At a glance......
- 1 Types of Tuberculosis
- 2 Pathoanatomy/Causes of Tuberculosis
- 3 Symptoms of Tuberculosis
- 4 Diagnosis of Tuberculosis
- 5 Associated diseases
- 6 Distribution
- 7 Treatment of Tuberculosis
- 7.1 First line
- 7.2 Second line
- 7.3 Third line
- 7.4 Latent Tuberculosis
- 7.5 Treatment of Active Infection
- 7.6 First-Line Medications, Group 1
- 7.7 Second-Line Anti-tuberculosis Drugs, Group 2
- 7.8 Second–Line Anti-Tuberculosis Drugs, Group 3, Oral and Injectable Fluoroquinolones
- 7.9 Second-Line Anti-tuberculosis Drugs, Group 4
- 7.10 Third-Line Anti-Tuberculosis Drugs, Group 5
- 7.11 Steroids
- 8 Surgical Technique
- 9 Complications
- 10 References
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Types of Tuberculosis
Active TB Disease
- Active TB is an illness in which the TB bacteria are rapidly multiplying and invading different organs of the body. The typical symptoms of active TB variably include a cough, phlegm, chest pain, weakness, weight loss, fever, chills and sweating at night. A person with active pulmonary TB disease may spread TB to others by airborne transmission of infectious particles coughed into the air. If you are diagnosed with an active TB disease, be prepared to give a careful, detailed history of every person with whom you have had to contact. Since the active form may be contagious, these people will need to be tested, as well.
- Multi-drug treatment is employed to treat active TB disease. Depending on the state or local public health regulations, you may be asked to take your antibiotics under the supervision of your physician or other healthcare professional. This program is called “Directly Observed Therapy” and is designed to prevent abandonment or erratic treatment, which may result in “failure” with a continued risk of transmission or acquired resistance of the bacteria to the medications, including the infamous multi-drug resistant TB (MDR-TB).
- Military TB is a rare form of the active disease that occurs when TB bacteria find their way into the bloodstream. In this form, the bacteria quickly spread all over the body in tiny nodules and affect multiple organs at once. This form of TB can be rapidly fatal.
Latent TB Infection
- Many of those who are infected with TB do not develop overt disease. They have no symptoms and their chest x-ray may be normal. The only manifestation of this encounter may be a reaction to the tuberculin skin test (TST) or interferon-gamma release assay (IGRA). However, there is an ongoing risk that the latent infection may escalate to active disease. The risk is increased by other illnesses such as HIV or medications which compromise the immune system. To protect against this, the United States employs a strategy of preventive therapy or treatment of latent TB infection.
Pathoanatomy/Causes of Tuberculosis
- begins in the metaphysics of the vertebral body
- spreads under the anterior longitudinal ligament and leads to
- contiguous multilevel involvement
- skip lesion or non-contiguous segments (15%)
- paraspinal abscess formation (50%) usually anterior and can be quite large (much more common in TB than pyogenic infections)
- initially does not involve the disc space (distinguishes from pyogenic osteomyelitis, but can be misdiagnosed as a neoplastic lesion)
- mean deformity in nonoperative cases is 15° in 5% of patients, the deformity is >60°
- infection is often diagnosed late, there is often much more severe kyphosis in granulomatous spinal infections compared to pyogenic infections
- in adults kyphosis stays static after healing of disease
- in children, kyphosis progresses in 40% of cases because of a growth spurt
Classification of progression (Rajasekaran)
- Type-I, increase in deformity until the cessation of growth should be treated with surgery
- Type-II, decreasing progression with growth
- Type-III, minimal change during either active / healed phases.
