Parasitology and Anti-parasitic Drugs Flashcards
What are the four classes of protazoa?
Which can be free-living?
- amoeba - free
- flagellate- free
- coccidia (sporozoan) - obligate intracellular
- ciliates- free
What is the definitive host?
How does this differ from an intermediate host?
A host that harbors a parasite that is sexually mature (an adult) and is reproducing
An intermediate host harbors larvae and asexual stages of the parasite and may increase in number but are not reproducing
What is dysentery?
diarrhea with blood and mucous accompanied by fever and ab pain
What are microsporidia?
Organisms characterized by the production of spores with coiled polar tubes
What type of protozoa has an oocyst stage?
When they are found in feces, what three type of infections can be suspected?
Coccidia. The oocyst contains infectious sporozoites.
- cryptosporidium
- cyclospora
- Isospora
What are the two types of reproduction utilized by protozoa?
- Schizogeny- asexual
2. Sporogeny- sexual
What is the motile, feeding form of a protozoa?
Trophozoite
Describe the structure and size of protozoa.
- single,celled eukaryotes
- similar to mammalian cells except they have food storage granules, contractile and digestive vacuoles, and organs of motility
- 2 to 100 microns
What are the two structural differentiation factors that allow classification of various species of protozoa?
- karyosome and chromatin arrangement of the nucleus
2. organs of motility
What regions have the most blood and vector borne protozoa?
What regions have the most intestinal protozoa?
Blood/vector= tropical/subtropical Intestinal = temperate
How is metabolism in most parasitic protozoa accomplished?
facultative anaerobic metabolism (fermentation)
How do protozoa survive harsh conditions like drying out, chlorination, etc?
they form cysts (similar to the bacterial spore)
What is the only protozoa to undergo sexual reproduction in the human host?
What do MOST protozoa do to divide in human hosts?
Most protozoa use binary fission
Cryptosporidium (a coccidia) reproduce in human hosts
What is the motility of amoeba?
Where is the trophozoite stage and cyst stage?
It has a pseudopod
The trophozoite stage is in the gut/lumen
Cyst stage in shed in the feces
What are the two major categories of flagellate protozoa? What is an example of each type?
- luminal parasites- G. lamblia
2. hemoflagellates (blood tissue)- Typanosoma and Leishmania
What is the life cycle of a hemoflagellate?
It is a complex life cycle that has intracellular (nonflagellated) and extracellular stage (flagella)
It requires an arthropod vector
What is the only ciliate that is pathogenic for humans?
How does it infect and what is the presentation?
Balantidium coli which is transmitted by fecal-oral transmission and causes dystenery
What are the three locations of sporozoa infection?
What is an example of each?
- blood- plasmodium
- intestinal- cryptosporidium, cyclospora, t. gondii
- tissue- T. gondii
What do intestinal sporozoa generally cause?
diarrhea
Describe the transmission of T. gondii. Identify the definitive host and intermediate host.
T. gondii multiplies in the GI tract of cats (definitive host). They form oocysts which are pooped out. The oocysts make sporozoites which are picked up by an intermediate host (cattle or pigs) for asexual reproduction. They form cyst in tissue of the hosts
Describe the life cycle of plasmodium/
It undergoes schizogeny (asexual reproduction) in the hepatic cells and erythrocytes in humans.
The sexual reproduction stage is in mosquitos
What are microsporidia?
How are they acquired?
What is their infective form?
They are small sprozoa that are ihgested or inhaled. Their infective form is the spore that contains polar tubules
What five factors determine the pathogenesis of the protozoa?
- infective dose (# of parasites)
- mode of acquisition
- passage and target organ
- parasite and antigen load
- host response
________ multiply within the human host while __________ do NOT multiply in the human host.
Protozoa multiply in the host while helminths multiply outside the host
What is the best known pathogenic amoeba of the GI tract?
Describe its life cycle.
E. histolytica are ingested as mature cysts.
In the human they invades the wall of the colon.
