Exam 3 Week 3

Question 1

Describe the structure of a fungal cell and identify how it differs from prokaryotic and mammalian cells (size, structure, composition, classification, virulence, pathogenic factors)

• *which is dimorphic?
• which is unicellular
• which is multicellular

**WHAT is the only fungi with a capsule?

Answer 1

Structure ; very different from bacteria in all essential aspects;

• size (larger than bacteria)
• structure (eukaryotic with nucleus and CELL MEMBRANE contain sterols - ERGOSTEROL)
• composition (chitin, glucan, mannan in CELL WALL) while bacteria has peptidoglycan, muramic acid and TA in cell wall
• identification, classification (dimorphic - unicellular yeast and multicellular filamentous mold). Yeast are single cells produced by budding while mold are multicellular filaments
• virulence and pathogenesis; very few. **ONLY C. NEOFORMANS HAS CAPSULE. Other pathogenic factors; adhesins (c. Albicans), capsule in C. NEOFORMANS, ability to survive in macrophage H. Capsulatum, lack of host resistance)
• *FUNGI is dimorphic- 2 different ways it can show (depending on temperature).
  1) body temperature - YEAST. Yeast is unicellular fungi produced by budding. They are moist mucous or waxy colonies that resemble bacteria
  2) room temperature - MOLD. Long filaments (hyphae; coenocytic or septate) or a mat (mycelium - intertwined hyphae)

**exception is Candida albicans; yeast outside the body and filamentous hyphae inside the body.

Question 2

Describe the clinical classification of fungal infection (4)

1. Outermost layers of skin/hair
2. Deeper into epidermis and invasive hair and nails
3. Dermis, subcutaneous tissue, muscle and fascia
4. Deep seated. Originate in the Lungs and spread to other organs (identify 4 examples)
5. Caused by members of normal flora

Answer 2

Classification
1. SUPERFICIAL mycoses; outermost layers of skin and hair

2. CUTANEOUS mycoses; extend deeper into the epidermis as well as invasive hair and nail disease. produce annular ring like infect (tinnea infection)??

3 SUBCUTANEOUS mycoses; infections involving dermis, subcutaneous tissues, muscle and fascia. They do not break skin barrier to enter. They only have access if the barrier is already broken.

4. SYSTEMIC (deep seated mycoses); infections originate primarily in the lung and can spread to many organ systems. ALL DIMORPHIC. Like to reside in SPECIFIC PART GEOGRAPHICALLY. Affinity for SPECIFIC ORGAN
   A. Coccidioidomycosis; phoenix in Arizona
   B. Paracocciidioidomycosis
   C. Blastomycosis
   D. Histoplasmosis
5. Opportunistic mycoses; infections caused by members of normal flow when host defenses have been severely compromised

Question 3

Describe various diagnostic techniques for fungal infection

• predisposing factors
  1. 3 Dx technique

2. Identify the use and what is seen in the following stains
   A. KOH mount
   B. Calcifor white stain
   C. PAS (periodic acid - Schiff reagent)
   D. GMS stain (Gomori METHENAMINE silver)
   E. Gram stain
   F. Giemsa stain

Answer 3

Diagnosis ; FUNGAL SPORES HELPS IN DIAGNOSIS

*Predisposing factors; intrinsic vs extrinsic
A. Intrinsic; age, stress, nutritional status, pregnancy, diabetes
B. Extrinsic; burns, steroid, immunosuppressive therapy, antibiotics

1. Diagnosis based on 3 lab approaches
   A. Microbiological; spore, hyphae
   B. Immunologic
   C. Histopathology;
2. Diagnosis of fungal infection
   A. KOH mount; 10% potassium hydroxide. Provides clarity of tissue so you can see fungi under light microscope (with or without staining)
   B. Calcifor white stain; detects fungal cell wall. Used in combo with KOH. Used for all fungi including pneumocystis jirovecii (carinii)
   C. PAS (periodic acid - Schiff reagent); forms aldehyde from chitin monomer in cell wall. Schiff reagent react with aldehyde to form RED DYE. Stains both yeast and hyphae in tissues
   D. GMS stain (Gomori METHENAMINE silver); respiratory specimen. BEST STAIN FOR DETECTING ALL FUNGI
   E. Gram stain; bacteria and fungi most fungi stain gram positive except for cryptococcus neoformans that appear gram negative
   F. Giemsa stain; does not stain cyst wall of pneumocystis but will detect intracellular histoplasmosis capsulatum and both intracystic and trophic forms of neumocystis jirovecii

Question 4

Describe the action of antifungal agents

1. CELL WALL inhibitors of glucan and chitin synthesis
   * 2. CELL MEMBRANE inhibitors of ergosterol synthesis
   * 3. Direct membrane damage (2)
2. Disruption of microtubules and inhibition of mitosis
   * 5. Nucleic acid synthesis
3. Inhibition of protein synthesis (2)

Answer 4

Action

1. CELL WALL inhibitors of glucan and chitin synthesis
   - Echincandins; inhibit glucan synthesis
   - Nikkomycin; inhibit chitin synthesis
2. CELL MEMBRANE inhibitors of ergosterol synthesis
   - azole
   - allylamines; target squalene epoxidase
3. Direct membrane damage
   - Polyenes e.g Amphotericin B, Nystatin; membrane sterols
4. Disruption of microtubules and inhibition of mitosis
   - Griseofulvin
5. Nucleic acid synthesis
   - Flucytosine
6. Inhibition of protein synthesis (2)
   - Sordarins
   - Azasordarins

Question 5

Describe Opportunistic fungal infections

• what must happen before this infection can occur?*
• 3 major examples (5 total)
• Yeast when outside the body, but hyphae in body?
• only one with capsule?
• septate vs aseptate ?

Answer 5

Opportunistic; require impairment of host immunity to cause serious infection (localized to severe systemic infection)

1. Yeast; candida and cryptococcal NEOFORMANS
   A. CANDIDA; yeast when outside the body and filamentous hyphae when inside the body. **exception to the rule
   B. Cyrtococcus NEOFORMANS; CAPSULE
2. Filamentous fungi; aspergillus and zygomycetes
   A. ASPERGILLUS (fumigatus, niger, flavus); SEPTATE (separated by cross walls)
   B. ZYGOMYCETES (rhizopus, Mucor, rhizomucor, absidia); NON-SEPTATE
3. Pheumocytis carnii

Question 6

Describe morphology, List clinical characteristics and laboratory diagnosis for Opportunistic fungal infections: Candida albicans, Aspergillosis:, Mucormycosis Cryptococcosis, Pneumocystis Carinii

• which is dimorphic? Which isn’t?
• which is Dx by germ tube formation
• which is filamentous fungi (2); which of 2 is septate vs aseptate?
• which invade blood and brain
• which occur as terminal event in patient with acidosis or uncontrolled diabetes
• which is only fungi with capsule
• which do not have ergosterol?
• what is most common cause of fungi meningitis
• which is common in AIDS patient?

Answer 6

1. CANDIDA ALBICANS; mixture of oval yeast like stain and pseudo hyphae - germ tube formation? (DIMORPHIC FUNGI)
   - part of normal flora (GI tract from mouth to rectum)
   - superficial; THRUSH - white patches on oral mucosa, vaginal candidiasis - thick curdlike discharge, dermatitis - diaper rash, onychomycosis and paronychia - nails
   - toxins; adhesins, gliotoxin (immunosuppressive toxin), germtube formation (hyphae formation associated with tissue invasion)
   * *Diagnosis with KOH PREP and staining, usually OPPRUTUNISTIC
   * *GERM TUBE FORMATION in human serum is specific to Candida albicans
   - treatment; uses azole for mucosal/cutaneous infection (attack cell membrane). For systemic infection use - Amphotericin B IV and flucytosine (only with Amphotericin B because of resistance)
2. Opportunistic filamentous fungi ; NOT DIMORPHIC MOLD
   A. MUCORMYCOSIS (ZYGOMYCOSIS, phycomycosis); SPONGIUM sporrulation. NO SEPTATE. Resemble twisted ribbon like structure. *Invade blood and brain. *Terminal event in acidosis or uncontrolled diabetes (rhinocerebral mucormycosis); also invasive with severely burnt patients. Symptoms; facial pain, headache, persistent change in mental status, bloody nasal discharge, discolored eyes, fixed pupil
   *Treatment; correct underlying condition and give Amphotericin B.
   B. ASPERGILLUS; CONIDIAPORES sporulation pattern. Not dimorphic; SEPTATE hyphae
   *Treatment - Amphotericin B or 5-flucytosine for invasive aspergillosis
3. Cryptococcal neoformans ; yeast like
   - only fungi that HAS CAPSULE (anti-phagocytic capsule)
   - pigeon droppings enriched soil
   - cause meningitis (fatal if you don’t treat). MOST COMMON CAUSE OF FUNGAL MENINGITIS
   Diagnosis; INDIA INK (CSF)
   Treatment; Amphotericin B and flucytosine
4. Pneumocystic jiroveci; looks like Protozoa (round cup shape)
   - HAS NO ERGOSTEROL
   - AIDS patients
   Diagnosis; microscopy of biopsy or bronchial alveolar lavage - ground glass appearance. Gomor methenamine silver stain show cup shaped organism.
   Treatment; sulfamethoxazole or pentamidine isothionate

Question 7

Define: a) Dimorphism. b.) Germ tube formation.

