GI Parasites - Zimmer Flashcards
1
Q
What is the main mechanism that parasites cause disease?
A
- Microbial proliferation and invasion
- growth and spread of microbes that causes damage that is significant in illness.
2
Q
What are the basic common features of GI parasites and parasitic infections?
A
- A worldwide issue
- Good sanitation in US make us less vulnerable
- Children hit severely
- High mobility
- Poorer standards of hygiene
- Multiple parasites at the same time
- Malnutrition makes them more vulnerable
- Gradual onset of symptoms
- Infections are commonly long lasting or chronic (or have the potential to become so)
- Malnutrition a common feature of chronic parasitic GI infections
- Childhood malnutrition
- Infected individuals are often asymptomatic
- Morbidity and mortality depend on
- parasite burden
- species
- preexisting immunity
- patient comorbidities
- Rate of parasitic infection is increasing in U.S. due to:
- international travel
- immigration
- children in day care
- AIDS and the immunocompromised
3
Q
What is the best way to prevent parasitic infection?
A
- Whether GI parasites are primarily water-borne, zoonotic, or live in soil, transfer from fecal material or from perianal region is an essential part of transmission
- Adequate disposal and treatment of human waste
- Adequate treatment of drinking water
- Hand washing, food washing
- Be aware during travel and after
4
Q
What are the three protozoan (unicellular eukaryotes) parasites that we need to know?
A
- Entamoeba
- Giardia
- Cryptosporidium
5
Q
What are the Helminths (multicellular eukaryotes) that we need to know?
A
- Nematodes → Roundworms
- Ascaris (giant roundworm)
- Trichuris (whipworm)
- Enterobius (pinworm)
- Ancylostoma/Necator (hookworm)
- Strongyloides
- Cestode → Tapeworms
- Diphyllobothrium
- Echinococcus
- Taenia
- Trematodes → Flukes
- Schistosoma
6
Q
What are the common symptoms of parasitic infections?
A
- Stomach/intestinal cramps, gas and nausea
- Fluid loss/diarrhea lasting longer than one week
- Often noted upon return from travel
- Onset gradual
- Incubation period can be weeks
7
Q
What are the typical treatments for parasitic infections?
A
- Often don’t treat with drugs
- Fluid replacement very important for treatment
8
Q
What are the common preventions for parasitic infections?
A
- Avoid contaminated water
- Live somewhere with good sanitation
- Practice good personal hygiene, and assume that others do not
- Wash fruits and veggies
- Vaccines are not available
9
Q
What is the common method of diagnosis for parasitic infections?
A
Stool sample
10
Q
What are the life cycle terminology differences for protozoa, nematodes, and cestodes/trematodes in mammal hosts and in the environment (i.e. excreted fecal matter)?
A
-
Protozoa
- Host: Motile, replicating form (e.g. Trophozoites, Sporozoites, Trypomastigotes)
- Environment: Cyst, Oocyst
-
Nematodes
- Host: Juvenile and adult worms, sexually reproducing (Male and female worms)
- Environment: Eggs, sometimes larvae
-
Cestodes/Trematodes
- Host: Juvenile and adult worms, sexually reproducing, hermaphrodite (Schistosome an exception)
- Environment: Eggs
11
Q
How are the 3 protozoan GI parasites transmitted?
A
- Water-borne
- Or food contaminated with fecal matter
- Or MSM and oral/anal sex
- Ingesting cysts or oocysts
12
Q
Where is Giardia lamblia (intestinalis) infection most likely?
A
- About 10-fold more common in developing countries
- 33% of individuals: developing countries
- Also most common intestinal parasite in US
- Giardiasis (aka Beaver Fever) is the foe of backpackers/hikers
13
Q
What is the mechanism of infection for Giardia lamblia (intestinalis)?
A
- Presence of parasite causes loss of epithelial absorptive surface area.
- Other factors may play a role, not well understood.
- Symptoms for 1-2 weeks or more, may seem to resolve and then come back
14
Q
How is Giardia lamblia (intestinalis) infection diagnosed?
A
- Ingest cysts
- Trophozoites: Attachment to epithelials cells but not penetration in small intestines
-
Fecal matter = Cysts
- cysts survive longer
- Symptoms useful for diagnosis:
- Foul-smelling diarrhea
- Flatulance
- Stools are greasy, tend to float (fatty)
- Malabsorption of fat, lipids, some vitamins
15
Q
What is the best way to prevent Giardia lamblia (intestinalis) infection?
