Tuberculosis COPY (Graeme M) Flashcards
How many of the 2 billion infected people with tuberculosis have HIV?
1.1 million
How likely is TB to cause death?
Second leading cause of death from an infectious disease worldwide
- 3 million deaths annually
- 3 million HIV positive
74 000 children
Describe the trend in incidence of TB before and after 1980?
Until mid-1980s TB in the UK was declining and considered to be under control
Where are 39% of TB cases in the UK?
London
What is the microrganism responsible?
Mycobacteria
What are the specific names for the organisms responsible for TB?
Mycobacterium tuberculosis
M. bovis (“bovine TB”)
What are the other mycobacterium that don’t cause tb?
Mycobacteria other than tuberculosis (MOTT) (about 30% of UK isolations)
Mycobacterium avium-intracellulare (HIV)
M. kansasii, M. malmoense, M. xenopii
Mycobacterium leprae leprosy
Describe the type of bacterium that Mycobacterium tb is?
Non-motile bacillus
Very slowly growing
Aerobic - predilection for apices of lungs (ventilated but not perfused)
Very thick cell wall lipids, peptidoglycans, arabinomannans
Resistant to acids, alkalis and detergents
Resistant to neutrophil and macrophage destruction
Aniline based dyes such as carbol fuschin complex with cell wall
Unable to remove dye from cell wall
Acid - and alcohol - fast bacilli (AAFB) (Ziehl Neilson stain)
What is the source of TB?
‘Open’ pulmonary TB = coughing and sneezing releases respiratory droplets which evaporate. These droplet nuclei remain airborne for very long periods.
What removes mycobacteria in outdoors?
UV radiation and infinite dilution
Which type of droplet nuclei impact in the alveoli and slowly proliferate?
Small nuclei, Larger droplet nuclei impact on large airways and cleared
How is infection of mycobacterium bovis spread?
Consumption of infected cows’ milk
- deposited in cervical, intestinal lymph nodes
What stimulates the macrophages to become activated?
Th1 helper cells from the lymph node, these Th1 cells are activated by antigen presenting cells.
These Th1 cells after receiving the signal from the antigen presenting cell then clonially proliferate in the lymph node
What are Th1 cells?
Type 1 T helper (Th1) cells produce interferon-gamma, interleukin (IL)-2, and tumour necrosis factor (TNF)-beta, which activate macrophages and are responsible for cell-mediated immunity and phagocyte-dependent protective responses.
Which specific chemical activates Macrophages?
Interferon gamma CD40 - which is produced by Th1 cells in the lymph node
What is the result of activated macrophages?
Damaged epithelioid cells
Langhan’s giant cells
Accumulation of macrophages, epithelioid & Langhan’s cells GRANULOMA
Central caseating necrosis (may later calcify)
What disease is caseus necrosis usually indicative of ?
TB
What is meant by the 2 edged sword of the Th1 cell mediated immunological response?
Eliminates / Reduces number of invading mycobacteria
Tissue destruction is a consequence of activation of macrophages
What are the factors affecting susceptibility?
Genetics
Race
Nutrition
Age
Immunosuppression
What is the pathology for a susceptible host?
Tissue destruction
Proliferation of organism
Progressive disease
What is the pathology for a resistant host?
Tissue destruction
Organism contained
Disease
Who is normally affected by the primary infection?
Usually children, 80% Infected focus in alveolus, (lymph nodes, gut)
Where do mycobacteria spread to once they are in the alveoli?
Spread via lymphatics to draining hilar lymph nodes
Then there is haematogenous seeding of mycobacteria to all organs of the body (lung, bone, genitourinary system)
What are the symptoms of TB?
Usually no symptoms, can be fever, malaise, Erythema nodosum (sarcoidosis also causes this), rarely chest signs
What is the mantoux test?
Injection of tuberculin into the transdermal layer of skin. After 48-72 hours amount of induration present can identify possible health problems.
What is responsible for the induration in the mantoux test?
Intra dermal administration of tuberculoprotein (PPD - Purified protein derivative) results in lymphocytic and macrophage based area of inflammation/induration after 48 hours
What are the three outcomes of a primary infeection?
Progressive disease - ineffective immune response from the patient
Contained latent - activates when the patient becomes immunosuppressed (old)
Cleared and cured
How common is a primary infection of TB?
Small percentage (1%)
How does a primary infection of TB progress?
Primary focus continues to enlarge - cavitation
Hilar lymph nodes become enlarged to the point they compress bronchi causing lobar collapse
Lymph node discharges into bronchus (tuberculosis bronchopneumonia)
Describe the incidence and findings in miliary TB?
Small percentage (1%)
6-12 months after infection
Fine mottling on the X-ray, widespread small granulomata - looks like millet seed in the lung - very serious
How can TB affect the CSF and the pleura?
Can cause meningeal TB (severe, CSF high protein, lymphocytes)
AND
Tuberculosis pleural effusion
What is menat by post primary disease?
Reactivation of mycobacterium from latent primary infection disseminated by the blood stream around the body.
New re-infection from outside source
What are the sites of post primary disease from TB?
