parasitic infetation: microscopic

Question 1

what are protozoa

Answer 1

• eukaryoites
• metabolic processes are more similar to those of the human host than prokaryotic bacteria pathogens
• less easily treated compared to bacterial infectsion

Question 2

types of microscopic parasitic diseases from protozoan infectsions

Answer 2

Entamoeba (amoebiasis), Giardia (beaver fever) Trichomonas and Plasmodium (malaria).

Question 3

what is entamoeba histolytica

Answer 3

• anerobic parasitic protozoan that causes amoebiasis

infects the GI tract: considered asymptomatic based on range of symptoms from mild diarrhea to blood and mucus in stool

• infects 500 million ppl yearly, 110,000 deaths

Question 4

what are teh two forms on entamoeba histolytica?

Answer 4

cysts and trophozoites

• cysts are infective and surivve outside of human body, will transform into trophozoites
• trophozoites = non infective but invasive form that can reproduce and invade the wall of the large intestine and migrate to other tissues like the liver

*trophozoites can transform to cysts and be exreted in feces

Question 5

what causes amoebiasis

Answer 5

entamoeba histolytica

Question 6

descibe the life cycle of entamoeba histolytica

Answer 6

• Ingestion of cysts through fecal-ral route (drinking contaminated water)
• Whether intestinal invasion occurs function of number of cysts infested, stain of parasite and motility of host GI tract and presence of appropriate enteric bacteria to serve as nourishment for the maoeba

Disease results when active trophozoites (active stage of life cycle) invade intetinal epithelium and spread to liver via protal circulrion

Lyses and destroys human tissue

Question 7

describe the clinical presentation of Ameobiasis

Answer 7

• asymptomatic intestinal infection, mild to moderate colitis, severe intestinal infection (dysentery), ameoboma, (psudotumoral lesion) and liver absecess or other extra-intestinal infection.

Question 8

what is the difference between asymptomatic infection and invasive disease of ameobiasis

Answer 8

In asymptomatic infection

• ingested cysts excyst (mature) in small intestine but do not invade the intestinal mucosa
• the trophozoites encyst in the colon and excretion via feces

Invasive disease

• active trophozoites invade intestinal eithelium resulting in asymptomatic colonization
• intestinal amebiasis (amebic dysentery)—which is characterized by diarrhea and abdominal cramps—or intestinal perforation.
• Spread of infection via the portal vein can cause liver abscesses.

Question 9

how is E. histolytica treated?

Answer 9

• amoebicidal drugs

Luminal Amoebicides: treat parasites in bowel lumen

• ex: iodoquinol, works against luminal stages which include trophozoites and cysts
  
  • side effects = rash, diarrhea and dose related peripheral neutropathy (optic neuritis)
  • evoid long term use

Systemic ameobicides: treat parasites in intestinal wall and liver

• ex treat liver abscess
• use high dose of metronidazole to eliminate trophozoites then iodoquinol

Mixed (luminal + systemic)

• choice for entamoeba distolytic infections
• kills trophozites but not cysts

Question 10

what does Metronidazole treat

Answer 10

• parasitic infection of E. histolytica
• can also use to treat Giardia lamblia, Trichonomas vaginalis, anaerobic cocci, anaerobic gram-negative bacilli and pseudomembranous colitis such as Clostridium difficile.

*drug of choice for treating diarrhea or dysentery

Question 11

what are the pharmacokinetics of metrondiazole

Answer 11

• can be administered orally and its readily abs
• extensive abs via simple diffusion, therapetuic concentrations reported in vaginal, seminal fluids, saliva and cerebrospinal fluids
• metabolized by depatic oxidation by mixed function oxidase
• phenobarbital enhances metabolism
• cimetidine inhibits hepatic mixed function oxidase so prolongs excretion

Question 12

describe the mechanism of action of metrondiazole

Answer 12

• involves ferroxin like, low redox potential, electron transport proteins which transfer electons to nitro groups of metronidazole and form cytotoxic reduced products bind to DNA and proteins

* is a Mixed amoebicide but not reliably efective for liminal parasites, must use in combo with luminal ameobicide like iodoquinol or paramocylin (aminoglycoside)

Question 13

what are the adverse effects of metrondiazole

Answer 13

nausea, vomiting, headache, abdominal cramps and metallic taste in mouyh

Nausea and vomiting also occur is alcohol is ingeted at same time

Drug is metagenic in bacteria so avoid if preg or nursing

Question 14

what is gardia lamblia

Answer 14

• aka beaver fever
• Most common intestinal parasitic infection of people - does not involve tissue development

Life cycle:

• Two stages: trophozoites and cysts
• Infection occurs following cyst ingestion which are usually in water
• Both people specific and zoonotic genotypes of infection
• Many infections are asymptomatic but severe diarrhea can occur

Question 15

what are risk factors for gardia lamblia

Answer 15

• ingesting contaminated water
• children in child care settings
• close contact with infected eprsons

swallowing contaminated pool water

outfoor activities like camping

Question 16

how is gardia lamblia treated?

