Acknowledge for Dr. Wiser gabre.refaat@yahoo.com KINETOPLASTIDS widespread parasites animals (fishhumans) insects plants kinetoplast near the base of the flagellum unifying feature = kinetoplast Giemsa staining structure Kinetoplast Nucleus Acknowledge for Dr. Wiser http://www.tulane.edu/~wiser/protozoology/notes/kinet.html
flagellum undulating membrane flagellar pocket nucleus mitochondrion subpellicular microtubules basal body kinetoplast
= trypanosomal = crithedial = leptomonad = Leishmanial
Disease Causing Kinetoplastids Trypanosoma brucei complex African trypanosomiasis Trypanosoma cruzi Chagas’ disease Leishmania species leishmaniasis African trypanosomiasis 60 million at risk 25-45,000 reported cases 3-500,000 estimated cases
Species Distribution
tsetse = Glossina
Endemic T. gambiense transmission
T. rhodesiense transmission wild animal reservoir Zoonosis: infection naturally transferable between animals and humans bush buck
Metacyclic trypomasitgotes transferred with saliva during tse-tse feeding. 2 1 Trypomastigotes replicate in blood stream and tissues of mammal. Preadaptation for tse-tse. 3 4 Ingestion by tse-tse.
Blood Stage blood-stream forms preadaptation for tsetse long slender rapid replication binary fission preadaptation for tsetse morphological (short stumpy) slower replication metabolic (mitochondria)
7 6 5 Maturation to metacyclic trypomastigotes. long-slender 7 Migration to salivary glands and transformation to epimastigotes. 6 intermediate Procyclic trypomastigotes replicate in tse-tse midgut. loss of surface coat metabolic changes (mitochondria) short-stumpy 5
Migration to Salivary Glands: Two Possible Routes
Maturation to Metacyclic Trypomastigotes in Salivary Glands
Infection Tsetse Bite pain hypersensitivity tsetse are pool feeders metacyclic trypomastigotes in saliva and enter bite wound Tsetse Bite pain hypersensitivity
Acute Symptoms and Blood Stage 1-3 week asymptomatic incubation period sometimes a local inflammation 'trypanosomal chancre' parasite replication at bite site invasion of blood characterized by irregular fever and headache T. rhodesiense can develop into fulminating infection T. gambiense can be self-limiting or slowly progressing to more serious disease
Lymphatic Stage cachexia disease progression often involves invasion of lymphatics Winterbottom’s sign rash itching edema continued febrile attacks weight loss weakness cachexia
CNS Disease Course and Symptoms parasites crossing blood-brain barrier result in CNS involvement and nervous impairment described as meningoencephalitis increased apathy and fatigue confusion and somnolence motor changes including tics, slurred speech, incoordination convulsions, coma progression to CNS involvement is rapid (weeks) in Tr and slow (6-12 months) in Tg death results from disease (eg., convulsions, hyperpyrexia) or other infections
Diagnosis Clinical Features Laboratory Diagnosis travel or residence in endemic area history or scar of 'trypanosomal chancre' irregular fever and enlarged lymph nodes particularly posterior cervical behavioral changes/mental symptoms Laboratory Diagnosis serological tests IFA, ELISA, CATT (card agglutination trypanosomiasis test) demonstration of trypanosomes especially during fever definitive diagnosis
Detection of African Trypanosomes Blood examine on several days stained thin or thick smears fresh (characteristic movement) buffy coat (microhematocrit) mini-anion exchange chromato-graphy technique (m-AECT) inoculate rats or mice
Detection of African Trypanosomes Lymph Node Aspirates fresh or stained Cerebrospinal Fluid examine sediment cells and protein (presumptive)
Treatment Early Stage--no CNS involvement suramin pentamidine excellent prognosis Late Stage--CNS involvement melarsoprol arsenical based drug high toxicity (4-12% mortality) eflornithine (resurrection drug) expensive 14 consecutive daily injections oral formulation in phase 3 trials
Acknowledge for Dr. Wiser Prophylaxis and Control drugs contraindicated mask infections toxicity insect repellants protective clothing community activities surveillance and treatment traps, insecticides habitat alteration Acknowledge for Dr. Wiser http://www.tulane.edu/~wiser/protozoology/notes/kinet.html