A
- Filter water in areas where Giardia cysts are likely to exist.
- Water does not need to be contaminated with human sewage.
- Wildlife can deposit cysts.
- “Beaver Fever”
16
Q
When is Cryptosporidium parvum infection seen?
A
- Often seen when a sanitation system fails
- Pool/waterpark chlorination/UV treatment
- Storms or issues with drinking water
- Diarrhea symptoms for 1-2 weeks to ~30 days, may seem to resolve and then come back
- “Crypto” is opportunistic
- HIV/Immunocompromised individuals
- Chronic Diarrhea/fluid loss
- Can be fatal
- Cannot be immediately infectious → No direct oral-fecal transmission
17
Q
What is the mechanism of Cryptosporidium parvum infection?
A
- Absorption impaired and secretion enhanced when intestinal epithelial cells are infected by Cryptosporidium → Cryptosporidiosis
18
Q
How do you differentiate the diagnosis of Cryptosporidiosis from Giardia?
A
- Watery, frequent, non-bloody stool
- Fever, sometimes. Nausea, sometimes.
- Disrupts epithelial microvilli, slides into host cells, enveloping itself in the host cell membrane
- Oocysts in feces → very small!
- can be Acid-fast stained (turn red)
- Oocysts in feces → very small!
19
Q
Cryptosporidium parvum belongs to which subclass of Apicomplexan protists?
A
Coccidia
20
Q
Where is Entamoeba histolytica typically contracted?
A
- More prevalent in tropical/subtropical climates
- Only 10-20% of infected individuals will become ill (CDC)
- Of US population, male homosexuals most vulnerable
21
Q
What type of infection does Entamoeba histolytica cause?
A
- Causes Amebiasis
- AKA Amebic Dysentery, Amebic liver abscesses
22
Q
How do you differentiate Entamoeba histolytica infection from other GI parasitic infections?
A
- Bloody, mucus-ey loose stool
- Relatively mild symptoms
- Can invade the liver and form an abcess
- X-ray/ultrasound to detect abscess or tissue damage
- Must differentiate symptoms from bacillary dysentery!!!
-
Lab diagnosis: Cysts in stool sample.
- Must differentiate from non-pathogenic entamoeba → takes a specialist
23
Q
Why is bloody diarrhea/hepatitis common/possible in Entamoeba histolytica infection?
A
- Cytotoxic
- maximally tissue-invasive
- adhere and kill
- phagocytose
- Mucosal cell invation
- results in replication
- cysts in feces
- Blood vessel invasion:
- Amebic hepatitis: single abscess in right lobe
- should present with right upper quadrant pain, fever, weight loss
24
Q
What are the antiparasitics targeting GI protozoans?
A
- Nitroimidazoles
- Metronidazole
- Tinidazole
- Nitazoxanide
- Iodoquinol
- Paromomycin
- TMP-SMX (Trimethoprim Sulfamethoxazole)
25
What is the MOA of Nitazoxanide?
* Interferes with pyruvate-ferredoxin oxidoreductase enzyme dependent electron transfer
* essential to anaerobic energy metabolism protein
26
What is Nitazoxanide used to treat?
* Cryptosporidosis
* Cryptosporidosis often not treated in immunocompetent hosts
* but Nitazoxanide effectiveness goes down in the immunocompromised
* For Crypto, used in combination with retroviral therapy for AIDS patients if at all, because of ineffectiveness
* HAART with immune reconstitution
* Anti-peristaltic agents (Loperamide) and oral rehydration is important
27
What is the MOA of Iodoquinol?
Unknown
28
What are the toxicities of Iodoquinol?
* Loss of visual acuity
* Use with caution in patients with thyroid disease – its use interferes with certain thyroid tests
29
Why is the distribution of Iodoquinol beneficial?
* only 10% of the drug is absorbed
* works locally on the protozoa including cysts in the GI tract
* luminal antiparasitic (amebicide)
30
What drug class does Paromycin belong to?
Aminoglycoside
31
What is the MOA of Paromycin?
Protein synthesis inhibitor = targets 30S subunit ribosome
32
What sort of toxicities are associated with aminoglycosides?
