LEC 36 & 37 Blood and Tissue Protozoans Flashcards

1
Q

What is Plasmodium?

A

Unicellular eukaryotic parasite (protozoan)

More than 150 species that infect many vertebrates

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1
Q

What are the 5 plasmodium species that infect humans?

A
  • P. falciparum
  • P. vivax
  • P. ovale
  • P. malariae
  • P. knowlesi
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2
Q

What is the vector for Plasmodium?

A

transmitted through the bite of a female Anopheles mosquito

A. gambiae most important species

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2
Q

What occurs in the Exoerythrocytic stage of the plasmodium life cycle?

A
  1. Mosquito bites host and injects anticoagulants along with the sporozoite
  2. Sporozoite (motile) travels (via blood or lymph) to the liver and invades hepatocytes and then begins asexual replication
  3. Merozoites are produced and burst open the hepatic cell releasing themselves into the blood

Hypnozoites: P. vivax and P. ovale; they lie dormant for a while then become active

No pathology or disease associated with this stage

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3
Q

What occurs during the Erythrocytic cycle of the plasmodium life cycle?

A
  1. Merozoites just released into blood will infect an RBC
  2. Asexual replication occurs in the RBCs which form distinct shapes of the RBC (Ring, Trophozoite, Schizont, Merozoite)
  3. RBC bursts releasing merozoites and starting the cycle anew

Clinical disease associated w/ high rates of replication

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3
Q

What stage of the intraerythrocytic cycle are these RBCs in?

Hint: Shape of the cell?

A

Rings

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4
Q

What stage of the intraerythrocytic cycle are these RBCs in?

Hint: shape of the cell?

A

Trophozoites

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5
Q

What stage of the intraerythrocytic cycle are these RBCs in?

Hint: the shape of the cell?

A

Schizonts

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6
Q

What stage of the intraerythrocytic cycle are these RBCs in?

A

Gametocytes

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7
Q

What happens during the sexual cycle of the Plasmodium life cycle?

A
  1. The mosquito sucks the blood of infected person
  2. The microgamete (male) and the Macrogamete (female) do sex and form a diploid zygote within the mosquito
  3. Meiosis occurs and forms Ookinete (motile)
  4. Ookinete lies in between epithelium and basal lamina and forms an Oocyst–> replication
  5. Sporozoites released in mosquito where they travel to salivary glands to be injected in next person via mosquito bite
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8
Q

What are the clinical signs and symptoms of uncomplicated malaria (mild)?

A
  • Classic attacks last 6-10 hours and occur every 2 days (Tertian) or 3 days (Quartan) - fever cycle
  • pt presents w/ fever, chills, sweats, BAs, HA, N/V, malaise
  • physical findings: elevated temp, perspiration, fatigue, hepatosplenomegaly, jaundice, weakness, increased respiration rate
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9
Q

Explain the tertian fever cycle.

A
  • Replication takes 48 hours
  • after initial 48 hours, pt will have fever (day 1)
  • Day 2, pt will NOT have fever
  • Day 3 (48 hours later) the pt will have fever again

P. vivax and P. ovale replicate with Tertian cycle

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10
Q

Explain the quartan fever cycle.

A
  • Replication takes 72 hours
  • pt will exhibit fever after initial 72 hours (day 1)
  • Days 2 & 3, pt will NOT have fever
  • Day 4 (72 hours later), pt will have fever again

P. malariae replicates this way

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11
Q

What do you know about P. vivax?

A
  • Most prevalent species; less common in W. and Central Africa
  • Invades reticulocytes
  • Tertian fever cycle - benign
  • Typically not associated with disease, bc reticulocyte count in circulating blood is low
  • Has dormant exoerythrocytic cycle which can last 1-5 years (hypnozoite)
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12
Q

What do you know about P. ovale?

A
  • Low frequency of infxn in humans
  • Similar geographic range as vivax but more common in subsaharan Africa
  • Virtually identical to vivax clinically and morphologically - reticulocytes
  • Tertian fever cycle
  • Hypnozoite (same as vivax)
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13
Q

What do you know about P. malariae?

A
  • Low frequency of infxn in humans
  • Wide global distribution
  • Prefers mature RBCs
  • Parasitemia <1%
  • Quartan fever cycle
  • Recrudence up to 30 years - can result in nephrotic syndrome
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14
Q

What do you know about P. falciparum?