Trophozoites multiply by binary fission and form cysts which are passed in feces.
What are the three free-living amoeba?
Where are they found?
When they do cause disease, how do they present?
Acanthamoeba Balamuthia Naegleria They are in water (tap, pools, lakes) They cause meningitis, meningoencephalitis, encephalitis
Describe the life cycle of Trypansoma brucei.
What type of protozoa is it?
What disease does it cause?
T. brucei is a blood/vector flagellate.
- Tsetse fly has a blood meal on a human and injects trypomastigotes into skin.
- Trypomastigotes go to lymphatics and then to bloodstream then to CSF
It causes African sleeping sickness
What is the life cycle of T. cruzi?
It is a blood/vector flagellate.
- Triatomine bugs bite the human and then poop.
- Trypomastigotes invate leukocytes and cells of subcutaneous tissue
- Trypomastigotes go to the heart and cause cardiomyophathy (Chaga’s)
- Spread back to triatomine through a second blood meal
Where are triatomine bugs located? What do they cause?
What is the tell-tale sign of infection?
They are located in mud huts and thatched roofs
Dogs can be vectors too
They cause Chaga’s.
The telltale sign is Romana’s sign (swollen eye and lips)
In addition to triatomine bugs, how else can T. cruzi be spread?
- blood donation
- transplacental
- fruit juices
- organ transplant
What is the arthropod vector for Leishmania?
Who would be likely to be infected by this?
Female sandflies
Soldiers in Afghanistan or Iraq
Describe the life cycle of C. parvum.
It is a luminal sporozoa.
The cyst is ingested in water contaminated with animal or human feces.
Sporozoites infect GI epithelial cells and undergo asexual and sexual reproduction to form oocysts that are passed in the feces
What is the definitive host for T. gondii?
felines. Cats ingest cysts that invade epithelial cells of the small intestine. They replicate and form oocsyts which are excreted.
How does human infection occur for T. gondii?
- eat meat of an animal that ingested oocyst
- litter box cleaning
- blood transfusion
Where do T. gondii cysts form in humans?
in patients with AIDS they form in skeletal muscle, myocardium and brain
Describe the life cycle of Plasmodium.
- Mosquitoes have a blood meal and inject sporozoites into human
- Sporozoites go to liver cells, rupture them and infect the bloodstream causing anemia due to hemolysis
- Mosquitoes ingest the sexually mature plasmodium from blood
- Plasmodium does sexual replication in the mosquito (definitive host) and the cycle continues
What is the first thing you test with an intestinal infection?
Stool:
- vial with 10% formalin preserves protozoa cysts and helminths
- PVA vial preserves trophozoites
How does one examine specimen from the formalin vial?
How does one examine a specimen from the PVA vial?
Formalin- wet mount sample and use iodine and saline.
Iodine is taken up by the cyst to allow visualization
PVA- trichrome or Fe heatoxylin stain to ID trophozoites
What stain must be done to see a sporozoa?
acid-fast bacteria to detect the oocyst of cryptosporidium, cyclospora, isospora
What protozoa can be detected with immunofluorescence?
G. lamblia and Cryptosporidium antigens in the stool
How does diagnosis of blood or tissue protozoa begin?
How is definitive diagnosis achieved/
Initially you consider the geographic exposure and clinical symptoms.
Definitive diagnosis requires demonstration of the parasite in blood smears stained with Wright or Giemsa
Tissue biopsy is needed for T. cruzi and leishmania
What are the five ways to diagnose protozoa?
- stool
- blood smear
- serology
- tissue biopsy (t. cruzi and leishmania)
- molecular testing
What geographical regions are associated with helminth infections?
Tropical and subtropical but intestinal are temperate
How do helminths acquire nutrients?
How do they metabolize?
They actively ingest host tissue and body fluids.
They catabolize carbs and use anaerobic glycolytic cycle as the source of ATP
What are the two major groups of helminths?
