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define heteroxenous, give an example
- Life cycle includes multiple hosts for different stages
- EX- blood/tissue of vertebrates AND intestines of blood-sucking invertebrates
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Why are blood protozoa referred to as hemoflagellates?
- They require hematin (obtained from blood hemoglobin) for aerobic respiration
- *NOTE- lab cultures for these organisms must contain blood
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What genera are associated with the term "hemoflagellates"?
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Give a brief physical description of hemoflagellates (applies to both genera)
- Elongated with 1 flagellum OR rounded with tiny non-protruding flagellum
- All forms have one nucleus
- Kinetoplast: DNA-rich conspicuous part of mitochondria
- K-B complex: kinetoplast is very near to basal body that flagellum arises from
- Sexual reproduction is absent
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What are the 4 distinct morphological forms that might be seen in the life cycle of hemoflagellates (both genera)? Which organism might they occur in? How do they differ morphologically? Be specific.
- "A. P.E.T."
- Amastigote (vertebrate host)
- Promastigote (invertebrate host - flies)
- Epimastigote (invertebrate host - flies)
- Trypomastigote (vertebrate host)
- differ in placement and origin of the flagellum in relation to the nucleus
- *NOTE- no specific sequence of progression between stages
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Describe the amastigote stage of Hemoflagellates in detail (morphological description, location, definitive stage?)
- Rounded
- 1 prominant nucleus
- 1 very short flagellum projecting barely (if at all) beyond cell surface
- kinetoplast
- Kinetoplast: aggregation of mDNA in hemoflagellates, easily seen by light microscopy
- Pellicular microtubules: provide structural support beneath cell membrane (like pellicle)
- Develops in vertebrate host cells
- Definitive stage in Leishmania (form taken in vertebrate host)
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What locations are L-D bodies likely to infect? Why? Describe the process of infection of these areas.
- Macrophages, spleen, and bone-morrow (cells responsible for defense against invasion)
- After macrophage ingestion they form a parasitophorous vacuole by surrounding the ingested vacuole in host ER (for camoflauge)
- The parasite lives/reproduces within this protected vacuole
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What are the Leishmania reservoirs? How do they contribute to Leishmania infection?
- Many mammals are reservoirs (canines and rodents most common) and are not diseased with infection
- Leishmaniasis is a zoonosis, so it cannot be transferred directly between humans
- Reservoir hosts cause sandfly infection after taking an infected bloodmeal
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Describe the life cycle of Leishmania
- Female sandfly takes blood meal from infected mammal and ingests amastigotes
- Amastigotes transform into promastigotes inside sandfly gut
- Promastigote reproduces by binary fission (1-3 weeks)
- Insect's anterior gut and pharynx become clogged with promastigotes which use their flagella to attach
- When sandfly feeds promastigotes become loosened and deposited in skin of mammal
- Macrophages quickly respond and engulf the promastigotes, which transform back to amastigote form (no need for flagella)
- Amastigotes fortify themselves in parasitophorous vacuole and reproduce by binary fission
- Eventually cell ruptures, releasing huge #s of amastigotes and spreading infection
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What factors determine the extent of Leishmania infection in a mammalian host?
- spp of Leishmania
- temperature
- immune status of host
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What are the 4 species of Leishmania? How are they categorized/named?
- L. donovani
- L. tropica
- L. major
- L. braziliensis
- Categorized based on biochemical differences
- Named after location
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Leishmania donovani- Discovery, disease names, distribution, # cases each year, geographical distribution, disease severity, location within mammals, vector
- William Leishman & Charles Donovan (1903) discovered in spleen smears of a solider who died of a fever in Dum-Dum, India
- AKA Dum-Dum fever, kala-azar, and visceral leishmaniasis
- ~500,000 new cases each year
- Global distribution (every continent except Australia and Antarctica)
- >90% in Bangladesh, Brazil, India, Nepal, and Sudan
- Often fatal (2nd deadliest parasitic disease)
- Found in liver, spleen, bone marrow, lymph nodes, intestine (VISCERA)
- vector is Phlebotomus
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Leishmania donovani- specific lifecycle events in humans, result of infection, incubation period
- Phlebotomus injects promastigotes into skin
- Promastigotes rapidly multiply and are engulfed by macrophage
- Binary fission continues inside macrophage, causing cell lysis and escape
- These "escaped" protozoa are again engulfed and the same process occurs
- Hosts immunity is HEAVILY damaged
- Incubation period may range from 10 days to 1 year (average 2-4 months)
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Leishmania donovani- disease development/symptoms, What less common forms of disease can be caused by Leishmania?
