PULMONARY TUBERCULOSIS
الدكتور خلدون ذنون- كلية طب نينوى- المرحلة الرابعةObjectives 1. Incidence is increasing in both developed and developing countries.
2. Tuberculosis is an infectious disease and involves the lungs and other
organs as well.
3. Differences between primary and post primary pulmonary TB should be known regarding pathology, clinical picture and outcome
4. Student should recognize TB meningitis, Miliary TB and cryptic
tuberculosis.
5. TB should be suspected in any patient with pyrexia of unknown origin
and ill health.
6. Radiological features of TB should be known.
7. Pulmonary complications of TB must be recognized.
8. Methods of diagnosis is quite important.
9. Student should know drug regimen of treatment, its duration and the
common side effects of antiTB drugs. He should understand
chemoprophylaxis.
10. Drug resistance is a major problem, its avoidance and management is
vital.
11. TB is a curable disease but if diagnosis is missed or delayed it may
Prove fatal and carries a lot of complications.
Epidemiology
Most common infectious disease, 1.5 million deaths in 2006.
10 million new cases in 2005, mainly in Africa & Asia.
Increased incidence in developed countries due to HIV &immigration.
Increased incidence in developing countries due to increased number of population, HIV, poor socioeconomic condition&drug resistance.
Risk factors of TB
Age: children >adults. Elderly>adults.
Immigrants from high prevalence countries.
Contact with smear positive cases.
CXR self healed TB.
Associated diseases e.g HIV, silicosis, immunocompromised,
Malignancy, type 1 DM, chronic renal failure, hypochlorhydria,
malnutrition, malabsorption, vitamin A, D deficiency.
Types of M.O
Human mycobacteria, Mycobacterium bovis(cattle), environmental (atypical) mycobactria. M. bovis due to drinking non- sterilized milk.Site
Pulmonary, lymph nodes, soft tissue & skin, disseminated, other organs.
Pathology & pathogenesis of Primary tuberculosis
Droplet infection.Small subpleural lesion (Ghons focus) with regional hilar lymphadenopathy form primary complex.
At 2-4 weeks cell mediated immunity starts which destroys macrophages containing bacilli & result in tissue necrosis& caseation.
Macrophage activated in to epitheloid cells with granuloma formation at the periphery of caseation.
Bacilli can multiply rapidly or remain inactive.
90% of primary complex heals spontaneously in 1-2months, healing is by fibrosis and calcification.
10% multiplication of bacilli continue & result in local spread or dissemination i.e miliary&TB meningitis.
Foci of infection in different organs progress to clinical disease after variable times e.g lung, bone, GIT, renal etc.
Pathology &pathogenesis of post primary tuberculosis
Occur due to reactivation or re- infection > 3 years from time of infection.
90% develop latent infection with +ve tuberculin or CXR.
5-10% of them reactivate resulting in post primary TB.
Re-exposure to smear +ve pulmonary TB. May result in post primary TB.in 1/3 of all cases.
Likelihood of infection increases in HIV patient.
Clinical features of primary pulmonary TB
History of contact with active pulmonary TB.Infection lasts 4-8weeks, asymptomatic , few develop self limiting febrile illness. Positive tuberculin test.
Disease may progress initially or after latent period.
Unilateral hilar, paratrachial or mediastinal LAP. Lead to collapse, consolidation of mainly right middle lobe. Obstructive emphysema. Cavity is rare.
Some develop endobronchial extension.
Hypersensitivity reaction e.g erythema nodosum, phlyctenular conjunctivitis, dactylics.
Miliary TB & meningitis (complication of primary TB)
It is a form of primary TB
2-3 weeks fever, night sweats, anorexia , weight loss & dry cough.
Hepatosplenomegaly.
Headache with TB. Meningitis.
Auscultation: normal, later: wide spread crackles.
Fundoscopy: choroidal tubercles 5-10%.
CXR: diffuse bilateral fine 1-2 mm. Millet seeds lesions.
Anemia, leucopenia.
Cryptic miliary TB
Elderly>60Y
Intermittent low grade fever(puo).
Unexplained weight loss, general debility.
Hepatosplenomegaly 25-50%.
Normal CXR, leukemoid reaction, pancytopenia, negative tuberculin test.
Diagnosis: liver or bone marrow biopsy show granuloma and positive acid fast bacilli (AFB).
Features of post primary pulmonary TB
Insidious course over several weeks.
