View source for Trypanosoma brucei

==Background==

*Causes '''African trypanosomiasis''', also known as '''African sleeping sickness'''

{| class="wikitable"
!
!West African
!East African
|-
|Organism
|''T. b. gambiense''
|''T. b. rhodesiense''
|-
|Vector
|tsetse fly, ''palpalis'' group
|tsetse fly, ''morsitans'' group
|-
|Habitat
|forests and wooded areas
|savanna and woodlands
|-
|Primary reservoir
|humans
|antelope and cattle
|-
|Human illness
|chronic (late CNS disease)
|acute (early CNS disease)
|-
|Duration of illness
|months to years
|&lt; 9 months
|-
|Lymphadenopathy
|prominent
|minimal
|-
|Parasitemia
|low
|high
|-
|Epidemiology
|rural
|tourists and workers in game parks/wild areas; rural
|-
|Treatment
|[[pentamidine]] (non-CNS) or [[eflornithin]] (CNS)
|[[suramin]] (non-CNS) or [[melarsoprol]] (CNS)
|}

===Microbiology===

*Vector-borne flagellated protozoan parasite transmitted by the tsetse fly belonging to the genus ''Trypanosoma'', subgenus ''Trypanozoon''
*Two subspecies that are morphologically indistinguishable
**''T. b. gambiense'', causing chronic African trypanosomiasis (“West African sleeping sickness”)
**''T. b. rhodesiense'', causing acute African trypanosomiasis (“East African sleeping sickness”)
**Also, ''T. b. brucei'', which infects cattle and occasionally other animals
*No intracellular phase, in contrast to Chagas disease

===Epidemiology===

*Present only in sub-Saharan Africa
*Transmitted by flies in the genus [[Vector::Glossina species|Glossina]] (tsetse flies) in their saliva during feeding
**Tsetse flies exists only in Africa
*Animal reservoirs include cattle and possibly wild ungulates (''T. b. rhodesiense''); non-human animals are less important for ''T. b. gambiense''

===Pathophysiology===

*Procyclic trypomastigotes develop in the midgut then migrate to the salivary glands, where they develop into epimastigotes and then metacyclic trypomastigotes
*Metacyclic trypomastigotes are transmitted in the saliva during feeding
**Local replication in the trypanosomal chancre followed by lymphatic and hematogenous dissemination
*They multiply in the bloodstream and are thus exposed continuously to the immune system
**They undergo antigenic variation to periodically change their external glycoprotein structures (VATs)
**VAT: variant antigen type

==Clinical Manifestations==

*Almost all cases lead to death if not treated

===West African trypanosomiasis===

*Typically more chronic than East African trypanosomiasis

====Trypanosomal chancre====

*Incubation period of 1 to 2 weeks
*Painful, indurated trypanosomal chancre, which resolves after several weeks
**May ulcerate
**May have regional lymphadenopathy
**Often not present

====Stage 1 disease (hemolymphatic)====

*Incubation period [[Usual incubation period::weeks to months]]
*Intermittent high fever lasting days, with intervening afebrile periods
*Lymphadenopathy develops
**'''Winterbottom sign''': enlargement of posterior cervical lymphadenopathy
*Hepatosplenomegaly
*Transient edema in face, hands, feed, and periarticular areas
*Pruritis, often with an irregular erythematous circinate rash on trunk, shoulders, buttocks, and thighs (5-10 cm with central clearing)
*May also have malaise, headache, weakness, weight loss/cachexia, arthralgias, and tachycardia
*Anemia, thrombocytopenia
*Mott cells on tissue biopsy

====Stage 2 disease (meningoencephalitic)====

*Multiple neurological manifestations are possible, following months to years of infection
**Irritability, personality changes, and loss of concentration may be the earliest symptoms
**Progressive indifference with daytime somnolence and sometimes restlessness and insomnia at night
**Headache is common
**Extrapyramidal signs with choreiform movements, tremors, fasciculations
**Ataxia
**Parkinsonian features
**Coma and death over weeks to months
*CSF should be abnormal, with elevated protein and WBCs
*Extraneurological symptoms may include hypothyroidism and adrenal insufficiency (not necessarily confirmed on bloodwork)

===East African trypanosomiasis===

*Typically more acute than West African trypanosomiasis
*Incubation period of days to weeks
*In returned travelers, may present with fever, malaise, and headache
*Fever becomes intermittent and a rash develops
*Lymphadenopathy is less prominent
*Persistent tachycardia
*No clear distinction between hemolymphatic and meningoencephalitic stages
*Patients may die from arrhythmias or heart failure related to pancarditis
*Untreated, death within weeks to months

==Diagnosis==

*Diagnosis requires demonstration of parasite in tissue or fluid on microscopy, '''including CSF in all patients'''
**For chancre, express fluid and examine under light microscopy for motile trypanosomes
**Fix and stain with Giemsa
**Aspiration of lymph nodes with kneading (may need multiple aspirates)
**Thin and thick Giemsa stained blood films is most useful in hemolymphatic stage
*PCR and LAMP may be sensitive and specific but is not currently well-enough developed

==Management==

*Treatment is more toxic in meningoencephalitic stage
*Monitor for side effects during treatment (common)

===CDC Guidelines===

{| class="wikitable"
!Species
!Drug
!Adult Dosage
!Pediatric Dosage
|-
|''T. b. rhodesiense'', hemolymphatic stage
|[[Suramin]]
|1 gm IV on days 1, 3, 7 ,14, and 21
|20 mg/kg IV on days 1, 3, 7, 14, and 21
|-
|''T. b. rhodesiense'', CNS involvement
|[[Melarsoprol]]
|2-3.6 mg/kg/day IV x 3 days. After 7 days, 3.6 mg/kg/day x 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
|2-3.6 mg/kg/day IV x 3 days. After 7 days, 3.6 mg/kg/day x 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
|-
|''T. b. gambiense'', Hemolymphatic stage
|[[Pentamidine]]
|4 mg/kg/day IM or IV x 7-10 days
|4 mg/kg/day IM or IV x 7-10 days
|-
|''T. b. gambiense'', CNS involvement
|[[Eflornithine]]
|400 mg/kg/day in 4 doses x 14 days
|400 mg/kg/day in 4 doses x 14 days
|}

*Patients should be followed with a lumbar puncture every 6 months (or sooner, if symptoms return) for 2 years after treatment to detect a relapse should it occur
*New treatment, [[fexinidazole]], may be a reasonable oral treatment

==Prevention==

*Vector control programs
*Treatment of infected humans and animals
*Vector avoidance with insect repellant, long-sleeve clothes, and avoiding known endemic areas

{{DISPLAYTITLE:''Trypanosoma brucei''}}
[[Category:Protozoa]]