Answer 7

A. DIMORPHISM; exist in 2 forms based on temperature

• body temperature; yeast (cellular form)
• room temperature; mold. Most commonly isolated dimorphic molds in the US are; histoplasmosis capsulatum, blastomyces dermatitidis, coccidioides immitis, sporothrix schenckii

B. Germ tube formation : CANDIDA ALBICANS form germubes in human serum and other culture media at 37 degree Celsius
- the germ tube test permits the exact identification of the yeast as Candida albicans within 3-5 hours

Question 8

Identify reasons for increase in fungal infections (4)

Answer 8

1. Advances in antibacterial therapies
   - Imipenem, 3rd Gen. Cephalosporins, other broad
   spectrum antibiotics
   - Result: fungal superinfections
2. Predisposing procedures
   - Placement of indwelling catheters
3. Predisposing treatments
   - Chemotherapy (cause immunosuppression)
4. Predisposing diseases
   - Leukemia, AIDS

Question 9

Lack of antifungal vs antibacterial

Answer 9

1. Bacteria (prokaryotic) invading a eukaryotic host; lots of differences to exploit.
2. Fungi (eukaryotic) invading a eukaryotic host; the number of basic differences to be exploited are limited.
   ● Cell wall - where differences lie between mammals and
   fungi (fungi has cell wall while mammmals don’t)
   ● Chitin (gives strength) and ergosterol

Question 10

Identify antifungal medication (GOLD STANDARD)

MoA; Binds to sterols (ergosterol) of the fungal plasma membrane. Alters the membrane permeability and Results in leakage of essential cell contents (K+ and other molecules) and eventually cell lysis and cell death.
- fungistatic at low conc, fungicidal at high conc

Distribution; poor CSF penetration (intrathecal administraton). Poor absorption if you give orally (not well absorbed in GI tract)

Adverse effect??? Identify the major one
Identify spectrum of activity?

Lipid formulation (3 agents) ?

Answer 10

AMPHOTERICIN B

1. Adverse effect
   - NEPHROTOXICITY ; hypokalemis. Reversible once you stop drug or switch to azole drug
   - Anemia
   - Electrolyte imbalance ; K, Mg and bicarb loss due to renal effects
   - infusion related adverse effects; shaking, chills, fever, myalgias and arthralgias. Premeditate with NSAIDS, acetaminophen, antihistamines or meperidine (severe pain)
2. Spectrum of activity; aspergillosis, Paracoccidioidomycosis, Histoplasmosis, Cryptococcus, Blastomycosis, Candida (Topical use), Coccidioidomycosis
3. Lipid formulations (3)
   A. ABLC; Amphotericin B lipid complex; patients with invasive aspergillosis who are refractory to or intolerant of treatment with conventional amphotericin B.
   B. ABCD; Amphotericin B colloidal dispersion
   C. Liposomal ampotericin B
   **All 3 agents are probably less nephrotoxicity - equivalent efficacy.

Question 11

Identify anti fungal medication

1. MoA;
   - Penetrates fungal cell where it is:
   - *Deaminated to 5-fluorouracil by a fungus specific enzyme, cytosine deaminase (mammalian cells do not convert to 5 FU in large amounts).
   - 5-FU acts as an antimetabolite competing with uracil, which inhibits pyrimidine metabolism and ultimately DNA, RNA and protein synthesis.
2. Distribution; CSF penetration is 60-100%
3. Identify adverse effect? **what is a risky double side effect if you combine with another anti-fungal

Indication/dosing?

Answer 11

FLUCYTOSINE (5-fluorocytosine)

Adverse effects
A. **BONE MARROW HYPOPLASIA; anemia, leukopenia, thrombocytopenia. Anemia common if combined with Amphotericin B

**Best used in combination
- Serious infections of candida and cryptococcus. Possible synergistic effect with Amphotericin B.
- Cryptococcal MENINGITIS in AIDS patients
(combo with Amphotericin B.)
*Resistance can be a problem when used alone, so combination therapy is recommended.

Question 12

Identify CLASS OF anti-fungal medication

MoA; *Interfere with the fungal cytochrome P-450-dependent enzyme (14-α-sterol demethylase) responsible for the
demethylation of lanosterol and conversion to
ergosterol. Ergosterol is the main sterol of the fungal cell membrane.
- inhibits conversion of lanosterol into ergosterol which is the main sterol of fungal cell membrane
*fungistatic in low conc and fungicidal in high conc

1. Identify first gen and second gen
2. Identify side effects (4)

Answer 12

AZOLE (miconazole, sulconazole, clotrimazole, fluconazole, ketoconazole, itraconazole)

1. • first generation; mostly topical use
   • second generation; used systemcally (triazoles). TRIAZOLES have increased affinity for fungal CYPs rather than the mammalian
2. Adverse effects
   A. dose dependent depression of serum testosterone and ACTH (drug used to treat Cushing syndrome)
   - gynecomastia, impotence, decreased libido, azospermia, menstrual irregularities
   B. Nausea and vomiting
   C. Hepatitis (rare)
   D. Increased aminotransferases (NOT RARE)

Question 13

Identify drug interactions of anti-fungal azole (4)

Answer 13

1. P450 interactions; 3A4** - only CYP altered by itraconazole and posaconazole
2. Antacids, PPI, H2 antagonist; decrease absorption of azole due to decrease in acidic environment
3. Warfarin; increased anticoagulation effect (bleed to death)
4. CYCLOSPORINE will increase in concentration (nephrotoxicity)

Question 14

Identify anti-fungal medication (azole)

1. Absorption; rapidly absorbed from GI tract
   - lots of drug interaction so now replaced by INTRACONAZOLE

Indications – largely replaced by Itraconazole
● Histoplasmosis
● Blastomycosis
● Coccidioidomycosis
● Candidiasis
● Tinea*
● Vulvovaginal candidiasis*
● *Not FDA approved indication.

Answer 14

Ketoconazole

Question 15

Identify anti0fungal (azole)

1 absorption; rapidly absorbed from GI tract
- Not affected by gastric pH and food

2. Good distribution ; PENETRATE CSF

*Coccidioidomycosis; Meningitis – DRUG OF
CHOICE due to EXCELLENT CSF penetration and
less morbidity than intrathecal amphotericin B

Answer 15

Fluconazole

• Cryptococcal Infections - Meningitis
• Coccidioidomycosis; Meningitis – Drug of Choice due to excellent CSF penetration and less morbidity than intrathecal amphotericin B
• Candidiasis*
  ● *Candida (Torulopsis) glabrata, Candida krusei
  resistant.
• Prophylaxis of Candidiasis

Question 16

Identify antifungal (azole)

• doesn’t have good CSF penetration
• good spectrum of activity
  Aspergillosis ● Cryptococcal Infections ● Coccidioidomycosis ● Histoplasmosis ● Blastomycosis ● Sporotrichosis ● Dermatophytosis ● Tinea unguium (onychomycosis)

Answer 16

ITRACONAZOLE

• Oral therapy of histoplasmosis/blastomycosis
• Useful for treatment of aspergillosis.
• Possibly useful in some patients with
  candidiasis, cryptococcosis, and
  coccidioidomycosis.
• Amphotericin B should be used if severe,
  life-threatening; can change to itraconazole
  once clinical improvement.

Question 17

Identify anti fugal (azole)

• good CSF penetration
• bioavailability decrease with high fat meal
• lots of drug interactions
• *contraindication?

Adverse effect; BLURRY VISION AND COLOR CHANGES

*8identify uses?

Answer 17

Voriconazole

Contraindications
● Decreased Voriconazole AUC: RIFAMPIN; Carbamazepine/Phenobarbital
● Increase drug concentrations: Quinidine (QT); SIROLIMUS; Ergot Alkaloids

 USES:
● Invasive aspergillosis
● Candidiasis
● May also be useful in patients with therapy-limiting toxicity
associated with conventional regimens.

Question 18

Identify antifungal (azole)

• newer drug (triazoles); similar in structure to itraconazole.
• mostly used in IMMUNOCOMPROMISED PATIENT for treatment of candida and aspergillus
• inhibits CYP3A4
• generally well tolerated but can elevate LFTs

Answer 18

Posaconazole

Question 19

Identify class of anti-fungal medication

1. Mechanism of Action
   - Echinocandin; blocks fungal cell wall synthesis
   - Glucan synthesis inhibitor (B-(1,3)-D-glucan); not found in
   mammalian cells
2. Indications
   - Invasive Aspergillosis – patients that are refractory or
   intolerant to other agents
   - CANDIDA INFECTIONS MAINLY

**identify adverse effects

Answer 19

Caspofungin Acetate (metabolized by P450)

Adverse effects

• *MONITOR Sr Creatnine (kidney effects)
• phlebitis, headache, fever
• increase LFTs

Question 20

Identify class of anti-fungal medication

1. MOA; Disrupts the cells MITOTIC spindle structure
   - Arrests cell division in metaphase.

**Used when other therapies have failed (try topical agents first)

Identify use and adverse effect

Answer 20

GRISEOFULVIN (oral medication, that’s why you want to use the topical options of other drugs first)

Indications
DERMATOPHYTOSIS; Tinea corporis, pedis, cruris, barbae,
capitus, unguium caused by trichophyton, microsporum,
epidermophyton.

