Trypanosomes

incubation period of T. spp. ?

4 to 40 days

where are the pathogenic species of trypanosomes found?

Africa

what is another name for Nagana?

African animal trypanosomiasis (AAT)

how do antibodies act at opsonins for trypanosomes?

Antibodies coat trypanosomes and act as opsonin to increase phagocytosis by macrophages

how are trypanosomes killed?

Antibody developed to the glycoprotein coat of the trypanosome kills the trypanosome --> results in the development of immune complexes

what occurs after conversion into procyclic trypomastigotes?

Asexual reproduction in fly gut --> turns into epimastigotes

ways we have tried to clear tsetse fly populations. did these work?

Bush clearing (ecologically unacceptable) Game elimination (ineffective and wasteful) Releasing sterile male flies (has reduced population in limited field trials Ground and aerial spraying with insecticides (not gonna work) ALL FAILED!!

what is Nagana caused by?

Caused by tsetse-fly-transmitted Trypanosoma congolense, T. vivax, or T. brucei brucei, or simultaneous infection with one or more of these trypanosomes

how does persistent infection of trypanosomes occur? what does this result in?

Changes in the surface glycoproteins result in a persistent infection --> results in a continuing cycle of trypanosome replication, antibody production, immune complex development, and changing surface-coat glycoproteins

do they infect a large or small range of animals?

Contains the largest number of species and infects a wide variety of hosts such as mammals, birds, fishes, amphibians, and reptiles

where do epimastigotes migrate to and transform into?

Migrate to salivary glands and transform into metacyclic trypomastigotes (infectious form)

do trypanosomes invade host cells?

NO only found in the blood and lymphatic fluids, body organs and tissues of their hosts but do not invade cells

are typanosomes obligate intracellular parasites?

NO they are extracellular!!

what factor makes it more or less difficult for trypanosomes to elicit a clinical disease?

STRESS! Stress, such as poor nutrition or concurrent disease, plays a prominent role in the disease process, and under experimental conditions, where stress may be markedly reduced, it is difficult to elicit clinical disease

how can one find out if an animal is infected with two forms of Nagana?

They have different genes bc express different surface proteins!! use PCR to differentiate the strains one strain cannot turn into another

what genus are typanosomes in?

Trypanosoma

what are trypanosomes sensitive to? what acts as a growth factor for them?

Trypanosomes are highly sensitive to TNF-a --> TNFa is signal for inflammatory response, Works effectively on this disease IFN (interferon) acts as a growth factor for trypanosomes (interferon associated with viruses)

how do trypanosomes evade the immune system?

While in the bloodstream, trypanosomes periodically change their surface coat every 5-9 days or so this allows a population that is not recognized by the circulating antibodies to emerge and multiply elicits primary response everytime can last weeks to years

are some breeds of cattle more resistant to African trypanosomiasis than others?

YES European breeds more susceptible to infection resistant = west African short-horned cattle (Muturu, Baoule, Laguna, Samba, and Dahomey) and the N'Dama, which is also of west Africa --> These cattle have existed in the region for over 5,000 years

what occurred during the time the immune system produced antibodies to the VSG on the trypanosomes?

a few of the trypanosomes have shed their coat, switched VSGs, and covered themselves with a new antigenically distinct VSG coat new population espressing new VSGs on surface The immune system again responds to this proliferated population by producing a new set of antibodies that succesfully kill 99% of the new trypanosome population But once again, VSG switching among a small portion of trypanosomes renders them undetectable, and they succesfully evade the host immune response indefinite cycle eventually causing death of host

The cardinal clinical sign observed in AAT is ___________

anemia Within a week of infection there is usually a pronounced decrease in packed cell volume, hemoglobin, red blood cell, and white blood cell levels, and within 2 months these may drop to below 50 percent of their preinfection values --> sets up for immunological failure

where is initial replication of trypanosomes occurring?

at the site of inoculation in the skin --> this causes a swelling and a sore (chancre) Trypanosomes then spread to the lymph nodes and blood and continue to replicate

Some trypanosomes require an element from __________ __________ for their respiration. consequently, they are called ___________

blood hemoglobin called hemoflagellates

how can African farmers get a better handle on this disease?

breed better cattle that are more resistant Breed resistant african cattle with high yielding European breeds to collect best traits of both

A mammalian host defends itself against the foreign protozoa by . . . ?

by manufacturing specific IgM and IgG antibodies against their variable surface glycoprotein coat (VSG)

what is the result of most trypanosome infections if no drug intervention? what is a consequence of infection?

death if no intervention of drugs One of the consequences of this battle is that much of the immune effort is dedicated to fighting the parasites, leaving the body exposed and susceptible to other infections!!

what is the severity of the clinical response dependent on?

dependent on the species and the breed of affected animal and the dose and virulence of the infecting trypanosome

is it easy or difficult to rid the vector tsetse fly on Africa?

difficult to rid fly from a whole continent

tsetse fly facts: genus, where they occur, what they feed on

dipterans of genus Glossina that occur only in Africa and only feed on the blood of vertebrates

what do trypanosomes encounter when in blood?

