Introduction
Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis.
It is an aerobic, Acid Fast Bacilli (mycolic acid on the cell wall)
Epidemiology Asia>Africa>Middle East>Latin America
Transmission via droplet nuclei (coughing, sneezing or speaking).
3000 infectious nuclei/cough in a sputum positive case.
Sputum contains 105–107 AFB/mL.
Each AFB positive case can infect 20 contacts.
Other organisms are-
M. bovis (unpasturised milk)
M. caprae (related to M. bovis)
M. africanum (isolated from cases in West, Central, and East Africa)
M. microti (the "vole" bacillus, a less virulent and rarely encountered organism)
Fatal if untreated, 5 year mortality 65%.
Estimated numbers of tuberculosis-related deaths in 2005.
Pathogenesis
Inhalation M. tuberculosis which reach alveoli.
Phagocytosis by alveolar macrophages,
Impaired fusion of phagosome-lysosome, bacteria multiplies in the macrophage,
Macrophage dies and rupture releasing chemoattractants,
Additional immature monocyte and dendritic cells recruitment, and migrate to the local lymph node to present antigen of the M. tuberculosis.
1. beginning of CMI and 2. Tissue damage response (DTH)
Either granuloma formation and calcification giving rise to Ghon focus or
Lung tissue destruction leading to progressive primary tuberculosis.
Ghon complex- Unilateral enlarged hilar lymph nodes + ghon focus- epitheloid cell granulomatous infalmation (consolidation) at site of paranchymal infection.
Bacteria may disseminate from the local lymph nodes (hilar or paratracheal) to the blood which leads to severe infection like fatal miliary TB or tubercular meningitis.
Time table of TB
Factors increasing the risk of TB
Patient-related
Age (children > young adults < elderly)
First-generation immigrants from high-prevalence countries
Close contacts of patients with smear-positive pulmonary tuberculosis
Overcrowding: prisons, collective dormitories
Chest radiographic evidence of self-healed tuberculosis
Primary infection < 1 year previously
Associated diseases
Immunosuppression-HIV, infliximab, high-dose corticosteroids, cytotoxic agents
Malignancy (especially lymphoma and leukaemia)
Type 1 diabetes mellitus
Chronic renal failure
Silicosis
Gastrointestinal disease associated with malnutrition (gastrectomy, jejuno-ileal bypass, cancer of the pancreas, malabsorption)
Deficiency of vitamin D or A
Clinical features of primary tuberculosis
Infection (4-8 weeks)
Influenza-like illness
Skin test conversion
Primary complex
Disease
Lymphadenopathy (hilar-often unilateral, paratracheal or mediastinal)
Collapse (especially right middle lobe)
Consolidation (especially right middle lobe)
Obstructive emphysema
Cavitation (rare)-(progressive primary tuberculosis).
Pleural effusion
Endobronchial
Miliary
Meningitis
Pericarditis
Hypersensitivity
Erythema nodosum
Phlyctenular conjunctivitis
Dactylitis
Miliary TB
Blood borne dissemination
Characterised by 2-3 weeks of fever, night sweats, anorexia, weight loss and a dry cough.
Hepatosplenomegaly,
Auscultation- usually normal, crackles in advanced cases.
Fundoscopy- choroidal tubercles
CXR- classical appearance of miliary shadow
Anemia and leucopenia.
Postprimary PTB/ Secondary TB
Also called adult-type, reactivation, or secondary tuberculosis.
Postprimary disease results from endogenous reactivation of latent infection.
Localized to the apical and posterior segments of the upper lobes (high oxygen tension)
In addition, the superior segments of the lower lobes are frequently involved.
The extent of lung parenchymal involvement varies greatly, from small infiltrates to extensive cavitary disease.
With cavity formation, liquefied necrotic contents are ultimately discharged into the airways, resulting in satellite lesions within the lungs that may in turn undergo cavitation.
Massive involvement of pulmonary segments or lobes, with coalescence of lesions, produces tuberculous pneumonia.
Chest radiograph showing a right upper-lobe infiltrate and a cavity with an air-fluid level in a patient with active tuberculosis.
Clinical features
Systemic symptoms include fever, night sweats, malaise, loss of appetite and weight, and are accompanied by progressive pulmonary symptoms
Progressive pulmonary symptoms
Chronic cough, often with haemoptysis
Pyrexia of unknown origin
Unresolved pneumonia
Exudative pleural effusion
Asymptomatic (diagnosis on chest X-ray)
Weight loss, general debility
Spontaneous pneumothorax.
Extrapulmonary TB
The extrapulmonary sites most commonly involved in tuberculosis are:
the lymph nodes,
pleura,
gastrointestinal,
genitourinary tract,
bones and joints,
meninges,
peritoneum, and
pericardium.
Virtually all organ systems may be affected.
As a result of hematogenous dissemination in HIV-infected individuals, extrapulmonary tuberculosis is seen more commonly today than in the past.
Lymphadenitis
The most common extrapulmonary site of disease.
Cervical and mediastinal glands are affected most frequently.
Supraclavicular lymph node are also affected and usually painless, initially mobile but become matted together with time.
When caseation and liquefaction occur, the swelling becomes fluctuant and may discharge through the skin with the formation of a 'collar-stud' abscess and sinus formation.
Tuberculin skin test is usually strongly positive.
Pleural TB
Involvement of the pleura is common in primary tuberculosis and may result from either contiguous spread of parenchymal inflammation or, as in many cases of pleurisy accompanying postprimary disease.