Roundworms and flatworms
What are the two types of flatworms?
- tapeworms (cestodes)
2. flukes (trematodes)
What is the major free-living nematode?
How does it replicate?
What is the definitive host?
C. elegans
There are separate sexes that mate to form eggs (larvae) in human hosts, so they are the definitve host
What is the structure of the cestode? How does replication occur?
It is long and flat (ribbon like=tapeworm).
It has a chain of egg producing segments called proglottids.
Proglottids go through budding.
Tapeworm are hemaphrodites and self-fertilize to make eggs that leave the host via feces
What is the structure of the trematode? How does it replicate?
It is a non-segmented, leaf shaped flat worm (fluke).
Fluke are hemaphrodites and go through sexual reproduction occurs in humans releasing eggs into circulation
Where are flukes found in human hosts?
Schistosomes are in blood and are non-hemaphroditic
There are also intestinal, liver, lung
What does the pathology of helminths result from?
- migration of larvae through body tissue
- bloodsucking activity of worms
- innate immune response
- allergic reaction to antigenic products
- cell-mediated immune response
What are the three major intestinal nematodes?
Where is the adult stage?
Where is the larval stage?
Ascaris, Strongyloides and hookworms
Adult stage is in the intestines where they lay eggs excreted in feces
Larvae migrate through tissue to get to target organs.
Describe the cycle of hookworms,
- Hookworm larvae can enter the host through intact skin causing local skin manifestation (ground itch)
- Larvae go through veins to the heart and then enter pulmonary circulation
- They are coughed and then swallowed
- In the intestine they mature to adults and attach to intestinal wall causing iron deficiency anemia at the site
What is Loeffler’s syndrome? What kind of helminth is it associated with?
It is associated with hookworms and is a eosinophilic pneumonitis from the pulmonary migration of the larvae
What is an example of a helminth where the human is a dead end host?
Trichinella spiralis.
- Rodents are definitive with adult worms in their intestines and larvae in muscle
- Pigs (intermediate host) feed on rodents with larvae cysts in the meat.
- In pig gut the cysts mature into adults and give birth to new larvae which go to pig muscle
- Humans eat pig with cysts
- In GI the cysts become adults which make larvae that migrate to muscle causing muscle aches and hypereosinophilia
What is filariasis?
What are the 3 organisms that are associated with it?
When nematodes live in tissue (skin or lymphatics) instead of the gut of humans
W. bancrofti
B. malayi
O. volvulus
Describe the life cycle of W. bancrofti.
- mosquito takes a blood meal and larvae enters human
- adult worms in the lymphatics
- adults produce sheathed microfilariasis that go in the blood and lymph channels
- mosquito takes another blood meal and ingests microfilaria
- Microfilaria sheds sheath goes to the midgut of the mosquito and then to thoracic muscles
- Larvae migrate to the head and mosquitos proboscis
The cycle continues
What is the most likely cause of pathology in W. bancrofti?
- Hypersensitivity reaction to the adult worms in the lymph nodes
- Filariasis symptoms (lymphedema/elephantitis)
How do you diagnose W bancrofti?
Microfilaria in blood smear
Which is more widespread, W. bancrofti or B. Malayi
B. malayi (asia and indonesia with cat reservoir)
W bancrofti- equator
How are human cestodes (tapeworms)acquired?
The larvae are ingested in raw or poorly cooked meat and fish
What is the life cycle of T. solium?
- Proglottid or embryonated eggs ingested by pigs
- Penetrate intestinal wall and circulate to muscles
- Humans ingest raw or undercooked meat and the tapworm hatches, attaches to intestinal wall
OR - Humans ingest eggs it hatches and circulates to the musculature where cyst form in the brain and eyes
Which tapeworm is associated with pigs?
which is associated with cattle?
T solium = pigs
T saginata = cattle
How does a human get E granulosus?
