African Sleeping Sickness & Trypanosomes
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Questions and Answers

What is a primary reason that African Sleeping Sickness disproportionately affects rural populations in sub-Saharan Africa?

  • Rural populations are more likely to consume bushmeat, which can be a source of trypanosome infection.
  • Rural populations have less access to diagnostic testing, leading to delayed treatment and increased disease prevalence.
  • Tsetse flies, the vectors of the disease, are predominantly found in rural areas where agriculture, fishing, and animal husbandry are common. (correct)
  • Urban populations have better sanitation and hygiene practices, which prevent the spread of the trypanosome parasite.

Eradicating Tsetse flies would completely eliminate the risk of African Sleeping Sickness in humans and Nagana in animals.

False (B)

What factors, beyond the direct health impacts on humans, contribute to the significant economic burden associated with Nagana in Africa?

Reduced livestock productivity, trade restrictions, and decreased agricultural output

African Sleeping Sickness, caused by Trypanosoma brucei, is transmitted to humans via the bite of the ______ fly.

<p>tsetse</p> Signup and view all the answers

Match the following disease with its respective impact or characteristic:

<p>African Sleeping Sickness (Human) = Fatal if untreated; caused by Trypanosoma brucei Nagana (Animal) = Major contributor to poverty; Economic impact US$4.5 billion per year in Africa Trypanosoma brucei = Unicellular and extracellular parasite Tsetse fly = Vector that defines disease distribution</p> Signup and view all the answers

Which of the following mechanisms contributes to the unlimited potential of the VSG repertoire in trypanosomes?

<p>Recombination of sub-telomeric VSGs with the expression site VSG, creating mosaic VSGs (D)</p> Signup and view all the answers

Trypanosomes evade the host immune system solely by preventing complement from accessing the plasma membrane.

<p>False (B)</p> Signup and view all the answers

Describe how variant surface glycoprotein (VSG) provides a physical barrier that protects trypanosomes.

<p>VSG shields other proteins, preventing the detection of other proteins from antibodies and preventing complement from accessing the plasma membrane.</p> Signup and view all the answers

The differentiation of trypanosomes from slender to stumpy forms leads to ______ which contributes to waves of parasitemia.

<p>immune clearance</p> Signup and view all the answers

Match the following mechanisms of trypanosome immune evasion with their effects:

<p>VSG shielding = Prevents detection of other proteins and blocks complement access Hydrodynamic-flow mediated endocytosis = Removes bound antibodies Antigenic variation = Changes the expressed VSG isotype</p> Signup and view all the answers

Which factor makes the development of a vaccine against trypanosomes particularly challenging?

<p>The antigenic variation allowing the cell to change the VSG isotype. (C)</p> Signup and view all the answers

What is the primary role of hydrodynamic-flow mediated endocytosis in trypanosome immune evasion?

<p>Removing antibodies that have bound to VSG. (C)</p> Signup and view all the answers

African Sleeping Sickness, caused by trypanosomes, is exclusively found in humans.

<p>False (B)</p> Signup and view all the answers

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Considering the complex interplay between vector ecology, parasite biology, and host immunity in the context of Trypanosoma brucei infections, which strategy would MOST effectively contribute to sustained, long-term control of African trypanosomiasis, taking into account ecological impact and potential for resistance?

<p>Integrated vector management strategies incorporating targeted insecticide application, sterile insect technique, and habitat modification, coupled with enhanced surveillance and treatment programs in high-risk areas. (C)</p> Signup and view all the answers

Given the limitations of current diagnostic methods for early-stage African trypanosomiasis and the need for accessible, field-deployable tools, which novel diagnostic approach holds the greatest promise for improving disease surveillance and control in resource-limited settings?

<p>Development of a loop-mediated isothermal amplification (LAMP) assay coupled with a portable microfluidic device for point-of-care detection of trypanosomal DNA in blood samples. (D)</p> Signup and view all the answers

Considering the complex lifecycle of Trypanosoma brucei and its dependence on both the mammalian host and the tsetse fly vector, what evolutionary advantage is MOST likely conferred by the parasite's ability to undergo antigenic variation?

<p>Prolonged survival within the mammalian host by evading adaptive immune responses. (D)</p> Signup and view all the answers

In the context of the economic burden imposed by Nagana on livestock agriculture in sub-Saharan Africa, which intervention strategy would provide the MOST sustainable and cost-effective solution for mitigating the disease's impact on rural livelihoods?

<p>Selective breeding programs to develop trypanotolerant livestock breeds, coupled with improved animal husbandry practices and targeted vector control measures. (A)</p> Signup and view all the answers

Given the observed geographical distribution of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, what environmental or socioeconomic factor MOST likely explains the lower incidence and slower progression of disease associated with T.b. gambiense compared to T.b. rhodesiense?

<p>More effective public health infrastructure and disease surveillance systems in <em>T.b. gambiense</em> endemic regions. (D)</p> Signup and view all the answers

Considering the complexity of antigenic variation in Trypanosoma brucei, what is the most significant obstacle in developing a broadly effective vaccine?

<p>The stochastic nature of VSG switching and mosaic formation leads to an effectively limitless repertoire of potential antigens. (D)</p> Signup and view all the answers

Given Trypanosoma brucei's reliance on variant surface glycoprotein (VSG) for immune evasion, what evolutionary pressure might explain the parasite's continued survival despite the host's ability to mount an antibody response?

<p>The selective advantage conferred by antigenic variation outweighs the metabolic cost of maintaining a large VSG repertoire. (B)</p> Signup and view all the answers

If a novel therapeutic agent were designed to disrupt VSG function specifically, which mechanism would represent the MOST DIRECT and EFFECTIVE means of compromising trypanosome survival in vivo?