Symptoms of Tuberculosis
Symptoms and signs of tuberculosis
- Cough—usually productive
- Sputum—usually mucopurulent or purulent
- Haemoptysis—not always a feature, volume variable
- Breathlessness—gradual increase rather than sudden
- Weight loss—gradual
- Fever—may be associated with night sweats
- Malaise— the patient may realize only retrospectively when feeling better after treatment
- Wasting and terminal cachexia—late, ominous signs
Although your body may harbor the bacteria that cause tuberculosis, your immune system usually can prevent you from becoming sick. For this reason, doctors make a distinction between:
- Latent TB – In this condition, you have a TB infection, but the bacteria remain in your body in an inactive state and cause no symptoms. Latent TB, also called inactive TB or TB infection, isn’t contagious. It can turn into active TB, so treatment is important for the person with latent TB and to help control the spread of TB. An estimated 2 billion people have latent TB.
- Active TB. This condition makes you sick and can spread to others. It can occur in the first few weeks after infection with the TB bacteria, or it might occur years later.
Signs and symptoms of active TB include:
- Coughing that lasts three or more weeks
- Coughing up blood
- Chest pain, or pain with breathing or coughing
- Unintentional weight loss
- Night Sweats
- Loss of appetite
Tuberculosis can also affect other parts of your body, including your kidneys, spine or brain. When TB occurs outside your lungs, signs, and symptoms vary according to the organs involved. For example, tuberculosis of the spine may give you back pain, and tuberculosis in your kidneys might cause blood in your urine.
Tuberculous spinal infections should be suspected in patients with an insidious, progressive history of back pain and in individuals from an endemic area, especially when the thoracic vertebrae are affected and with a pattern of bone destruction with relative disc preservation and paravertebral and epidural soft tissue masses
- The onset is gradual.
- Back pain is localized.
- Fever, night sweats, anorexia, and weight loss.
- Signs may include kyphosis (common) and/or a paravertebral swelling.
- Affected patients tend to assume a protective, upright, stiff position.
- If there is neural involvement there will be neurological signs.
A psoas abscess may present as a lump in the groin and resemble a hernia
- A psoas abscess most often originates from a tuberculous abscess of the lumbar vertebra that tracks from the spine inside the sheath of the psoas muscle.
- Other causes include extension of renal sepsis and posterior perforation of the bowel.
- There is a tender swelling below the inguinal ligament and they are usually apyrexial.
- The condition may be confused with a femoral hernia or enlarged inguinal lymph nodes.
Diagnosis of Tuberculosis
Tuberculin skin testing: Mantoux test (skin testing with PPD)
The Mantoux reaction following injection of a dose of PPD (purified protein derivative) is the traditional screening test for exposure to Tuberculosis. The result is interpreted taking into consideration the patient’s overall risk of exposure. Patients are classified into 3 groups based on the risk of exposure with three corresponding cut-off points. The 3 major groups used are discussed below.
- Individuals with minimal probability of exposure are considered to have a positive Mantoux test only if there is very significant induration following intradermal injection of PPD. The cut-off point for this group of people (with minimal risk of exposure) is taken to be 15 mm.
- Individuals with intermediate probability are considered positive if the induration is greater than 10 mm.
- Individuals with a high risk of a probability of exposure are considered positive if the induration is greater than 5 mm.
Examples of Patients in the Different Risk Categories
- Low Risk/Low Probability: Patients with no known risk of exposure to TB. Example: No history of travel, military service, HIV-negative, no contact with a chronic cough patient, no occupational exposure, no history of steroids. Not a resident of a TB-endemic region.
- Intermediate Risk/Probability: Residents of TB-endemic countries (Latin America, Sub -Sahara Africa, Asia), workers or residents of shelters, Medical or microbiology department personnel.
- High Risk/Probability: HIV-positive patient, a patient with evidence of the previous TB such as the healed scar on an x-ray), contact with chronic cough patients.
Note that a Mantoux test indicates exposure or latent tuberculosis. However, this test lacks specificity, and patients would require subsequent visits for interpreting the results as well as chest x-ray for confirmation. Although relatively sensitive, the Mantoux reaction is not very specific and may give false positive reactions in individuals who have been exposed to the BCG-vaccine.