Adverse effect
- CYP450 inducer; may need to increase warfarin
Nausea/Vomiting/Diarrhea ● Hypersensitivity/Rash ● Hepatotoxicity ● Nephrotoxicity ● Hematologic effects ● Headache/dizziness (15%)

Question 21

Identify anti-fungal

1. MoA
   - Synthetic allylamine derivative
   - Inhibits squalene epoxidase; Key enzyme in sterol biosynthesis in fungi
2. Adverse effects
   - hypersensitivity
   - hematologic effects (neutropenia, pancytopenia); erythema multiforme, toxic epidermal necrolysis
   - liver enzyme abnormalities
   - HEADACHE, N/V

**lots of drug interaction with P450, cimetidine, rifampin, cyclosporine, warfarin

• *Identify indication of use
• *Contraindication

Answer 21

TERBINAFINE (topical and oral);

• use topical if you also on warfarin due to interaction (can bleed to death)***

Use; ONYCHOMYCOSIS
- At least as effective as itraconazole, less expensive, less drug interactions; however, more possible side effects.
- Onychomycosis is mainly a cosmetic problem;
expense of treatment may outweigh benefits.
- Not recommended if liver or renal dysfunction present; should be avoided during pregnancy.

***AVOID IN PREGNANCY

Question 22

Identify anti-fungal used to treat oral candidiasis (thrush) -3

Answer 22

1. Nystatin; similar to Amphotericin B
   - vaginal suppository can be held in mouth and used as troches but it is bitter
2. Clotrimazole troches
3. Amphotericin B suspension

Question 23

1. Gold standard for SEVERE/SYTEMIC fungal infection
2. Moderate
   - exception?
3. Mild

Answer 23

1. AMPHOTERICIN B
2. Intranazole >Flu
   - exception in candidiasis - stay with Amphotericin B or Flu or Cas
   - IN COCCIDIODOMYOSIS (meninges, disseminated, Pulmonary); use flu or azole
3. Itr > Flu

Question 24

General principles of topical therapy

Answer 24

● Use creams, ointments, and liquids as primary therapy; powders are adjunctive therapy, unless
mild conditions.
● Creams/solutions: preferred for fissured or
inflamed intertriginous areas, such as toe webs,
groin, or scrotum.
● Powder: Shake container or aerosol; confined to
mild lesions or preventive therapy in tinea pedis.
● Sprays: Not recommended for face.
● Treatment of tinea pedis is generally 4 weeks or
longer; others are 2 weeks or more.

Question 25

3 classes of anti-malaria drugs

1. Drugs effective against exoerythrocytic form
2. Drugs effective against erythrocytic form (5)
3. Drugs effective against gametocytic form

**progression of malaria infection

Answer 25

1. Acts in the liver; Primaquine
2. Against spread in RBC
   - chloroquine
   - quinine
   - mefloquine
   - pyrimethamine
   - chloroguanide
3. Primaquine

**Infected mosquito infects sporophytes - liver to form merozoites - released and invade RBC - trophozoite - RBC lyse and infect other RBC - female mosquito pick up gametocytes from infected individual

Question 26

Identify anti-malaria drug

MoA; inhibit sequestration of heme and inhibits the heme polymerase that parasite use to protect itself from ferri IX (Hgb degradation product of host toxic to parasites)
- The result is oxidative damage to cell membrane,
digestive enzymes, and/or other critical macromolecules.
- **Can build resistance
- Has effects on asexual and erythrocytic forms of susceptible parasites
- Use; prevention and treatment of malaria. Not FDA approved for extraintestinal amebiasis and inflammatory disease

**Identify adverse effects
Contraindication?

Answer 26

CHLOROQUINE

Adverse effects
- HA, N/V, blurred vision, dizziness, fatigue, confusion
- Rare: depigmentation of hair, corneal opacities, hematological
disorders, exacerbation of psoriasis, dose related retinopathy, hemolysis in G6PD deficient patients.
- Not recommended for treating patients with epilepsy,
myasthenia gravis. Contraindicated in psoriasis and retinal disease
- CYP2D6 inhibitor

Question 27

Identify anti-malaria drug

**ONLY AGENT available for treating exoerythrocytic
hypnozoite forms of P. vivax and P. ovale in the liver
MoA; interferes with mitochondrial function
- Used; RADICAL CURE of P. Vivax and P.ovale (prevention of relapse). Used after chloroquine in treatment or shortly before or
right after chloroquine prophylaxis ends in persons with
known exposure to P. vivax, P. ovale.

**identify adverse effects? Toxicity

Answer 27

PRIMAQUINE

Adverse effects
● *Hemolysis when G6PD deficiency (contraindicated)
● Abdominal cramps, nausea, mild anemia
● Rare: Hematologic abnormalities

Toxicity; Uncommon in whites at usual doses.  Mild
abdominal distress; methemoglobinemia. Hemolysis is
G6PD deficiency (11% African Americans).

Question 28

Identify anti malaria drug (2)

1. MoA; similar to chloroquine. Increased use due to chloroquine resistance
   Use; Can be used for parenteral therapy (not available in U.S.)
   against chloroquine and multi-drug resistant P. falciparum

Adverse Effects
● Poorest therapeutic to toxic ratio of all antimalarial agents
- *Cinchonism: (dose related and reversible)
● Tinnitus, decreased hearing, HA, N/V, visual disturbances
● Rare: Hypersensitivity, hypoglycemia, hemolysis (G6PD)

2. MoA; similar to choloroquine
   - A drug of choice for parenteral therapy in chloroquine
   resistant P. falciparum in countries where parental quinine not available. Being replaced by oral and parenteral artemisinins
   **identify 2 adviser effects

Answer 28

1. Quinine
   - used when you resistant to chloroquine
2. Quinidine
   - parentheral therapy where chloroquine resistant and parental quinine is unavailable
   - Adverse effect; EKG changes and hypotension

Question 29

Identify anti malaria

● Used for prophylaxis against and treatment of drug resistant P. falciparum and P. vivax for travelers
spending weeks, months or years in endemic areas.
● Schizontocidal drug; no effect on exoerythrocytic
stage; generally not first line treatment.
● Resistance is increasing in Thailand and
West Africa
● *Causes vivid dreams. Neuropsychiatric symptoms.

Answer 29

MEFLOQUINE

Question 30

Identify anti malaria

● Formally used in combination with a sulfonamide and quinine for treatment of chloroquine resistant plasmodia;
occasionally used for chemophrophylaxis in pregnancy in
endemic areas.
● Mechanism of Action
- *Structurally related to trimethoprim; binds to and
reversibly inhibits dihydrofolate reductase
● Adverse Effects
- Hypersensitivity reactions, hematologic reactions
- Anemia due to decrease in folic acid (give leucovorin)
*Resistance - Becoming a serious problem; use limited

Answer 30

Pyrimethamine (± sulfadoxazine)

Question 31

Identify

1. • fixed concentration drug containing atovaquone and proguanil with minimal toxicity.
   • Used for malaria chemoprophylaxis and the treatment of
     uncomplicated P. falciparum malaria in adults and children.
   • effective against asexual blood forms and liver stages of P. falciparum (but not P. vivax).
2. • Derived from qing hao or sweet wormwood; parent plus
     three derivatives (dihydroartemisinin, artemether and
     artesunate)
   • Effective against P. falciparum and asexual erythocytic stages
     of P. vivax. Gametocytocidal activity. May produce toxic
     heme adducts and oxidant stress.
   • Generally not used alone, but in combination with other
     drugs for treatment of severe P. falciparum malaria. May be
     given orally or parenterally. Not used for chemoprophylaxis.