<p>Inhibiting VSG glycosylation to disrupt protein folding and stability. (A)</p> Signup and view all the answers

How does hydrodynamic-flow mediated endocytosis contribute to immune evasion?

<p>It facilitates the rapid internalization and removal of antibodies bound to VSG. (A)</p> Signup and view all the answers

Consider a scenario where a novel drug inhibits the expression site switching mechanism in Trypanosoma brucei. What is the MOST LIKELY consequence of this drug on the parasite population within an infected host?

<p>A rapid increase in parasitemia followed by eventual immune clearance due to lack of antigenic variation. (D)</p> Signup and view all the answers

Which of the following reflects the MOST COMPLETE understanding of how VSG provides a physical barrier for trypanosomes?

<p>VSG forms a dense steric barrier that shields underlying invariant surface proteins from antibody recognition and complement deposition. (B)</p> Signup and view all the answers

In a strain of Trypanosoma brucei with a genetically modified VSG repertoire limited to a single VSG gene, what would be the most probable outcome in a mammalian host?

<p>Rapid immune clearance following an initial wave of parasitemia. (A)</p> Signup and view all the answers

If a mutation arose in Trypanosoma brucei that completely abolished the ability to differentiate into stumpy forms, what would be the MOST LIKELY consequence on disease transmission and progression?

<p>Reduced transmission rates due to the failure of parasites to establish infection in the tsetse fly. (C)</p> Signup and view all the answers

Flashcards

Trypanosoma brucei

A unicellular, extracellular parasite transmitted by Tsetse flies, causing sleeping sickness in humans and Nagana in animals.

Sleeping sickness

Fatal disease in humans caused by Trypanosoma brucei, with ~1,000 cases/year.

Nagana

Disease in animals (especially cattle) caused by Trypanosoma brucei, leading to significant economic losses in Africa.

Tsetse fly

The insect responsible for transmitting Trypanosoma brucei, defining the geographical distribution of African sleeping sickness.

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HAT

Human African Trypanosomiasis; occurs in 36 sub-Saharan countries where tsetse flies are present. Rural populations are most at risk.

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Rhodesiense Cases

Severe cases of Trypanosoma rhodesiense.

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Mosaic Formation

The process where sub-telomeric VSGs recombine with the expression site VSG, creating new VSG variants.

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Waves of Parasitemia

Slender form proliferation and differentiation into stumpy forms, followed by immune clearance and expression of new VSGs.

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Trypanosome Immune Evasion

Shielding of other proteins, prevention of complement access, removal of bound antibodies, and antigenic variation.

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VSG Protective Barrier

VSG provides a physical barrier, hindering antibody detection and complement access.

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Antigenic Variation

Allows the cell to change the VSG isotype expressed through expression site switching, inserting different VSGs, or creating mosaic VSGs.

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Trypanosome Disease

African Sleeping Sickness.

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Trypanosome Hosts

Mammals and are transmitted by tsetse flies.

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African Sleeping Sickness

A parasitic disease caused by Trypanosoma brucei, transmitted by tsetse flies in sub-Saharan Africa.

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Disease Distribution (HAT)

The geographical regions in 36 sub-Saharan countries where tsetse flies are present, thereby defining where African sleeping sickness occurs.

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Populations at Risk (HAT)

Rural populations that depend on agriculture, fishing, animal husbandry, or hunting are most likely to be exposed to the tsetse fly and contract African sleeping sickness.

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VSG Shielding

Variant Surface Glycoprotein; shields other proteins from detection by antibodies.

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Hydrodynamic-flow mediated endocytosis

Facilitates removal of antibodies that bind to VSG

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Expression Site Switching

Switching where the VSG is expressed.

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VSG Insertion

Inserting a different VSG into the expression site.

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VSG Repertoire

The potential VSG repertoire is unlimited.

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Slender Form

Proliferation of slender form.

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Slender to Stumpy Differentiation

Differentiation from slender to stumpy.

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Study Notes

  • Trypanosomes express a single VSG "isotype" at one time
  • It is eventually overwhelmed by antibody response

Immune Evasion in detail

  • Extracellular parasites are vulnerable to antibodies, complement, and immune cells, yet still can thrive in the same host for a year or longer
  • Variant Surface Glycoprotein (VSG) surrounds the cell
  • Has 1 x 10^7 densely packed VSG per cell (approximately 10% of total cellular protein)
  • Shields other proteins from detection by antibodies
  • Shields the membrane by preventing complement
  • VSG-bound antibodies are 'swept' to the posterior of the cell by hydrodynamic flow, which is essential for host infection and relies on trypanosome motility
  • Antigenic Variation allows the cell to change the VSG isotype that is expressed
    • Including Expression site switching
    • Inserting a different VSG into the expression site
    • And Making entirely new, mosaic VSGs
  • Due to Trypanosome immune evasion, a vaccine is unlikely

Summary 1

  • Trypanosomes cause African Sleeping Sickness, a neglected tropical disease
  • Trypanosomes infect mammals and are transmitted by tsetse in sub-Saharan Africa
  • These extracellular parasites can survive for years in the bloodstream
  • Trypanosomes have evolved mechanisms to overcome the host immune system

Summary 2

  • The characteristic 'waves of parasitaemia' observed in a chronic infection are explained by these key features:
    • Slender form proliferation
    • Slender to stumpy differentiation
    • Parasite death caused by anti-VSG antibodies (when hydrodynamic flow is overwhelmed)
    • Antigenic variation

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Description

Explore African Sleeping Sickness (Trypanosomiasis) caused by Trypanosoma brucei, transmitted by the Tsetse fly. Understand its disproportionate impact on rural Africa and the economic burden of Nagana. Learn about VSG and trypanosome immune evasion.

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