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Flashcards in M34: Opportunistic Infections Deck (26)
1

Immunocompromise and opportunistic infection:

1. An immunocompromised person is deficient in a mechanism(s) required for complete _

2. An opportunistic pathogen is defined as one that exists in the _ and _.

a. can be (4).

b. Disease can be caused by _ or _ with an opportunistic pathogen

1. protection against a pathogen

2. environment (or even the host)
does not usually cause disease in a immunocompetent host

a. bacteria, parasites, fungi, or viruses

b. initial infection or reactivation of previous infection

2

Types of immunocompromised:
Barrier impairment/damaged integument

a. Normal barrier (_, _) is broken so microorganisms can enter (2)

b. Nosocomial infections are often the result of _ impairment (e.g. _-related infections)

c. Examples of infections associated with skin barrier impairment (e.g. intravenous catheter) (4)

a. skin, mucosa
i. burn wounds
ii. catheter

b. barrier
catheter

c.
- Coagulase negative staphylococci
- Pseudomonas aeruginosa
- Acinetobacter
- Candida

3

Types of immunocompromised:
Changes in ability to physically clear bacteria

a. An example is (bacteria) lung infections due to _ (lung cannot clear bacteria due to mucus production)

b. _: changes in complement components, antibodies, resulting in loss of _ function: susceptible to severed infections with (bacteria, bacteria)

a. Pseudomonas aeruginosa
cystic fibrosis

b. Splenectomy
phagocytic
Streptococcus pneumoniae, Haemophilus influenzae

4

Types of immunocompromised:
Loss of specific immune function due to inherited defect

a. Mutations are usually (dominant / recessive), several are _ linked. Most are in (innate / adaptive), not (innate / adaptive), immunity.

b. With a loss of B cells or helper T cells, _ are not made.

i. Infections with (intracellular / extracellular) bacteria are common

ii. Pyogenic bacteria and encapsulated bacteria cause infections in these immunocompromised patients. (3)

a. recessive
X-chromosome
adaptive
innate

b. antibodies

i. extracellular

ii.
- Streptococcus pneumoniae
- Staphylococccus
- Haemophilus influenzae

5

Types of immunocompromised:
Loss of specific immune function due to inherited defect

c. Loss of (B / T) cells (all or one subset) usually more severe immuno-compromise than loss of (B / T) cells. Infections with _, _, and _ are seen.

Herpes virus infections:
• (4)
• (1)
• Respiratory viruses (2)
(5)

c. T
B
bacteria, viruses, fungi

• HSV, zoster, Epstein Barr Virus, cytomegalovirus
• Adenovirus
• Respiratory viruses (RSV, influenza)
• Listeria monocytogenes
• Mycobacterial infections
• Pneumocystis
• Cryptococcus
• Histoplasma

6

Types of immunocompromised:
Loss of specific immune function due to inherited defect

d. Loss of _ cell function results in infections with microorganisms that are usually controlled by _ or _

i. Examples: bacteria: (2)

ii. Example: fungi: (1)

e. _ deficiency also a genetic
mutation. These patients are susceptible to _ infections.

d. phagocytic
macrophage or neutrophils

i. Staphylococcus aureus, Serratia marcescens

ii. Aspergillus

e. Complement (C5-9, membrane attack complex)
Neisseria

7

Types of immunocompromised:
Infection with another pathogen

a. Acute infection with some pathogens can cause (transient / long-lasting) and (mild / severe) immunosuppression, leading to _ infections (e.g. measles)

b. Treatment with antibiotics can result in increased _, e.g. yeast infections

c. Physical changes (chancre sores, viral respiratory infections) provide _ for other pathogens.

a. transient
mild
secondary

b. proliferation of other normal flora

c. entry sites

8

Types of immunocompromised:
Infection with another pathogen

d. _ infection eventually causes widespread immunosuppression

i. loss of _ cells, changes in _ regulation

ii. Infections are primarily those that are usually controlled by _

iii. Opportunistic and standard pathogens cause disease in _ patients.