Usually in adults, cough, haemoptysis, dysnea, anorexia, weight loss, fever, night sweats & general debility.
May present as PUO, unresolved pneumonia, pleural effusion, spontaneous pneumothorax.
May be asymptomatic discovered by CXR.
Auscultation: normal or local signs.
Early CXR: ill defined opacity in upper lobes ( oxygen favors growth of TB bacilli. Two or more areas involved & may be bilateral. Later: consolidation, collapse, cavitation.
Chronic complications of TB
1. Pulmonary Massive haemoptysis, core pulmonale, lung fibrosis, empyema, aspergilloma, lung & pleural calcification, obstructive airway disease, bronchiectasis, bronchopleural fistula.
2. Non pulmonary and extra- pulmonary
Empyema necessitans, laryngitis, anorectal disease, enteritis,Amyloidosis, polyarithritis. Lymphadenitis, GIT, pericardial, CNS,
Bone & joints, genitourinary.
Investigations
Chest X-ray features:
Primary Gohns complex: hilar lymph node shadow with subpleural small opacity or calcification.
Apical lung opacity unilateral or bilateral, cavity formation indicate active disease, calcification.
Miliary shadowing indicates active disease also.
Pneumonic consolidation.
Collapse: lung, lobe, segment. Tracheal and mediastinal shift.
Obstructive emphysema.
Bronchiectasis and honey combing.
Extensive fibrosis.
Pleural effusion and empyema.
Differential diagnosis of pulmonary TB. In CXR
Pneumonia ( lung abscess
Bronchogenic CA. ( Pulmonary infarct
Wegeners granulomatosis ( Connective tissue disease
Sarcoidosis ( Metastasis to the lung
Pneumoconiosis ( Histoplasmosis
Direct microscopy of samples using Ziehl-Neelsen & Auramine stain to detect acid and alcohol fast bacilli AFB.
Sputum examination: can be induced by hypertonic normal saline. Three early morning samples.
Gastric washing in children.
Broncho-alveolar lavage and transbronchial biopsy.
Culture
Solid media: Lowenstein-jensen media need 4-6 weeks.Liquid media, faster , need 1-3 weeks. Example: radioactive BACTEC system measures liberation of 14CO2 from the media.
Drug susceptibility profile using BACTEC system. Not indicated in all cases but in:
Previous TB
Treatment failure
Chronic disease
In areas of drug resistance
HIV patients.
Molecular DNA technology
Rapid confirmation at low cost.
Nucleic acid amplification like polymerase chain reaction PCR. It detects active TB.
Detection of drug resistance e.g rpo gene in rifampicin resistance.
Finger printing of isolates with restriction-fragment length polymorphism RELP, or PCR to detect common source of infection.
Tuberculin skin test
Low sensitivity & specificity, useful in primary TB & deep seatedinfection.
ESR, CRP are nonspecific, blood count.
Therapeutic trails in difficult to diagnose cases by giving anti TB drugs for 5-10 days.Chemotherapy of TB
First line drugs rifampicin, INH, ethambutol, pyrazinamide, streptomycin,rifabutin, thiacetazone (bacteriostatic).
Second line drugs clarithromycin, ciprofloxacin, ethionamide, cycloserine,
capreomycin, PAS.
INH: (Cell wall synthesis), Peripheral neuropathy (PN), hepatitis, rash.
Rifampicin: (DNA transcription), fever, hepatitis, rash,GIT disturbance.
Pyrazinamide: Hepatitis,GITdisturbance, hyperuricaemia.
Streptomycin: (protein synthesis), 8th n.damage, rash, nephrotoxic
Ethambutol ETB: (cell wall synthesis), retrobulbar neuritis, arthralgia, PN.
Adverse effects: in 10% of patients, more common in HIV patients.
Short course therapy:
Given for new onset uncomplicated pulmonary or extrapulmonary TB.
Initial phase: four drugs (rifampicin, INH, ETB, pyrazinamide) given for two months.
Continuation phase: rifampicin and INH for four months.
Drugs are given as a single daily dose before breakfast.
Longer courses 9-12M: meningeal disease, HIV, drug intolerance, relapse, treatment failure.
Pyridoxine should be given to pregnant and malnourished patients to prevent PN.
Patient is non infectious after 2weeks of quadruple therapy.
Consider comorbidity in drug selection e.g renal, liver disease
eye disease, PN, HIV, drug interaction (rifampicin enzyme inducer
may decrease effect of contraceptive pills).