Accidental ingestion of dog poop
Except for ______________________ all trematode infections are food-borne.
schistosomiasis
How are most trematode infections acquired?
Food-borne
Describe the life cycle of fasciola hepatica.
There is a mollusk (snail) intermediate host and a human definitive host.
- infected water
- snail
- watercres
- sheep
Humans get it from eating watercress
Describe the cycle of schistosomes.
- infect humans through the skin after having been matured in the snail
- Spread in circulation, become adult and reside in small venules of the portal system.
- Mate and release eggs that are released in urine or stool
- eggs hatch in water and infect snails
etc etc
What do infections with schistosomes cause?
liver fibrosis
portal hypertension
bladder fibrosis
cancer
All caused by granulamatous reaction to eggs
What is the main technique for identifying helminth eggs and larvae?
Get a stool sample and wet mount to examine
What is unique about the E. vermicularis pinworm?
It deposits eggs around the anal opening
“scotch tape test”
Muscle biospy is recommended to check for which helminth?
Trichinella spiralis
How do you diagnose cestode infections?
ID eggs or proglottids in the stool
What three drugs are used as anti-helminths?
Mebendazole
Ivermectin
Praziquantel
What are the main effects of helminth infections?
- interference with host nutrition
- trauma to organs (bile duct, lymph, capillaries)
- mechanical blockage
- anemia, toxemia
What are the six major nematodes?
Which three are most common worldwide?
Which is most common in the US?
Most common worldwide = WW
- Acsaris (WW)
- whipworm (WW)
- Hookworm (WW)
- Pinworm (US)
- Trichinosis (t. spiralis)
- threadworm
What are the three methods of transmission for nematodes?
- orally - ingesting eggs, intestinal nematode, passed in feces
- Skin penetration- hookworms and threadworms
- Insect vector- filarial parasites
Helminths do not usually cause opportunistic infections in AIDs patients except_______________.
threadworm that can complete its life cycle in humans
Describe Pinworms:
- host tissue
- infective form
- route
- intestines
- eggs
- orally
Describe whipworms:
- host tissue
- infective form
- route
- intestines
- eggs
- orally
Describe Roundworm:
- host tissue
- infective form
- route
- intestine AND lungs
- eggs
- orally
What are the two nematodes that live in host intestines AND lungs? What is different between the 2 organisms?
- Roundworm (ascaris) infects via eggs
2. Trichinosis infects via larvae
What two organisms infect host skin, intestines and lungs?
What is their infective forms and routs of transmission?
- Hookworm infects the skin through larvae
2. threadworm infects the skin through larvae
What is the consequence of a pinworm infection?
Who is usually infected?
What is treatment?
Cutaneous irritation of the perianal region from scratching and self-induced trauma.
School-aged children in temperate and tropical areas
Mebendazole
What is the consequence of a whipworm infection?
Who is usually infected?
What is treatment?
- Classic dysentery, colitis with growth retardation
- worldwide
- mebendazole
What is the cycle of Ascaris infection?
What are the consequences?
Who gets infected?
What is treatment?
The roundworm is in soil. It gets into intestine, hatches, the larvae go to the lungs, coughed up, reswallowed, adults replicate, poop eggs.
Consequence= it absorbs nutrients from the host affecting the growth of children
Tropical regions (most prevalent WW)
Mebendazole
What is the cycle of the hookworm?
What are the consequences?
Who is affected?
What is treatment?
Enter skin, migrate through veins to lungs, coughed and swallowed, reside in intestines, pooped out to soil.
Consequences = iron deficient anemia because the intestinal hookworm sucks blood
Tropical and subtropical
Mebendazole
What is the cycle of threadworm?
What are the consequences?
Who is affected?
What is treatment?
Larvae infect through skin and then the life cycle is completed in the human intestine.
Consequences= causes problems for HIV patients, rash at site of skin infection, ab pain and bloody diarrhea, malabsorption/weight loss
Affect immune compromised patients
Ivermectin
How does a human acquire Trichinosis?
