Flashcards in L69 – Lower Respiratory Tract Infections II Deck (78):
What is the gram staining of Mycobacterium tuberculosis?
Structurally Gram positive (exam) but not stained by the Gram stain
What stains can reveal Mycobacterium tuberculosis?
Acid-fast stains, e.g. Ziehl-Neelsen (ZN) stain
Fluorescent stains, e.g. auramine O
When is Fluorescent stains, e.g. auramine O used to stain M. tuberculosis?
Used to confirm Mtb:
More sensitive than ZN for examination of clinical specimens
But need confirmation** with ZN stain
What is the result of acid fast stain on Mtb?
blue background, red acid-fast bacilli
Is Acid fast bacilli = Mtb?
Definitely not ** important **
Mtb is susceptible to which abiotic factors as much as other non-spore-forming bacteria?
susceptibility to heat, ultraviolet light
Mtb is more resistant to which abiotic factors compared to other non-spore-forming bacteria?
More resistant to drying
Higher resistance to acids, alkalis, some chemical disinfectants
What chemicals are used to kill Mtb?
What is the motility and spore formation of Mtb?
What are the 2 most important mycobacterial infections?
M. tuberculosis > tuberculosis
M. leprae > leprosy
What is the aerobic requirement of Mtb?
Obligate/ strict aerobe
Why does Mtb cause chronic infections?
Slow generation time: 16-18 hours
What is the culture for Mtb?
1) Egg-based medium:
** Löwenstein-Jensen (LJ) **medium > form breadcrumb colonies
2) Non-egg-based medium
What is the culture medium for M. bovis?
Transmission of Mtb?
mostly airborne route (droplet nuclei) >> pulmonary
Transmission of M. bovis?
ingestion (e.g. unpasteurized milk)
Recall IASM: unpasteurized milk also contains Brucella
What is the difference between primary and post-primary tuberculosis?
Primary tuberculosis: after initial exposure, host immune response is absent until lymphocytes and macrophages are activated >> unrestrained bacterial multiplication
Post-primary tuberculosis (usually adults): reactivation, re-infection
What re the 2 sites of infection for Mtb?
(e.g. apex of lung common)
Extrapulmonary tuberculosis (e.g. bone> Pott's puffy tumour)
Which of the 2 sites of Mtb infection is more common? Which one is more infectious?
Pulmonary tuberculosis is more common and infectious
Extrapulmonary tb is non-infectious and less common
What is the pathogenesis of Mtb? (think which WBC involved first)
1) Survive in macrophages
2) inhibit fusion of lysosomes with phagosome, but not actively dividing >> no host immune response yet
3) Cellular immunity and delayed hypersensitivity reaction (type IV) controls infection
4) Host immune response forms granulamatous inflammation and caseous necrosis
Does granulomatous inflammation occur in Mtb infecting an immunocompromised host?
Immunocompromised = less activated T cells = no gran. inflam.
What are the most useful and fastest diagnostic tools for Mtb?
-Acid fast stain (red bacilli on blue background)
-Culture>> use liquid media instead of solid media
-Tuberculin skin test
-In vitro gamma interferon release assays (IGRA)
Difference between the 2 types of medium for cultureing Mtb?
Difference in speed
Solid media = 8-12 weeks
Liquid medium using automated culture and sensitivity testing = fast
What are some less sensitive/ effective ways to diagnose Mtb?
PCR > Not sensitive especially when bacteria load is low (e.g. when Mtb is dormant)
Antibody dectection is not useful for clinical diagnosis
What is obsevred in histopathology of Mtb?
Granulomatous inflammation: activated T cells, macrophages
Caseous necrosis, cavitation
How does Tuberculin skin test / Mantoux testwork?
Intradermal injection of 0.1mL purified protein
>> measure delayed-type hypersensitivity reaction to M.tuberculosis
What is a positive result for Tuberculin skin test?
positive if red induration achieves certain diameter
bleb; painful because tearing skin
What are some problems/ limitations of Tuberculin skin test?
Cross-reaction with other mycobacteria
Confounded by previous BCG vaccination
Cannot distinguish past exposure / current infection
What is the difference in MoA between pyrazinimide and other anitbiotics?
Pyrazinimide = only one to kill Mtb by acid inhibition, can kill during dormancy
Others = only kill Mtb during **continuous growth, cannot kill during dormancy
What are the 1st line agents for Mtb? **important**
What are the 2nd line agents for Mtb?
Fluoroquinolones (levofloxacin, moxifloxacin)
What is the name given to the tuberculosis (TB) control strategy recommended by WHO?
Directly observed treatment, short-course = DOTS
What is the duration of therapy for Mtb? Under what circumstances is it longer?
Minimum 4-6 months
Infections of central nervous system, bones
Patients who cannot tolerate standard first-line agents
What are the 3 strains of antibiotic resistant Mtb?
Multidrug resistant tuberculosis (MDR-TB)
Extensively drug-resistant tuberculosis (XDR-TB)
‘Totally drug-resistant tuberculosis’ (TDR-TB)
What is MDR-TB resistant to?
at least isoniazid and
What is XDR-TB resistant to?
+ any fluoroquinolone
+ at least 1 of 3 following injectable drugs: amikacin, kanamycin, capreomycin
What is the BCG vaccine?
Bacille Calmette-Guérin (BCG) vaccine
= attenuated strain of Mycobacterium bovis
How effective is BCG vaccine?
