6/12- Protozoans 2: Leishmaniasis, Chaga, African Trypanosomiasis Flashcards
Breakdown of the Phylum Protozoa?
PHYLUM PROTOZOA
Apicomplexa (IC parasites)
Zoomastigophorea (flagellated protozoan)
–Kinetoplastic infxns (tissue protozoan)
Sarcodina (amebas)
Ciliophora (ciliated protozoan)
What are some etiologies of tissue infections?
- Leishamnia spp
- Trypanosoma cruzi
- Trypanososoma brucei/gambiesis
- Others: toxo, malaria…
Etiology of Leishmaniasis?
(organism, vector, tranmission)
Leishmania spp
- > Sandfly -> BITE/vomit -> Human
- > Leishmaniasis
Etiology of Trypanosoma cruzi?
(organism, vector, tranmission)
Trypanosoma cruzi
- > Reduviid gut -> BITE/scartch -> human
- > American Trypanosomiasis
Etiology of Trypanosoma brucei/gambiesis?
(organism, vector, tranmission)
Trypanosoma brucei/gambiesis
- > TseTse fly -> BITE -> Human
- > African Trypanosomiasis
What are the different forms of Leishmaniasis?
- Visceral Leishmaniasis (VL)- aka Kala-azar
(major cause of morbidity/mortality; opportunistic infection in HIV/AIDS)
- Cutaneous Leishmaniasis (CL)
- Mucocutaneous Leishmaniasis
What organs does visceral lesh attack?
- Bone Marrow
- Liver
- Spleen
What is the vector for Leishmaniasis?
What serves as a major reservoir?
Vector: Sandfly
Reservoir: canines
Are the different forms of Leishmaniasis Old or New world?
- Visceral: mostly old
- Cutaneous: ?
- Mucocutaneous: ?
Life cycle of Leishmania
- Sandfly takes blood meal (injects promastigote [flagellated] stage into skin)
- Promastigotes are phagocytized by macrophages
- Promastigotes transform into amastigotes inside macrophages
- Amastigotes multiply in cells (including macrophages) of various tissues; result in nests/granulomas of parasites
- Sandfly takes a blood meal (ingests macrophages infected with amastigotes)
- Ingestion of parasitized cells
- Amastigotes transform into promastigote stage in midgut
- Divide in midgut and migrate to proboscis
What species cause Visceral Leishmaniasis? Where?
- L. donovani (Asia-Africa)
- L. Infantum (Southern Europe)
- L. chagasi (Brazil)
90% of new cases in: India, Bangladesh, Brazil, and Sudan
Often found in jungle-like areas because that’s where the sandflies are
Treatment for Visceral Lesh?
until 1990, limited to pentovalent antimony (sodium stibogluconate), once daily for 28 days (poorly tolerated)
What are some of the problems being encountered with the prevalence/treatment of Visceral Lesh?
- State of Bihar contains 90% of infections; large scale resistance
- Emerging opportunistic infection among AIDS
- Prohibitive costs of lipid formulations of Amphotericin B
Clinical Features of Kala-Azar (“Black Fever”) or Visceral Leshmaniasis?
- Majority of infections are self-resolving
For full-blown Kala-azar:
- Fever
- Weight loss
- Hepatosplenomegaly (spleen becomes very hard due to concentration of amastigote; some vasoconstriction and decreased blood flow); picture shows massive spleen (marker)
- Neutropenia
- Hypergammaglbulinemia
- Hyperpigmentation (“Black Fever”)
What age group is most susceptible to visceral lesh?
Children under 5 yo
What does the temperature curve look like in Leishmaniasis?
- Hyperpigmented, active border
- Kind of a heal-center
- Biopsy on the border (not scarred/healed area)
How is Kala-Azar (Visceral Lesh) diagnosed?
- Fine needle aspiration of spleen (>90% sensitivity; hemorrhagic complications)
- Bone marrow aspiration
- Poor sensitivity and specificity of ELISA
- Intradermal Leishmanin skin test (often injected in girl’s buttocks to prevent contraction of dz, like early vaccine to avoid facial disfigurement)
What is this?
Leishmania on microbiology
- Donovan body! Nidus of infection: macrophage with many amastigotes ready to burst out (top pic)
- Leishamnia in bone marrow (bottom pic)
What is the difference in splenomegaly with visceral lesh vs. something like mono?
In mono, the spleen is soft rather than rock hard like in Visceral Lesh
Case:
- 30 yo man from Ethiopia admitted for fever (103’F), pancytopenia, and hepatosplenomegaly
- CBC: WBC 3.5 Hg 9.7 Plt 98K
- HIV + (AIDS 156 Vload 2.5 million)
- Work-up negative. Started on TB treatment and after 6 wks, started on Atripla
- Returns with fever, WBC 0.5
- Diagnosis?
Leishmaniasis and HIV co-infection
Countries reporting Leishmaniasis/HIV co-infection?
- Mediterranean area
- Ethiopia, Angola
- Brazil, Peru, Colombia
- India
Treatment of Visceral Lesh?
Pentavalent Antimony (SbV)
- Common side effects: nausea, vomiting, abdominal pain, chemical pancreatitis, ECG changes (prolonged QT with risk of arrhythmias)
- Documentation of cure by symptomatic improvement
New, less toxic alternatives:
- Ointments (paromycin + gentamicin)
- Azole (but resistance!)
