Background
- Causes African trypanosomiasis, also known as African sleeping sickness
| 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 | < 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 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 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
| 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