- Visceral leishmaniasis
- Develops weeks to months after sandfly bite
- Initial symptoms are slow (104F fever, vomiting, weakness)
- Then progress to anemia, protrusion of abdomen from hepatosplenomegaly, weight loss, and even death in untreated cases (1-2 years)
- *NOTE- death is often caused by secondary pathogens due to incapacitated immunity
- Infantile kala-azar: affects children
- Post-kala-azar dermal leishmanoid: (reddish depigmented nodules in skin) develops in some cases after 1-2 years of inadequate treatment.
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What are the different forms of Leishmaniasis? Give symptoms/differences. How is temperature involved?
- Visceral (systemic): affects entire body
- Occurs 2-8 months after sandfly bite (do not remember bite)
- Can lead to deadly complications
- Parasites heavily damage immune system by destroying macrophages
- Cutaneous: affects skin
- skin sores typically start at site of sandfly bite
- Mucocutaneous: affects mucous membranes and skin
- Leishmania that prefer 35C causes cutaneous/mucocutaneous manifestation, while those that prefer 37C cause visceral manifestation
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Leishmania donovani- diagnosis, treatment, control
- Hepatosplenomegaly suggests visceral leishmaniasis
- Confirmatory tests include demonstration of parasites via biopsy (microscopy or xenodiagnosis)
- xenodiagnosis: direct innoculation of lab animals with tissue from patient, infection in animal confirms suspected parasite in human
- Not easily treated, many transfusions are required
- Chemotherapy requires careful intermuscular injections of antimony (serious side effects if injected in excess, relapse or post-kala-azar dermal leishmanoid if insufficient)
- Only prevention is protection from Sandfly bites and extermination of infected dogs (reservoirs)
- *NOTE- sandflies are small enough to fit through mosquito nets
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Leishmania tropica- disease name, development/symptoms, geographical location, prevention
- cutaneous leishmaniasis, Jericho boil, oriental sore, Delhi boil
- similar life cycle/clinical symptoms to L. donovani
- Initial sign of infection is appearance of vascularized nodule on skin at bite site (commonly hands, feet, legs, and face)
- Found primarily in M0 around cutaneous sores/ulcers (unlike L. donovani which is found in M0 in blood)
- Lesion is dry, filled with amastigotes, persists for months before ulcerating
- Nodule may erupt and spread forming additional cutaneous lesions
- Found in densely populated areas of middle east, India, Peru, Bolivia, Brazil, and Mexico
- Prevention is to avoid Sandfly bite and destroy canine reservoires
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Leishmania major- disease names, development/symptoms, geographical location, prevention
- cutaneous leishmaniasis, Jericho boil, oriental sore, Delhi boil
- similar life cycle/clinical symptoms to L. donovani
- Initial sign of infection is appearance of vascularized nodule on skin at bite site (commonly hands, feet, legs, and face)
- Found primarily in M0 around cutaneous sores/ulcers (unlike L. donovani which is found in M0 in blood)
- Lesion is moist, contains few amastigotes, and disappears quickly
- Nodule may erupt and spread forming additional cutaneous lesions
- Found in sparsely populated areas of Africa
- Prevention is to avoid Sandfly bite and destroy canine reservoires
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Leishmania braziliensis- disease name, vector, disease development/symptoms, severity, geographical location, diagnosis, treatment
- American leishmaniasis, chiclero ulcer, espundia, uta, or mucocutaneous leishmaniasis
- vector is Lutzomyia
- Primary lesion appears as small red nodule on skin after sandfly bite
- secondary lesion always appears elsewhere on the body and this site is always distinctive based on geographic location (Mexico/Central America- chiclero ulcer on ear, Brazal- espundia or uta in nasal tissue)
- Amastigotes are found in macrophages in ulcerations of the skin (similar to L. major/tropica)
- Severe mucous membrane destruction leads to permanent disfigurement
- Amastigotes are found in M0 in skin ulcers
- Found in South and Central America
- Diagnosed by finding L-D bodies in infected tissue, culturing parasite in vitro if possible
- Treatment with antimony compound injections, antibiotics for secondary infections
- *NOTE- relapse is common, but a person has lifelong immunity after elimination of parasite
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How does Trypanosoma affect livestock in Africa?