Ototoxicity, nephrotoxicity
33
Why can we use Paromycin on GI parasites and avoid the toxicities in patients?
It is a luminal antiparasitic
34
Why we need to consider absorption and tissue distribution in treatment of GI parasitic infections?
* Entamoeba histolytica destroys tissue
* A symptomatic infection means organism has invaded tissue, but also still at lumen
* Luminal amebicide
* Iodoquinol or Paromomycin
* Tissue amebicide
* Metronidazole or Tinidazole
35
What GI parasitic infections is Bactrim effective against?
* Apicomplexans including:
* Toxoplasma
* Cystoisospora (formerly Isospora)
* Cyclospora
36
When does Enterobius vermicularis (pinworm that is one of the roundworms) infection occur?
* Worldwide distribution, most common helminth infection in US
* Prevalence can reach 50% in children, caregivers of infected children, and institutionalized individuals.
* Acquired by ingestion of pinworm eggs
* Eggs can remain viable on surfaces for 2-3 weeks
37
Why do infections/outbreaks of Enterobius vermicularis (one of the roundworms) last a very long time?
* Takes 1-2 months from egg ingesion to adult males and females
* Adults live ~ 2 months
38
How is Enterobius vermicularis (one of the roundworms) infection diagnosed?
* Hx of anal itching
* Confirmation:
* Tape or “pinworm paddle”- obtained eggs
* Appearance of worms 2-3 hrs after person is asleep
* A.M. Scotch tape method to pick up eggs from perianal region
* Sample from under fingernails
* Eggs will likely NOT be found in stool sample!
39
What are the soil-transmitted roundworms?
* Hookworms (Necator)
* Southern US
* Whipworms (Trichuris)
* Southern US
* Giant Roundworms (Ascaris)
* Rarely in US
* Strongyloides – much less common
* Large North American Cities, Southern US
40
How is Necator acquired?
* Skin penetration
* 9-11 mm (small staple size)
41
How is Trichuris acquired?
* Egg ingestion
* 3-5 cm
42
How is Ascaris acquired?
Egg ingestion
15-35 cm (spaghetti, a ruler)
43
How is Strongyloides acquired?
Skin penetration
a few mm
44
How does Necator americanus/Ancylostoma duodenale and Strongolides stercoralis cause symptoms?
* Larvae in soil
* Skin penetrations
* barefoot
* Circulatory system
* Coughing/swallowing
* Make home in small intestines
45
What type of infection does Necator americanus/Ancylostoma duodenale and Strongolides stercoralis cause?
Cause hookworm and strongyloidiasis
46
How are Necator americanus/Ancylostoma duodenale and Strongolides stercoralis diagnosed?
* Stool sample for diagnosis:
* Necator eggs
* Strongolides larvae
47
What type of rash does Necator americanus/Ancylostoma duodenale infection cause?
Pruritic Papular Erythematous Rash
48
What is a major symptom of hookworms?
* Hookworms are bloodsuckers…
* Major symptom is iron-deficiency anemia
* ¼ ml/day/worm
49
What are the symptoms of Strongolides stercoralis (one of the roundworms) infection?
* Stomach and GI complaints
* Respiratory
* dry cough
* throat irritation
* Skin
* an itchy, red rash that occurs where the worm entered the skin
* recurrent raised red rash typically along the thighs and buttocks
* What makes it different:
* Autoinfection possible, especially with Immunosuppressed individuals
50
What diseases are caused by Trichuris trichiura (one of the roundworms)?
Whipworm or Trichuriasis
2.2 million cases/yr in U.S.
51
How do you diagnose Trichuris trichiura (one of the roundworms) infection?
* Diagnosis:
* Eggs in feces have a characteristic barrel-shaped appearance
* Finger clubbing best indicator of severity of infestation
* Bloody diarrhea = iron deficiency anemia
* Heavy cases:
* Frequent, painful stools with mucus, water and blood, tenesmus
* Rectal prolapse
52
Where does Ascaris lumbricoides (giant roundworm) cause infection?
* About half of the populations in tropical and subtropical areas are infected with this parasite
* 1 billion/yr affected
53
What are the symptoms of Ascaris lumbricoides infection (Ascariasis)?
* Disease: IF symptoms are experienced, abdominal discomfort
* If a severe case, intestinal blockages
* Ultrasonography and radiology to determine
* Has a lung stage of life cycle, may cause **cough**
* Chest radiograph of newly-infected individual may reveal infiltrate
54
How do you diagnose Ascariasis?
