2: Antiparasitics - Not Malaria

Question 1

definitive host of toxoplasma gondii

Answer 1

cat

Question 2

transmission of toxoplasma gondii

Answer 2

eating raw meat or cat feces

Question 3

what is the 3rd most common food-borne illness?

Answer 3

toxoplasma gondii

Question 4

describe the life cycle of T. gondii?

Answer 4

• sexual development only in cat!

- cysts develop in other mammals

Question 5

who does toxoplasmosis usually effect?

Answer 5

• NOT people with functioning immune systems

- severe toxoplasmosis seen in : HIV, organ transplants, chemotherapy

Question 6

how do babies get congenital toxoplasmosis?

Answer 6

fetus becomes infected via placenta in women who are infected for the first time

Question 7

what is first line treatment for toxoplasmosis? alternate?

Answer 7

primethamine + sulfadiazine

alternate: atavaquone or pentamidine

Question 8

what parasitic infections are associated with HIV in the US?

Answer 8

• pneumocystis jirovecii (pneumonia)
• toxoplasma gondii (encephalitis)
• cryptosporidium (cryptosporidiosis)

Question 9

what parasitic infections are associated with HIV globally?

Answer 9

• malaria
• leishmania
• trypanosoma cruzi (Chagas disease)

Question 10

structure of pentamidine

Answer 10

aromatic diamidine

Question 11

administration of pentamidine and mechanism

Answer 11

• parenteral

- mechanism unknown, but preferentially accumulates in parasites

Question 12

how toxic is pentamidine?

Answer 12

very - 50% of patients show side effects

-can cause hypoglycemia or hyperglycemia

Question 13

what is pentamidine first line use for? what is an alternate treatment for?

Answer 13

first line: West African trypanosomiasis

alternate: visceral leishmania and pneumocystosis

Question 14

what are 3 anaerobic protozoa that cause disease?

Answer 14

• entamoeba histolytica (amebiasis)
• giardia lamblia (giardiasis)
• trichomonas vaginalis

Question 15

what is one of the most common water-borne diseases in the US?

Answer 15

giardia lamblia

Question 16

describe entamoeba histolytica infection process

Answer 16

ingest cysts -> forms trophozoites in ileum -> penetrates intestinal wall -> multiplication of trophozoites w/i colon wall -> systemic invasion

some cysts (infective) and trophozoites (non-infective) pass with feces

Question 17

what does entamoeba histolytica infection cause?

Answer 17

diarrhea + ulcers on the intestinal lining

Question 18

how can one kill entamoeba cysts?

Answer 18

boiling, but NOT chlorination

Question 19

what promotes the spread of amebiasis?

Answer 19

poor sanitation and fecal contamination of food and water

Question 20

where is amebiasis more common?

Answer 20

Latin America, Africa, and Indian subcontinent

Question 21

where does amebiasis initially infect?

Answer 21

intestine - sometimes reaches other organs, such as liver

Question 22

symptoms of amebiasis

Answer 22

most asymptomatic, but if present:

• diarrhea
• increased flatulence
• abdominal cramps
• sometimes liver abscesses

Question 23

symptoms of giardiasis

Answer 23

range from asymptomatic to severe diarrhea and malabsorption

Question 24

treatments of choice for giardiasis

Answer 24

• metronidazole

- nitazoxanide

Question 25

what is the most frequent cause of recreational water-related disease outbreaks?

Answer 25

cryptosporidium

Question 26

what is the most common symptom of cryptosporidium? what are other symptoms?

Answer 26

watery diarrhea*** - stomach cramps/pain - dehydration - nausea/vomit - fever - weight loss - more serious illness in immunocompromised people

Question 27

drug of choice for cryptosporidium

Answer 27

nitazoxanide

Question 28

where does trichomonas reside in males and females?

Answer 28

males: urethra and prostate females: lower genital tract

Question 29

how does trichomonas present in both genders?

Answer 29

males: often asymptomatic females: - vaginitis + purulent discharge - vulvar and cervical lesions - abdominal pain - dysuria - dyspareunia

Question 30

what is metronidazole the drug of choice for? what does it kill?