A
  • Common worldwide
  • Invades erythrocytes of all ages
  • Produces the highest parasitemia in humans - up to 50%
  • Poses greatest risk of mortality
  • Capable of sequestering in blood vessels
  • Adherence to endothelial cells and adjacent RBCs
  • Typically, does not display a synchronous erythrocytic cycle
  • Tertian fever cycle – malignant

Lots of diseases associated with P. falciparum

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15
Q

What are some of the diseases/pathologies that P. falciparum malaria can cause?

A
  • Cerebral malaria - confusion, impairment of consciousness, coma, seizures
  • Severe anemia - hemolysis
  • Hemoglobinuria
  • Acute respiratory distress syndrome
  • Acute kidney failure
  • Shock-like syndrome
  • Placental malaria - Premature delivery, low birth weight, loss of fetus
16
Q

What do you know about Bebesia microti?

A
  • Intracellular protozoan parasites
  • Primary cause of Babesiosis in US
  • NE US and Upper Midwest - same range as Lyme disease
  • Transmitted by nymph stage of Ixodes scapularis - deer ticks (also same tick that carries Lyme)
  • Natural hosts are mice, voles, cattle - humans are accidental host
17
Q

What are the major differences in the life cycle of Babesia compared to Plasmodium?

A
  • Vector: uses tick and not mosquito
  • Babesia directly infects RBCs and does NOT go to the liver first
  • Once inside RBC, Babesia only makes 4 merozoites where Plasmodium makes many and lyses the cell
18
Q

What are the clinical symptoms of Babesiosis?

A
  • Often asymptomatic (25-50%)
  • Flu-like symptoms
  • Can be severe in: Immunocompromised, Splenectomy pts, elderly
  • Severe disease: Hemolytic anemia, low and unstable BP, DIC, thrombocytopenia, kidney failure, death
19
Q

How do you diagnose Babesia infxn?

A
  • Thick and thin blood smears w/ Giemsa - however parasitemia is often <0.2%
  • Rings form (like Plasmodium) and a tetrad shape forms in RBCs
  • Send to CDC for confirmation
  • Serology tests
  • PCR
20
Q

How do you treat Babesia infxn?

A
  • Combo of Azithromycin and Atovaquone - mild disease
  • Combo of Clindamycin and quinine - severe disease
  • Blood transfusion
21
Q

What do you know about Trypanosoma brucei?

A
  • Extracellular flagellated protozoa
  • 3 sub species: T. brucei - gambiense/rhodesiense/brucei
  • Transmitted by Tsetse fly - Trypomastigotes resides in the salivary glands
22
Q

Explain the life cycle of T. brucei.

A
  • Epimastigotes in salivary glands divide and produce trypomastigotes
  • Tsetse fly bites host releasing trypomastigotes into host blood
  • Trypomastigotes replicate via binary fission in blood, lymph, and CNS
  • New fly bites host and takes up newly produced trypomastigotes and their flagellas shorten forming epimastigotes
  • Process repeats
23
Q

What do you know about T. b. gambiense?

A
  • Tropics of central and western Africa
  • Humans are primary reservoir (anthroponotic)
  • Chronic infxn can result in death
  • Red sore around bite developes within 1-3 weeks
  • Weeks to months before later symptoms develop
  • Death can occur after several years of infxn
24
Q

What do you know about T. b. rhodesiense?

A
  • Grasslands of Eastern Africa
  • Domestic animals and wild game animals are reservoirs
  • Disease progresses rapidly - symptoms in 1-3 weeks; death within 9-12 months
25
Q

What are the clinical symptoms of T. b. gambiense?

A
  • Hemolymphatic phase: disseminates through blood and lymph - Recurrent fever, lymphadenopathy, rash, HA, Winterbottom’s sign (swelling of post. cervical lymph node)
  • Neurological phase: parasite crosses blood brain barrier & infects CNS - occurs 1-2 years later, Sleeping Sickness (Lethargy, tremors, inability to move, insomnia, daytime sleeping, confusion, reduced coordination, progresses to comatose state)
Winterbottom's Sign
26
Q

What are the clinical symptoms of T. b. rhodesiense?

A
  • Hemolymphatic phase: disseminates through blood and lymph - Occurs more rapidly, Large sore (chancre) @ bite site, Lymphadenopathy is UNCOMMON, higher #’s of parasite in blood
  • Neurological phase: parasite crosses blood brain barrier & infects CNS - occurs more rapidly, kidney damage & myocarditis may kill host prior to CNS pathology development
Large sore at bite site (chancre)
27
Q

How do you diagnose a Trypanosome infxn?