Highly variable protective efficacy in different populations:
Against lung disease: 0-80%
Against meningitis: 46-100%
Name other Mycobacterium that are not Mtb or M.leprae?
non-tuberculous mycobacteria (NTM):
mycobacteria other than tubercle bacillus (MOTT)
What does M.marium infect?
causes skin, soft tissue infection after exposure to seawater
What are some rapid growth mycobacterium? FA
M. fortuitum, M. abscessus
What type of pathogen causes pneumocytosis? Transmission?
= fungus (not protozoa)
Probably spread by inhalation
What is pneumocytosis?
commonly = pulmonary infection: pneumocystis pneumonia
What is the action of pneumocytis jiroveci?
colonize / asymptomatically infect the respiratory tract of normal healthy individuals
What are the 2 groups of patients affected by pneumocytis jiroveci?
- Non-HIV/AIDS patients
- HIV/ AIDS patients
What Non-HIV/ ADIS patients are commonly affected by pneumocytis jiroveci?
- Premature infants, malnourished or overcroswded children
- severely immunocompromised persons (e.g. transplant recipients, immunosprressive therapy)
Can pneumocytis pneumonia be used as an indicator disease of AIDS?
HIV/AIDS patients: 85% with pneumocystis pneumonia
What are the resultant infection, CXR and general symptoms of pneumocytis jiroveci?
Mostly pulmonary infections
CXR = bilateral diffuse infiltrates
Hypozaemia, fever, cough
What are some general pneumonia symptoms?
cough, sputum, reduced air entry, bronchial breath sounds, crepitations,
shortness of breath, respiratory failure
What are the 2 diagnostic tools for pneumocytis jiroveci causing pneumocytosis?
1) commonest = bronchoalveolar lavage
2) Induced sputum for HIV positive, immunosuppressed hosts
3) Rare = Transbronchial biopsy, open lung biopsy
** Expectorated sputum is not acceptable
What staining is done to diagnose p.jirocevi?
Methenamine silver stain or similar silver stains >> cup-shaped
What are the options of managing pneumocytosis?
1) Specific chemotherapy,
2) Chemophylaxis in high risk individuals, e.g. HIV/AIDS, transplant recipients
3) Respiratory support
Influenza is caused by which viruses?
Belong to Orthomyxoviridae
enveloped RNA virus
What is the structure of nucleoplasmid?
Nucleocapsid: segments of single-stranded RNA + RNA polymerase + nucleoprotein:
What is H and N in viruses?
Functions of H and N in Influenzavirus A?
Haemagglutinin (HA, H): 18 types (H1-18)
Attachment to host cells
Neuraminidase (NA, N): 11 types (N1-11)
Facilitates release and spread of virus
What are the most commonly found influenzavirus A in humans?
Compare the nucleopasmid segments between the 4 types of Influenzavirus A?
A= 8 seg. of ssRNA
B = 8 seg
C and D = 7 seg
What is the nautral reservoir of inflenzavirus D?
What is antigenic drift?
Relatively minor changes
Occur frequently within an influenza subtype (e.g. H1N1, H3N2)
What is antigenic shift?
Major changes in antigenic composition >> appearance of a new HA or NA
Can result in a pandemic if transmitted efficiently from person to person (e.g. 2009
What does both antigenic shift and drift result in?
Ressortment and variation of viral genetic composition
What are the inflenza peak seasons in hong kong?
2 peak seasons:
1. Winter: February to March
2. Summer: July to August
Magnitude, duration of peak seasons vary from year to year
Trasmission of influenzavirus?
respiratory droplets (exam) >> local multiplication at respiratory epithelium
Incubation period of influenzavirus?
When does viral shedding occur in influenzavirus?
day before to 3-5 days after onset of symptoms
Children: may be prolonged (up to 21 days)
What are the respiratory and systemic symptoms of influenzavirus?
Respiratory: dry cough, nasal discharge
Systemic (much more prominent than respiratory): headache, fever, myalgia, malaise
What is the respiratory complication of influenza?
primary viral (can be rapid progress) / secondary bacterial pneumonia
What is the systemic complication of influenza?
Myositis, seizure, encephalopathy /encephalitis
Worsen Cardiopulmonary diseases
Reye syndrome (swelling in brain, liver)
What are the USEFUL clinical diagnostic tools for Influenza?
Molecular diagnosis via PCR
** Viral antigen detection: immunofluorescence staining, enzyme immunoassay (EIA),
Clinical diagnosis (symptoms, seasonality...etc)
What are some LESS usedful diagnostic tools for Influenza?
Serology (generally not useful for clinical diagnosis because need paired sera)
Viral culture (takes too long)
What are some general symptomatic treatments for influenza?
Analgesics (relieve pain), antipyretics (prevent / reduce fever)
What drugs are avoided in children with influenza?
aspirin (Reye syndrome)
non-steroidal anti-inflammatory agents
Name some neuraminidase inhibitors?
peramivir, laninamivir, Baloxavir
What are the 3 prevention methods against influenza?
Seasonal or pandemic influenza Vaccines
Infection control measures in institutions, health care facilities
What are the inactivated vaccines for influenza?
Trivalent: 2 influenza A + 1 influenza B strain; or
Quadrivalent: 2 influenza A + 2 influenza B strains
(Composition of vaccine strains is updated yearly)
Compare the administration between inactivated, live-attentuated and recombinant vaccines for influenza?
Inactivated vaccine:Intramuscular / intradermal administration
Live-attenuated vaccine: intranasal administration
Recombinant vaccine: intramuscular