- Huge numbers of livestock (up to 10,000/day) are killed by Trypanosoma
- This makes agriculture impossible
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What are the two major categories of Trypanosomes with a brief description and the disease they cause?
- African trypanosomes: found in Africa
- T. brucei rhodesiense (African sleeping sickness)
- T. b. gambiense (African sleeping sickness)
- American trypanosomes: found in the western hemisphere
- T. cruzi (Chagas disease AKA American trypanosomiasis)
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Describe the nomeclature of African Trypanosoma, describe the general similarities/differences between them
- In early 1900s 3 African spp were named - T. brucei (didn't infect humans), T. rhodesiense (acute disease), and T. gambiense (chronic disease)
- Later discovered to be closely related and reduced to subspecies of species T. brucei
- Life cycle is identical
- Epidemiologically distinct
- Vector is Tsetse fly of Glossina
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Describe the life cycle of African trypanosomes (start with infected blood meal. Very long)
- T. b. rhodesiense and T. b. gambiense
- Tsetse Fly (Glossina) ingests bloodmeal containing short, stumpy trypomastigotes (this is the only form that can infect the fly)
- *NOTE-Mitochondrion with prominent cristae allow this form of the trypomastigote to live in the anaerobic environment of the insect midgut
- After ingestion the stumpy trypomastigotes elongate, lose their surface coat, and become procyclic trypomastigotes
- The procyclic trypomastigotes increase via binary fission and migrate anteriorly
- Enter fly's midgut ~10th day after ingestion as epimastigotes (metamorphosis during migration)
- Epimastigotes move to salivary glands/ducts and multiply ~12th day after ingestion
- Epimastigotes have transformed into metacyclic trypomastigotes by end of 3rd week
- Tsetse fly (Glossina) injects saliva infected with metacyclic trypomastigote into skin of victim
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- Once in the circulatory system metacyclic tryopmastigotes spread rapidly and migrate to the CSF
- *NOTE- trypomastigotes are polymorphic in the blood and have 3 potential forms (long and slender, short and stumpy, and intermediate)
- *NOTE- both epimastigote and trypomastigotes are required for life cycle completion
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How can you differentiate between metacyclic trypomastigote and trypomastigote of African trypanosomes?
