Human African Trypanosomiasis (HAT): Not Something to Sleep On By Chris Rota BIOL 402 – Duronio and Peifer

Where in the World is HAT? Figure 3. Map of HAT prevalence in Sub-Saharan Africa, its only endemic region. Figure 4. Distributions of T. bruteis species and Glossina (tsetse fly) species overlap in HAT endemic regions.

How do I Know if I Have HAT? Patient symptoms change as HAT progresses Early (blood, lymph nodes): Headaches, fever, weakness, pain in the joints, and stiffness Late (central nervous system): Psychiatric disorders, seizures, coma and ultimately death What are the relative numbers of early/late cases in terms of treatment? Is HAT always lethal if untreated? Estimates on DALY loss due to HAT? (epidemiological numbers) How exactly do they test for the trypanosomes (antigen?) Early diagnosis is critical to managing HAT, but often unreliable in the field

The Perpetrators: Trypanosoma brucei Family of parasites with two members Trypanosoma gambiense (“West African”) Trypanosoma rhodesiense (“East African”) Figure 2. Trypomastigotes of T. brucei within a blood sample

The Cycle of Human African Trypanosomiasis Solidify my explanation of this slide!! Bloodstream vs. procyclic – what’s the difference? How do these parasites cause symptoms once they are in the bloodstream? (clogging arteries?) Figure 1. Life cycle of the Trypanosoma bruteis parasite family in humans and tsetse flies

Treatment of HAT Early HAT Late HAT Pentamidine Suramin Late HAT Melarsoprol Eflornithine (W. HAT only) Check effectiveness of these drugs against HAT (cure rates)

A Short History of Humans & HAT First recorded case in 1378 Migrated out of Africa with slave trade in 1500’s Colonization expedited disease spread  1890’s outbreak in Congo Studied intensely and controlled into 1950’s Resurged in post-independence Africa (1960’s – 2000) International efforts at control  Targeted for elimination in 2011 by WHO Figure 4. HAT prevalence is correlated with Sub-Saharan African historical periods in the DRC.

The T. bruteis Genome Project Go into depth about the background of the science (how they sequenced the genome, how they assembled it) Not unlike our own immune system’s antibody production, these organisms can change their external glycoprotein antigens using their genetic diversity to avoid detection Figure 5. Documentation of VSG and ESAG gene diversity in T. brutei genome, thought to contribute to immune system evasion. (Adapted from Berriman et al 2005)

References An African woman caring for her comatose husband , who is dying of HAT in Uganda, 1990. Photograph. Stanford University. 31 Mar 2014. <http://www.stanford.edu/group/parasites/ParaSites2001/trypanosomiasis/trypano.htm> In vitro rapid detection test of T. gambiense Ab in blood or plasma. Photograph. Coris Bio-Concept. 31 Mar 2014. <http://www.corisbio.com/Products/Human-Field/Human-African-Trypanosomiasis.php> Hasker E, Lutumba P, Chappuis F et al. 2012. Human African Trypanosomiasis in the Democratic Republic of the Congo: A Looming Emergency? PLOS Neglected Tropical Diseases 6 (12): 1950. (2012). Heiman Wertheim, Peter Horby & Jack Woodall (Eds.), Atlas of Human Infectious Diseases. Oxford: Wiley-Blackwell. Brun R, Blum J, Chappuis F, Burri C. 2010. Human African Trypanosomiasis. The Lancet 375 (9709): 148-159. Parasites – African trypanosomiasis. Graphic. Center for Disease Control. 31 Mar 2014. <http://www.cdc.gov/parasites/sleepingsickness/biology.html> Berriman M, Ghedin E, Hertz-Fowler C. 2005. The Genome of the African Trypanosome Trypanosoma brucei. Science 309 (5733): 416-422. "Human African Trypanosomiasis." WHO Programmes. World Health Organization. Web. 31 Mar 2014. <http://www.who.int/trypanosomiasis_african/en/>.