A
  • Thick/thin blood smear stained with Giemsa - T. b. rhodesiense easy to identify on smears d/t high replication
  • Exam of lymph node aspirate from post. cervical lymph node for gambiense
  • Spinal tap must be performed for all confirmed cases of Trypanosomiasis to determine course of tx
28
Q

How do you treat a Trypanosome infxn?

for both rhodesiense and gambiense

A
  • Hemolymphatic phase: suramin (rhodesiense) or pentamidine (gambiense)
  • Neurological phase: melarsoprol (rhodesiense) or eflornithine-nifurtimox (gambiense)
  • Examination of CSF for 2 years to ensure no relapse

only pentamidine widely available; rest must come from CDC

29
Q

What do you know about T. cruzi?

A
  • Found in Mexico, Central and South America - associated with impoverished areas
  • Transmitted by “kissing bug” - reduviid bug or triatomine bug - found in AR but not with T. cruzi
  • Feeds on humans, mammals, and birds (reservoirs)
  • Resides in intestine of reduviid bug
  • Transmitted when feces deposited by the biting insect are introduced into the bite by scratching
30
Q

Explain the life cycle of T. cruzi.

A
  • Bug bites host and defecates (contains parasite) - host scratches infecting the bite wound with the trypomastigote
  • Trypomastigote travels to smooth muscle (heart) and rounds up and begins replicating
  • New trypomastigotes are released into the blood to be taken up by a new vector in a blood meal
  • Within the vector, the flagella shorten forming epimastigotes which multiply in the midgut
31
Q

What is the name of the disease caused by American Trypanosomiasis?

A

Chagas Disease

32
Q

What are the clinical symptoms of Chagas disease?

A
  • Acute phase: produces local rash & edema at site of infxn; Romana’s sign - Site of infxn is often the face, high parasitemia for 2 months, can form ulcer (chancre) at site of bite, often asymptomatic
  • Chronic phase: parasite resides in multiple tissues especially heart and digestive smooth muscle - low parasitemia, can be asymptomatic for life of individual, Life-threatening heart and GI disease in 20-40% of chronically infected but may take years to manifest
33
Q

How do you diagnose Chagas disease?

A
  • Thick/thin blood smear stained with Giemsa
  • Serological tests (chronic)
34
Q

How do you treat Chagas disease?

A
  • Nifurtimox and Benznidazole
  • Less effective against chronic infxn
  • Nifurtimox not FDA approved but is still available from CDC
35
Q

What do you know about Leishmania?

A
  • Flagellated protozoan parasite
  • Found primarily in tropical and subtropical regions
  • Many different species
36
Q

How is Leishmania transmitted?

A
  • Transmitted by phlebotomine sandflies
  • Rodents and dogs are major reservoirs
  • Anthroponotic: human-vector-human
  • Infxns in US are primarily seen in US troops and gov contractors returning from N. Africa and Middle East
37
Q

What kind of cells does Leishmania infect?

A

Phagocytic cells

Prefers macrophages over neutrophils

38
Q

What are the clinical manifestations of Leishmaniasis?

A
  • Cutaneous: local skin infxn; ulceration - weeks to months, often heal spontaneously
  • Mucocutaneous: rare, occuring months after clearance of cutaneous lesion - primarily occurs in Bolivia, Brazil, & Peru
  • Viseral (kala-azar): weight loss, hepatosplenomegally, anemia, fever - within months to years; 100% fatal in 2 years if untreated
39
Q

How do you diagnose Leishmaniasis?

A
  • Histological exam of biopsy material (skin ulcer, LN aspirates, buffy coat of venous blood, bone marrow aspirate)
  • Amastigotes visualized with Giemsa or H&E stains, but are indistinguishable from T. cruzi
  • in vitro culturing of parasites from bx material
  • Species ID by isoenzyme or DNA analysis
40
Q

How do you treat Leishmaniasis?

A
  • Sodium stibogluconate - not FDA approved
  • Amphotericin B - Viseral; given IV
  • Miltefosine - select new world spp.; tx of cutaneous, mucosal, and viseral
  • Sitamaquine - viseral
  • Fluconazole, Ketoconazole, Itraconazole - oral; not FDA approved