What are the consequences?
Who is affected?
What is treatment?
Ingested in pork (muscle of animals) and severity is gauged by # of larvae consumed
Fever, GI, myositis, eosinophilia
People who eat poorly processed meat
mebendazole
What drug is used to treat filariasis?
What 3 strains does it usually treat?
What is the dosage, and why?
ivermectin for W bancrofti, B malayi and O volvulus (river blindness)
It is given once a year because it can’t kill adult worms, but it can reduce microfilaria burden and reduce the chances of transmission
Describe the life cycle of O volvulus.
It is transmitted to humans by bites of black flies.
Adult worms become encysted in fibrous skin nodules where they live 12-15 years.
Lesions in the eye cause river blindess and are caused by localized death of microfilaria
What is the spectrum of Mebendazole?
How is it administered?
What is the mechanism of action?
Which nematodes is mebendazole used for?
It is a broad spectrum drug given once orally
It inhibits microtubule assembly and blocks glucose uptake by nematodes. Takes several days to clear the nematode from the gut
It is used for everything EXCEPT filariasis and threadworm
What is the spectrum of Ivermectin?
How is it administered and what is the mechanism of action?
It is broad spectrum (and natural! found in soil)
so it is effective against nematodes, arthropods (ticks, fleas, mites), heartworm in dogs
It acts against microfilaria but not adult worms
Contraindicated with impaired BBB (african sleeping sickness)
It is an agonist for glutamate-gated Cl channels and leads to worm paralysis
How are cestodes acquired by humans?
What are the consequences?
What is the typical mode of treatment?
Consumption of beef, pork or fish infected by the tapeworm. Dwarf tapeworm (most common in humans) is acquired by food/water contaminated with hu
Consequences= little pathology, mild GI
Treat with praziquantel
What is the spectrum of praziquantil?
What is the method of action?
Broad to treat cestodes (tapeworms) and trematodes (fluke)
It causes paralysis and vacuolization in the cells of the infecting worm
How are trematode infections acquired?
What are the consequences?
How are they treated?
They are acquired through the skin in water that has infection shed from mollusks.
Infects GI, liver and spleen causing hepatosplenic diseas with ascites
Praziquantil treats it
What are the 7 antiprotozoal drugs?
- chloroquine
- quinine
- artemether
- atovaquone plus proguanil (Malarone)
- mefloquine
- metronidazole
- iodoquinol
Who is most at risk for malaria infection?
Pregnant women and children
What has prevented eradication of malaria?
- acquired resistance
2. lack of effective vaccine
What is the most lethal malaria causing infection?
If you suspect your patient what must you consider when selecting a drug?
Plasmodium falciparum
You need to consider what region of the world they had been in because different areas of the world have different levels of resistance to the drugs
What are the four major malaria causing organisms?
- P falciparum - rapid disease onset and death
- P vivex- milder but recurrent due to sequestering in the liver and reemerging years later
- P ovale- mild but recurrent (liver sequestering)
- P malariae- tropics, low parasitemia
What is the life cycle of plasmodium falciparum?
Which stage is the “disease stagE”?
- Sporozoites invade blood stream during mosquito blood meal
- Go to liver (5-16 days) then burst into the bloodstream
- Merozoites in the bloodstream infect RBC and burst from the cells for a second round of infection. This causes febrile disease
What is a diagnostic sign for P. falciparum?
Dark polymerized heme seen on the slide from the bursted RBC
What drug is used to treat chloroquine sensitive Plasmodium infections?
What drug combinations are used to treat chloroquine resistant falciparum and vivax?
Which is best prophylaxis?
Which is best due to its fast action?
Sensitive= use chloroquine
Resistant:
- Atovaquone+guanadil (Malarone)
- Artemether + lumefantrine (Coartem)
- Quinine sulfate + doxy, tetracycline, clindamyacin
- Mefloquine
#1- Malarone is best prophylaxis #2 Coartem (artemether+lumefantrine) is best for fast acting
What is the mechanism of chloroquine?
