LOs: 33-35 Flashcards
33 Mycobacterium tuberculosis:
Disease
Spectrum of Disease (3)
Epidemiology
- Location
- Risk factors
Transmission
Factors contributing to susceptibility (5)
Vaccines (2)
Prevention (3)
Treatment
D
- Tuberculosis
- Mostly pulmonary: lung destruction, hemoptysis
- Also extra-pulmonary (meningitis) & miliary
- Wasting from inflammation
S
- primary: active TB, PPD+
- latent: infection w/o disease, not contagious, PPD+
- reactivation: active, contagious
E
- worldwide
- AIDS, HIV, immigration, drug resistance
T
- respiratory (aerosolized bacteria, droplet nuclei)
- multiple contacts w/ infected person
- only active disease
F
- poor living conditions, crowding
- malnourishment
- compromised immune system
- exposure potential
- genetic component
V
- BCG: most effective in children
- future vaccines: include subunit proteins, recombinant mycobacteria, viral
vectors expressing Mtb proteins, or DNA vaccines
P
- improve social conditions
- screen
- isolated infected pts
T
- *first line: 4 first-line for 2 months, isoniazid & rifampin for 4 months
- rifampin: inhibits DNA-dependent RNA polymerase
- isoniazid: inhibits mycolic acids & catalase-peroxidase enzyme
- pyrazinamide
- ethamutol: interferes w/ cell wall biosynthesis
- *second line: FQs (moxifloxacin)
- *drug resistance: multi-drug & extensively drug resistant strains
33 Mycobacterium tuberculosis:
Biologic Characteristics
- Type
- Growth
- Cell wall
Virulence Factors
- Factors (6)
- Major virulence determinant
Survival within macrophages & persistence within the host (4)
Course of Infection
- Transmission
- Initial infection
- Primary TB
- Majority of infected persons
- Reactivation
- Active TB
Diagnosis (6)
BC
- acid-fast bacilli: stain w/ carbolfuschin, gives red rod-shaped organisms
- slow-growing on various media
- lipid rich, hydrophobic “waxy” cell wall
VF
- mycolic acids, lipids, liparabinomannan (~LPS), cytolysin, adhesin/invasin genes, secretion systems (ESX loci)
- allow survival & replication of M. tuberculosis within macrophages using complement receptor
S
- M. tuberculosis inhibits phagosome-lysosome fusion within the macrophage
- respiratory burst (ROIs) has little effect
- respiratory nitrogen intermediates (RNIs) can kill M. tuberculosis
- down-regulation of MHC class II presentation
C
- aerosolization
- interaction w/ alveolar macrophages, inflammation, hematogenous spread, recrutiment of monocytes & lymphocytes to lungs, formation of granuloma
- replicating bacteria, active disease, & infectious if immune response isn’t effective
- latent, not infectious
- can occur many years later, causes active & infectoius TB
- liquefaction of lesion, necrosis of lung tissue, cavity formation, large numbers of bacilli, often released into airways, often a wasting disease, with weight loss, lethargy, etc
D
- symptoms: cough, fever, difficulty breathing
- tuberculin skin test (TST): indicates infection, not active disease
- IFN-gamma based immunoassays: distinguish M. tuberculosis infection from BCG vaccinated or other
- chest x-rays: lesion or cavity indicates infection
- acid-fast bacilli in sputum smear: red rods on blue background
- cultivation
33 Immune Response to Tuberculosis:
Cell mediated immunity (2)
Cytokines (4)
Macrophage activation (3)
Granuloma formation (3)
CMI
- CD4 T cells produce cytokines to control infection
- lysis of infected macrophages by CD8 T cells may kill intracellular organisms or release them to be taken up by more activated macrophages
C
- IFN-gamma: req’d for macrophage activation, controls infection