* Charcot-Leyden crystals
* Charcot-Leyden crystals are formed from the breakdown of eosinophils and may be seen in the stool or sputum of patients with parasitic diseases. Cause may or may not be a parasitic infection, may be asthma.
* Diagnosis: eggs w/thick shells
55
What are the general goals for antiparasitic treatment of GI helminths (roundworm + tapeworm)?
* Remove adult worms from the GI tract
* Usually can be accomplished with drugs
* In the case of severe blockages, imaging and surgery may be required
* Multiple-helminth infections common
* Mass drug administrations of albendazole and ivermectin to school children in developing nations
* No vaccines
* upcoming says NPR
56
What are the selective toxicity strategies used to target/treat GI roundworms?
* Exploit the biochemical differences between the parasite and host
* **Differentially distribute** the drug.
* The parasite is exposed to high concentrations of the drug in its intestinal habitat by the use of orally administered non-absorbable drugs.
* Mechanisms
* target worm **motor activity** or reactions that **generate metabolic energy**
57
What are the two broad-spectrum benzimidazole drugs used to treat roundworms and tapeworms?
Albendazole and Mebendazole
58
What is the drug distribution of Albendazole and Mebendazole?
* Limited oral absorption
* Albendazole is better absorbed if targeting tissue-migrating larvae is important
59
What is the MOA of Broad-spectrum benzimidazole drugs?
* Binds to parasite β-tubulin and inhibits the formation of microtubules
* Death can take several days, for some helminths more than one dose may be necessary
60
What are the potential toxicities of Albendazole and Mebendazole?
* Systemic toxic affects on liver/bone marrow rare
* Abdominal pain, nausea, dizziness, headache
* Embryotoxic and teratogenic in pregnant rats
* Evidence suggests safe for use in children when warranted
61
What are the two cholinergic antihelmintics?
Pyrantel pamoate and Levamisole
62
What is the MOA of Pyrantel pamoate and Levamisole?
* selectively opens a restricted subgroup of nematode acetylcholine receptor (AChR) ion channels in nematode nerve and muscle
* depolarization entry of calcium through the opened channels, and an increase in sarcoplasmic calcium
* produces spastic muscle contraction the parasite is then unable to maintain its location (often in the intestine) and is then swept away
63
What are the toxicities of Pyrantel pamoate and Levamisole?
Causes nausea, vomiting, diarrhea
64
What is the macrocyclic lactone that binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing deactivation of channel: worm paralysis and death by starvation?
Ivermectin
65
What are the toxicities associated with Ivermectin?
* Generally well-tolerated
* Itching, swollen lymph glands and rarely dizziness
* Inflammatory reaction due to death of adult worms
66
What other parasitic infections is Ivermectin used to treat?
Nematodes- Ascaris, Strongyloides and Onchocerca
67
What are the three Tapeworms that cause zoonotic disease?
* *Taenia*: your typical human tapeworm, beef or pork tapeworm
* 3 – 10 meters in length!
* *Diphyllobothrium* fish tapeworm
* The monster: up to 30 ft in length
* *Echinococcus:* causes echinococcocis → a disease of liver, lungs, brain, and other organs
* Tiny, a few mm in length
68
How is Diphyllobothrium: Fish tapeworm acquired?
* Acquired by eating the musculature of fish where larvae have migrated
* Adheres to mucosa of small intestine
69
How is Diphyllobothrium: Fish tapeworm diagnosed?
* The standard intestinal “problems”
* **Anemia** due to competition for Vitamin B12 in intestine
* Stool contains eggs and/or proglottids
70
How is Taenia sp: Beef or pork tapeworm acquired?
* Acquired by human when meat containing Cysticeri is consumed
* Cysticerci grows into tapeworm in small intestines
* Eggs and broken pieces of mature tapeworm are passed into feces for excretion
71
How is Taenia sp: Beef or pork tapeworm diagnosed?
* The standard intestinal “problems”
* Stool contains eggs and/or proglottids (mature tapeworm segments)
* Cysticercosis possible if cysticerci migrate to muscle, brain, or other tissue
72
How does Echinococcus cause Echinococcosis?