- Metacyclic trypomastigote mitochondria have few cristae, are blunt shaped, and have short/free flagellum
- Trypomastigotes have prominant cristae, are elongated (although different forms exist)
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Describe the polymorphic forms of African trypanosome trypomastigotes (image answer)
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T. b. gambiense- vector, location, disease, progression
- Tsetse fly (Glossina papalis and Glossina tachinoides)
- West Africa
- West African (or Equatorial or Gambian) sleeping sickness
- Less dangerous (chronic) disease
- 1-2 weeks after bite a red sore appears at site
- Weeks to months later fever, headache, swelling near eye/hands, and swollen lymph nodes will occur
- After infection invades CNS personality changes, loss of concentration, difficulty walking/talking, and sleeping all day with insomnia at night may may occur
- Fluctuation in parasite #s in blood produces period remission alternating with high parasitic density (caused by variant antigenic types)
- If left untreated infection worsens until death occurs (months-years after infection)
- Many African animals (antelopes, buffalo) are reservoirs
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T. b. brucei- vector, location, disease
- Tsetse fly
- Found exclusively in Africa
- does not affect humans
- Causes nagana ("to be in low spirits") in domestic African animals (pigs, camels, goats, sheep)
- Symptoms include fever, anemia, diarrhea, and often death
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T. b. rhodesiense- vector, location, disease, progression
- Tsetse fly (Glossina morsitans)
- East Africa
- East African (or Rhodesian) Sleeping Sickness
- More deadly form of disease
- 1-2 weeks after bite a red sore appears at site
- Weeks to months later fever, headache, swelling near eye/hands, and swollen lymph nodes will occur
- Patient often dies before any CNS symptoms appear (3-9 months)
- Wild game and domestic animals serve as reservoir
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What are VATs and how do they affect the host? (give all info available)
- VATs (variant antigenic types) is the name given to the different surface coat chemical compositions that can be employed by Trypanosoma
- >1000 VATs are possible
- The ability to change surface antigens is what allows Trypanosoma to persist in the blood in the face of the immune system and causes periodic fluctuation in #s
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Describe the symptoms of infection with African trypanosomes (can be discussed together)
- T. b. gambiense and T. b. rhodesiense
- Inflammatory response occurs at bite site for 1-2 days (trypanosomal chancre)
- Chancre includes reddening of skin, swelling of 2-5cm, and enlargement of adjacent lymph nodes
- After blood and lymph are invaded, headache and fever develop
- Lymph glands in the neck region swell (Winterbottom's sign)
- Tremors of the tongue and tongue, mental dullness, and other neurological symptoms appear (loss of appetite, extended sleeping, and paralysis)
- Rapid weight loss results from anorexia, anemia, drowsiness, coma, and eventually death results
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Describe the diagnosis of infection with African trypanosomes (can be discussed together)
- T. b. gambiense and T. b. rhodesiense
- Preliminary diagnosis based on clinical and other neurological symptoms
- Chancre can be used if the patient is seen early enough (1-2 weeks)
- Winterbottom's sign (swollen cervical glands in neck) is a classic diagnostic tool
- Examination of blood smears, marrow, or CSF for trypomastigotes is performed after initial assessment
- Antibody testing may also be available
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Describe the treatment of infection with African trypanosomes (can be discussed together)
- T. b. gambiense and T. b. rhodesiense
- prior to CNS involvement treatment usually involves suramin which is effective, but can be toxic to some patients
- After CNS involvement the only treatment is arsenic drug Melarsen Oxide (Mel B)
- Mel B is highly toxic and must be given under strict supervision, plus it isn't always effective!
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Describe the prevention and control of infection with African trypanosomes (can be discussed together)
- T. b. gambiense and T. b. rhodesiense
- Avoiding being bitten by Tsetse flies in endemic areas
- This is difficult due to daytime feeding, persistence, large numbers, and ability to bite through thin clothing
- Attempted control through vector control (usually unsuccessful)
- 1) Tsetse flies cover huge landmass in Africa and aerial spraying is expensive
- 2) Clearing vegetative bush is expensive and ecologically destructive
- 3) Trapping flies (traps w/ insecticide) is popular in some areas
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Describe the abnormal ways that Trypanosoma can be tranismitted
- Sexual intercourse (fluids)
- Placenta
- Mother's milk
- Milk from infected cattle
- Consumption of contaminated blood (Masai tribe from Kenya engage in this behavior)
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Trypanosoma cruzi- AKA, discovery, disease name
- American Trypanosome
- Carlos Chagas (1909) dissected several hemipteran bugs and found hindguts swarming with tryanpanosome epimastigotes