encounter antibodies, which primarily target the surface of the parasite that is covered by a monolayer of about 100,000 molecules, the variant surface glycoproteins, VSGs that are encoded by a single gene

expression of VSG picture

epimastigote does not express VSG (not needed to evade tsetse fly immune system) metacyclic tryp. and trypomastigote both express VSG

how many genes encode VSGs in each trypanosome's genome? where does the transcribed VSG gene lie? how does the one VSG switching mechanism work?

hundreds transcribed VSG gene always lies near the telomere In one VSG switching mechanism, an interior VSG copy is duplicated onto a cassette, translocated to the expression site at the telomere, and becomes activated

what are three other symptoms seen in african trypanosomiasis? can abortion/infertility occur after infection?

intermittent fever, edema and loss of condition abortion may be seen infertility common

trypanosomes are protozoa in the order ___________

kinetoplastida

what is a chancre?

localized immune reaction (inflammation) that can be seen as a rash on the skin

what are lesions the result of?

may be the result of the deposition of immune complexes that interfere with, or prevent, normal organ function ex. anemia and glomerulonephritis lesions

infected fly takes blood meal from a new animal and injects ________________ into animal. what then occurs?

metacyclic trypomastigote transforms into trypomastigote and replicates (vegetative reproduction form) new fly picks up trypomastigote from bloodstream, becomes procyclic, turns epimastigote, back to metacyclic and ready to infect again

what is the infectious form of trypanosomes?

metacyclic trypomastigotes

how can the parasite be detected (3)?

microscopic examination of a blood slide ELISA test PCR - species specific DNA probes

what animal does African animal trypanosomiasis most commonly infect?

most important in *cattle* but can cause serious losses in pigs, camels, goats, and sheep

what is the most resistant breed of cattle to African trypanosomes? what is the most susceptible?

most resistant = N'Dama most susceptible = Zebu

what other disease besides sleeping sickness is caused by trypanosomes and is causing a large socio-economic impact on sub-Saharan Africa? what does this disease affect?

nagana (agricultural disease) The disease affects productivity of livestock by: -inducing abortions -depriving farmers of milk -meat and draught oxen for ploughing and transport

do regions of tsetse fly occurrence and cattle production overlap?

no cannot put cattle in areas with tsetse flies --> lots of losses tsetse flies migrate seasonally/with rain, causing infection in purple areas on map

do most species of trypanosomes cause damage to their host?

no Although most of the species cause no damage to their hosts, there are several which produce serious diseases in humans, domesticated animals, and wild animals

is there a vaccine for trypanosomes? why or why not?

no --> would need a lot of vaccines bc not sure which gene expressed on VSG

there are 4 forms of this disease and ____ form(s) are infectious

only one infectious form of trypanosome

what is the most significant factor in the pathogenesis of trypanosomiasis? why?

profound immunosuppression that occurs following infection by these parasites immunosuppression lowers the host's resistance to other infections and thus results in *secondary diseases*, which greatly complicates both the clinical and pathological features of trypanosomiasis

Trypomastigotes must be in __________________ to infect

salivary glands

where do the trypanosomes spread after the localized infection? how and when are they detectable?

spread to the blood and lymphatic system are detectable within days using various techniques, which include direct observation by microscopy and indirect methods such as serology

what does infection of cattle by one of the three AAT trypanosomes result in (3 options)? what is this characterized by?

subacute, acute, or chronic disease (Depends on animal conditions, amount of trypanosomes infected) characterized by intermittent fever (inflammatory response to infection), anemia, occasional diarrhea, and rapid loss of condition and often terminates in death

trypanosomes are highly immunogenic and elicit a robust response from the host (T/F)

true start primary immune response

The host's antibodies facilitate the neutralization and killing of approximately 99% of the original protozoan population (T/F)

true!!

what is the replication form of the trypanosome? what occurs after ingestion of this form?

trypomastigotes fly ingest these when it feeds on infected animals --> converts into procyclic trypomastigotes

what are the four forms of a trypanosome?

trypomastigotes procyclic trypomastigotes epimastigotes metacyclic trypomastigotes

how are most trypanosomes transmitted?

tsetse fly

what is the vector of sleeping sickness caused by African trypanosomes?

tsetse fly sleeping sickness fatal if not treated

how does transmission of trypanosomes occur?

tsetse fly that is infected feeds, passing trypanosomes through the saliva into the bloodstream of the host --> The trypanosomes divide rapidly at the point of entry, often resulting in a chancre

do drugs work against trypanosomes?

used to work but they have developed a resistance to each drug introduced very fast resistance most effective only for 3-6 months

what do immune cells look for on trypanosomes?

variant surface glycoproteins (VSGs)

when is Trypanosomiasis suspected? how is it confirmed?

when an animal in an endemic area is anemic and in poor condition *Confirmation depends on the demonstration of the organism in blood or lymph node smears*

does trypanotolerance have a genetic basis?

yes

do trypanosomes have flagella?

yes - A group of colorless flagellates possessing one or two flagella at some stages of their life cycle small organisms with very pliable bodies (variable in size/length)

are lesions seen in trypanosome infections?

yes, Immunologic lesions are significant in trypanosomiasis