The fluid is straw-colored and at times hemorrhagic;
it is an exudate with a protein concentration >50% of that in serum (usually ~4–6 g/dL),
a normal to low glucose concentration,
a pH of ~7.3 (occasionally <7.2), and
detectable white blood cells (usually 500–6000/L). Neutrophils may predominate in the early stage, while mononuclear cells are the typical finding later.
AFB are seen on direct smear in only 10–25% of cases,
Cultures may be positive for M. tuberculosis in 25–75% of cases.
Tuberculous empyema is a less common complication of pulmonary tuberculosis.
Gastrointestinal TB
Ileoceceal disease most common (as right iliac fossa mass)
May present with acute abdomen,
USG and CT- thick bowel wall, abdominal lymphadenopathy, mesentric thickening or ascitis.
Barium enema or small bowel enema- narrowing shortening and distortion of bowel with caecal involvement.
Laparoscopy- multiple white tubercles over the peritoneal and omental surface.
D/d is Crohn’s disease.
Pericardial disease
Two main forms present:
Pericardial effusion and constrictive pericarditis.
Other features: breathlessness, abdominal swelling, pulsus paradoxus, raised JVP, hepatomegaly, prominent ascitis, absence of peripheral edema is common in both.
Pericardial effusion (blood stained in 85% cases)
Coexistent pulmonary disease is rare.
Diagnosis: Open pericardial biopsy
Corticosteroid with anti-TB chemotherapy has been beneficial.
CNS disease
TB meningitis is the most common form.
Rapidly fatal if not diagnosed or untreated.
Mortality rate 30% even after treatment.
Clinical features:
Symptoms
Headache
Vomiting
Low-grade fever
Lassitude
Depression
Confusion
Behaviour changes
Signs
Meningism (may be absent)
Oculomotor palsies
Papilloedema
Focal hemisphere signs
Depression of conscious level
Treatment: anti-TB, adding corticosteroid has been controversial.
Bone and joint disease
Most common site- spine (pott’s disease) usually presents with chronic back pain and involve lower thoracic and lumbar spine.
Starts as discitis and spreads along the spinal ligament to involve the adjecent anterior vertebral bodies with subsequent kyphosis.
Leads to paravertebral and psoas abscess formation. May present with large abscess in the inguinal region (cold abscess)
Diagnosis: CT scan- extent of disease, amount of cord compression, needle biopsy or open exploration.
Complication- cord compression, spinal instability.
Hip and knee joint are the commonly affected joints.
Genitourinary disease
Fever and night sweats are rare with renal tract TB.
Only mildly symptomatic
Hematuria, fequency and dysuria often present.
Sterile pyuria- in urine microscopy and culture.
Infertility in women- endometritis.
In men- TB Epididymitis or prostatitis
Diagnosis of TB
Specimen
Respiratory
Sputum* (induced with nebulised hypertonic saline if not expectorating)
Gastric washing* (mainly used for children)
Bronchoalveolar lavage
Transbronchial biopsy
Non-respiratory
Fluid examination (cerebrospinal, ascitic, pleural, pericardial, joint)
Tissue biopsy (from affected site; also bone marrow/liver may be diagnostic in patients with disseminated disease
Diagnostic test
Circumstantial (ESR, CRP, anaemia etc.)
Tuberculin skin test (low sensitivity/specificity; useful only in primary or deep-seated infection)
Stain
Ziehl-Neelsen
Auramine fluorescence
Nucleic acid amplification
Culture
Solid (Löwenstein-Jensen, Middlebrook)
Liquid (e.g. BACTEC)
Response to empirical antituberculous drugs (usually seen after 5-10 days)
Skin testing
Mantoux test
Read at 2-4 days
Using 10 tuberculin units
Positive when induration 5-14 mm (equivalent to Heaf grade 2) and > 15 mm (Heaf grade 3-4)
False negatives
Severe TB (25% of cases negative)
Newborn and elderly
HIV (if CD4 count < 200 cells/ml)
Recent infection (e.g. measles) or immunisation
Malnutrition
Immunosuppressive drugs
Malignancy
Sarcoidosis
Treatment
First line
Ethambutol E,
isoniazid H,
pyrazinamide Z,
rifampicin R,
streptomycin S.
Second line
aminoglycosides: e.g., amikacin, kanamycin;
polypeptides: e.g., capreomycin, viomycin, enviomycin;
Fluoroquinolones: e.g., ciprofloxacin, levofloxacin, moxifloxacin;
thioamides: e.g. ethionamide, prothionamide
cycloserine (the only antibiotic in its class);
p-aminosalicylic acid.
Chemotherapy recommended by WHO
Drug-resistant tuberculosis (MDR- and XDR-TB)
Definitions
Multi-drug resistant tuberculosis (MDR-TB) is defined as TB that is resistant at least to INH and RMP. Isolates that are multiply resistant to any other combination of anti-TB drugs but not to INH and RMP are not classed as MDR-TB.
As of Oct 2006, "Extensively drug-resistant tuberculosis" (XDR-TB) is defined as MDR-TB that is resistant to quinolones and also to any one of kanamycin, capreomycin, or amikacin.
The old case definition of XDR-TB is MDR-TB that is also resistant to three or more of the six classes of second-line drugs.
Treatment of MDR-TB
When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities):
an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin)
PZA
EMB
a fluoroquinolones: moxifloxacin is preferred (ciprofloxacin should no longer be used[62]);
rifabutin
cycloserine
a thioamide: prothionamide or ethionamide
PAS
a macrolide: e.g., clarithromycin
linezolid
high-dose INH (if low-level resistance)
interferon-γ
thioridazine
meropenem and clavulanic acid
