2 - Microbiology Flashcards
Lectures: Bacterial Upper Respiratory Infections Viral Infections of Upper Respiratory Mycobacteria and Pulmonary TB Common Acquired Pneumonia Atypical Pneumonia Endemic Mycoses Urinary Tract Infection
What are the major pathogens responsible for infections in the:
1) Nasopharynx,
2) Oropharynx,
3) Middle ear/parasinuses,
4) Epiglottis.
1) Nasopharynx - VIRUS -> rhinov., coronav.
2) Oropharynx - Strep. pyrogens, Corynebacterium diphtheriae, EBV, adenovirus, enterovirus
3) Middle ear/parasinuses - Strep. pneumoniae, Haemophilus influenza (non-typable)
4) Epiglottis - Haemophilus influenza type B
What are the identifying characteristics of Streptococcus pyrogens that could be seen in the labratory?
1) gram +, cocci (typically in chains)
2) catalase positive
3) B-hemolytic
4) bacitracin sensitive
other -> anti-A sera sensitivity
What is the primary virulent factor of Strep. pyrogens? What is its importance in disease progression?
M-Protein - helical, anti-phagocytic protein on the surface of S. pyrogens
Due to Molecular Mimicry, antibodies to M-protein can cross react with cardiac tissue and cause Rheumatic Fever/Rheumatic Heart Disease.
What are the microbiological characteristics of Haemophilus influenza?
1) gram -, coccobacilli (curved on short rods)
2) growth on chocolate agar
3) requires X and V factors to grow
4) best in 5-10% CO2
5) slide agglutination serotyping positive for capsule type
What are the microbiological characteristics of Corynebacteria diphtheriae?
1) gram +, rods (“Chinese letters)
2) non-motile, non-spore forming
3) catalase +
What are the primary diseases associated with Streptococci pyrogens?
Pharyngitis, scarlet fever, TS-like syndrome, pyoderma, impetigo, cellulits, rheumatic fever
What are the primary diseases associated with Haemophilus influenza?
Type b -> meningitis, epiglottis, cellulitis, acute pneumonia
Non-encapsulated - otitis media, sinusitis, conjunctivitis
What are the primary diseases associated with Corynebacteria diphtheriae?
Diptheria!!
Toxin can also target heart, nerves and cause pseudomembrane in throat.
What is the mechanism of Haemophilus influenza vaccine?
Anti-capsule antibodies act as opsonins that mediate complement-dependent phagocytosis. The Ab-Complement pair can also cause lysis.
VERY effective vaccine - high risk groups are <5mo (no/incomplete vaccination) and elderly (diminished immunity).
What is the structure of Rhinovirus?
- Non-enveloped
- ssRNA genome
- icosohedral capsid
- small
- > 100 serotypes
- prefers “cooler” temps of nasal passages over GI tract
Briefly describe the mechanism of Rhinovirus replication.
+ssRNA genome => encodes its own RNA polymerase
- > binds to ICAM-1 to gain entry into the cell
- > ssRNA undergoes translation
- > core proteins are produced
- > replicated virus (RNA + protein) is assembled
- > exit cell via lysis
What is the clinical manifestation of Rhinovirus?
Lasts 2-4d and is SELF-LIMITING
- nasal discharge/congestion
- sore throat
- muscle aches, fatigue, headaches, loss of appetite
How is Rhinovirus diagnosed and treated?
Diagnosis is made from symptoms.
Tx is to control symptoms and wait for virus to run its course.
What is the structure of RSV?
Respiratory Syncytial Virus
(-)ssRNA genome
Helical capsid
Envelope proteins -> G (attachment) and F (fusion)
Describe the general mechanism of RSV replication.
- ssRNA genome => bind via G and F envelope proteins to fuse with cellular membrane
- > encodes its own RNA-dependent RNA polymerase
- > transcription to mRNA
- > translation to produce required proteins
- > new RNA and proteins assembled
- > exit via exocytosis
What are the clinical manifestations of RSV?