Answer 31

1. Atovaquone-proguanil (Malarone)
   - Atovaquone is a mitochondrial toxicant in parasites, while
   - proguanil in it’s cyclic active form inhibits
   dihydrofolate-thymidylate synthase (↓ DNA synthesis).
2. Artemisinin and Derivatives

Question 32

Malaria prophylaxis and treatment

1. 5 prophylaxis
2. P. Falciparum treatment
3. P. Vivax treatment
4. Other plasmodia

Answer 32

1. Prophylaxis
   - malarone (atovaquone-proguanil); all areas
   - mefloquine; areas with mefloquine-sensitive malaria
   - Chloroquine (or hydroxychloroquine; restricted to areas of chloroquine-senstive malaria)
   - Primaquine (short stays in areas that are primarily P. vivax; anti-relapse therapy P. vivax and ovale)
   - Doxycycline (all areas ?)
2. P. Falciparum treatment
   - Chloroquine-resistant: artemisinin derivatives, Malarone, mefloquine, clindamycin + quinine (or quinidine), doxycycline + quinine (or quinidine)
   - Chloroquine –sensitive: chloroquine
3. P.vivax treatment
   - Malarone, chloroquine (sensitive areas), primaquine (radical
   cure, also P. ovale)
   - chloroquine-resistant areas –Malarone, clindamycin +
   quinine (or quinidine),
   - doxycycline + quinine (or quinidine)
4. Other plasmodia
   - Chloroquine phosphate or hydroxychloroquine, quinidine

Question 33

Identify parasite

● Most prevalent enteric parasite in the United States ● Symptoms - Diarrhea (89%), malaise (84%), flatulance (74%),
foul smelling GREASY STOOLS (72%), Abd. cramps (70%), fever
(13%)

Answer 33

Giardiasis - Giardia Intestinalis

Treatment

• METRONIDAZOLE - now most common agent used in therapy 250mg TID x 5-7 days (80-95% efficacy)
• Tinidazole – new alternative, single treatment
• Nitazoxanide – used in children < 12 y.o.

Question 34

Identify parasite

Prevalence
● U.S. ~ 4%; 10% worldwide
● High risk: Institutionalized (mentally retarded), AIDS,
Immigrants/migrant workers, Foreign travel

Clinical Presentation
● GI complaints (Abdominal cramping, BLOODY DIARRHEA)
● RUQ pain, hepatomegally - suggests liver abscess
● **ASK about history of travel

Answer 34

AMEBIASIS - Entamoeba species

Question 35

Identify 3 classes of treatment for amebiasis

Answer 35

1. Luminal Agents; may be poorly absorbed to be active in tissue
   - diloxanide furoate (not available in US)
   - paromomycin
   - tetracyclines
2. Tissue agents; may be so well absorbed that only small amounts stay in lumen
   - Emetine (bowel only)
   - dehydroemetine
   - chloroquine (liver only)
3. Mixed agents; luminal and systemic activity
   - METRONIDAZOLE; Nitro group serve as electron acceptor forming reduced cytotoxic agent.
   - Tinidazole

Question 36

Identify amebicidic agents

1. • Nitro group serves as an electron acceptor forming a
     reduced cytotoxic agent. Toxic form can bind to protein and DNA and may generate free radicals.
   • Indications; Useful in the treatment of anaerobic bacteria,
     entamoeba histolytica and E. polecki, enteritis due to Giardia lamblia, and vaginitis due to Trichomonas vaginalis . Related nitro compounds tinidazole and nitazoxanide have similar activities.
     ● Alternative for blastocystis hominis and balantidium coli.
     **adverse effects?
2. Luminal active agent - eradicates cysts in asymptomatic person
   * *Adverse effects; GI complaints, seizures, encephalopathy. High iodine can interfere with TFTs
3. Aminoglycoside, poorly absorbed after oral
   administration
   - Adverse Effects; GI complaints, potentially nephrotoxic, ototoxic (IV)

Answer 36

1. Metronidazole
   Adverse effects; GI effects, metallic taste, *disulfiram-like effect (alcohol intolerance)
2. Iodoquinol
3. Paromomycin

Question 37

Identify protozoan infections based in medications

1. • Drug of Choice - Antimonial agents
   • Sodium stibogluconate (CDC only)
   • Meglumine antimoniate (Not available in U.S.)
   • Alternatives: Amphotericin B, Pentamidine
2. • South American (Chagas Disease)
     ● Drug of Choice: Nifurtimox (CDC only)

• African (Sleeping Sickness) - tsetse fly
  ● Drug of Choice: Eflornithine, suramin (CDC only)
  ● Pentamidine also effective

3. • Transmitted in raw or inadequately cooked
     meat which is infected
   • Drug of choice - Pyrimethamine + sulfadiazine
   • Alternate - Pyrimethamine + clindamycin

Answer 37

1. Leishmaniasis (female sand fly)
2. Trypanosomiasis
3. Toxoplasmosis
   - caused by toxoplasma gondii

Question 38

Identify 6 nematode infections and medications to use

Answer 38

1. Enterobiasis (Pinworm)
   - Pyrantyl pamoate or Mebendazole or Albendazolde
2. Ascariasis (Roundworm)
   - Pyrantyl pamoate or Mebendazole or Albendazolde (off label)
3. Filariasis
   - Diethylcarbamazine
4. Trichuriasis (Whipworm)
   - Mebendazole or Albendazole
5. Hookworm
   - Albendazole > Mebendazole or Pyrantyl pamoate
6. Strongyloidiasis (Threadworm)
   - Ivermectin (Alternative: Thiabendazole)

Question 39

Identify trematode and cestode infection and drugs used to treat

Answer 39

1. Trematodes (flukes); PRAZIQUANTEL used to treat all forms of SCHISTOSOMIASIS.
   - MoA; increased trematode cell membrane permeability to calcium – paraylsis.
2. Cestodes (tapeworms/flatworms) ; PRAZIQUANTAL
   Alternative drug is: Niclosamide – Mechanism of action;
   decreased ATP production by tapeworm mitochondria.

Question 40

Identify medications for nematode infections based on MoA and adverse effects

1. Selectively binds to helminthic tubulin and blocks
   microtubule assembly in helminths and inhibits glucose
   uptake, resulting in immobilization and death
   Adverse effects; Abdominal pain, relatively no side effects at normal doses
2. MoA; GABA receptor agonist. GABA controls neurotransmission by sending inhibitory signals to motor neurons. This drug potentiates these inhibitory signals (paralysis)
   DOC for STRONGYLOIDIASIS.
   Minimal ADR; GI complains, drowsiness
3. MoA; Depolarizing neuromuscular blocking agent
   - Alternative to mebendazole or albendazole
   for: Ascariasis (roundworm), hookworm, and pinworm
   - ADRs; Minimal, GI complaints, HA, drowsiness
4. MoA; Inhibits the fumurate reductase of susceptible helminths; may interfere with microtubule assembly
   * * Most commonly used for strongyloidiasis but not drug of choice.

Answer 40

1. Mebendazole
2. Invermectin
3. Pyrantel pamoate (Antiminth)
4. Thiabendazole

Question 41

Identify 10 clinically significant Nematodes (round worms)

Answer 41

1. Ascaris lumbricoides (roundworm)
2. Necator americanus, Ancylostoma duodenale (hookworms)
3. Cutaneous larva migrans
4. Strongyloides stercoralis (threadworm)
5. Toxocariasis (Visceral larva migrans, ocular larva migrans)
6. Enterobius vermicularis (pinworm)
7. Trichuris trichiura (whipworm)
8. Trichinella spiralis
9. Angiostrongyliasis (rat lungworm)
10. Onchocerciasis (river blindness), Wuchereria Bancroft, Brugia
    malayi (filiariasis), Loa, Dracunculus medinensis (Guinea worm)

Question 42

Identify Nematode general characteristics

1. Segment or not?
2. Physical xters? (3)
3. Multiply or not? Exception?

Answer 42

1. Non-segmented roundworms belonging to phylum Nematoda
2. Physical Characteristics:
   - Smooth borders
   - Even shape with tapered ends
   - Unpigmented
3. Do not multiply within hosts (exception Strongyloides)

Question 43

Identify nematode

• round worm infection (most common and largest helminth infection). NO ANIMAL RESERVOIR. Aka “fish worm”
• the head consumed by a child from the soil. **You cough it up and swallow it back down to the stomach - completes life cycle and produce thousands of eggs daily. **PULMONARY SYMPTOMS - LOEFFLER’S SYNDROME (EOSINOPHILIC PNEUMONITIS)
• most patients are asymptomatic. If you have symptoms they are mild
• GI; Biliary (aberrant migration). High fever or anesthesia can provoke aberrant migration
• *pulmonary symptoms occur in what 3 worms?
• *diagnosis and treatment ??