- TNF: controls infection, damages tissues, activates macrophages, forms granuloma
- TNF neutralizing agents: major reactivation risk for TB
- other T cell & macrophage cytokines (IL-12, IL-6): control infection
M
- macrophage activation involves interaction w/ T cells & cytokines produced by T cells (IFN-gamma & -alpha)
- unactivated macrophages can’t destroy M. tuberculosis (organisms replicate within macrophages)
- reactive nitrogen intermediates (RNIs) kill intracellular mycobacteria
G
- T cells, macrophages, & TNF are involved
- center of granulmoa can be necrotic or caseious
- persistent mycobacteria reside within the granuloma
33 Leprosy:
Etiology
- Caused by…
- Transmission
- Location
- Infectable organisms
Pathogenesis
- Cell wall
- Capsule
- Growth
- Resides…
- Research difficulties
Clinical Manifestations: characteristics, bacteria #s, lymphocytes, granulomata, other
- Tuberculoid Leprosy
- Lepromatous Leprosy
Immunology: type, cytokines, result, DTH
- Tuberculoid Leprosy
- Lepromatous Leprosy
Diagnosis
- Tests (2)
- Tuberculoid vs. Lepromatous
Treatment
E
- Mycobacterium leprae
- respiratory (nasal secretions), not contagious
- Africa, Asia, & Latin America
- Humans, armadillos
P
- consists of lipoproteins, mycolic acids, & other lipids
- lipid-rich outer “capsule” contains phenolic glycolipid 1 (PGL-1)
- acid fast, slow-growing
- resides within macrophages & Schwann cells (tropism for peripheral nerves)
- can’t be cultivated in the lab & no animal model
CM: TL
- skin lesions & peripheral nerve damage
- low #s of bacteria
- lymphocytes in lesions
- granulomata at lesion sites
- nerve damage form inflammation –> loss of fingers or toes
- skin ulcers, infection, amputation
CM: LL
- skin lesions, sensory deficits, enlarged peripheral nerves, dermal edema, nose & face disfigurement
- high #s of bacteria
- few lymphocytes, but more foamy macrophages in lesions
- no granulomata
- more infectious
- complication: erythema nodosum leprosum
I: TL
- Type 1: CD4 > CD8
- T cells produce cytokines (IFN-gamma, IL-2) & activate macrophages
- inflammation –> granuloma –> nerve damage
- DTH+ to lepromin (skin test antigen)
I: LL
- Type 2: CD8 > CD4
- T cells produce cytokines (IL-4, IL-10) & activates antibodies
- bacteria invade Schwanna cells & macrophages –> nerve damage
- DTH(-) to lepromin (skin test antigen)
D
- skin biopsy
- # s of acid-fast bacilli & lymphocytes in skin lesion
- tuberculoid: low bacterial #s, high lymphocytes & granulomata
- lepromatous leprosy: high bacterial #s, few lymphocytes, many “foamy” macrophages
T
- Dapsone
- Rifampin
33 Most Common Non-Tuberculous Mycobacteria (NTM) (5)
All (5)
M. avium-intracellulare
- most common
- causes chronic pulmonary disease
M. marinum
- marine organism
- swimmer’s / fish tank granuloma
M. ulcerans
- causes Buruli ulcer
- toxin necrotizes skin
M. kansasii
M. fortuitum
All
- difficult to treat
- acid-fast
- grow faster than M. tuberculosis
- environmental
34 Factors that can result in an immunocompromised state (8)
Barrier impairment/damaged integument
Changes in ability to physically clear bacteria
Loss of specific immune function due to inherited defect
Infection with another pathogen
Treatment with immunosuppressive drugs or regimens (granulocytopenia)
Age
Stress or malnutrition
Hodgkin’s disease
34 Factors that can result in an immunocompromised state:
Barrier impairment/damaged integument
Changes in ability to physically clear bacteria
Loss of specific immune function due to inherited defect