Infection is usually self-limiting in 7-10d
- runny nose
- fever
- labored, rapid breathing w/ wheezing/cough
- lips turn blue (cyanosis)
How is RSV diagnosed and treated?
Dx- nasal swab/aspirates -> ELISA/DFA for rapid dx; culture for confirmation
Tx - treat symptoms, infants may need hospitalization w/ O2 supplementation
Vaccine - ribavirin used with mixed success, RespiGam and palivizumab are antibodies for RSV components (new)
What is the structure of Adenovirus?
- ds linear DNA
- icosahedral capsid
- BIG (largest non-enveloped virus)
- hexon and pentose fibers/proteins emanate from capsid (like “spikes”) that aid in attachment to cells
Describe the replication of Adenovirus.
- infects mucoepithelial cells in respiratory tract, GI tract and eye (conjunctiva or cornea)
- attach to receptors of host cell via fiber protein (hexon and pentose fibers)
- migrate to clathrin-coated pits on surface and form endosomes
- after internalization the pH drops and causes endosome rupture
- migrates to nucleus via microtubules and nuclear pore
- displays temporal regulation (immediate, early and late phases)
- DNA replication
- virion assembly
- lyse host cell to release virus
What are the clinical manifestations of adenovirus?
Anyone -> Pneumonia
Infants/Young Children -> febrile, undifferentiated URI; Pertussis-like syndrome
Children/Adults -> pharyngoconjunctival fever
Military recruits -> Acute Respiratory Disease
How is Adenovirus infection diagnosed? Tx?
Diagnose:
-adenovirus antigen or virus can be identified in nasopharyngeal aspirates or swabs
-Serology or PCR assays are also available
TX:
-control symptoms
-self-limiting 7-10d
-limited vaccine is recently approved for military recruits in concentration areas
Describe the structure of Epstein Barr Virus.
- enveloped
- icosahedral capdis
- linear dsDNA
- encodes its own DNA-dependent DNA polymerase
Describe the replication of Epstein Barr Virus.
- highly regulated, temporal expression of dsDNA leads to replication(immediate-early, early and late phases)
- attach and fuse with host cell membrane
- migrate to nucleus via microtubules
- transcription initiated via own DNA-dependent DNA polymerase
- some immediate-early proteins help inactivate host apoptotic signals
- after replication, DNA exit nucleus via budding
- exit from cell via exocytosis or cell death
What are the clinical manifestations of Epstein Barr Virus infections?
- majority are clinically inapparent
- Acute Mononucleosis Syndrome: low-grade fever, fatigue, pharyngitis, cervical lymphadenopathy, splenomegaly, and peripheral blood monocytosis
- in newborn infants infected in utero (transmitted from mother) can cause significant multiorgan disease
- EBV latency can manifest in several other diseases: Lymphoma (Hodgkin’s, Non-Hodgkin’s, burkitt’s)
How is Epstein Barr Virus diagnosed? Tx?
Diagnose: 1) atypical lymphocytes 2) agglutination test for heterophile antibodies 3) ELISA for EBV antibody 4) PCR for EBV genes Tx: -typically self-limiting -treat symptoms -no vaccine available
Describe the cell wall of an Acid-Fast organism. What are the advantagesbfor the organism?
-hallmark of mycobacteria
-retain basic dyes within mycobacterial envelope when treated with acidic solutions
-due to waxes (ie. mycolic acid) reducing permeability => neither gram (-) or (+) since stain can’t penetrate
ADV -> waxes make cell much more resistant to drying, allowing it to survive both in and out of the body
->also makes them resistant to killing in phagocytes
->still susceptible to heat (ie. pasteurization)
Describe the transmission and stages of infection for Pulmonary TB.