Interferon release assays (IGRA, Quantiferon Assays)
- This is a tuberculosis screening test that is more specific and equally as sensitive as the Mantoux test. This test assays for the level of the inflammatory cytokine, especially interferon gamma.
- The advantages of Quantiferon, especially in those with prior vaccination with BCG vaccine, includes, the test requires a single blood draw, obviating the need for repeat visits to interpret results. Furthermore, additional investigations such as HIV screening could be performed (after patient consent) on the same blood draw.
- Quantiferon’s disadvantages include cost and the technical expertise required to perform the test.
Screening in Immunocompromised Patients
- Immunocompromised patients may show lower levels of reaction to PPD or false negative Mantoux because of cutaneous anergy.
- A high level of suspicion should be entertained when reviewing negative screening tests for tuberculosis in HIV-positive individuals.
The Significance of Screening
- A positive screening test indicates exposure to tuberculosis and a high chance of developing active tuberculosis in the future. Tuberculosis incidence in patients with positive Mantoux test averages between 2% to 10% without treatment.
- Patients with a positive test should have a chest x-ray as a minimum diagnostic test. In some cases, these patients should have additional tests. Patients meeting the criteria for latent tuberculosis should receive prophylaxis with isoniazid.
Screening Questionnaires for Resource-Poor Settings
- Several screening questionnaires have been validated to enable healthcare workers working in remote and resource-poor environments screen for tuberculosis.
These questionnaires make use of an algorithm that combines several clinical signs and symptoms of tuberculosis. Some of the commonly used symptoms are:
- A chronic cough
- Weight loss
- Fever and night sweats
- History of contact
- HIV status
- Blood in sputum
Several studies have confirmed the utility of using several criteria rather than a focus on only chronic cough or weight loss.
Confirmatory and Diagnostic Tests
- A chest x-ray is indicated to rule out or rule in the presence of active disease in all screening test positive cases.
- Acid Fast Staining-Ziehl-Neelsen
- Nuclear Amplification and Gene-Based Tests: These represent a new generation of diagnostic tools for tuberculosis. These tests enable identification of the bacteria or bacteria particles making use of DNA-based molecular techniques. Examples are Genexpert and DR-MTB.
The new molecular-based techniques are faster and enable rapid diagnosis with high precision. Confirmation of TB could be made in hours rather than the days or weeks it takes to wait for a standard culture. This is very important, especially among immunocompromised host where there is a high rate of false negative results. Some molecular-based tests such as GeneXpert and DR-MTB also allow for identification of multi-drug resistant tuberculosis.
- Pyogenic osteitis of the spine.
- Spinal tumours.
- neurologic deficits (present in 10-47% of patients with Pott’s Disease)
- mechanical pressure on cord by abscess, granulation tissue, tubercular debris, caseous tissue
- mechanical instability from subluxation/dislocation
- paraplegia from healed disease can occur with severe deformity
- stenosis from ossification of ligamentum flavum adjacent to severe kyphosis
- 66% will have an abnormal CXR
- should be ordered for any patients in which TB is a possibility
- early infection shows involvement of anterior vertebral body with sparing of the disc space (this finding can differentiate from pyogenic infection)
- late infection shows disk space destruction, lucency and compression of adjacent vertebral bodies, and development of severe kyphosis
Risk factors for buckling collapse (“spine at risk signs”)
- lateral translation
MRI with gadolinium contrast
- indications >remains preferred imaging study for diagnosis and treatment diagnose adjacent levels ,multiple levels involved in 16-70%
- low signal on T1-weighted images, bright signal on T2-weighted images
- presence of a septate pre-/ paravertebral / intra-osseous smooth walled abscess with a subligamentous extension and breaching of the epidural space
- end-plate disruption sensitivity 100%, specificity 81%
- paravertebral soft tissue shadow sensitivity 97%, specificity 85%
- high signal intensity of the disc on the T2-weighted image sensitivity 81%, specificity 82%
- demonstrates lesions <1.5cm better than radiographs ,inaccurate for defining epidural extension
- types of destruction ,fragmentary, osteolytic ,subperiosteal ,sclerotic
- CT guided biopsy with cultures and staining effective at obtaining a diagnosis
- should be tested for acid-fast bacilli (AFB) mycobacteria (acid-fast bacilli) may take 10 weeks to grow in culture
- PCR allows for faster identification (95% sensitivity and 93% accuracy) , smear positive in 52% ,culture positive in 83%
Nuclear medicine studies
- obtain with a combination of technetium and gallium
- shown to have the highest sensitivity for detecting infection
- relative lymphocytosis
- low hemoglobin
- Strongly positive Mantoux skin test.