Examples: (9)

d. HIV

i. CD4 T
cytokine

ii. CMI

iii. AIDS

• Mycobacterium tuberculosis
• Mycobacterium avium
• Candida
• Varicella zoster virus
• Pneumocystis (carinii) jiroveci
• Cryptococcus neoformans
• Cytomegalovirus
• Histoplasma capsulatum
• Toxoplasma gondii

9

Types of immunocompromised:
Treatment with immunosuppressive drugs or regimens predisposes patients to opportunistic infections (often granulocytopenia)

a. _ with chemotherapy or irradiation, causing granulocytopenia

b. _ drugs used in treatment of malignant diseases

c. The immunosuppressive regimen causes _ and diminished functioning of _ cells, in addition to diminished _-mediated immunity.

d. loss of function of _ can occur with treatment regimens

e. Granulocyte deficiency can result in (3)

f. most common pathogens associated with granulocytopenia (6)

a. Transplants (bone marrow and organ)

b. cytotoxic

c. neutropenia
phagocytic
cell

d. granulocytes

e. local infection, disseminated infection, sepsis

f.
- Staphylococcus aureus
- Coagulase negative staphylococci
- Streptococcus
- Enerococcus
- E. coli
- Aspergillus

10

Types of immunocompromised:

6. Immunocompromise due to _ leads to an increase in susceptibility to opportunistic infections in the _ and _.

7. Immunocompromise due to _ or _
- Eg stress-associated reactivation of _ = _

8. Other factors
- _ (malignant lymphoma): impaired _ immunity

6. age
elderly and infants

7. stress or malnutrition
varicella zoster virus = shingles

8. Hodgkin’s disease
cellular

11

Common opportunistic infections in immunocompromised patients:

Viral (2)

Bacterial (6)

Protozoal (3)

Fungal (6)

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

12

Opportunistic infections in immunocompromised patients:

Reactivation of latent infections can lead to disease (5)

a. Herpes simplex virus
b. Mycobacterium tuberculosis
c. Toxoplasma Gondii
d. Varicella zoster (shingles)
e. Cytomegalovirus (CMV)

13

Opportunistic infections in immunocompromised patients:
Common infections seen in HIV+ patients

a. Oral: (3)

b. Skin: (1)

c. Ocular: (3)

d. Pulmonary (numerous) (9)

e. Neurologic (2)

i. Candida albicans
ii. Oral Hairy Leukoplakia (EBV-related)
iii. HSV

i. Kaposi’s sarcoma (HHV8)

i. Cytomegalovirus (CMV)
ii. Varicella-zoster retinitis
iii. Toxoplasma gondii

i. Mycobacterium tuberculosis (also M. avium, M. kansasii)
ii. Streptococcus pneumoniae
iii. Staphylococcus aureus
iv. Haemophilus influenzae
v. Pneumocystis
vi. Cryptococcus neoformans
vii. Histoplasma capsulatum
viii. Coccidioides immitis
ix. CMV

i. Toxoplasma gondii
ii. CMV

14

A 37 year-old homosexual male comes to the emergency room complaining of fever and headache. Four years earlier, he tested positive for the human immunodeficiency virus (HIV), but his immune system was judged to be functioning well, and no therapy was prescribed. One year ago, he was admitted to a hospital with pneumonia-like symptoms, and was diagnosed with Pneumocystis carinii pneumonia. At this time, his T cell count was low (175/mm3). After successful therapy, he was started on zidovudine, lamuvidine and efavirenz for HIV and sulfamethoxazole/trimethoprim to prevent recurrence of Pneumocystis infection. He was in relatively good health until two weeks ago when intermittent, dull, generalized headache began. He was also confused and disoriented. One week ago, the headache became more severe andconstant. His fever was 38.1°C. Physical examination suggested the patient's condition to be normal.

Computer tomography (CT) scan of the head shows two space-occupying lesions of 1.7 cm in diameter in the left parietal lobe and 1.0 cm in the posterior right frontal lobe. Both lesions show circumferential ("ring") enhancement following injection of contrast medium. The CT scan is considered to be most consistent with a diagnosis of _. In addition, his serum is positive for IgG antibody to _. The patient is treated with sulfadiazine and pyramethamine, and responds favorably.