* Eggs excreted in feces of definitive host (dog)
* Oncosphere hatches in small intestines and penetrates the lining
* Enters circulatory system
* Causes slow growing cysts in organs
73
How is Echinococcus infection diagnosed?
* Not really a GI illness at all
* Pain or discomfort in the upper abdominal region or chest
* Sheep farming + uncontrolled living with canines; trappers
* common patient profile
74
What are the antiparasitics that target Tapeworms?
* Benzimidazoles
* Albendazole and Mebendazole
* Praziquantel
75
What is the MOA of Praziquantel?
causes increased permeability of the parasite to divalent cations leading to contraction of the worm’s musculature
76
What are the toxicities of Praziquantel?
Generally well-tolerated, but dizziness and nausea are side effects
77
What parasitic infections can be treated with Praziquantel?
Cestodes (tapeworms) and trematodes (flukes)
78
What parasite is responsible for the following:
A 38-year-old male who recently spent a month in rural Mexico complained of a spiking fever, malaise, headache, and right upper quadrant abdominal pain. He had bloody diarrhea with mucus and tenesmus. Physical examination revealed a fever of 39.6°C, pallor, slight jaundice, and tender hepatomegaly.
Entamoeba hystolytica
| (protozoan)
79
What does Giardia trophozoite look like?
two nuclei → "eyes"
and Dr. Zimmer thinks it is "cute"
80
What disease is second only to malaria as the most devastating parasitic disease according to the CDC?
Schistosomiasis
81
What are the two major forms of schistosomiasis?
* Two major forms of schistosomiasis – **intestinal and urogenital** – disease incidence numbsecond only to malaria as the most devastating parasitic diseaseers lump both together
* Urogenital caused by the species Schistosoma haematobium
82
Why is the Schistosoma spp. called the "Valentines Parasite"?
Male & female flukes hang out together
83
What is the intermediate and definitive hosts of Schistosoma spp.?
* Intermediate → snail shells
* Definitive → Humans
* one in which sexual reproduction can occur
84
What is the mechanism of disease caused by Schistosoma spp.?
* Symptoms are caused by immune response to egg stage of Schistosoma
* Eggs shed by the adult worms become lodged in the intestine or bladder, causing inflammation, scarring.
* After years, this damages the liver, intestine, spleen, lungs, and bladder
* Repeatedly-infected children can develop anemia, malnutrition, and learning difficulties
85
What are the symptoms of Schistosomiasis?
* Within days of infection: rash or itchy skin
* 1-2 months of infection: fever, chills, cough, and muscle aches
* Chronic: abdominal pain, enlarged liver, blood in the stool or urine, and problems passing urine.
* Chronic infection can also lead to increased risk of bladder cancer.
86
How do humans acquire Schistosoma spp.?
* Eggs hatch in water
* Eggs penetrate snails
* Maturing form gets deposited in water
* Humans drink water
* Mature form develops in human
87
After skin penetration, how do Schistosoma spp. develop in humans?
* After skin penetration → schistosomulae find capillaries (blood)
* migrate first to lungs
* second to heart
* and third to LIVER
88
What is the average lifespan of Schistosoma spp.?
Average lifespan is 5 years, but adult worms can live up to 20 years.
89
How is Schistosomiasis diagnosed?
* Stool or urine samples can be examined microscopically for parasite eggs
* Eggs are passed in small amounts intermittently, it may be necessary to perform a blood (serologic) test.
90
What is the treatment for Schistosomiasis?
* Antiparasitic: praziquantel
* Low efficacy against immature worms → may need to give a second dose if eggs still present in stool or urine 2-3 months later
* In acute cases, treatment with praziquantel is usually delayed until three months after infection as this is when it is most effective
* Steroid medication (corticosteroids) may be used to relieve the symptoms of acute schistosomiasis, as they help control the allergic reaction to the eggs responsible for the symptoms.
91
How are the various GI parasites transmitted?
* Nematodes (roundworms): soil\*
* Cematodes (tapeworms): zoonotic
* Protozoa: water (food)
* Trematodes (flukes): water, other flukes: undercooked fish
* Universal: poor hygiene/sanitation
92
What GI Parasites are you most likely to see in the US?
* Giardiasis
* “Crypto”
* Pinworm
93
What patients should you especially suspect parasitic GI infections?
* Children
* Immigrants
* World travelers
* Immunocompromised
* Chronically “unwell” individuals losing weight
