African Trypanosomiasis

Question 0

What are the two species that cause trypanosomiasis in Africa, what phases of the disease are they associated with, and which side do they affect?
Is the disease Stercorarian or salivarian in transmission?

Answer 0

Trypanosoma brucei cause sleeping sickness, with T.b. rhodesiense being acutely associated in East Africa, and T.b. gambiense usually being more chronic, targeting West and Central Africa
Salivarian

Question 1

What are the three phases of the disease African Trypanosomiasis?

Answer 1

Phase 1: local inflammation at the site of the bite, a ‘chancre’ forms, resulting in edema, erythema, tenderness and heat
Phase 2: associated with waves of parasitemias as trypanosomes spread throughout the body. Fever, headache and joint pain accompany these waves, which can decrease as the disease becomes more chronic. Splenomegaly and lymphadenopathy are major features
Phase 3: final stage in which parasite has entered organs and/or crossed BBB, attacking the CNS. Manifestation can occur as ataxia, disrupted circadian rhythm, aggressiveness and paralysis. Nearly always fatal

Question 2

What is the main vector for Trypanosoma brucei?
How many vectors are believed to be infected?
How many people are at risk from Trypanosomiasis?
What is the estimated new cases each year?
Why is this only an estimate?

Answer 2

The main vector are tsetse flies of the Glossina spp.
Around 1 in 1000 are believed to be infected
Around 60 million believed to be at risk
Estimated 10,000 new cases each year
Only estimates due to poor diagnosis and socio-economic issues such as war, lack of medical resources and political instability

Question 3

Give details of the case study Tororo including year, origin of the epidemic and how this was discovered

Answer 3

Tororo, Uganda, 1988-1992
Epidemic of SS occurred despite the area not suffering from it previously. A team took blood samples from tsetse files, cattle and patients for analysis. Molecular fingerprinting in the form of restriction length fragment Polymorphisms comparison was conducted between the isolates, and those of other outbreaks. It was found that the isolates shared similarity, sometimes even identical fingerprints to those found in other areas, as far back as 1969. Concluded the epidemic was from a ‘local’ origin and found that cattle were reservoirs of the parasite, with patients and cattle having 23% of the same isolates present.

Question 4

Give details of the case study Soroti including year, origin of the epidemic and how this was discovered

Answer 4

Soroti, Uganda, 1998
Like Tororo before it, the area had rarely suffered from SS until the epidemic. Knowing that cattle could be a reservoir, it was hypothesised that they had brought it to the area. Data for cattle movements, medical records and geographically distribution of the disease with time added to the argument. Compared to controls, the number of cases diagnosed was closer to Brooks Corner cattle market compared to controls, establishing the root of the infection. To prove that the cattle had human infective trypanosomes, blood samples were taken and applied to FTA filter paper. PCR was then performed for the SRA gene and it showed that indeed the cattle contained human infective trypanosomes. MGE-PCR was used to compare cattle from Tororo and Soroti, discovered the same genotype for human infective trypanosomes was present, and the cattle had brought it

Question 5

Compare the tools of RFLP and blood/FTA filter paper in the case of the Soroti epidemic

Answer 5

As considerable effort is needed for RFLP sample extraction and export, and its cumbersome, an alternative was used. Blood spotting onto FTA filter paper was conducted due to stability, easy shipping/fieldwork and the ability for DNA to be extracted at a later date for further analysis.

Question 6

Key points of the Trypanosoma brucei life cycle

Answer 6

Meta in proboscis -> transform to long slender in blood -> binary fission -> invade fluids [possible liver cycle] -> differentiate to short, stumpy, in blood -> ingested -> procyclic in midgut -> binary fission -> epimastigote -> salivary gland attachment -> binary fission -> metacyclic differentiation -> enter host

Metacyclic trypomastigotes in proboscis of Glossina –> enter bloodstream, transform into long, slender trypomastigotes that replicate by binary fission –> trypomastigotes invade CSF/interstitial spaces and other bodily fluids, continue replication [some may enter liver and form a multinucleate giant that eventually differentiate into sphaeromastigotes that then return to long slenders] –> long, slender trypomastigotes transform to non-infective, shorty stumpy phase and are ingested by tsetse fly during a meal –> within the midgut transformation to procyclic form begins, further binary fission –> procyclics become epimastigotes that attach and replicate in the salivary gland –> epimastigotes transform into metacyclic trypomastigotes and wait for next feed