- usually elevated but may be normal in up to 25%
- PPD (purified protein derivative of tuberculin)
- positive in ~ 80%
Other etiologies of granulomatous infection may have a similar clinical picture as TB and include
- Actinomyces israelii
- Nocardia asteroids
- Coccidioides immitis
- Blastomyces dermatitidis
- Cryptococcus neoformans
- Treponema pallidum
- Tuberculosis co-infection with HIV has become common. It is up to 11% in some areas of the UK and over 60% in countries such as Zambia, Zimbabwe and South Africa.
- In the developed world, the disease is more common in certain sections of society, such as those with alcohol dependency, the undernourished, ethnic minority communities and the elderly.
- The disease is also more common in patients after gastrectomy for peptic ulcer.
- The most common area affected is T10 to L1.
- The lower thoracic region is the most common area of involvement at 40-50%, with the lumbar spine in a close second place at 35-45%.
- The cervical spine accounts for about 10%
Treatment of Tuberculosis
|Daily||Twice or thrice weekly|
|Isoniazid||5 mg/kg oral (maximum 300 mg)||900 mg twice weekly|
600 mg thrice weekly
|Hepatitis, peripheral neuritis, drug induced lupus, seizures, and hypersensitivity with rash and fever. Drug interactions with dilantin and disulfiram|
|Rifampicin||10 mg/kg oral (maximum 600 mg)||10 mg/kg|
600 mg twice weekly
600 mg thrice weekly
|Orange body secretions, flu-like syndrome, hepatitis, thrombocytopenia, nausea, anorexia, diarrhoea, renal failure, and multiple drug interactions|
|Pyrazinamide||25-30 mg/kg oral||30-35 mg/kg||Hyperuricemia, hepatitis, rash, nausea, and anorexia|
|Ethambutol||25 mg/kg initial 2 months, then 15 mg/kg oral||50 mg/kg twice weekly|
30 mg/kg thrice weekly
|Optic neuritis and gastrointestinal discomfort|
|Streptomycin||15 mg/kg intravenously or intramuscularly (maximum 1.0 g) 5 days a week||15 mg/kg (maximum 1.5 g) twice weekly or thrice weekly||Ototoxicity, vestibular dysfunction, nephrotoxicity, rash, and hypersensitivity reactions|
All first-line anti-tuberculous drug names have a standard three-letter and a single-letter abbreviation:
- ethambutol is EMB or E,
- isoniazid is INH or H,
- pyrazinamide is PZA or Z,
- rifampicin is RMP or R,
- streptomycin is SM or S.
First-line anti-tuberculous drug names are often remembered with the mnemonic “RIPE,” referring to the use of a rifamycin (like rifampin), isoniazid, pyrazinamide, and ethambutol. The US uses abbreviations and names that are not internationally recognised: rifampicin is called rifampin and abbreviated RIF; streptomycin is abbreviated STM. In the US only, streptomycin is no longer considered a first line drug by ATS/IDSA/CDC because of high rates of resistance. The WHO have made no such recommendation.