Answer 43

ASCARIS LUMBRICOIDES (ROUNDWORM)

1. Clinical manifestation; asymptomatic, GI, pulmonary
   A. Most patients asymptomatic
   B. GI; mild to moderate abdominal discomfort. Symptoms of obstruction; intestinal, pancreatic (aberrant migration), biliary (aberrant migration), high fever or anesthesia can provide aberrant migration
   C. Pulmonary; Loeffler’s syndrome; eosinophilic pneumonities
   - Transient pulmonary infiltrates, dyspnea, dry cough - Eosinophilia
   - Occurs with Ascaris, Strongyloides, hookworm

**Main cause of mobility/mortality ; INTESTINAL OBSTRUCTION

2. Diagnosis
   - O&P x3
   - Passage of a worm
   - **will not find eggs till 2-3 months after pulmonary symptoms
3. Treatment; Mebendazole, albendazole
   * *Single dose appears to be 100% curative

Question 44

Identify nematode

• penetrates feet (wear shoes when working abroad).
• go to lungs cough it and swallow back down. **PULMONARY SYMPTOMS - LOEFFLER’S SYNDROME (EOSINOPHILIC PNEUMONITIS)
  **ANEMIA; secrete anticoagulants that increase blood loss and protein loss (1/3rd pregnant women affected - lead to IUGR, low birth weight)
  *Decreased school attendance, impaired cognitive ability,
  reduced work output (helminth-poverty cycle)
  **Females with palpitations
  *Rash at entry site but not all the time

1) clinical manifestions (4);
2. Diagnosis
3. Treatment (3)
4. Prevention

Answer 44

Necator americanus, Ancylostoma duodenale (HOOKWORMS)

1. Clinical manifestations; pulmonary, GI, Hematologic, Skin
   A. Pulmonary; loeffler’s syndrome (pneumonitis with dyspnea, dry cough, infiltrates)
   B. GI; mild abdominal pain
   C. Hematologic; symptoms of anemia - mental apathy, impaired physical performance, pallor, palpitations, swelling of hands or feet, pregnancy
   D. Skin; localized urticarial papulovesicular rash at entry site
2. Diagnosis
   - Hookworm eggs on MICROSCOPIC exams; must examine within 1-2 hours else they can hatch and look different (resemble strongyloides)
3. Treatment; Mebendazole, albendazole and Ivermectin
4. Prevention; Shoes and Latrines

Question 45

Identify nematode

• it is a dog or cat hook worm not a human hook worm so can’t complete its life cycle in humans
• You need to look under microscope quickly because egg can hatch and look different

** A 28 yo medical resident and his wife returned from hiking in Central America with pruritic, erythematous , single-track linear and serpiginous lesions located predominantly on lower extremities. This rash is caused by what type of nematode?

Answer 45

Cutaneous larva migrans; aka “ground itch” or “creeping eruption”
*Typically caused by ancylostoma braziliense or ANCYLOSTOMA CANINUM

• Cannot complete normal life-cycle in accidental human host but persist for a time under the skin

Question 46

Identify nematode

-most clinically significant
- *cause auto-infection and last for decades
- **CAUSE HYPERINFECTION in immunocompromised (but not HIV); LEAD TO LIFE THREATENING GRAM NEGATIVE SEPSIS (enteric bacteria enter mucosa) - cause extreme eosinophilia
Life cycle; cough up and swallow back down and go to intestine. *PULMONARY SYMPTOMS - LOEFFLER’S SYNDROME (EOSINOPHILIC PNEUMONITIS)
- half of people asymptomatic
- clinical manifestations; Urtcaria Rash moves rapidly (butt and groin), hyperinfection in immunocompromised, loefflers syndrome, GI (pain in pit of stomach with diarrhea, indigestion, cramping)

Identify

1. Complications
2. Diagnosis
3. Treatment (2)

Answer 46

STRONGYLOIDES STERCORALIS (THREADWORMS)

1. Complications; hyperinfection in immunocompromised can lead to LIFE THREATENING GRAM NEGATIVE SPESIS.
   - typically cause EXTREME EOSINOPHILIA but septicemia state can suppress eosinophilia
   - can lead to 100% mortality if left untreated
2. Diagnosis
   - Dramatic eosinophilia in an endemic area (including WV)
   - Larvae in stool (NOT eggs) – low sensitivity (30-60%)
   - Serology available
   - Agar culture method
3. Treatment
   - Ivermectin
   - Albendazole

Question 47

Identify nematode

• CAUSES 2 THINGS; viscera larva migrans and ocular larva migrans
• raccoon ascaris is very rare but cause deadly eosinophilic meningitis*
• life cycle; 4 weeks in the soil - animal poop in the soil - child can be playing with the infected soil and get it (dog can be born with this cause it cross the placenta). NOT part of loefflers but has a pulmonary symptoms - not coughed up but can get into pulmonary veins and present with ASTHMA-LIKE ATTACKS, larvae can also go to eyes - VISUAL LOSS

Identify

1. Get infected from what animals? (3)
2. Clinical manifestations (5)
3. Diagnosis
4. Treatment (2)

Answer 47

TOXOCARIASIS (Visceral larva migrans, ocular larva migrans)

1. Results from infection with; dog (toxocara canis), cat (toxocara cati) or raccoon ascarid (baylisascaris procyonis)
2. Clinical manifestations (5)
   - asthma like attacks
   - N/V, abdominal discomfort
   - urticarial rashes
   - liver enlargement
   - visual loss due to larvae entering the eye*
3. Diagnosis ; made without finding the actual parasite
   - suspected on basis of EXCEPTIOANLLY HIGH EOSINOPHIL COUNT (up to 90%)
   - ELISA is very specific
   - CT scan helps differentiate ocular LM from retinoblastoma
4. Treatment (2)
   - Albendazole
   - Mebendazole

Question 48

Identify nematode

• 20% in kids. Humans are the only host (but eggs can be transferred from fur of household pets). Fecal-oral transmission
• *INTENSE ITCHING AT NIGHT around the anus
• important cause of travelers diarrhea - Dientamoeba fragility transmitted within eggs
• Diagnosis; SCOTCH TAPE TEST
• *MUST TREAT WHOLE FAMILY

Diagnosis (3)
Treatment (3)

Answer 48

ENTEROBIUS VERMICULARIS (PINWORM)

Diagnosis

• direct visualization
• O&P is very low yield
• Scotch tape test

Treatment

• Mebendazole
• Albendazole
• pyrantel pamoate
• *Must treat WHOLE family. Retreatment may be required

Question 49

Identify nematode

• very common and high mortality
• life cycle; ingest eggs - larvae hatch in small intestine - hatch in cecum - produce eggs that in stool?
• some people ate this to help treat ulcerative colitis
• *RECTAL PROLAPSE; children with heavy infections, chronic dysentery, pregnancy or post-partum
• **Diagnosis; no eosinophila because no lung stage

**what has similar egg form in picture to whipworm?

Identify

• clinical manifestation
• diagnosis
• treatment

Answer 49

TRICHURIS TRICHIURA (WHIPWORM)

1. Clinical manifestation
   - light infections usually asymptomatic
   - lower abdominal pain, abdominal distention, chronic diarrhea
   - colitis mimicking IBD +/- rectal bleeding
   - **RECTAL PROLAPSE; children with heavy infections, chronic dysentery, pregnancy or post partum
2. Diagnosis
   - characteristic barrel-shaped eggs; “bipolar plugs”
   - proctoscopy revealing worms
   - typically no eosinophilia (no lung stage)
3. Treatment
   - Ivermectin
   - Albendazole or mebendazole
   - single dose seems to work but generally treated for 3 days for clinically significant infections

**Capillariasis eggs is similar to whipworm under microscope; only found in Philippines. C. Phillippinensis can cause severe diarrhea, massive protein loss and death from heart failure within weeks to months

Question 50

Identify nematode

• don’t eat undercooked pork; you can get it from muscles of WILD ANIMALS (domestic pigs, wild boars, arctic walruses and seals)
• 2 STAGES; INTESTINAL STAGE AND MUSCLE INVASION STAGE
• life cycle; eat muscle of polar bear that has some yeasts - get into intestine - gastric acid release larvae - penetrate intestine and go to all parts of body - only ones in striated muscle survive and creat a cyst again to survive (CYST IN MUSCLE)
• manifestation; intestinal stage, muscle invasion, periorbital edema, myocardial (CHF) and neurologically involved (meningitis, encephalitis), chronic stage (vague muscle pain and malaise lasts for months)

Identify
Diagnosis
Treatment
Prevention

Answer 50

TRICHINELLA SPIRALIS
**muscle invasion; muscle pain and tenderness, periorbital edema, splinter hemorrhage in nailbed, diffuse rash

Diagnosis

• history of pork consumption with intestinal then muscular symptoms
• labs; marked eosinophilia, elevated CPK, elevated AST
• ELISA TEST
• MUSCLE BIOPSY is DEFINITIVE test

Treatment

• steroid + mebendazole in severe cases
• antipyretics may be sufficient in mild cases

Prevention

Question 51

Identify nematode

• most common cause of human EOSINOPHILIA MENINGITIS (raccoon ascaris also has this)*** dont necessary penetrate CNS parenchyma but cause inflammation around
• transmitted through snails and slugs and their slime on green leafy vegatables
• life cycle; they actually live in the lungs of rats - infected slugs/snails
  2 TYPES?