Cause: _

toxoplasmosis

Toxoplasma gondii

Toxoplasma encephalitis

15

Toxoplasma Gondii:

a. (Obligate / Facultative) (intracellular / extracellular) parasite

_ and _ are a source of infection

_ are natural hosts for T. gondii, and infection with the parasite can cause rats (or mice) to become _ to cats (and therefore _)—ensuring the parasite will be able to undergo the _ cycle in cats…the parasite modifies the brain and behavior of infected rodents…

b. _: common latent infection in population of many countries. _ (acute infection during pregnancy) can lead to severe complications for fetus/newborn (chorioretinitis, CNS disease)

c. Reactivation of latent infection (_ in brain) can occur in _ patients

d. Immune response to T. gondii is primarily _ mediated immunity characterized by _ and _ production by CD4 T cells and NK cells

e. _ live in macrophages but can be destroyed by immune responses (_ form in humans)

f. Latent (cyst) form in the _ can remain clinically dormant for _

a. Obligate
intracellular

Cat feces and uncooked meat

Rodents
attracted
eaten
sexual

b. Toxoplasma
Congenital toxoplasmosis

c. cysts
AIDS

d. cell
CD8 CTL and IFN-g

e. Tachyzoites
replicative

f. brain
lifetime of host

16

Toxoplasma Gondii:
Prevention and diagnosis can control spread of infection.

a. _ need to be especially careful to avoid coming into contact with the microbe (don’t change cat box!)

b. Diagnosis of toxoplasmosis infection in _ patients

i. _ symptoms, _ testing (increase in antibody titer indicates possible disease), _ (classic ring-like structure in brain)

c. Diagnosis of _
• can be asymptomatic at first
• presents as ocular or CNS abnormalities

d. Treatment in the form of _ is available.

a. Pregnant women

b. HIV+

i. neurologic
serologic
CT scan

c. congenital toxoplasmosis

d. drugs

17

Fungal Infections:

a. Fungal infections are an increasing problem in _ patients.

b. 40% deaths from _ infections are due to fungi.

c. Fungi cause many common superficial infections in immunocompetent persons
e.g. _, _

d. Composition of fungi cell walls

i. Cell wall is _, composed of (peptidoglycan / chitin) (not (peptidoglycan / chitin)) and polysaccharides

ii. _-containing (ergosterol and zymosterol) cytoplasmic membrane is target for antifungal drugs, such as _, _, and _ antibiotics (amphotericin B, nystatin)

e. Fungi are stained by _ methenamine silver stain

a. immunocompromised

b. nosocomial

c. ringworm, athletes foot

i. rigid
chitin
peptidoglycan

ii. Sterol
azoles, allylamines, and polyene macrolide

e. Gomori

18

Fungal Infections:

Fungi are (prokaryotes / eukaryotes) with different morphologic forms

i. (unicellular / dimorphic / filamentous) fungi (molds) grow by branching and longitudinal extension
- example: _ species

ii. (unicellular / dimorphic / filamentous) fungi (_) reproduce by budding
- Examples:
--> _ (can be considered dimorphic because of pseudohyphae)
--> _

iii. (unicellular / dimorphic / filamentous) fungi have both hyphae and yeast forms
- examples: (4)

eukaryotes

i. filamentous
- Aspergillus

ii. unicellular
yeasts
--> Candida albicans
--> Cryptococcus neoformans

iii. dimorphic
--> Histoplasma capsulatum
--> Blastomyces dermatitidis
--> Coccidioides immitis (hyphae and spherules)
--> Sporothrix schenckii

19

Fungal Infections:
Infections can be due to pathogenic or opportunistic fungi

Pathogenic fungi

i. _ (pulmonary infection)

ii. _ (systemic disease)

iii. _ (pulmonary infection)

Opportunistic fungi

i. _ (yeast infections, thrush)

ii. _ sp. (deep fungal infections)

iii. _ (CNS, pulmonary infections)

i. Histoplasma capsulatum

ii. Blastomyces dermatitidis

iii. Coccidioides immitis

i. Candida albicans

ii. Aspergillus

iii. Cryptococcus neoformans

20

Fungal Infections:

There is a lack of good treatments for fungal infections, although improving

Relatively few effective anti-fungal drugs are available

i. Fungi share characteristics with _ cells, making it difficult to design effective, _ drugs

ii. treatments include newer (3)

There has been an increasing _ to anti-fungal drugs.

i. mammalian
non-toxic

ii. azoles, echinocandins, amphotericin

resistance

21

Case study: A 34 year old woman visits her doctor complaining of lower respiratory infection symptoms: cough, malaise, fever, chills, and a lack of appetite. Her previous history reveals that the woman is also a diabetic. She tells the doctor that she has just returned from a visit to the San Joaquin Valley in California. Chest x-rays show a lower lobe infiltrate and she is treated with oral amoxicillin, for suspected pneumonia. No improvement is seen. A PPD skin test for tuberculosis is negative, as is an HIV serology test. Sputum specimens are negative for acid fast bacilli and are sent for fungal cultures and stained for fungi. Skin tests with fungal antigens were positive for _ and negative for Histoplasma capsulatum antigens, and a high antibody titer to _ antigens was observed. The patient was treated with amphotericin B and recovered.

