LOs: 33-35 Flashcards Preview

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Flashcards in LOs: 33-35 Deck (22):
1

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

2

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

3

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

4

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

5

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

6

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

7

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

8

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

9

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

10

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)

11

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

12

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

13

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

14

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

15

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

16

35 Standard Vaccinations (5)

–TdaP (Tetanus, Diphteria and acellular Pertussis)

–Influenza

–Pneumovax

–Polio

–Measles

17

35 Traveler's Diarrhea:

Causes
- Bacterial (4)
- Viral (2)
- Parasites (2)

Treatment
- Antibiotics
- Other (3)

C
- E. coli, Campylobacter, Salmonella, Shigella
- V: Norovirus, Rotavirus
- P: Giardia, Cryptosporidium

T
- FQs, azithromycin, (cotrimoxazole, doxycycline, & rifaximin) if diarrhea has fever, blood, & loose stools
- hydration, loperamide (imodium), pepto-bismuth

18

35 Malaria:

Highest Risk

Endemic Areas

Preventative Measures

Chemopropylaxis
- P. falciparum (4)
- P. vivax & P. ovale (1)

Travelers visiting friends & relatives

Rural or primitive places in Africa, SE Asia, & Central/South America

Protective clothing, insect repellants with DEET and permethrin impregnated bednetting

- Chloroquine: limited use b/c of widespread resistance
- Doxycycline: daily dosing, 4 week course, low cost per dose
- Mefloquine: weekly dose, 4 week course, cheaper > 7 days
- Atovaquone/proguanil: daily dose, 1 week course, cheaper < 7 days

Primaquine

19

35 Typhoid Fever (Salmonella typhi):

Endemic areas

Efficacy of the inactivated or live attenuated vaccine

Treatment

India, Central/South America, & Asia/Africa

Lasts 3-5 years, 50-70% effective

- Bactrim
- Amoxicillin
- FQs
- Ceftriaxone (for resistance)

20

35 Travelling:

Yellow Fever outbreak areas

Meningococcal vaccine given to travelers to...

Rabies vaccine

Japanese encephalitis endemic areas

South America & Africa

Meningococcal belt in Africa during the period Dec-June for pilgrimage to Mecca (Hajj)

Unvaccinated individuals need rabies IgG in addition to 4 doses of the rabies vaccine as
post-exposure prophylaxis

Rural & prolonged stays in South East Asia

21

35 Evaluating a returning traveler with fever:

Physical Exam (4)

Laboratory Exam (6)

Other (2)

PE
- neurologic exam: encephalopathy, meningismus
- skin: rashes, lesions
- abdominal exam: hepatosplenomegaly
- lymphnode: lymphadenopathy

LE
- CBC
- liver enzymes
- thick & thin blood smear
- urine analysis
- blood & stool cultures
- ova & parasite exam of stool

O
- chest xray
- abdominal ultrasound

22

35 Incubation Time:

Specific
- Malaria
- Typhoid fever
- Viral hemorrhagic fever

Short Duration (less than 10 days) (3)

Intermediate Duration (10-21 days) (2)

Long (greater than 21 days) (5)

Specific
- 7-90 days
- 7-21 days
- 2-21 days

Short
- Dengue: rash, thrombocytopenia
- Rickettsia: eschar, lymphadenopathy
- Legionella: pulmonary infiltrate

Intermediate
- Malaria: thick blood smear, thrombocytopenia
- Typhoid fever: leukopenia, an-eosinophilia

Long
- Hepatitis A: fever absent, elevated LFT’s
- Schistosomiasis: eosinophilia
- Tuberculosis
- Amebic liver abscess: leukocytosis, ESR elevated
- Leishmaniasis: splenomegaly, pancytopenia