The second line drugs (WHO groups 2, 3 and 4) are only used to treat disease that is resistant to first line therapy (i.e., for extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB)).A drug may be classed as second-line instead of first-line for one of three possible reasons: it may be less effective than the first-line drugs (e.g., p-aminosalicylic acid); or, it may have toxic side-effects (e.g., cycloserine); or it may be effective, but unavailable in many developing countries (e.g., fluoroquinolones):
- aminoglycosides (WHO group 2): e.g., amikacin (AMK), kanamycin (KM);
- polypeptides (WHO group 2): e.g., capreomycin, viomycin, enviomycin;
- fluoroquinolones (WHO group 3): e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF);
- thioamides (WHO group 4): e.g. ethionamide, prothionamide
- cycloserine (WHO group 4)
- terizidone (WHO group 5)
Third-line drugs (WHO group 5) include drugs that may be useful, but have doubtful or unproven efficacy:
- macrolides: e.g., clarithromycin (CLR);
- linezolid (LZD);
- thioacetazone (T);
- vitamin D;
These drugs are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid, R207910). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive.
Drug of choice is isoniazid. It is usually given with vitamin B6, pyridoxine (to prevent nerve damage). Isoniazid is recommended for Mantoux or quantiferon positive individuals and should be continued for 6 or 9 months.
The WHO recommends the following treatment regimen for treating latent tuberculosis:
- 6-month or 9-month isoniazid daily
- 3-month rifapentine plus isoniazid weekly
- 3-month or 4-month isoniazid plus rifampicin daily
- 3–month or 4-month rifampicin alone daily
Treatment of Active Infection
- Treatment of confirmed TB requires a combination of drugs. Combination therapy is always indicated, and monotherapy should never be used for tuberculosis. The most common regimen for TB includes the following anti-TB medications:
First-Line Medications, Group 1
Isoniazid and Rifampicin follow a 4-drug regimen (usually including Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide) for 2 months or six months. Vitamin B6 is always given with Isoniazid to prevent neural damage (neuropathies).
Several other antimicrobials are effective against tuberculosis including the following categories:
Second-Line Anti-tuberculosis Drugs, Group 2
Injectables aminoglycosides and injectable polypeptides
Second–Line Anti-Tuberculosis Drugs, Group 3, Oral and Injectable Fluoroquinolones
Second-Line Anti-tuberculosis Drugs, Group 4
- Para-aminosalicylic acid
Third-Line Anti-Tuberculosis Drugs, Group 5
These are medications with variable but unproven efficacy against TB. They are used for total drug-resistant TB as drugs of last resort.
- Amoxicillin/clavulanic acid
- Multi-drug resistant TB is becoming increasingly common.
- The combination of first-line and second-line medications are used at high doses to treat this condition.
- On December 28, 2012, the United States Food and Drug Administration Agency (FDA), approved Bedaquiline as a drug for treating MDR-TB. This is the first FDA approval for an anti-TB medication in 40 years. While showing remarkable promise in drug-resistant tuberculosis, cost remains a big obstacle to delivering this drug to the people most affected by MDR-TB.
Clinical and Laboratory Monitoring
- Liver function test is required for all patients taking isoniazid. Other monitoring in TB includes monitoring for retinopathies for patients on ethambutol.
- The usefulness of corticosteroids (e.g., prednisolone or dexamethasone) in the treatment of TB is proven for TB meningitis and TB pericarditis. The dose for TB meningitis is dexamethasone 8 to 12 mg daily tapered off over six weeks (for those who prefer more precise dosing should refer to Thwaites et al., 2004). The dose for pericarditis is prednisolone 60 mg daily tapered off over four to eight weeks.
Steroids may be of temporary benefit in pleurisy, extremely advanced TB, and TB in children:
- Pleurisy: prednisolone 20 to 40 mg daily tapered off over 4 to 8 weeks
- Extremely advanced TB: 40 to 60 mg daily tapered off over 4 to 8 weeks
- TB in children: 2 to 5 mg/kg/day for one week, 1 mg/kg/day the next week, then tapered off over 5 weeks
Steroids may be of benefit in peritonitis, miliary disease, tubercular osteomyelitis, TB osteomyelitis, laryngeal TB, lymphadenitis and genitourinary disease, but the evidence is scant and the routine use of steroids cannot be recommended. Steroid treatment in these patients should be considered on a case by case basis by the attending physician.