Answer 16

• metrondiazole
• dose much lwoer than for amoebiasis so better tolerated
• treated often not used for asymptomatic infections bc those will clear on own

Question 17

what is trichomonas vaginalis

Answer 17

• anaerobic parasite that resides in lower genital tract of femals urethra and male prostate
• no cyst form, replicates via binary fission so does not survive well in external environment

*most common pathogenic protozoan infection of industrialied countries (common STI)

Question 18

symptoms of trichomonas vaginalis

Answer 18

Symptoms - vaginal dischage, vulvar itching and discomfort during urination with occasional dysuria

In men no signs or symptoms but urethral dischange and burning during purination is possible

Question 19

treatment of trichomonas vaginalis

Answer 19

• use metronidazole as single or multiple dose regimen

Single dose therapy more effective due to compliance

Resistant infections can occur, may need to treat with higher dose

Systemic treatment preferred over topical therapy due to multifocal nature of the infection. Simultaneous treatment of the sexual partner is very important as well.

Question 20

what causes malaria

Answer 20

Caused by one of five species of plasmodial parasites: Plasmodium falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi

P. falciparum is the most serious disease and results in the most deaths.

Resistance is major prophylactic and therapeutic problem

Question 21

describe the lifecycle of plasmodia parasites

Answer 21

• involves parasite, mosquito vector and human host
• mosquito can ingest sexual forms of malarial parasites (gametocytes) from blood of infected human
• male and female gametocutes fuse and zygote matures within mosquito
• sporozoites released from an oocyst and migrate to mosquitos salivary gland, can be incolulated into blood of another human host (asymptomatic stage)
• 1-12 weks after ifnective bite the liver cells release parasites into bloodstream as merozoites
• infected erthyrocyte eventually reptures releasing another gen of merozoite that continue cycle
• Rare merozoites also mature into gametocytes and ingestion of these by an appropriate mosquito completes the life cycle.

Question 22

whta do drugs that treat malaria target?

Answer 22

• different stages of ifnection

Liver stages = tissue schizonticides

Erythrocytic stages = blood schizonticides

Sexual stages = gametocides

• can also treat by killing erythrocytic parasites before they grow in number and cause disease, but this is based on the species that caused the infection

Question 23

infection cycle of

Answer 23

One cycle of multiplication in liver

Liver infection ceases in less than 4 weeks

Elimination of erythrocytic parasites cures infection

Question 24

decribe infection of P. vivax + P. ovale:

Answer 24

Dormant hepatic stage (hypnozoite) is not killed by most drugs

Must eliminate both erythrocytic and hepatic parasites

Question 25

how do you prevent mosquito bites

Answer 25

insect repellents, insecticides, bed nets and appropriate clothing is necessary.

Preventatative medications include chloroquine, mefloquine (most malarious areas) and doxycycline (if high prevalence of multidrug-resistant falciparum malaria).

Question 26

what is chloroquine

Answer 26

drug of choice for chemoprophylasis if chloroquine-S parasites are known to be found in the area (mainly in caribean and central america)

• synthetic 4-aminoquinoline that is admin orally
• concentrates in parasties acidic food vacuole to prevent polymerization of heme into hemozoin and results in oxidative damage which lyses the parasite and red blodo cell

*when parasite is in the RBC it digests host hemoglobin, heme is toxic to the parasite and it is polymerized to form homozoin in the food vacuole

Question 27

pharmacokinetics of chloroquine, adverse effects and resistance

Answer 27

• Rapidly abs and distributed to tissues wehre it had blood schixonticide activity(but no activity against liver parasites)
• Drug is dealkylated by hepatic mixed-function oxidase system meaning that the parent drug and metabolites are eliminated in urine
• resistance v common due to mutations in membrane transporter
• adverse efects minimla @ low dose but nausea, vomiting and blurred vision can occur at higher doses

*Dosing after meals can reduce adverse efefct

Question 28

what is mefloquine?

Answer 28

recommended chemoprophylatic drug in areas with chloroquine-R Plasmodium falciparum

• synthetic 4-quinoline methanol which means it is chemically related to quinine

has blood schizonticide activity against P. falciparum but not activity against hepatic stages of gametocytes.

MOA is unknown but believed to be due to concentration of parasite and inhibition heme polymerization with a final result of membrane damage

Question 29

pharmacokinetics of mefloquine, adverse effects and resistance

Answer 29

Orally admin and well abs, showing extensive distribution to tissues

Very slow elimination

• resistnace uncommon escept in south east asia bc high rates of multidrug resistance associated w/ quinine and halofantrine but not chloroquine

*adverse effects are a concern

• neuropsychiatric toxicities, nausea, vomiting, dizziness and sleep and behaviour disturbances

* not known if the frequency of serious adverse effects is no higher compared to other anti-malarials.

*Contraindicted in pt with history of epilepsy and psychiatric disorders

Question 30

what is doxycycline

Answer 30

standard chemopropylactic drug in areas of Southeast Asia with multidrug-R parasites (including mefloquine-R)

• oral administration, dont use as single agent based on slow action
• use with quinidine or quinine, allows for shorter but better tolerated course of these drugs
• MOA: inhibition of protein synthesis, also has blood schizonticide activity and is not active against liver stages

adverse effects gastrointestinal symptoms and photosensitivity.