Answer 51

Angiostrongyliasis (RAT LUNGWORMS)

A. A. Cantonensis; eosinophilic meningitis (most common cause)

• eosinophilic meningitis (HA, neck stiffness, CSF with 20+ eosinophils without fever)
• distinctive paresthesias (sensitivity to touch)
• no specific treatment, patients usually recover fully

B. A. Costaricensis ; causes intestinal symptoms that mimics appendicitis

• fever, vomiting, abdominal pain with possible RLQ mass
• high blood eosinophil count
• treatment controversial

Question 52

Identify nematode

**not discussed on this lecture

Answer 52

Onchocerciasis (river blindness), Wuchereria Bancroft, Brugia malayi (filiariasis), Loa, Dracunculus medinensis (Guinea worm)*

Question 53

Nematode abx chart and MoA

• what antibiotic can be used for all intestinal nematodes (ascaris, trichuris, hook worm, strongyloides)

Answer 53

ALBENDAZOLE

Question 54

Nematode association

1. Autoinfection (2)
2. Anemia
3. Loeffler syndrome (3)
4. Hyperinfection with immunosuppression
5. Rectal prolapse
6. Eosinophilic meningitis (2)
7. Humans with aberrant host
8. Skin eruption
9. Wild animal consumption

Answer 54

1. Autoinfection: pinworm, Strongyloides (also capillaria and dwarf
2. Anemia: hookworm
3. Loeffler’s syndrome: Ascaris, Hookworm, Strongyloides
4. Hyperinfection with immunosuppression: Strongyloides
   - Gram negative sepsis
5. Rectal prolapse: Trichuris
6. Eosinophilic meningitis: Raccoon ascarid, Angiostrongylus cantonensis
7. Humans as aberrant hosts: CLM, VLM (toxocariasis),
8. Skin eruption: CLM (slow), larva currens/Strongyloides (fast)
9. Wild animal consumption: Trichinella tapeworm)

Question 55

Overview of ectoparasites (8)

Answer 55

1. Scabies
2. Head lice
3. Body lice
4. Crabs
5. Bed bugs
6. Jigger fleas
7. Bot-flies
8. Delusional parasitosis

Question 56

Identify ectoparasite

• Seen where you have fold; under breast, penis, in between hands, axilla, nipples
• HYPERINFESTATION in IMMUNODEFICIENT PATIENTS (scabies crustosa)
• Highly contagious and itching may be absent (frequently misdiagnosed with PSORIASIS). Itching is intense when present especially at night

Dx; scrape lesion and look under microscope. INK TEST - see how it has travelled
Treatment; must have diagnosis first before tx. Treat entire family

Identify
A. Transmission?
B. Diagnosis
C. Treatment

Answer 56

SCABIES

A. Transmission; skin to skin contact but can also be transferred from fabrics

B. Diagnosis

• intense itching, especially at night. 2 people in same house hold with nocturnal itching
• scrape lesions and examine under microscope
• INK TEST

C. Treatment

• Don’t treat without diagnosis
• Treat ALL family members simultaneously
• Permethrin 5% from neck down overnight (TOC)
• Ivermectin 1-2 oral doses (Norwegian scabies)
• THOROUGH WASHING of clothes and bedding
• Children can return to school 24 hours after treatment

Question 57

Identify ectoparasite

• *3 types
• Transmission: physical contact, sharing of hats, brushes, etc.
• Clinical manifestation: itchy scalp, particularly back of neck (not in eyelashes, eyebrows)
• Diagnosis: direct visualization (usually of nits)
• Treatment: Permethrin (TOC), ivermectin, malathion, pyrethrins

Answer 57

Head lice

3 types of lice

• head louse (pediculus humans capitis)
• body louse (pediculus humans corporis)
• crab louse (phthirus pubis, “papillon d’amour”)

Question 58

Identify ectoparasite

• *Vectors of louse-borne typhus, trench fever, and louse-borne relapsing fever
• VERY ITCHY. Tends to move from the host to the clothing and back again
• Worldwide distribution, but more common in colder regions. Overcrowding, wars, famine, natural disasters

Identify 
Transmission 
Clinical manifestations 
Diagnosis 
Treatment

Answer 58

Body lice

A. Transmission; person to person
B. Clinical manifestations; itching, itchy red pin point lesions, s/s of associated diseases
C. Diagnosis; direct visualization (seams of garments rather than on the body)
D. Treatment; permethrin and malathion

Question 59

Identify ectoparasite

• Worldwide distribution
• Transmission: SEXUAL CONTACT
• Clinical manifestations: “moving freckles”, “frass”
• Diagnosis: direct visualization
• Treatment: Permethrin, malathion

Answer 59

Crab louse (phthirus pubis)

Question 60

Identify ectoparasite

• Dramatic increases in infestations since 2000
• Difficult to control infestations; Can survive up to 6 months without feeding
• Nocturnal creatures (bite only at night)
• Possible transmission of hepatitis B and Chagas?

Answer 60

Bed bugs (Cimex lectularius)
Aka breakfast, lunch and dinner; bites in 3 spots together 

**NO TREATMENT ; just treat symptoms

Question 61

Identify ectoparasite

• Cause of TUNGIASIS (inflammatory skin condition) but do not transmit diseases to humans
• Native to Central and South America, now also found in Africa and India
• Fertilized female fleas penetrate cracks in the soles of the feet**
• Prevention through wearing shoes
• *first look like abcess and become complicated (spread) when not taken out

Answer 61

Jigger fleas (tuna penetrans, chigoe flea, Nigua)

Question 62

Identify ectoparasite

• cause myiasis (infection by the larva of the higher flies)
• 2 types;
  1) AFRICA ; dogs are natural reservoir. Adult flies lay eggs on contaminated soil or clothes laid out on the ground
  2) LATIN AMERICA; involves mosquito
• *first looks lie abcess

Answer 62

**Myiasis (mango fly, human bot-fly)

1. Cordylobia anthropophage (tumbu fly, mango fly)
   - ONLY FOUND IN AFRICA
2. Dermatitis hominis (human botfly)
   - OCCURS IN LATIN AMERICA

Question 63

Identify ectoparasite

• not actually a parasitic infection; patient has delusion of a parasite
• inanimate object coming out of their skin (fibers)
• Predominant in females (3:1)
• patients are bright and well educated (even health care provider like nurses)
• History; Itching, scratching, “crawling-creeping-burning” sensations. Bizarre symptoms with exhaustive descriptions. Can come on after reading about parasites or with increased stress. Frequently have seen multiple physicians and have received numerous anti-parasites. Long-term can lead to workplace and relationship issues. Significant internet research

Treatment; psychiatry referral. ANTIPSYCHOTICS - pimozide, olanzapine (zyprexa)
**Patients may request Lyme disease treatment

Identify diagnosis?

Answer 63

Delusional parasitosis ; (Parasitophobia, Monosymptomatic hypochondriacal psychosis, MORGELLONS DISEASE)

**some researchers belief it is caused by excess extracellular dopamine

DIAGNOSIS OF EXCLUSION; rule out other diseases; actual infestation, liver/renal disease, alcoholism or drug abuse, diabetes, anemia with B12 deficiency, dermatitis herpetiforms, thyroid disease, pellagra, environmental irritants (glass fiber, carpet fibers), bipolar disease and paranoia

Question 64

1. Classification of parasites (how do you eventually get trypanosoma vs leishmania)
2. Differences btw trypanosoma and leishmania (examples)

Answer 64

1. Parasites; Protozoa and metazoa

A. Protozoa (3)

• BLOOD/TISSUE; trypanosoma and leishmania
• urogenital
• intestinal

B. Metazoa (2)

• Helminths; Nematodes, trematodes, cestodes
• Arthropods

2. A. Trypanosoma (2)
   - American trypanosomiasis (chaga’s)
   - African trypanosomiasis (African sleeping sickness)

B. Leishmania (3)

• Cutaneous
• Mucocutaneous
• Visceral

Question 65

American trypanosomiasis (Chaga’s)

1. Epidemiology; common cause of what in Latin American immigrants?
2. Trypanosoma Cruzi (vector, location)
3. Transmission/life cycle (5)
   - do they multiply in cells or bloodstream
4. Stages of disease (acute vs chronic)
   * ***SIGNS
5. Diagnosis; acute (4) vs chronic (2)
6. Special issues
7. Treatment (main side effects)
8. Prevention

Answer 65

1. Epidemiology; 1 of CDC 5 neglected parasitic infections. Most COMMON CAUSE of HEART FAILURE among Latin American immigrants. Can be vertically transmitted to babies
2. Trypanosoma Cruzi (vector, location)
   - Vector; triatomine bugs - “kissing bugs”, REDUVIID BUGS
   - Endemic Mexico, central and South America; mud brick walls and thatch roof
3. Transmission/life cycle
   A. Feces of insect; bug bites you and poops on you, you scratch yourself and the poop gets into your system (innoculate yourself)
   B. Others; vertical, oral, blood transfusion, transplant
   **Life cycle; go into your cells and multiply (binary fission) and then go into cells at their END ORGANS. **The bloodstream trypomastigotes do not replicate (unlike African trypanosomes)
4. Stages of disease (acute vs chronic)
   A. Acute; can last 6-8 weeks after initial infection. Asymptomatic or mild disease that can progress to chronic stage. Patient has high parasitic load but clinical signs often absent.
   **S&S; ROMANA’S SIGN (swollen eye), CHAGOMA (arm), fever, myalgias, hepatomegaly, encephalitis, myocarditis.