It kills blood schizonts by inhibiting polymerization of heme in the food vacuole of the parasite
- plasmodium use Hb as a food source.
- Non-polymerized heme is toxic
What is quinine?
The most ancient malarial drug from the bark of the cichona tree.
It is used in combination with doxycycline for chloroquine resistant falciparum.
What is atonvaaquone+guanil (Malarone) used to treat?
What is the mechanism of action?
It is prophylaxis for acute, uncomplicated P. falciparum and is effective in chloroquine resistant regions.
It has broad spectrum activity against parasites including malaria, toxoplasmosis and pneumocystis.
Atonavaquone:
It inhibits mitochondrial ECT at the level of cytochrome bc1 complex which collapses mit. membrane potential
Proguanil:
DHFR inhibitor
What is the drawback of artemether?
At high levels it is neurotoxic but it can treat drug resistant malaria especially when in combination with lumefantrine
Which anti-malarial would be best for pregnant women?
Who should NOT use this medication?
Mefloquine is good against chloroquine resistant malaria and works on all 4 plasmodium strains.
Mefloquine should not be used in any depressed patients because it has neurologic and psychiatric side effects
What drug is recommended for treating dormant liver forms of P vivax and P ovale?
Who is it contraindicated in?
Primaquine
Cannot be used by pregnant women or patients deficient in G6PD because it can cause hemolytic anemia
What is the major example of an amoeba that infects humans?
What is the life cycle?
What drugs treat it?
E. histolytica in the tropics and poor areas
Fecal-oral transmission
Cysts in GI tract are dormant and become pathogenic in the blood and liver to cause dysentery
Drugs:
iodoquinol - mild infections
Metronidazole - systemic and severe intestinal ameoba
What is the mechanism of action of metroidazole?
It enzymatically reduces in a hypoxic environment, generates free radicals that degrade DNA (similar to nitrofuratoin)
What is the pharmacokinetics of metroiodazole?
- absorption
- distribution
- elimination
- orally absorbed really well so often doesnt make it to the colonic lumen (treat with luminal drug as well)
- distributes in all tissue and fluid
- Excreted renally
What is metronidazole less effective at treating?
What is it contraindicated with?
It can effect all stages of amoeba life cycle but it is less effective against virulent intestinal forms because of its quick absorption.
Can’t take it with alcohol
Who would be at the greatest risk of acquiring a G. lamblia infection? What is the life cycle?
What is treatment?
Hikers or campers because guiardia cysts are in feces or contaminated water
It causes epidemic diarrhea.
Treat with metronidazole
What kind of protozoa is T. vaginalis? What does it cause? How is it spread?
What is treatment?
It is a flagellate protozoa spread through sexual contact and causes urethritis and vaginitis. Both partners get foamy yellow discharge.
Treat with metronidazole
How is Leishmaniasis transmitted?
What are the 2 forms? What are their severities?
Sand fly and can cause
- visceral- can spread via blood transfusion and is severe Kala-Azar, fever, malaise, etc. can cause death
- cutaneous infection- skin lesions, blisters, self-limiting
What protozoa causes African Sleeping Sickness?
How is it trasmitted?
T. brucei transmitted via the tsetse fly
What are the two stages of African Sleeping Sickness?
- Early/Acute- within 3 wks of infection–>fever and malaise
- Chronic/Late- invade CNS and lead to headache, coma, death
What are the two types of T brucei?
Which causes neurological symptoms and which causes rapid weight loss, heart involvement and death?
T brucei gambiense = neuro
T brucei rhodesience = heart problems and death
What causes Chaga’s disease?
What are the early symptoms?
What are the late symptoms?
T. cruzi causes Chagas
The early symptoms are fever, lymphadenopathy,rash
The late stage (10-20 years later) is cardiomyopahty
