungs an experience doctor should identify the crackle noise in the chest, pleural effusion.

Tuberculosis should also be suspected when a persistent respiratory illness in an otherwise healthy individual does not respond to regular antibiotics.

If TB is suspected in a patient, doctors advice the tuberculin skin test. If positive this test indicates that the patient has been infected with the tubercle bacilli irrespective of time i.e. whether the TB is active or latent cannot be confirmed based on this test.

If the result of the skin test is positive, patient is sent for a chest x-ray. X-ray shows the presence of tubercle or any other signs of TB in the lungs.

The last and final test of diagnosis of pulmonary TB is a sputum smear. Sputum of the patient is strained with chemicals to make any bacilli visible. If presence of bacilli is found, it is then culturedto determine whether they are Mycobacterium tuberculosis or other bacilli. By doing sensitivity test on these culture doctors can also determine the most effective medicine against these bacteria. Even if the sputum smear is negative, TB can only be ruled out if the culture is also negative.

Culture, biopsy, CAT scan and MRI can diagnose extrapulmonary disease. For example:

• Biopsy of affected area is examined for TB causing bacteria
• CAT scan show whether miliary TB has spread through out the body
• MRI shows TB in the brain or spine
• Urine culture detects renal TB
• Cerebrospinal fluid is tested for Meningitis TB

Treatment

Until the mid 20th century, the sole treatment for TB was long period isolation in sanatoriums. It was believed that the clean, cold air, abundant food and enforced rest stopped the spread of the disease and healed the lungs. Sometimes this treatment reinforced not only to help cure the disease but also control it’s spreading.

Even today there is no single specific cure for TB. New antibiotics are used to control and cure TB in a measured way. The exact drugs and length of treatment depends on the patients’ age, overall heath, the results of susceptibility and whether they have the TB infection or active TB disease.

As the TB bacteria grows slowly, the treatment becomes and long and lengthy process, 6 to 12 months. After a few weak of medication, patient becomes non-contagious and starts to feel better. However it is very important that they continue with full course medicine as partial/ improper use of antibiotics may lead to multidrug-resistant TB bacteria, greatly reducing the chance of being cured.

Using preventive drug therapy to destroy dormant bacteria that might become active in the future treats latent TB infection. Patient is given a daily dose of isoniazid for 6 months.

The short standard treatment for active pulmonary TB is isoniazid, rifampicin, pvrazinamide and ethambutol for 2 months and then isoniazid and ridampicin for another four months. After the 6-month course patient is considered to be cured.

However depending upon the result of susceptibility test and drug resistance ability medication may be changed or stopped after a few months.

Once treatment starts, sputum smears are done regularly to examine the improvement in individuals.

Surgery is only used to when patient with multi-drug resistant TB bacteria does not respond effectively to the treatment. A patient, who has TB culture result positive after many months of treatment, may be referred for lobectomy or peumonoectomy, where the infected tissue is surgically removed.

Majority of TB relapses occur within 6 months of finishing treatment. Patients that took medication irregularly are more likely to relapse. However studies show most of patients who relapse do so with fully sensitive strain and is possible that these patients have not relapsed but perhaps has been re-infected. Such patients can be re-treated with the same medication regimen as before.

Side Effects of Tuberculosis Medication

• Jaundice/ hepatitis
• Persistent itchiness
• Upset stomach
• Nausea
• Loss of appetite
• Pins and needles, numbness or tingling in the hands or feet
• Rash, bruising or yellowing of the skin
• Dark colour urine [orange/ red]
• Tenderness/ soreness in abdomen
• Blood in urine
• Blurred vision/ coloured blindness

Side Effects of Specific TB Medication

• Isoniazid –
  • Tired or nauseous or loss of appetite
  • Numbness or tingling in your hands or feet
• Rifampicin –
  • Reduces the effectiveness of the contraceptive pill
  • It can stain lens implants and contact lenses
• Ethambutol –
  • Cause visual problems
• Pyrazinamide –
  • Nausea and a loss of appetite
  • Unexplained rashes, fever, aches or joint pains

Prevention

1. The Bacillus Calmette-Guérin vaccination is used in many part of the world. It prevents the spread of TB bacteria in babies but does not prevent the infection.
2. Preventive therapy is used for people at risk of developing active TB disease before they become affected. It is of significant importance to people with:
   1. Latent TB
      1. Lose contact with infectious pulmonary TB patient
      2. At risk of / are HIV infected
      3. Medical conditions known to increase risk of TB e.g. renal disease
3. Ultraviolet overhead light used to help prevent the spread of disease at hospital where non-infected people come in contact with contagious TB patients

Control

1. Screening to identify persons who have active TB disease or latent TB infection
2. People who have suspected or confirmed TB disease/ infection should be identified promptly and initiate appropriate medical treatment
3. People suspected of having infectious TB disease should be placed immediately in an appropriate TB isolation room
4. People infected with M. tuberculosis, especially those in high-risk groups, should have a thorough medical evaluation and preventive therapy when appropriate. Preventive therapy should be directly observed.
5. People who are careless about taking their medication and risk the chance of creating multi-drug resistant TB bacteria should contact the Directly Observed Therapy Short-course [DOTS] program, where a heath care professional administrate the drugs so the patients don’t have to remember to take it on their own

Treatment and prevention has greatly reduced the number of tuberculosis cases in developed countries. But it still remains as a major problem in homeless people and third world countries.