Human african trypansomiasis (sleeping sickness)

Background

• Caused by the protozoan parasite Trypanosoma brucei
  • Two distinct sub-species exist T. brucei rhodesiense and T. brucei gambiense
    • rhodesiense - Eastern and Southeastern Africa
      • Transmitted by tsetse flies that live in woodlands on the savanah
    • gambiense - Central and Western Africa (More common of the two infections)
      • Transmitted by tsetse flies that live in denser vegetation and along rivers
    • Crude demarcation line runs through the Great Rift Valley
• Endemic in 36 countries in Sub-Saharan Africa and about 30,000 are currently infected
• Spread by the Tsetse fly
• Data from 2009 and 2011 suggest that the prevalence is decreasing
• The Democratic Republic of the Congo reported about 80% of new cases in 2012
• Vertical Transmission (Mother to fetus) is also possible

Clinical Features

• Clinical syndromes produced by T. brucei gambiense and T. brucei rhodesiense are similar in nature, however the rhodesience strain is much more rapidly progressive and can present with fulminant disease over the course of a few months, not years like the gambiense strain
• May present differently in travelers

Early symptoms

• Known as the hemolymphatic stage
• Chancre
  • May be earliest sign
  • Painless, well circumscribed, rubbery lesion. (More common with rhodesiense sp.)
• Winterbottom's sign
  • Lymphadenopathy of posterior cervical lymph nodes-characteristic but not always present
• Intermittent symptoms corresponding to waves of parasitemia
  • Fever, headache, malaise, arthralgias, rash, pruritus

Late symptoms

• 100% fatal if untreated
• Involvement of the CNS
  • Progressive meningoencephalitis
  • Brain edema
  • Cerebral microhemorrhages
  • Multifocal white matter demyelination
  • Mott cells in CSF
    • Activated plasma cells with IgM inclusions
  • Neurologic symptoms
    • Headache, personality changes, inability to concentrate, difficulty with complex mental tasks, psychosis, ataxia, alteration of wake/sleep cycles, parkinsonian like movements
    • Eventually progresses to the point where the patient is stuporous and/or in a comatose state

Differential Diagnosis

Altered mental status and fever

• Infectious
  • Sepsis
  • Meningitis
  • Encephalitis
  • Cerebral malaria
  • Brain abscess
• Other
  • Neuroleptic malignant syndrome
  • Serotonin syndrome
  • Malignant hyperthermia
  • Sympathomimetic toxicity (cocaine, amphetamine, ketamine)
  • Anticholinergic toxicity
  • Heat stroke
  • Delirium tremens
  • Hypothalamic stroke
  • Pheochromocytoma
  • Thyroid storm

Evaluation

• Direct visualization of the trypanosomes (Gold Standard)
  • Blood smears with either Giemsa or Wright's stain
  • Samples can include CSF, blood, lymph node aspirates, and chancre aspirates
    • Must examine CSF to staging and treatment purposes
  • Low levels of parasitemia may require concentration of sample
• Serologic testing
  • Card agglutination test for trypanosomiasis (CATT)
    • Agglutination of freeze dried trypanosomes
  • Useful for epidemiologic studies
• CSF analysis
  • Pleocytosis
  • Elevated protein levels
  • Mott cells
  • Direct visualization of trypanosome
• Imaging
  • MRI - hyperintense signals in periventricular white matter
  • EEG - Delta waves

Management

Early treatment (Hemolymphatic stage)

• Pentamidine (T.b. gambiense)
• Sumarin (T.b. rhodesience)

Late Treatment (Neurologic stage)

• Eflornithine (DMFO) for 14 days (T.b. gambiense only, no activity against T.b. rhodesience)
  • Can combo with nifurtimox
    • More effective than Eflornithine alone
• Melarsoprol for 12 days (T.b. rhodesience)
  • Can combo with nifurtimox also
  • Less effective than Eflornithine

Research and Development

• DB289, a new drug that acts like pentamidine with less side effects

Monitoring

• Repeat LP Q 6months for 2 years

See Also

• Neglected Tropical Diseases
• Chagas Disease (American Trypanosomiasis)

External Links

• http://www.who.int/trypanosomiasis_african/en/
• http://www.cdc.gov/parasites/sleepingsickness/