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African Sleeping Sickness (ASS)

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Alexander Pike

on 6 February 2014

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Transcript of African Sleeping Sickness (ASS)

African Sleeping Sickness (ASS)
What is it?
African trypanosomiasis
Protozoan parasitic disese
Associated with Tsetse fly bite
Typansoma
brucei (95%)
Endemic to sub-Saharan Africa
36 countries
30,000 est. infected
~70 million at 'very high' risk
4 major outbreaks since 1890's (2008)
Sub species
T.b. gambiense
T.b. rhodesiense
Routes of exposure
Tsetse fly (Glossina) bite
host
and
vector for trypansome
parasites "injects" trypomastigotes into skin where they enter lymphatic system then onto the bloodstream
From here the trypomastigotes move to other areas of the body.
Replication during this time: binary fission.
Other routes of infection
Mother-Child
the bug can cross the placental barrier
blood transfusion
[Possible] sexual contact
Typanosoma
brucei
Obligate protozoan parasite
carried by an insect vector - mammalian host
humans though to be reservoir host
3 sub species
T.b.
gambiense
in 95% of cases
Causes slow onset of chronic Trypanosomiasis
humans will have red sore, fever, swollen lymph glands.
Can affect domestic pets (horses, dogs, etc).
Have a specialized coat (VSG) which undergo antigenic variation allowing for host immunity evasion
Symptoms
Two stages
haemolymphatic (first stage)
headaches, fever, joint pain
insomina, mode changes, weakness, inflamed bite
neurological (second stage)
disruption of sleep cycle
New (2013) research on preventing disease fatality.
Symptoms and Diagnosis
Examination
Treatment
References
Robinson, Victor, Ph.C., M.D. (editor) (1939). "African Lethargy, Sleeping Sickness, or Congo trypanosomiasis; Trypanosoma gambiense". The Modern Home Physician, A New Encyclopedia of Medical Knowledge. WM. H. Wise & Company (New York)., pp. 20–21.

MedlinePlus Encyclopedia Sleeping sickness

WHO Media centre (2012). Fact sheet N°259: Trypanosomiasis, Human African (sleeping sickness).

Simarro PP, Cecchi G, Franco JR, Paone M, Diarra A, Ruiz-Postigo JA, Fèvre EM, Mattioli RC, Jannin JG (2012). "Estimating and Mapping the Population at Risk of Sleeping Sickness". PLoS Negl Trop Dis 6 (10)

"New treatments raise hope of cutting sleeping sickness deaths". The Guardian. May 15, 2009.

"Uganda: Sleeping Sickness Reaching Alarming Levels," New Vision, May 11, 2008.

Medlock 2013, p. e2374

GB Lundkvist, K Kristensson, M Bentivoglio (2004). "Why Trypanosomes Cause Sleeping Sickness". Physiology19: 198–206. doi:10.1152/physiol.00006.2004.
Brun R, Blum J, Chappuis F, Burri C (2010). "Human African trypanosomiasis".
http://www.cdc.gov/parasites/sleepingsickness/gen_info/faqs-east.html

Dr Charlie Easmon, “Sleeping sickness overview” http://www.netdoctor.co.uk/travel/diseases/sleeping_sickness.htm 18.09.2013

Infection
The insect vector for T. brucei is the tsetse fly (genus Glossina). The initial site of infection is the midgut of the fly (procyclic life cycle stage) and as the infection progresses it migrates via the proventriculus to the salivary glands where it attaches to the salivary gland surface (linked with a differentiation into the epimastigote life cycle stage). In the salivary glands some parasites detach and undergo adaptations (differentiation into the metacyclic life cycle stage) in preparation for injection to the mammalian host with the fly saliva on biting. In the mammal host the parasite lives within the bloodstream (slender bloodstream life cycle stage). Some parasites undergo adaptations (differentiation into the stumpy bloodstream life cycle stage) where it can reinfect the fly vector as it takes a blood meal after biting. In later stages of a T. brucei infection of a mammalian host the parasite may migrate from the bloodstream to also infect the lymph and cerebrospinal fluids.
T. brucei gambiense : slow onset - chronic trypanosomiasis
T. brucei rhodensiense : fast - acute (more severe)
T. brucei brucei : cause African Trypanosomiasis.

All carried by insect vectors and lead to meningoencephalitis
Examination
Blood Smear
Cerebrospinal fluid test
IgM and possible IgG elevation
CBC
First Stage
Eflornithine
Was first use as topical for women
Injection became popular in the 2008 epidemic
Fromerly melarsoprol but many adverse effects (arsenic)
Second Stage
Intravenous melarsoprol (12 days)
can be combined with oral nifurtimox
can relapse without mlarsoprol
or eflornithine (14 days)

Sodalis glossinidius
Sodalis glossinidius is a Gram-negative, nonspore-forming, rod-shaped, filamentous bacteria.

"S. glossinidius is ... possibly enabling the creation of tsetse flies that are incapable of transimtting trypanosomes and thus controlling the spread of African sleeping sickness"
VSG Coat
Antigenic variation
high variable N terminal domain (350 amino acids)
allows for persistent evasion of host adaptive immunity
allows for chronic infection to persist
Shielding
prevents host immune system from accessing plasma membrane
Gene 'archive'
full-length intact genes vs pseudoenes and often frameshift mutations to allow for gene alteration.
Silent
often switched on or changed.
Full transcript