B. Chronic; lifelong infection w/out tx, may not have symptoms until a year later. Most asymptomatic

• S&S; GI or Cardiac; AMASTIGOTES in heart or gut, TRYPOMASTIGOTES can infect new sites (brain)
• CARDIAC (30%); right bundle branch block**, arrthymias, dilated cardiomyopathy, CHF, apical aneurysm, stroke
• GI (10%); I) MEGAESOPHAGUS - dysphasia, pain/ondynophagia, weight loss, regurgitation, aspiration. II) MEGACOLON - prolonged constipation, abdominal pain, increased risk of volvulus and consequent bowel ischemia

5. Diagnosis (acute vs chronic)
   A. Acute; i) parasites in blood/cord blood or PCR - must have 2 positive tests. II) EKG. III) Echo. IV) GI studies (barium swallow)
   B. Chronic; i) antibodies - do 2 times for confirmation. II) Muscle biopsy
6. Special issues;
   - screening blood transfusion. Can’t donate blood if you are positive.
   - Low in vertical transmission (test cord blood twice).
   - Immunocompromised (can be more severe and progress to brain)
7. Treatment ; benznidazole, nifurtimox (contraindicated with neuro/psych disorders)
   * *Treatment is only available from CDC. Both are effective in early acute phase
   - Big side effect is POLYNEUROPATHY, anorexia (weight loss), nausea/vomiting
8. Prevention
   - insect control (spray house)
   - screen blood donors and blood cord (newborns)
   - construct homes to prevent nests, bed nets, good hygiene

Question 66

African trypanosomiasis (African sleeping sickness)

1. 2 types (3 differences - location, reservoir, acute vs chronic)
2. Vector /life cycle; multiply or blood or cell?
3. Early infection in both types(SIGN?)***
4. Late infection in both types (affect what?)
5. Diagnosis (4)
   * how do you determine stage?
6. Treatment (based on stage and type)
7. Prevention (4)

Answer 66

1. 2 types 
A. Trypanosoma Brucei gambiense
- west/central Africa 
- Reservoir; humans 
- **CHRONIC ILLNESS 
B. Trypanosoma Brucei Rhodesiense 
- East Africa 
- Reservoir; animals (cattle/sheep) 
- **RAPIDLY FATAL 

2. Vector /life cycle
   - vector is TSETSE FLY
   - multiply in BLOOD
3. Early infection (Hemo-lymphatic)
   - WINTERBOTTOM SIGN (invasion of lymph nodes)
   - occasionally painful CHANCRE at site of bite, fever, myalgias, arthralgias
4. Late infection (Hemo-encephalitic); progress to CNS
   - sleeping sickness (lethargy, headache, delusions/hallucinations), psychosis, personality change.
   - quicker progression and rapidly fatal (100% w/out treatment)
5. Diagnosis
   A. Microscopy; thick and thin smears, higher load with rhodesiense
   B. Lymph nose biopsy; better with gambiense
   C. Serology; rapid agglutination test available outside US. Still need confirmatory biopsy/microscopy
   D. CSF; how you determine the stage

6. Treatment; depends on stage and type 
A. Rhodesiense
- hemolymphatic; suramin 
- CNS involvement; Melarsoprol
B. Gambiense
- hemolymphatic; pentamidine 
- CNS involvement; Eflornithine 
**Treatment only available from CDC; serial LP x 2years, extensive side effects. 

7. Prevention
   - Fly traps
   - Insecticide
   - Eradication of brush and breeding site
   - Light colored clothing

Question 67

Leishmania

1. 3 types
2. Vector/life cycle
3. Transmission
4. Classification (2)
5. Cutaneous leishmaniasis (differential)
   - Diagnosis
   - Treatment
6. Mucocutaneous leishmaniasis
7. Visceral leishmaniasis
   - diagnosis
   - treatment
   - prevention

• *Which type looks like malaria at first
• which will disfigure your face and these people commit suicide?
• which is mostly presented in army veterans from Middle East with painless ulcer with rolled margin

Answer 67

1. 3 types; cutaneous, visceral, mucocutaneous
2. Vector/life cycle; SAND FLY
   - from bite of infected female phlebotomine sandfly
3. Transmission; saliva (PROMASTIGOTE)
   - lose flagella and become AMSTIGOTE, infects macrophages
4. Classification
   A. Old world; wet lesions.
   B. New world; dry lesions.
5. Cutaneous leishmaniasis (differential); PAINLESS ULCER FORMATION (ROLLED MARGIN, CRUSTING). Army veteran coming from Middle East and has a painless ulcer with rolled**
   - Diagnosis(4); i) TRAVEL HISTORY - solider in Middle East. II) Smear or biopsy - see AMASTIGOTES. III) culture - hard to find. IV) PCR - only with CDC
   - Treatment; some go away on their own but leave scar. Cryotherapy/heat/surgical excision, topical paromycin, azoles (ketoconazole, itraconazole, fluconazole), sodium stibugluconate (pentostam) only from CDC - side effects; HA, N/V, arthralgias
6. Mucocutaneous leishmaniasis; involves mucous membranes. DISFIGURE YOUR FACE (nose, mouth, nasal septum)
   - untreated primary skin lesions may progress over years
   - stuffy nose, epistaxis, dysphagia
7. Visceral leishmaniasis; look like malaria initially
   ”Kala-azar” or “black fever”
   S&S; GREYING OF SKIN from anemia. Fever/weight loss/chills, hepatosplenomegaly, oral lesions, low WBC count. May be silent for years. **can be rapidly fatal. Typical cause of death is something other than leishmaniasis; pneumonia, measles, TB, dysentery.
   - diagnosis; i) reservoir/nodules full of parasites (post-kala-azar leishmania dermatitis). II) TRAVEL HISTORY. III) Microscopy. IV) Serologic testing. V) PCR (via CDC)
   - treatment; i) AMPHOTERICIN B (visceral) . II) Antimonials - sodium stibogluconate (pentostam). III) Mitefosine.
   - prevention; avoid outdoors from dust to dawn, wear protective clothing, insect repellent, sleep in well screened areas, spray your house

Question 68

Summary of trypanosoma

American vs African

Answer 68

1. American ; ROMANA’S SIGN (acute chaga’s)
   - Chaga’s
   - Triatomine bug in central/south America
   - Romana’s sign
   - Acute vs. chronic
   - Cardiac arrhythmias and “mega-syndromes”
   - Benznidazole/Nifurtimox
2. African; WINTERBOTTOM’s (early hemolymphatic stage)
   - African Sleeping Sickness
   - Tsetse fly
   - Gambiense; chronic
   - Rhodesiense; Rapidly fatal
   - Early vs. late
   - PAINFUL chancre
   - Winterbottom’s sign

Question 69

Summary of leishmaniasis

Cutaneous vs visceral

Answer 69

1. Cutaneous
   - Middle East/South America
   - Painless chancre
   - Self-limiting, but can form a scar
   - Freeze lesion or oral treatment
   - Can progress to mucocutaneous; “Espundia”
2. Visceral
   - Kala-Azar
   - Rapid or slowly progress
   - Liver/spleen/bone marrow
   - Amphotericin B, sodium stibogluconate (antimonial)

Question 70

Classification of parasite (Protozoa) - 3

Answer 70

Protozoa

1. Free-living amoeba
   - NAEGLERIA
   - Balamuthia
   - Acanthamoeba
   - Sappinia
2. Babesiosis
3. Malaria

Question 71

Free-living amoeba

• found where
• types (4)

Answer 71

Free living amoeba

1. • Found in soil and contaminated lakes, streams, etc.
   • Most human infections during warm, summer months
2. Types (4)
   - Naegleria
   - Balamuthia
   - Acanthamoeba
   - Sappinia

Question 72

Free living amoeba - NAEGLERIA

• 3 stages? (Which cause invasive human disease? Which is resistant to heat?)
• patient present with what history?
• what does this cause?
• diagnosis
• treatment

Answer 72

1. 3 stages; Trophozoite, flagellates, cysts
   - trophozoite (reproductive stage); causes invasive human disease
   - flagellates
   - cysts; resistant to heat (thermophilic up to 45 degree C)
2. History; history of freshwater exposure
   - get from forceful exposure to fresh water
3. Causes; PRIMARY AMEBIC MENINGOENCEPHALITS (PAM)
   - NASAL INOCULATION by disruption of olfactory mucosa
   - Penetrates cribriform plate and enters CNS
   - Symptoms: intense HA, sore throat, fever, stiff neck, Kernig sign
   - Hemorrhage, edema and tissue necrosis
   - Rapidly fatal (139/143); DEATH IN 4-5 DAYS
   * *Difficult to treat because you think it’s meningitis and give wrong medication
4. Diagnosis
   - Purulent CSF with erythrocytes and amebae
   - Motile trophozoites on CSF wet mount (Gram stain destroys trophozoites)
   - Hemorrhagic CSF
   - Serology– most die before seroconversion
   - CSF PCR
5. Treatment
   - IV +/- intrathecal amphotericin B
   - Miltefosine (Impavido)? **Now available commercially
   (Real World – Contact CDC ASAP)

Question 73

Free living amoeba - balamuthia

• patient present with what history?
• what does this cause? (S&S)
• diagnosis
• treatment

Answer 73

1. Epidemiology; lives in soil around the world (maybe water as well)
   - originally isolated from brain of baboon
   - inhalation of cysts or direct skin contact with open wound e.g gardening, playing with dirt.
2. Causes/results ; GRANULOMATUS AMEBIC ENCEPHALITIS (GAE)
   - causes single/multiple brain abscesses
   - typically in immunocompromised (higher in Hispanics). 10 days incubation; slower course than NAEGLERIA
   - S&S; dermatological/nasal lesion, fever, HA, N/V, edema of brain tissue
3. Diagnosis
   - Often diagnosed at autopsy
   - CSF
   - Serology/PCR?
4. Treatment
   - Not well defined
   - Few patient survive as a result of treatment
   - Miltefosine combination?