Infection with another pathogen
Treatment with immunosuppressive drugs or regimens (granulocytopenia)
Age
Stress or malnutrition
Hodgkin’s disease
Barrier impairment/damaged integument
- burn wounds
- catheter (nosocomial)
- staphylococci
- P. aeruginosa
Changes in ability to physically clear bacteria
- P. aeruginosa: lungs can’t clear bacteria due to mucus production (cystic fibrosis)
- splenectomy: changes in complement & phagocytes
Loss of specific immune function due to inherited defect
- mutations: recessive or X-linked
- loss of B or helper T cells: antibodies not made
- loss of T cells: more severe (herpes)
- loss of phagocytic function
- changes in complement (Neisseria)
Infection with another pathogen
- acute infection
- treatment w/ antibiotics: yeast infections, C. difficile
- physical changes: chancre sores, viral respiratory infections
- HIV infection: loss of CD4 T cells
Treatment with immunosuppressive drugs or regimens (granulocytopenia)
- transplants
- cytotoxic drugs
- causes neutropenia, granulocytopenia, local infection, disseminated infection, & sepsis
- most common pathogen associated w/ granulocytopenia: Aspergillus
Age (elderly & infants)
Stress or malnutrition
Hodgkin’s disease (malignant lymphoma): impaired cellular immunity
34 Opportunistic pathogens in AIDS patients (9)
Common types of infections in HIV+ patients (5)
- Mycobacterium tuberculosis
- Mycobacterium avium
- Candida
- Varicella zoster virus
- Pneumocystis (carinii) jiroveci
- Cryptococcus neoformans
- Cytomegalovirus
- Histoplasma capsulatum
- Toxoplasma gondii
Oral
- Candida albicans
- Oral Hairy Leukoplakia (EBV-related)
- HSV
Skin
- Kaposi’s sarcoma
Ocular
- Cytomegalovirus (CMV)
- Varicella-zoster retinitis
- Toxoplasma gondii
Pulmonary
Nerulogic
34 Opportunistic Pathogens:
Viral (2)
Bacterial (6)
Protozoa (3)
Fungal (6)
Reactivation of latent infections (1)
- Herpes Simplex
- Cytomegalovirus (CMV)
- Pseudomonas sp.
- Staphylococcus aureus
- Streptococcal sp.
- Haemophilus influenzae
- Escherichia coli
- Mycobacterium sp.
- Toxoplasma gondii
- Cryptosporidium
- Microsporidium
- Aspergillus
- Candida
- Pneumocystis carinii
- Histoplasma capsulatum
- Coccidiodes immitis
- Cryptococcus
Toxoplasma gondii
34 Toxoplasma Gondii:
Pathogenesis
- Type of pathogen
- Found in…
- Reservoir
- Undergoes sexual cycle in…
- Common latent infection
Immune System
- Immune response
- Replicative form
- Latent form
Disease Course (4)
Diagnosis (3)
Prevention
P
- obligate intracellular parasite
- cat feces & uncooked meat
- rodents
- cats
- toxoplasma
I
- cell mediated immunity characterized by CD8 CTL and IFN-g production by CD4 T cells and NK cells
- tachyzoites: live in macrophages, destoryed by immune responses
- cyst: in the brain
D
- Common asymptomatic infection
- Acute infection in immunocompetent: usually resolves w/o treatment
- Immunocompromised patient: toxoplasma encephalitis (neurological symptoms) & ocular toxoplasmosis (congenital)
- Congenital toxoplasmosis: results in serious, chorioretinitis, CNS disease
D
- neurologic symptoms
- serologic testing
- CT scan (classic ring-like structure in brain)
P
- pregnant women need to be careful (don’t change cat box)
34 Fungal Infections:
General
- Composition of cell walls
- Composition of cytoplasmic membrane & drugs that target them
- Stain
Forms: reproduction & example(s)
- Filamentous (molds)
- Unicellular (yeasts)
- Dimorphic fungi
Infections: Pathogenic Fungi (3)
Infections: Opportunistic Fungi (4)
Antifungal Drugs
G
- chitin & polysaccharides (rigid)
