1. Sleeping sickness (Human African Trypanosomiasis)
By Rachel Kaplan

2. Trypanosomiasis affects thousands in central Africa
Only found in 36 sub-saharan African countries where tsetse fly is found
~50 million people in at-risk areas
In 1993 there were 55,000 deaths
-Note: if contracted and not treated, sleeping sickness is fatal.

3. Most African nations gained independence from colonial powers in the 1960’s.
Colonial administrations were very effective at trypanosomiasis control, but independence brought new social and political problems and new governments let it fall by the wayside. Picture: celebration of independence in Democratic Republic of the Congo

4. After independence, the incidence of sleeping sickness rose dramatically.
New governments saw massive upsurge in sleeping sickness. There were 2 epidemics in the early 1900’s (1900 and 1920), then another in 1970 after independence.

5. It is now being brought back under control.
Current estimate=30,000 infected
It is now being brought back under control.

6. The trypanosome is the causative agent.
Trypanosomes
Parasitic protozoan
Eukaryotes- just like us!

7. It’s transmitted by the tsetse fly

8. How Transmission Works
Reservoir: usually cattle, sometimes wild animals or even humans- something that survives with disease for a while
Fly bites infected member of reservoir. Trypanosomes multiplying in its midgut. When it bites a human, trypanosomes get into to chancre (swelling at site of bite) and then into blood. Other forms of transmission: mother to child, lab accidents, other insects.
-Sometimes also transmitted by mother to child, lab accidents, or other insects, but all of these very rare.
Reservoir

9. How Transmission Works
Left map: tsetse and cattle- shows important of reservoir
Right map: where sleeping sickness is found (all w/in tsetse areas)

10. There are 4 forms of trypanosomiasis.
Chagas disease- American Trypanosomiasis, found in Latin America
Nagana- “to be depressed,” animal form
Trypanosoma brucei rhodesiense- East Africa, acute
Trypanosoma brucei gambiense- West Africa, chronic, 95% of cases
2 African forms, American form, Animal form (Nagana=zulu word)

11. Stage 1
Trypanosomes are multiplying in subcutaneous tissues (inner layer of 3 layers of skin), blood, and lymph
Symptoms: fever, headaches, joint pains, itching

12. Stage 2- Trypanosomes cross the blood/brain barrier
Symptoms: behavior/personality changes, confusion, disturbance of sleep cycle
In general, things going wrong with the brain. Also perception issues and lack of coordination. Disturbances in sleep cycle=insomnia at night, fatigue during the day, sometimes even coma

13. T. Rhodesiense has similar symptoms to T. Gambiense, but it is faster.
Stage
T. Rhodesiense (acute)
T. Gambiense (chronic)
Stage 1
Weeks to months after infection
Months to years after infection
Stage 2
Several months after infection
Up to several years after infection

14. You can mount an immune response, but the trypanosome fights back.
VSG- variant surface glycoprotein
Chromosome repair moves new gene to surface
New surface structure evades immune response
Trypanosomes have about 1000 VSG genes but only display 1 at a time. When they repair chromosomes, they switch to a new VSG and can now avoid antibodies we have developed. We develop antibodies to it again and fight it off, but then it changes again and go back up. This will continue until it crosses the blood-brain barrier and causes death.
Parasites in body
Time

15. Because symptoms can remain hidden for so long, testing is vital.
Testing is necessary b/c sometimes symptoms don’t appear until it’s too late. Symptoms are only suggestive, not conclusive– need to find evidence of trypanosomes to diagnose and treat. There are tests available to test for antibodies in blood (CATT Card Agglutination Test for Trypanosomes- above- used for mass screening), actual trypanosomes in blood, and skin biopsy of bite site.

16. There are effective treatments available.
Happily, the main 4 drugs for Human African Trypanosomiasis are supplied to endemic countries free of charge.
But…

17. Treatment Drug What it can treat How it is administered Side effects
Pentamidine
1st stage t.b. gambiense
7-10 intramuscular injections a day or alternate days
Minimal but significant
Suramin
1st stage both forms
5 intravenous injections every 5-7 days
Urinary tract problems, allergic reactions
Eflornithine
1st and 2nd stage t.b. gambiense
Intravenous injection every 6 hours for 14 days
Some, but less toxic than melarsoprol
Melarsoprol
1st and 2nd stage both forms
3-4 series of intravenous injections separated by 1 weeks
Many undesirable side effects, including death in 1-5% of patients
Trypanosomes close to us- drugs are more toxic and have more side effects, especially those that treat 2nd stage
-Difficult to administer… leads to impediments

18. There are massive impediments to diagnosis and treatment.
-Remote, rural areas where majority of cases are never even diagnosed. Treatment is very difficult to administer and many people aren’t even tested
-Most affected countries are poor: health budget less than $10/ person

19. Vector control has been found to be effective.
-Simply having people trap and kill tsetses has proven to be quite effective
-Insecticides also used
-In general, tsetse eradication seems to be the way to go
-Also can treat cows or whatever the reservoir animal is to slow infection rate

20. We’re making dramatic progress.
-Obviously, remarkable progress has been made
-2009 saw lowest # of reported cases in 50 years
-BUT even in 2009, difference between reported and estimated actual >20,000: that many people didn’t get diagnosed or treated

21. Photos http://www.doctorswithoutborders.org/news/issue.cfm?id=2401

22. Sources http://www.who.int/mediacentre/factsheets/fs259/en/
Documentary: Survival- The Deadliest Disease
Man against Tsetse: Struggle for Africa by John J. McKelvey