PULMONARY TUBERCULOSIS Flashcards
What is TB?
Tuberculosis (TB) is a chronic infectious
disease cause by Mycobacterium tuberculosis complex
• It is one of the oldest diseases known to affect humans
• It typically affects the lungs (pulmonary TB), although other organs are involved in up to one-third of cases (extrapulmonary TB)
Epidemiology
What % of people are infected with TB globally?
About 25% of people are infected with
Mycobacterium tuberculosis globally
• Only 5-10% of these people will develop TB disease during their lifetime
• TB is the 13th leading cause of death
worldwide
• It is the 2nd leading cause of death from a
single infectious agent (after COVID-19),
ranking above HIV/AIDS.
• In 2020 1.5 million people died of TB
(including 214,000 PLWHIV)
• An estimated 10 million (M) people (5.6M
males, 3.3M females &1.1M children) fell ill
with TB.
• In the same year, 8 countries accounted for 2/3 of the world’s new TB cases with India being 1st and Nigeria being 6th.
• Nigeria has an incidence rate 219/100,000.
CAUSATIVE ORGANISM and its characteristics
• Tuberculosis is caused by M. tuberculosis
complex
• M. tuberculosis is the most common and
important agent of human disease among the pathogenic species belonging to the M.
tuberculosis complex
• M. tuberculosis is a rod-shaped, nonspore-forming, thin aerobic bacterium measuring
0.5µm by 3µm.
• Often neutral on Gram’s staining.
• However, once stained, the bacilli cannot be decolorized by acid alcohol; hence acid-fast bacilli(AFB).
• Acid fastness is due mainly to the organisms’ high content of mycolic acids, long-chain cross-linked fatty acids, and other cell-wall lipids.
Other members of the complex includes;
– M. bovis,
- M. microti - M. mungi
– M. caprae,
- M. pinnipedii -M. orygis
– M. africanum,
- M. canetti
RISK FACTORS
• Age (commoner in children and elderly)
• Close contacts of patients with smear-positive pulmonary TB
• Overcrowding (prisons & dormitories)
• Cigarette smoking
• Malnutrition
• Deficiency of vitamin D or A
• Recent infection (<1 year)
• Immunosuppression: HIV, anti-tumour necrosis factor (TNF) therapy, high-dose corticosteroids, cytotoxic agents
• Malignancy (especially lymphoma and leukaemia)
• Diabetes mellitus
• Chronic kidney disease
• Silicosis
• Recent measles in children
MODE OF TRANSMISSION
How many bacilli does a single droplet contain?
How is it transmitted?
What is the infectious dose?
How long can they remain airborne?
Difference between smear positive and smear negative TB?
• Spread from person-to-person is through the air by droplet nuclei
• Droplet nuclei are produced by coughing,
sneezing, talking or singing.
• Droplet nuclei may also be produced by;
– aerosol-producing investigations such as sputum induction,
– bronchoscopy and;
– through manipulation of lesions or processing of tissue or secretions in the laboratory.
• Droplet nuclei contain 1-5 bacilli and are
highly infectious.
• They can remain airborne for up to 4 hours.
• Infectious dose is 1 to 10 bacilli.
• The most infectious cases are those with
smear positive pulmonary TB.
• Smear negative pulmonary TB cases are much less infectious.
• Extra-pulmonary cases are almost never
infectious.
• Transmission generally occurs indoors, in dark, poorly ventilated spaces.
• M. bovis infection arises from drinking non-sterilised milk from infected cows.
What are 3 factors determine the likelihood of transmission of M. tuberculosis?
– Number of organisms expelled into the air
– Concentration of organisms in the air, determined by the volume of the space and its ventilation
– Length of time an exposed person breathes the contaminated air
How many number of droplets of nuclei is spread in:
I. Talking
II. Coughing
II. Sneezing
I. Talking: 200
II. Coughing: 3000
II. Sneezing: 1,000,000
Pathogenesis
• Once inhaled, the organisms lodge in the
alveoli and initiate the recruitment of
macrophages and lymphocytes.
• Macrophages undergo transformation into epithelioid and Langhans cells, which
aggregate with the lymphocytes to form the classical tuberculous granuloma
• Numerous granulomas aggregate to form a primary lesion or ‘Ghon focus’ which is
characteristically situated in the lung
periphery
• Spread of organisms to the hilar lymph nodes is followed by a similar pathological reaction
• Combination of the Ghon focus and regional lymph nodes is referred to as the Ghon or primary complex
• Reparative processes encase the primary
complex in a fibrous capsule, limiting the
spread of bacilli (latent TB).
• If no further complications ensue, this lesion eventually calcifies
• Lymphatic or haematogenous spread may occur before immunity is established
• Organisms may seed into other parts of the lungs or other organs, including lymph nodes, serous membranes, meninges, bones, liver and kidneys where they may lie dormant for years.
• If these reparative processes fail, clinical
disease ensues
• Clinical illness directly following infection is classified as primary TB and is common among children in the first few years of life and among immunocompromised persons.