- sterols: azoles, allylamines, & polyene macrolide antibiotics (amphotericin B, nystatin)
- Gomori methenamine silver stain
F
- Branching & longitudinal extension; Aspergillus
- Budding; Candida albicans & Cryptococcus neoformans
- Hyphae & yeast forms; Histoplasma capsulatum, Blastomyces dermatitidis), & Coccidioides immitis
I: PF
- Histoplasma capsulatum: pulmonary, Ohio/Mississippi River
- Blastomyces dermatitidis: systemic disease
- Coccidioides immitis: pulmonary infection), SW US
I: OF
- Candida albicans: yeast infections, thrush
- Aspergillus sp.: deep fungal infections
- Cryptococcus neoformans: CNS, pulmonary infections
- Pneumocystis jirovecii: pulmonary, PCP, AIDS patients
AD
- newer azoles
- echinocandins
- amphotericin
34 Coccidioides immitis:
Biologic Characteristics
- Type of pathogen
- Disease resembles…
- Eliminated by…
Phases (4)
Endemic areas (2)
Clinical Manifestations
- Most
- Fewer
- Immunocompromised
- Correlates w/ disease severity
BC
- dimorphic fungus
- tuberculosis
- T cell responses & macrophage activation
P
- mycelial form in soil: infectious
alternate cells along hypha become barrel-shaped (arthroconidia)
- disruption by wind allows them to become airborne as spores
- spores convert to spherules: not infectious
- spherules reproduce, rupture, & release endospores
E
- southwestern states
- Arizona
CM
- asymptomatic
- primary disease, usually resolves spontaneously
- susceptible to chronic or disseminated infection & reactivation
- antibody titers & antigen concentration in blood
34 Candida albicans:
Biologic Characteristics
- Type of pathogen
- Reproduction
- Reservoir
- Transmission
Interruption of host defenses (2)
Clinical manifestations (4)
Treatment
BC
- unicellular yeast
- pseudohyphae (elongated budding)
- commensal
- human to human
I
- T cell deficiency increases susceptibility (AIDS, diabetes, *neutropenia)
- iatrogenic causes: antibiotics, catheters
C
- vaginal yeast infections: antibiotics, diabetes, pregnancy
- thrush: oral candiasis
- cancer or AIDS pts: infections of esophagus & GI tract
- disseminated candida infections: multiple organ involvement
T
- antifungal drugs
35 General Travel Advice (9)
1) Food/drinks: avoidance of contaminated food and water
2) Road trauma
3) Sex-STI’s: syphilis, genital herpes, gonorrhea, Chlamydia, lymphogranuloma venereum (LGV), HIV and Hepatitis B
4) Insect precautions: for malaria, Dengue, Chikungunya, and WNV; use protective clothing, insect repellants, & bednetting
5) Avoidance of animal bites: feeding monkeys, biking and jogging make dogbites more likely
6) Local medical care: test results may not be reliable, medication may not contain active ingredients, have an emergency medical kit
7) High altitude destinations: Peru, Bolivia, Tibet, & Africa; travelers who dive need to allow sufficient decompression time prior to flying
8) Swimming and rafting in fresh water lakes and rivers: risk for schistosomiasis and leptospirosis
9) Pre-existing illnesses: carry own medication & letters stating necessity
35 Specific Travel Advice:
Host
Environment
Immunocompromised
Region & Season
Health Care Workers
Government
Age, pregnancy status, underlying health conditions, immunosuppressed state, medications and immunization history
Season, duration, itinerary
Immunizations, inactivated vaccines
Malaria, yellow fever, tick-borne encephalitis, Japanese encephalitis and meningococcus
N95 respirators (TB), vaccination (Hepatitis B), Post-exposure prophylaxis (HIV)
Vaccinations before entering a country