Using Amphotericin B for Kala Azar (Visceral Lesh)
- Why use?
- What form?
- Different forms have what?
- Single dose regimen?
- Cost?
- Use promoted by Sb resistance in India
- Lipid formulation of AmphoB allows for short course (90% cure with Abelcet over 5d)
- Extensive regional variation of Abelcet vs. Ambisome vs. Amphotec
- Single dose regimen: 90% cure with AmBisome (5-7.5 mg/kg)
- Not cost effective ($700)!
What is Miltefosine?
- Structure
- Form
- Used for
- Cure rate
- Adverse reaactions
- Membrane active phospholipid
- Hexadecylphosphocholine
- Oral medicine
- Originally use as anti-neoplastic
- 95% cure rate (phase 3 studies in Bihar)
- Adverse reactions: Teratogenicity in animals
Case
- 38 yo woman from Cuba comes to the Tropical Medicine clinic due to a non-healing ulcer in her arm
- What is this?
Cutaneous Leishamniasis
- Notice dryness around
- Satellite lesions
Commonly seen in people immigrating in from Cuba as they sleep in rural areas near rivers and avoid healthcare
Symptoms of Cutaneous Lesh?
Develops at site where parasites are inoculated
- Wet lesion: pizza-like with raised borders and overlying purulent exudate
- Dry lesion: smaller and covered with crust
Diffuse Cutaneous Leishmaniasis:
- Cutaneous nodules and plaques
- More common in HIV/AIDS
What is this?
Mucocutaneous Leishmania (wet in top picture, dry in bottom)
Highest disease burden of Chagas?
Bug likes to live in cracks in the adobe houses (originated in Brazil; now see in TX, often under bark and at deer leases in deer blinds)
- Bolivia
- Gran Chaco: Lowland Plains
- Argentina
- Bolivia
- Paraguay
- Central America
- Honduras
- El Salvador
- Southern mexico
- Andean
- Amazon
Life Cycle of American Trypanosomiasis?
- Triatomine bug takes a blood meal (passes metacyclic trypomastgotes in feces, trypomastgotes enter bite wound or mucosal membranes like conjunctiva)
- Metacyclic trypomastigotes penetrate various cells at bite wound site. inside cells they transform into amastigotes
- Amastigotes multiply by binary fission in cells of infected tissues
- IC amastigotes transform into trypomastigotes, then burst out of the cell and enter the bloodstream
**Trypomastigotes can infect other cells and transform into IC amastigotes in new infxn sites; clinical manifestations can result from this infective cycle**
- Triatomine bug takes a blood meal (trypomastigotes ingested)
- Epimastigotes in midgut
- Multiply in midgut
- Metacyclic trypomastigotes in hindgut
- Triatomine bug takes a blood meal…
CAN CAUSE CARDIOMEGALY IF GOES TO HEART, OR MEGACOLON IN GUT (?)
Life Cycle of Trypanosoma cruzi (American Tryposomiasis)? Different presentation
- Blood sucking vector bites and defecates on skin after blood meal
- Metacyclic trypomastigote rubbed into wound made by biting vector or into eyes
- Trypomastigotes enter cell by phagocytosis. Reproduces intracellulary as amastigote
- Cell dies releasing amstigotes which infect new cells
- Amastigotes in circulation transform into trypomastigotes. These remain in circulation
- Blood sucking insect ingests amstigotes or trypomatigotes
- Trypomastigotes reproduced in gut of insect (asexual)
- Metacyclic trypomastigotes migrate into rectum of vector
What is this?
Romana Sign of Chaga’s Disease
Symptoms of chronic Chaga’s Disease?
Cardiomyopathy (chamber enlargement)
- 10-30% of pts develop this yrs after infxn
- Left ventricular aneurysm
- Conduction deficits; can cause AV blocks or other problems leading to Vtac (one of the most common causes of strokes in S America)
Megacolon and Megaesophagus
What is this?
Trypanosome amastigotes (Chaga’s parasites) in the heart
What is this?
Microbiology of Trypanosoma cruzi (of blood)
Globalization of Chaga’s Disease (picture)
Chagas disease is in the US Autochthonous transmission Lousiana, Mississippi, Tennessee
What subspecies of trypanosomes cause African Tryp?
- Trypanosoma b. gambiense (Gambian HAT); W Africa
- Trypanosoma b. rhodesiense (Rhodesian HAT); E Africa
Life cycle of tsetse fly?
- Tsetse fly takes a blood meal (injects metacyclic)
- Injected metacyclic trypomastigotes transform into bloodstream trypomastigotes, which are carried to other sites
- Trypomastigotes multiply by binary fission in various body fluids, e.g. blood, lymph, and spinal fluid
- Trypomastigotes in blood 5. Tsetse fly takes a blood meal (bloodstream trypomastigotes are ingested)
- Bloodstream trypomastigotes transform into procyclic trypomastigotes in the tsetse fly’s midgut. Procyclic tryposmatigotes multiply by binary fission
- Procyclic trypomastigotes leave the midgut and transform into epimastigotes
- Epimastigotes multiply in salivary gland. they transform into metacyclic trypomastigotes
No specific site where they cluster! (difference)
What is this?
Trypanosoma (gambiense/rhodesiense) in blood smear
- S-form, flagellated