Base line LFT in liver disease.
During use of rifampicin, INH, ETB, mild increase in liver transaminases is common but serious liver damage is rare.
Rifampicin colours urine &secretions bright orange red.
Decrease dose of ETB in renal failure.
Decrease dose of streptomycin in renal failure &elderly.
Effectiveness of therapy is judged by repeating sputum smear at two and five months, positive smear at 5 months indicates treatment failure.
Treatment given at home.
Indications of admission to hospital:
Uncertain diagnosis.
Complications
Aderse social conditions
Non-compliance
Drug intolerance
Drug resistance
Drug resistance
Drug resistance TB: resistance to any first line agent.
Multidrug resistance TB (MDRTB)
Resistance to at least rifampicin and INH with or without resistance to other agents.
Positive culture after two months on treatment.
Contact with known MDRTB case.
Sensitivity test is needed.
Therapy: Five or more drugs are used for two years.
Extensive drug resistance: resistance to rifampicin, INH, quinolone, and at least one second line agent. More common in those with prior history of TB or HIV, carries high mortality.
Directly observed therapy (DOT)
First line agents given thrice weekly (WHO). The indications are:Non-compliance, alcoholic, injection drug users, mentally ill, past treatment failure, homeless.
Drug resistance
Language difficulties
Developing countries
Indication of steroid therapy in TB
1. Pericarditis & pericardial effusion.
2. TB meningitis
3. pleural effusion
4. Ureteric disease
5. Primary endobronchial disease in children.
6. Severe dissemination
SURGERY: is indicated in:
Massive haemoptysis
Loculated empyema
Constrictive pericarditis
Lymph node suppuration
Cord compression
TB in HIV patient
Infection, progression, reactivation & reinfection are more likely
Decrease in smear +ve rate in pulmonary TB.
Less cavitation .
Atypical CXR.
Increased dissemination.
More extrapulmonary disease.
Greater risk of adverse drug reaction.
TB is a leading cause of mortality in HIV patients.
Control &prevention
Improvement in socioeconomic state & raising health standard.Compulsory notification of all TB cases.
Contact tracing.
Detection of latent TB by tuberculin skin test and other new tests.
BCG
Chemoprophylaxis.
Tuberculin skin test
Low sensitivity & specificity, useful in primary TB & deep seated infection.
Latent TB can be identified by tuberculin skin test that
Prevents infection progressing to clinical disease.
Mantoux test: read in 2-4 days, 10 U of tuberculin injected intradermally, >5 mm induration is positive.
Heaf test: 4 needle pronges injection, grade 1-4, using purified protein derivative (tuberculoprotein), read in 3-7 days. Grade 3-4 need clinical & CXR confirmation.
False negative test: in severe TB, new born, elderly, immunocompromised, malignancy, sarcoidosis
HIV <200 CD4/ml, recent measles disease or vaccine.
False positive test: due to BCG or non-tuberculous mycobacteria.
Interferone gamma release assay: more specific, overcomes false results of tuberculin test, may replace skin test in low incidence-high income countries.
BCG (Bacillus Calmette-Guerin) vaccine
It is mycobacterium bovis live attenuated vaccine, used as intradermal injection.Prevents disseminated and meningeal disease in children.
but its efficacy in adults is debated.
In IRAQ it is given for all newborn infants as TB is endemic.
Its indications vary world-wide according to TB incidence and health-care resources.
It is very safe with occasional local abscess.
Close contacts and high risk individuals should receive BCG vaccine.
It should not be given to pregnant and immunocompromised e.g HIV patients.
Chemoprophylaxis
Rifampicin & INH given for 3 months or INH for 6 months.
Indications are:
Asymptomatic contact with positive tuberculin skin test and normal chest X-ray.
Children <16Y with strong +VE Heaf test.
Children <2Y close contact with smear +VE pulmonary cases.
Babies with mothers having pulmonary TB.
Recent tuberculin conversion
HIV infected smear +ve patients close contacts.
PROGNOSIS
Short course therapy using 4 drugs is curative.Relapse rate <5% usually within 5months after end of therapy.
Death rate is 25% in the first year if untreated.
Mortality is increased in HIV patient mainly due to
superimposed bacterial infection.
Death is due to:
Severe infection e.g miliary,TB meningitis, bronchopneumonia, core pulmonale.
Unexpected death soon after therapy may be due to subclinical hypoadrenalism (rifampicin is enzyme inducer that degrade cortisol?).