Transmission:
- carried in “droplet nuclei” that can be aerosolized by coughing and sneezing
- can remain suspended for hours, but prolonged exposure is typically required for infection
-can also be ingested (M.bovis) in contaminated milk/milk products
Stage 1:
-seeding in mid-lower lung
-multiply in alveolar spaces
-ingested by alveolar macrophages and are killed or grow inside
Stage 2:
-logarithmic growth in macs
-dissemination of infected macs via lymph and blood
-NO HOST reaction for first 1-2wks
Stage 3:
-host humoral response -> activated macs/CD-8 T-cells destroy
-form granulomas to “wall off” infection -> primary lesion
Stage 4:
-bacteria continue to multiply in granulomas, but are isolated from immune response
-caseous necrosis in granulomas
-lesions may heal, but bacteria is still viable inside
Reactivation:
-disturbance of immune surveillance and microbial growth
-viable bacteria released to lung (typically)
-Triggers-> diminished immune response, malnutrition, aging
Describe the epidemiology of Pulmonary TB.
Historical: decreased from ‘53-‘84, but increased from ‘84-‘92 largely due to HIV epidemic and immigration; steady decrease since ‘92 due to improved public health controls
Current: highest rate in Africa and China, but incidence continue to fall
-High Risk includes increased contact with persons infected with TB, low-income populations, ILLICIT DRUG use, HIV
-small portion of those infected with develop symptoms
How does PPD-T work? Interpreted?
Culture is the “gold standard,” but too slow for screening. PPD-T looks for a memory reaction due to previous infection with TB. Positive test criteria vary by population.
>5mm is positive for:
-HIV positive
-recent contact with TB case
-persons w/ fibrotic changes on CXR
-organ transplants/immunosuppressed
>10mm is positive for:
-recent arrivals from high-risk populations
-IV drug users
-residents/employees of high-risk congregate settings
-pre-disposing illnesses
-children 15mm is positive for:
-other
** PPD-T should only be conducted on those in high-risk groups
How is Pulmonary TB tx?
Drug combination therapy is now standard due to development of drug-resistant strains. (Rifampin and Isoniazid OR Rifampin, Isoniazid, and Pyrazinamide)
To help with compliance, and thus fight development of resistance, Direct Observed Therapy (DOT) is increasing in popularity.
XDR TB is resistant to ALL known therapies.
What is the pathogenesis of a primary Influenza infection? What is a secondary infection?
- Virus transmitted as aerosol and imbedded in respiratory epithelium.
- local replication in epithelium cells
- **damage to epithelium from the virus and the subsequent immune response makes the airway susceptible to SECONDARY BACTERIAL INFECTIONS
- no viremia
- immune response (macrophages, lymphocytes =>cytokines, INF-g)
- antibodies to virus generated and clearance from tissue
Secondary Infection occurs when person is re-infected, but their own symptoms are mild due to the IgA response. However, they can still infect others with the active virus.
What is the clinical presentation of Influenza infection?
- Abrupt onset!
- headache
- high fever (101-103F; higher in children)
- myalgia
- sore throat
- non-productive cough
- runny/stuffy nose
What are some common complications of Influenza?
- *Secondary Infection -> injury to respiratory epithelium from virus and the subsequent immune response makes them more susceptible to infection
- Bacterial (common)-> after improvement of symptoms, fever reappears with productive cough Step. pneumoniae, Staph. aureus, H. influenzae
- Viral (rare)-> failure of infection to resolve, dyspnea, hypoxia, cyanosis, severe infammation of alveoli -> ARDS
- Cardiac infection
- Neurological symptoms: Guillan-Barre, encephalopathy, encephalitis, Reye’s syndrome (associated with Aspirin use during infection)
Who is at high risk for influenza infection?
1) Elderly (>65)
2) residents/nurses of chronic care facilities (prolonged exposure to >65)
3) chronic pulmonary/cardiovascular disorders(including asthma)
4) frequent/regular hospitalizations
5) 6mo-18yrs who receive chronic Aspirin
6) pregnant (2nd-3rd trimester) during flu season
Describe the structure of Influenza virus.
- RNA virus (8 segments)
- envelope
- haemaggutinin (HA) and neuraminidase (NA) surface projections (spikes) that support attachment/fusion and release/disaggregation, respectively
- membrane within viral envelope
- membrane ion channel(M2) important for acidification of endosome