Pulmonary disease
Lymph nodes, usually cervical
Bone and joint; spine, hip, etc
Genito-urinary; kidney, ureter, bladder
Males; infertility - vas deferens
Females; infertility - uterus, Fallopian tubes
Pericardium; constrictive pericarditis
Abdomen; ascites, ileal TB ® obstruction
Adrenal ® Addison’s disease
Skin; lupus vulgaris
Just about any other tissue!
What are the features of TB usually after 6-12 months?
Miliary , meningeal, pleural TB
What are the features of TB after 1-5 years?
Post primary disease - pulmonary and skeletal
What are the features of TB after 10 years?
Genitourinary, Cutaneous TB
How would you decribe the progression of Post-primary TB?
Slow, may be no symptoms for many months
What are the symptoms for Post primary TB
Respiratory; cough, sputum, haemoptysis, pleuritic pain or breathlessness
Systemically unwell
malaise, fever, weight loss (“night sweats”) - very characteristic of TB
What is characteristic PMH for Post-primary Pulmonary Tuberculosis?
Diabetes, Immunosuppressive diseases, Previous TB
What are common drugs included in Drug history for Post-primary Pulmonary Tuberculosis?
Immunosuppressive drugs
What is the past social history for Post-primary Pulmonary Tuberculosis?
Alcohol – poor nutrition, immune system is suppressed, IVDA (intravenous drug users? Immnue system suppressed), poor social circumstances, Immigrants from high incidence areas
What are the signs for Post-primary Pulmonary Tuberculosis?
May be none at all - extensive TB can be present without physical signs!
If more advanced, may be crackles, bronchial breathing.
Finger clubbing is rare unless very chronic infection
When is there going to be a high index of suspicion?
Immunosuppressed - HIV, corticosteroid therapy, etc.
In Africa 70% of TB patients are HIV+
Malnutrition, alcoholism, vagrants,previous gastric surgery, malignancy
Diabetes mellitus
Adolescence, elderly
Recent immigrants from high prevalence countries
What are the means of diagosing TB?
Sputum analysis
Chest radiograph
CT scan of thorax
Bronchoscopy with alveolar lavage, transbronchial biopsy
Pleural aspiration and biopsy if peural effusion
How do we analyse sputum samples for TB?
ZN stain - immediate answer if AAFB
Culture
Sputum PCR
What features of a chest radiograph confirms presence of TB?
Patch shadowing, often in apices/upper zones, or apex or lower lobes
Cavitation
Calcification if chronic or healed TB
What happens after the fluid is collected from the pleural aspiration?
FLuid cytology (lymphocytes)
Fluid for AAFB and culture
Biopsy histology
1 biopsy sent in Saline for culture
What is treatment of tuberculosis?
Vitamin D causes macrophages to release Cathelecidin which is a very potent antibiotic.
Surgery - Collapse of the cavity by: Phrenic crush (crushing the phrenic nerve causes the diaphragm on that side to become paralysed and rise up, closing the cavity), artificial pneumotorax (collapses the lung and therefore the cavity), pneumoperitoneum, thoracoplasty (Six to eight ribs were broken and pushed into the thoracic cavity to collapse the lung beneath), lung resection (removal of a segment of lung).
What is prognosis of cavitating disease?
5 year survival of 25%
How are drugs used against TB?
Multiple used to prevent resistant organisms forming,
Therapy at least 6 months, slowly growing organism
ONLY SPECIALISTS TREAT
What are the legal requirements behind treating TB?
Legal requirement to notify all cases
(low threshold for HIV testing, AIDS defining condition)
What are the current TB regimens?
Isoniazid
Ethambutol
Pyrazinamide
Rifampicin
What are the side effects of Rifampicin?
Orange urine, tears, induces liver enzymes,prednisolone, anticonvulsants, oral contraceptive pill is ineffective. Hepatitis
What are the side effects of Isoniazid?
Hepatitis, peripheral neuropathy
What are the side efects of ethambutol?
Optic neuropathy
What are the side effects of pyrazinamide?
Gout
What is the point of TB contact tracing?
Find out where the patient has caught it and who they might have spread it to
Likelihood of infection with TB depends on?
Duration of contact
Intensity of infection
What is the general guidance for TB contact tracing?
First screen close household contacts
5-14% become infected (1 in 6 develop disease)
If close contacts have been infected, virulent organism/high transmission
screen casual contacts
‘stone in pond principal’
How do you screen for TB using tuberculoprotein?
If younger than 16 and no BCG there should be no immunity to Tuberculoprotein
What other test besides the mantoux test can determine the presence of TB?
Heaf test
How would you treat a patient who is heaf positive (2-4) exposed to TB?
If their X-ray is normal they are at risk of disease (miliary, or meningeal)
Chemoprophylaxis to kill mycobacteria
Rifampicin + Inh (isoniazid) 3 months
Inh 6 months
If their X-ray is abnormal - Treat as primary TB
What should you do 6 weeks after a heaf negative result?
2nd heaf test
If it is negative - BCG
If it is positive - follow procedures with a chest X-ray and follow up procedures
If older than 16 with an abnormal chest X-ray?
Investigate for TB and treat if necessary
What is the drug combination pattern?
Treat with 4 drugs 2 months, 2 drugs 4 months