Cause: _

Coccidioides immiti

C. immitis

Coccidioides immitis

22

Coccidioides immitis:

A _ fungus.

i. mycelial phase in the _.

Alternate cells along the hypha become _-shaped (_) and are very fragile. Disruption of hyphae at these sites (by wind) allows arthroconidia to become _ as _.

The mycelial form is the (infectious/ non-infectious) form.

dimorphic

i. soil

barrel (arthroconidia)
airborne as spores

infectious

23

Coccidioides immitis:

ii. Spores within humans convert to _

iii. Spherules reproduce by forming _

iv. Spherules rupture and release _, which form _. Spherules are (infectious / not infectious) to others, and thus this infection (is / is not) passed person to person.

b. Endemic areas are the _ states of the United States, and _ with 2/3 infections in _. In U. S., ~100,000 are infected annually

c. The disease resembles _ pathologically and symptomatically

d. _ cell responses are important for elimination of fungus, probably by activation of _

ii. spherules

iii. internal endospores

iv. endospores
more spherules
not infectious
is not

b. southwestern
Northern Mexico
Arizona (Phoenix and Tuscon most affected)

c. tuberculosis

d. T
macrophages

24

Coccidioides immitis:
Clinical Manifestations

i. 60% of those infected are (symptomatic / asymptomatic)

ii. 40% of those infected have _ disease 1-3 weeks after infection. This disease usually resolves _. Small percentage of infected people may have cavities in _

iii. Immunocompromised patients are more susceptible to _ or _ infection; chronic infection can lead to “_” of lesions

Immunocompromised patients with increased susceptibility include _ patients, _ patients, and patients receiving _ therapy

iv. Chronic or immunocompromised patients are treated with _

v. _ and _ in blood correlate with disease severity

i. asymptomatic

ii. primary
spontaneously
lungs

iii. chronic or disseminated
reactivation

diabetic
AIDS
immunosuppresive

iv. anti-fungal drugs

v. Antibody titers and antigen concentration

25

Candida albicans (example of “opportunistic” fungus)

a. C. albicans is a _. The organism is (unicellular / multicellular), but can have _ (elongated budding), and so is sometimes considered _

b. It is a _--most “infections” are of _ origin. In some instances, can be passed from human to human

c. Interruption of _ must occur for C. albicans to cause disease

i. Naturally occurring _ (including _, _, and _) increases susceptibility. _ are susceptible, probably due to immature immune system

ii. iatrogenic causes include _, indwelling intravenous _

iii. antibiotics suppress other _

iv. _ predispose to disseminated infection

a. yeast
unicellular
pseudohyphae
dimorphic

b. normal commensal
endogenous

c. host defenses

i. immunocompromise (including T cell deficiency, AIDS and diabetes)
Newborns

ii. antibiotics
catheters

iii. normal bacterial flora

iv. catheters

26

Candida albicans (example of “opportunistic” fungus)

d. Clinical manifestations can be _ or _

i. _: predisposing factors include antibiotic therapy, diabetes, pregnancy. Very common infection (~75% of women during lifetime)

ii. _ is _. Newborns (possible infection from mother’s vaginal tract), also common in AIDS and cancer patients

iii. Cancer or AIDS patients can have Candida infections of _ and _. _ can occur in AIDS patients

iv. _ candida infections occur primarily in immunocompromised
patients.
- multiple organ involvement: (4) most common.
- Disseminated candida can be difficult to diagnose, therefore treatment is often too _, and patient succumbs.

e. _ and _ can contribute to disseminated infection

f. Treatment includes _, depending on site of infection

d. cutaneous or disseminated

i. Vaginal yeast infections

ii. Thrush is oral candidiasis

iii. esophagus and GI tract
Mucosal candidiasis

iv. Disseminated
- kidney, brain, eye, and myocardium
- late

e. neutropenia and catheters

f. antifungal drugs