T. brucei

• Trypanosoma brucei


  Causative agent for human African sleeping sickness and human African trypanosomiasis (HAT)

  
• Subspecies of Trypanosoma brucei


  • Trypanosoma brucei gambiense
  • Trypanosoma brucei rhodiense
  • Trypanosoma brucei brucei
• Trypanosoma brucei brucei


  • Affects animals

  
• Forms of Trypanosoma brucei


  • Epimastigote
  • Trypomastigote
• Tissues affected by Trypanosoma brucei


  • Blood
  • Lymph
  • Spleen
  • CSF
• Multiplication of Trypanosoma brucei


  Longitudinal binary fission: Trypomastigote, epimastigote
• Modes of transmission for Trypanosoma brucei


  • Vector borne: Tsetse fly (Genus Glossina)
  • Blood transfusion
  • Needle-prick
  • Transplacental
  • Organ transplantation
• Infective stage


  Metacyclic trypomastigote
• Diagnostic stage


  Trypomastigote (in blood, CSF, lymph node aspirate)
• Vector


  Tsetse fly (Genus Glossina)
• Tsetse fly (Genus Glossina)


  • One wing rests directly on top of the other over their abdomen when resting
  • Long proboscis extends directly forward
  • Large thorax and abdomen that are shorter than wings

  
• Forms in the life cycle of Trypanosoma brucei


  • Human: Trypomastigote
  • Vector: Procyclic trypomastigote, Epimastigote, Metacyclic trypomastigote

  
• Trypomastigote


  • Polymorphic: Slender or short stumpy form
  • Flattened, fusiform shape
  • Body: Tapers anteriorly, blunt posteriorly
  • Nucleus: centrally located with large central karyosome
  • Kinetoplast: posterior end
  • Undulating membrane with single flagellum
• Epimastigote


  • Body: Tapers anteriorly, blunt posteriorly
  • Nucleus: centrally located
  • Kinetoplast: anterior to nucleus
• Life cycle of Trypanosoma brucei


  1. Metacyclic trypomastigote multiplies rapidly in blood and tissues when infected fly bites human/animal

  2. Blood trypomastigote ingested by vector, transforms to procyclic trypomastigote in midgut

  3. Procyclic trypomastigotes transform to epimastigotes, migrate to foregut and salivary glands

  4. Epimastigotes multiply in salivary glands, transform to metacyclic trypomastigotes

  
• Summary of Trypanosoma brucei life cycle

  • Blood trypomastigote -> procyclic trypomastigote -> epimastigote -> metacyclic trypomastigote -> blood trypomastigote
• Types of Human African Trypanosomiasis (HAT)


  • Acute HAT: T. brucei rhodiense
  • Chronic HAT: T. brucei gambiense
• Trypanotolerance


  Long term persistence of parasites without clinical features

  
• Initial lesion


  • Local, painful, pruritic, erythematous chancre located at the bite site progressing into eschar that spontaneously resolves within 2-3 weeks

  
• Early stage (1-6 months)


  • Hemolymphatic phase: Parasite proliferating in blood and lymphatics, trypanids (circinate or serpiginous rashes), toxin release causing tissue damage, irregular and remittent fever, headache, joint/muscle pain, fatigue, malaise, rare complications (disseminated intravascular coagulopathy, anemia, myocardial inflammation, renal insufficiency)

  
• Winterbottom's sign


  Enlarged, nontender, rubbery posterior cervical lymphadenopathy (sometimes in axillary and supraclavicular region) in Gambian trypanosomiasis

  
• Late stage


  • Meningoencephalitic phase: Involvement of CNS (brain, meninges), neurologic symptoms (seizures, behavioral changes, apathy, headache, sleeping disturbances, tremors, speech/reflex defects, paralysis), Kerandel's sign (deep delayed hyperesthesia), somnolence, coma, death
• Affected areas in late stage

  • Frontal lobes
  • Pons
  • Medulla
  • Perivascular areas
• Trypanosomes can evade the immune system through antigenic variation
• Stages in diagnosis


  • Screening test: Immunologic (serologic) method, Card agglutination test for trypanosomiasis (CATT)
  • Confirmatory test: Direct visualization of trypomastigote in blood/lymph, microhematocrit method
  • Staging: CSF examination by lumbar puncture, PCR
• Definitive diagnosis


  Trypanosomes in the CSF
• Pathognomonic diagnosis


  High IgM level in CSF
• Other CSF findings


  • Increased cell count: >5/uL
  • Increased opening pressure
• Management: Early stage


  • IV suramin sodium
  • IV pentamidine
• Adverse effects of early stage drugs


  • Suramin: paresthesia
  • Pentamidine: hypotension, tachycardia, hypoglycemia
• Early stage drugs cannot cross the blood-brain barrier and cannot be used to treat late stage
• Management: Late stage


  • Gambian: Eflornithine + Nifurtimox
  • Rhodesian: IV melarsoprol with steroids for prevention of arsenic encephalopathy
• Jarisch-Herxheimer reaction


  Febrile episode following lysis of trypanosomes, release of endotoxins and inflammatory cytokines, potential symptoms (flu-like, achiness, headache, mental fog, skin rash, loose stools, fatigue, fever, sweating, chills)
• Combination therapy


  • Ease of administration
  • Decreased risk of developing drug resistance
  • Example: Nifurtimox-Eflornithine Combination Therapy (NECT)
• First line drugs by disease and stage

  • T. b. gambiense, first stage: Pentamidine, Suramin
  • T. b. gambiense, second stage: Eflornithine + Nifurtimox
  • T. b. rhodiense, first stage: Suramin, Pentamidine
  • T. b. rhodiense, second stage: Melarsoprol
• Prevention and control measures


  • Vector control: Insecticides, protective clothing
  • Regulation and treatment of reservoir hosts