Thalidomide may be of benefit in TB meningitis and has been used in cases where patients have failed to respond to steroid treatment.
Some supplements may be useful as adjuncts in the treatment of tuberculosis, but for the purposes of counting drugs for MDR-TB, they count as zero (if you already have four drugs in the regimen, it may be beneficial to add arginine or vitamin D or both, but you still need another drug to make five).
- arginine, some clinical evidence (peanuts are a good source)
- Vitamin D, (some in-vitro evidence & see Vitamin D and tuberculosis treatment )
The drugs listed below have been used in desperation and it is uncertain whether they are effective at all. They are used when it is not possible to find five drugs from the list above.
On December 28, 2012, the U.S. Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multi-drug resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.
The follow drug is experimental compounds that are not commercially available, but which may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown:
- Pretomanid (manufactured by Novartis, developed in partnership with TB Alliance)
There is increasing evidence for the role of surgery (lobectomy or pneumonectomy) in the treatment of MDR-TB, although whether this is should be performed early or late is not yet clearly defined.
Anterior decompression/corpectomy, strut grafting ± posterior instrumented stabilization ± posterior column shortening
- indications for kyphosis with active disease
Techniques for single-stage transpedicular 2-stage
- anterior decompression with bone grafting
- posterior kyphosis correction and instrumentation
- single-stage extrapleural anterolateral
Anyone can get tuberculosis, but certain factors can increase your risk of the disease. These factors include:
Weakened immune system
A healthy immune system often successfully fights TB bacteria, but your body can’t mount an effective defense if your resistance is low. A number of diseases and medications can weaken your immune system, including:
- Severe kidney disease
- Certain Cancers
- Cancer treatment, such as chemotherapy
- Drugs to prevent rejection of transplanted organs
- Some drugs used to treat rheumatoid arthritis, Crohn’s disease and psoriasis
- Very young or advanced age
- the highest risk after anterior decompression and grafting alone slippage and breakage of the graft (especially if ≥ 2 levels)
- the lowest risk after both anterior and posterior fusion
- Retropharyngeal abscess affects swallowing/hoarseness
- TB arteritis and pseudoaneurysm
- Respiratory compromise if there is costopelvic impingement
- Sinus formation
- Pott’s paraplegia spinal cord injury can be caused by abscess/bony sequestra or meningomyelitis
- abscess/bony sequestra have a better prognosis than meningomyelitis as the cause of spinal cord injury
- definition of compressive myelopathy without visible spinal deformity, without the typical radiological appearance
- etiology intraspinal granuloma, neural arch involvement, concertina collapse of vertebral body, sclerotic vertebra with bridging of the vertebral body
- indications extradural extraosseous granuloma & subdural granuloma
Decompression and myelotomy
- indications intramedullary granuloma
Traveling or living in certain areas
The risk of contracting tuberculosis is higher for people who live in or travel to countries that have high rates of tuberculosis and drug-resistant tuberculosis, including:
- Eastern Europe
- Latin America
- Caribbean Islands
Poverty and substance abuse
- Lack of medical care – If you receive a low or fixed income, live in a remote area, have recently immigrated to the United States, or are homeless, you may lack access to the medical care needed to diagnose and treat TB.
- Substance abuse – IV drug use or alcohol abuse weakens your immune system and makes you more vulnerable to tuberculosis.
- Tobacco use – Using tobacco greatly increases the risk of getting TB and dying of it.
Where you work or live
- Health care work – Regular contact with people who are ill increases your chances of exposure to TB bacteria. Wearing a mask and frequent hand-washing greatly reduce your risk.
- Living or working in a residential care facility – People who live or work in prisons, immigration centers or nursing homes are all at a higher risk of tuberculosis. That’s because the risk of the disease is higher anywhere there is overcrowding and poor ventilation.
- Living in a refugee camp or shelter – Weakened by poor nutrition and ill health and living in crowded, unsanitary conditions, refugees are at especially high risk of tuberculosis infection.