Question 74

Free living amoeba - Acanthamoeba

• epidemiology
• causes/results*** (2)
• *What is misdiagnosed as HSV?
• diagnosis
• treatment

Answer 74

1. Epidemiology
   - Several species pathogenic for humans
   - Found in soil, dust, water
   - Trophozoite and Cyst stages
   - Inhibited by temperatures >35ºC
   - Many healthy people seem to have pharyngeal colonization
2. Causes/results; ACANTHAMOEBA KERATITIS (contact lenses**) AND GAE (granulomatous amebic encephalitis)
   A. Acanthamoeba keratitis; corneal trauma with exposure to acanthamoeba. Contact lenses. Corneal ulceration and severe ocular pain. Sight threatening. **MISDIAGNOSED AS HSV
3. Diagnosis
   - Microscopy; Brain biopsy, corneal scrapings
   - serology; not often useful
   - Neuroimaging; space occupying lesions. Must keep a broad differential
4. Treatment
   - GAE; combination abx - antifungal, antiprotozoa, mitefosine (impavido)
   - AK; topical antiseptic agents, repeated corneal transplant, enucleation

Question 75

Free living amoeba - Sappinia

Answer 75

Epidemiology ; found in the soil and animal feces
**First isolated in 1908

1 reported case in human 2001
38yo M
Sinusitis
Developed chronic meningoencephalitis
Temporal lobe mass containing Sappinia
Treated with azithromcin, pentamidine, itraconazole, flucytosine
Survived

Question 76

Protozoa - Babesiosis

• *geography location
• *vector ??
• *Signs and symptoms

Answer 76

General; NORTH EAST ** (New Zealand)

• life cycle; deer/mouse/rodent** has different cycles - bite human (infective stage) - spotozoite released and affect RBC - trophozoite - infect further RBC (repeat pattern)
• S&S; HEMOLYSIS IN RBC
• vector; IXODES TICK (nymph)

Results/presentation

• Incubation 1-4 weeks
• Malaise, fever, headache, chills, sweating, fatigue, weakness
• May develop HEMOLYTIC ANEMIA as more erythrocytes are destroyed
• Renal failure, Hepatomegaly, splenomegaly, Asplenia, immunosuppression increases susceptibility

Diagnosis

• Blood smear (see ring forms that look like plasmodium)
• Hemolytic anemia and thrombocytopenia

Treatment 
Asymptomatic: no treatment 
Atovaquone + azithromycin
Clindamycin + quinine in severe illness
Blood transfusion/exchange transfusion
Hemodialysis

Question 77

Protozoa - Malaria

• *A. know hosts
• *B. 4 main species

C. anopheles vs aedes feeding? (Which transmit malaria?)

Answer 77

A. 2 hosts ;

• human host (multiply in liver and then RBCs)
• FEMALE ANOPHELES MOSQUITO

B. 4 (5) species infect humans 
P. falciparum
P. vivax
P. ovale
P. malariae
(P. knowlesi)– can infect, but only under certain circumstances

C.

• Female anopheles mosquito; malaria
• Aedes mosquito; dengue/yellow fever

Question 78

Plasmodium life cycle (3)

• which infect liver cells?
• which infect RBC?
• which is dormant in liver?
• *outcomes of life cycle? (2)
• asexual reproduction?
• sexual erythrocytic stage?

Answer 78

1. Sporozoite; mosquito release sporozoite into liver cells
   - From mosquito
   - Infects liver cells
   - Matures into schizonts
2. Schizont
   - Ruptures and releases merozoites 6-14 days after infections
   - Multiple nuclei
   - Can release up to 30 merozoites
   - ASYMPTOMATIC
3. Merozoite
   - Infects RBCs
   - Surface antigen is vaccine target
   - Undergo asexual multiplication
   - erythrocytic schizogony; more schizont can produce more merozoite in the blood

Outcomes (2) 
A. Ring stage trophozoite;  
- Asexual reproduction 
- Diagnostic
- Mature and release more merozoites OR release Gametocytes
B. Gametocytes; 
- Sexual erythrocytic stage
- Taken up by mosquito to complete reproductive cycle

4. Hypnozoite; Dormant in liver in P.vivax and P. Ovale ***
   - Releases parasites weeks to months after primary infection
   - Reason for presentation if fever <1 year from returning from endemic area.

Question 79

Malaria

Clinical;
Cerebral malaria (culprit?_ 
Diagnosis (3) 
Treatment (4) 
Prophylaxis (4) 
Protective factors (3)
At risk groups (2) 
Prevention

Answer 79

1. Clinical; flu-like symptoms but worse.
   * *Cyclical HA, fever, chills. History of travel
   - Anemia; pale conjunctiva, nailbeds, oral mucosa, palm of hands. Tachycardia, murmur if severe, respiratory distress.
2. Cerebral malaria; P. FALCIPARUM
   - P. Falciparum is culprit; can multiply better and adhere to cells, sequestration and cause end-organ failure
   - S&S; Prostration, Impaired consciousness, Respiratory distress, Convulsions, Jaundice, Pulmonary edema, Hypotension
   * *VERY POOR PROGNOSIS
3. Diagnosis
   - Microscopy; thick blood films/smears - see parasite. Thin films - species differentiation
   - Rapid diagnostic antigen test; antigen capture “Binax Now”
   - molecular (PCR)
4. Treatment
   - Chloroquine; If not resistant; (i.e. Central America; Middle east)
   - Atovaquone/proguanil (Malarone)
   - Artemether-lumefanteine (LA); Artimesinin category. Can given IV artemisinin for cerebral malaria
   - Mefloquine (Lariam); Black box warning, Psychosis and psychological effects years later
5. Prophylaxis
   - Atovaquone / Proguanil (Malarone)
   - Mefloquine (Larium); Not with history of psychiatric disorders
   - Doxycycline; Photosensitivity, Candidal yeast infections
   - Primaquine; Not in G-6-PD
6. Protective factors ; Red cell abnormalities
   A. Sickle cell trait; cell sickle when infected with parasite which will trigger macrophages - Take the infected cells out of circulation prior to release of more parasite
   B. Duffy-negative blood type; west Africans typically lack Duffy antigen which is a red cell antigen needed for invasion of P.vivax
   C. Immunity; you become resistant to reinfection of same strain after multiple infections. *No cross-immunity
7. At risk groups
   - Children; not yet built immunity, poor nutrition
   - pregnant women; cause fatal demise and severe anemia
8. Prevention
   - Light colored clothing
   - Bed nets; Preferably treated with Permethrin
   - Permethrin
   - Picaridin
   - DEET; No need for >35%

Question 80

Summarize the life cycle of malaria (12 stages)

Answer 80

The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected femaleAnopheles mosquito inoculates sporozoites into the human host

1. Sporozoites infect liver cells
   2and mature into schizonts
   3, which rupture and release merozoites
2. (Of note, inP. vivaxandP. ovalea dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocytic schizogonyA), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogonyB). Merozoites infect red blood cells-
3. The ring stage trophozoites mature into schizonts, which rupture releasing merozoites-
4. Some parasites differentiate into sexual erythrocytic stages (gametocytes)-
5. Blood stage parasites are responsible for the clinical manifestations of the disease.
   The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by anAnopheles mosquito during a blood meal-
6. The parasites’ multiplication in the mosquito is known as the sporogonic cycle-C. While in the mosquito’s stomach, the microgametes penetrate the macrogametes generating zygotes-
7. The zygotes in turn become motile and elongated (ookinetes)-
   10.which invade the midgut wall of the mosquito where they develop into oocysts-
8. The oocysts grow, rupture, and release sporozoites-
   12, which make their way to the mosquito’s salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle .

Question 81

Malaria disease states (3)

• first clinical episode following sporozoite attack?
• release of hyponozoite
• persistent bloodstream infection

Answer 81

1. PRIMARY ATTACK; First clinical episode of illness following a sporozoite inoculation
2. RELAPSE
   - Release of blood stage parasites from a liver stage
   - P. vivax/P. ovale
3. RECRUDESCENCE
   - Persistent bloodstream infection
   - Seen with sub-optimal treatment