Answer 30

- extraintestinal Entamoeba histolytica - giardiasis - trichomoniasis kills trophozoites but not cysts

Question 31

what is metronidazole treatment usually followed by and why?

Answer 31

luminal drug to eliminate asymptomatic infection

Question 32

what is the mechanism of action of metronidazole

Answer 32

not definitively known - anaerobes have electron transport proteins with low redox potential - activate metronidazole

Question 33

what is a drug similar to metronidazole? how does it differ slightly?

Answer 33

tinidazole - less toxicity

Question 34

describe metronidazole + alcohol effects

Answer 34

may cause an antabuse effect (similar to disulfram + alcohol) -nausea, vomit, increased HR -inhibits acetaldehyde DH -> accumulate acetaldehyde

Question 35

drugs for intestinal forms of amebiasis

Answer 35

- paromomycin | - iodoquinol

Question 36

what type of drug is paromomycin?

Answer 36

aminoglycoside | -not significantly absorbed in GI tract

Question 37

effectiveness and other use for paromomycin

Answer 37

similar efficacy and less toxic than other drugs also active against cryptosporidium

Question 38

what is iodoquinol commonly used in combo with?

Answer 38

metronidazole

Question 39

mechanism of iodoquinol

Answer 39

unknown

Question 40

mechanism of action of nitazoxanide

Answer 40

prodrug - rapidly turned into active tizoxanide mechaism uncertain: - interferes with pyruvate:ferredoxin (PFOR) enzyme-dependent electron transfer rxn - inhibits anaerobic metabolism

Question 41

what is nitazoxanide effective against?

Answer 41

inhibits growth of sporozoites and oocysts of cryptosporidium parvum and trophozoites of giardia

Question 42

what are the kinetoplastid parasites?

Answer 42

- leishmania - african trypanosomes (brucei gambiense, brucei rhodesiense) - american trypanosomes (cruzi)

Question 43

what types of infection does leishmania cause?

Answer 43

skin, mucocutaneous, organ

Question 44

what do african trypanosomes cause?

Answer 44

african sleeping sickness (95% gambiense)

Question 45

what do american trypanosomes cause?

Answer 45

Chagas disease

Question 46

what common features do kinetoplastid parasites share?

Answer 46

- unique organelles: kinetoplast, glycosome | - distinct mechanisms of gene expression

Question 47

anti-kinetoplastid drugs for leishmaniasis

Answer 47

- sodium stibogluconate or Ampho B | - alternatives: pentamidine or MILTEFOSINE

Question 48

anti-kinetoplastid drugs for african trypanosomiasis

Answer 48

- early stage: pentamidine (west) or suramin (east) | - late stage: melarsoprol (east and west) or eflornithine (west)

Question 49

anti-kinetoplastid drugs for american trypanosomiasis

Answer 49

-nifurtimox or benznidazole

Question 50

what type of drug is miltefosine?

Answer 50

phospholipid analog - developed as an anticancer drug - approved for use against visceral leishmaniasis (India)

Question 51

miltefosine: mechanism, resistance, side effects, contraindications?

Answer 51

unknown - resistance has been observed, side effects tolerable *don't use in preggers: teratogenic!

Question 52

how many daily doses of miltefosine yields cure rates ~100%?

Answer 52

28 daily doses

Question 53

MOA of nifurtimox and benznidazole

Answer 53

unknown - activated by an NADH-dependent mitochondrial nitroreductase -> generation of nitro radical anions

Question 54

how much do nifurtimox and benznidazole reduce severity in acute phase?

Answer 54

eliminates parasite in 80% of acute infections and ~50% of chronic infections, but does not reverse tissue damage in chronic infections

Question 55

how are nifurtimox and benznidazole administered?

Answer 55

- p.o. | - 3-4 month course

Question 56

toxicity of nifurtimox and benznidazole

Answer 56

common - hypersensitivity, GI complications -> leads to premature stoppage of treatment