• Bacilli may persist for years before reactivating to produce secondary (or postprimary) TB
• Post primary TB may also be due to new
infection.
• 10% of infected persons will eventually
develop active TB in their lifetime, half of
them during the first 18 months after
infection.
CLINICAL FEATURES
• SYMPTOMS include;
– Cough of ≥2 weeks (any duration if HIV positive) with or without sputum production
– Hemoptysis
– Breathlessness
– Chest pain
– Fever
– Drenching night sweats
– Malaise
– Weight loss
– Loss of appetite
• Common physical SIGNS include;
• Fever
• Tachycardia
• Tachypnoea
• Bronchial breath sounds
• Crackles in the lung apices
• Localised wheeze
• Dull percussion note
• In chronic disease there may be extensive fibrosis with the trachea pulled to one side.
How to classify investigations
• This can be grouped into;
– Bacteriologic tests
– Radiography
– Other supportive tests
Bacteriologic tests
• Sputum smear microscopy for acid-fast bacilli (AFB)
• Microscopy can be by;
– Light microscopy following Ziehl Neelsen staining or;
– Fluorescence microscopy following auramine– rhodamine staining.
• Molecular Methods for rapid diagnosis
– Gene Xpert (MTB/RIF): Recommended by the WHO as the initial diagnostic test for suspected TB. It detects both MTB and rifampicin resistance in <2hrs
– Line probe assay: It detects MTB, rifampicin and isoniazid resistance in 5hrs
Bacteriologic tests: Culture
• Solid culture (4-8wks)
– Löwenstein-Jensen;
– Middlebrook 7H10;
– Middlebrook 7H11
• Liquid culture (2-3wks)
– Middlebrook 7H9;
– Middlebrook 7H12
– BACTEC and MGIT (newer methods with organism detection as early as 5 days)
Chest radiography
• Chest X-ray which classically shows upper lobe disease may reveal;
– Consolidation;
– Cavities
• Other features particularly when there are complications include;
– Pleural effusion
– Pneumothorax
– Lung fibrosis
– Lung collapse
• NB:
• Any abnormality can be seen on Chest X-ray in patients with Pulmonary TB
• Chest X-ray can also be normal in patients
who have PTB and HIV or any other
immunosuppressive illness.
Other supportive tests
• FBC
• ESR
• HIV screening
• E, U & Cr
• Liver function test
• Random blood sugar
Diagnosis of latent TB
• Tuberculin skin test
– Mantoux test
– Heaf test
• Interferon gamma release assays
– T-SPOT. TB
– QuantiFERON-TB Gold test
TREATMENT: first line drugs
• This is via directly observed treatment short course (DOTS)
• First line drugs include;
– Rifampicin
– Isoniazid
– Pyrazinamide
– Ethambuthol
• Treatment lasts for 6months
Treatment is divided into;
– Intensive phase lasting 2months using all four drugs and;
– Continuation phase lasting 4months using isoniazid and rifampicin.
• Pyridoxine is used as an adjunct to prevent peripheral neuropathy
DRUG RESISTANT TB
• Defined as laboratory confirmation of
resistance to one or more of the 1st line anti- TB drugs
• Mono resistance
– Resistance to one of the first line TB medicines
• Rifampicin Resistant TB (RR-TB)
– Resistance to rifampicin, with or without
resistance to other TB medicines. This maybe mono, poly, multi or extensive drug resistance
• Poly drug resistant TB
– Resistance to more than one first line TB medicines excluding resistance to both rifampicin and isoniazid.
• Multi drug resistant TB (MDR-TB)
– Disease caused by a strain of M. tuberculosis that is resistant to at least both isoniazid and rifampin
• Extensively drug-resistant TB (XDR-TB)
– MDR-TB with additional resistance to any
fluoroquinolone and at least one of the second-line injectable agents.
Second line anti TB drugs
• Fluoroquinolone antibiotics; levofloxacin,
moxifloxacin and gatifloxacin
• Injectable aminoglycosides; kanamycin,
amikacin, and streptomycin (now rarely used);
• The injectable polypeptide; capreomycin;
• Ethionamide and prothionamide
• cycloserine and terizidone (therizidone),
• Para amino salicylic acid
Other anti TB drugs
• Clofazimine,
• Linezolid,
• Amoxicillin/clavulanic acid,
• Clarithromycin,
• Carbapenems such as imipenem and meropenem
• Thioacetazone
• The diarylquinoline; bedaquiline and;
• The nitroimidazole; delamanid
COMPLICATIONS
• Massive hemoptysis
• Pleural effusion
• Pneumothorax
• Lung fibrosis
• Lung collapse
• Dissemination to other organs e.g. miliary TB,
tuberculous meningitis, TB spine
PREVENTION
• Primary prevention : (prevent infection )
– Reduce TB exposure & transmission
– Vaccination
• Secondary prevention (Prevent infection)
– Chemoprophylaxis (Isoniazid Preventive Therapy)
– Antiretroviral therapy
• Tertiary prevention (prevent relapse)
– Chemoprophylaxis, Antiretroviral therapy