- Chagas sent the bugs to the Oswaldo Cruz institute where they were allowed to feed on marmosets/guinea pigs
- Trypanosomes appeared in their blood in 1 month
- Diseased children inhabiting a small Brazilian village were later found to harbor the same flagellates
- T. cruzi causes Chagas' Disease
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Trypanosoma cruzi- vector (name, information)
- Panstrongylus megistus "Kissing bug" (bite face and around lips during sleep) and other hemipteran insects
- BOTH sexes feed on blood
- Infection occurs when infected fecal material is rubbed into bite/eyes- not directly injected during bite
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Trypanosoma cruzi- life cycle (starting with insect bloodmeal)
- Kissing bug ingests blood containing trypomastigotes
- Trypomastigotes undergo repeated binary fission during passage through GI tract of insect
- Metamorph into epimastigotes by the time they reach the midgut
- Continued replication occurs as the epimastigotes pass into insect hindgut
- Infective metacyclic trypanosomes appear in rectum ready to be excreted in feces by the 10th day
- *NOTE- 50-100% of bug population is typically infected, much higher than other trypanosomes
- Kissing bug bites host and defecates simultaneously
- Host typically unknowingly rubs feces into bite or eye during sleep
- Trypomastigotes enter blood stream and invade cells (incl M0) and transform into amastigotes where they reproduce by binary fision
- NOTE- spleen, liver, lymph glands, and muscles are most vulnerable to infection
- Infected cells eventually rupture and amastigotes are released into other cells
- Nervous, reproductive, and digestive systems are also invaded
- pseudocyst: large amount of amastigotes in cardiac muscle fiber (can also form elsewhere)
- Some of the released amastigotes revert to trypomastigote form and re-enter the bloodstream
- *NOTE- unlike other trypanosomes T. cruzi NEVER repr in blood and cannot produce variable antigens (VATs)
- *NOTE- in chronic cases trypomastigotes are rarely seen in blood because circulating antibodies easily destroy them
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How do trypomastigotes of T. cruzi differ from T. b. gambiense and T. b. rhodesiense?
- Trypomastigotes of T. cruzi are shorter (~20um compared to 40um) and show a caracteristic "U" or "C" shape in blood stains
- T. cruzi does not have VATs and thus cannot survive in the blood
- T. cruzi NEVER reproduces in the blood (likely for this reason)
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Trypanosoma cruzi- geographic location, prevalence, risk factors, Brazil vs American
- Distributed in most of Central and South America
- Affects 12-20 million people (some surveys have reported ~30% of adults die of T. cruzi infection)
- Incidence is greatest in rural areas, among the poor (old houses facilitate easy access from Kissing bugs)
- American trypanosmiasis affects cats, dogs, bats, opossums, armadillos, rodents, and other reservoirs (common in southern states)
- Few cases of naturally acquired human infections reported (preference of reservoirs for blood meal + defecation occurs AFTER meal)
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T. cruzi- symptoms
- Chagas disease is chronic
- Infected persons show few (if any) signs of disease
- Often survive for decades while infected
- Chagoma: analogous to a chancre, it is the first sign of infection
- Romana's sign: chagoma involving the eye (extremely swollen) if infection occurred through conjunctiva
- Acute cases show fever, headache, and weakness 1-3 weeks after infection, but it is never fatal. Chronic condition resumes afterward.
- Although signs may not be apparent repeated cycles of intracellular multiplicatio continuously destroy cells (especially neurons)
- If pseudocysts are concentrated in the GI tract peristalsis may be inhibited and organs may become hugely distended (megaesophagus, megacolon)
- megaesophagus- victim unable to swallow, may starve
- megacolon- may lead to rupture and death
- If pseudocysts aggregate in heart muscle (common) the neuronal and muscle cells are destroyed, weakening the heart wall and potentially causing aneurysm, irreversible damage, and death from heart attack
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T. cruzi- diagnosis
- Exam of fresh blood within the 1st month following infection may reveal T. cruzi trypomastigotes (especially if acute phase is in progress)
- Xenodiagnosis- uninfected kissing bugs are forced to feed on patient then feces/gut are examined 3-4 weeks later (looking for T. cruzi)
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T. cruzi- treatment, prevention, control
- No effective treatment for Chagas disease
- Nifurtimox has shown some promise in early cases, but course is long
- Once the flagellate invades the host cell it is shielded from the action of any drug (chronic phase cannot be treated)
- Well built and maintained homes are unlikely to harbor bugs
- Bed or mosquito nets may help to prevent contact between bugs and sleepers
- *NOTE- in heavily infected homes bugs crawling over nets may still defecate on person
- Spraying the house interior with insecticide is effective, but expensive
- In some areas (Brazil) infection via blood transfusion is a serious risk, and blood should be screened
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