Trypanosoma brucei: Difference between revisions
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Trypanosoma brucei
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+ | ==Background== |
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− | = ''Trypanosoma brucei'' (African trypanosomiasis) = |
||
− | also known as African sleeping sickness |
+ | *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 |
||
− | | Primary reservoir |
||
+ | |forests and wooded areas |
||
− | | Humans |
||
− | | |
+ | |savanna and woodlands |
|- |
|- |
||
+ | |Primary reservoir |
||
− | | Human illness |
||
+ | |humans |
||
− | | Chronic (late CNS disease) |
||
+ | |antelope and cattle |
||
− | | Acute (early CNS disease) |
||
|- |
|- |
||
− | | |
+ | |Human illness |
+ | |chronic (late CNS disease) |
||
− | | Months to years |
||
+ | |acute (early CNS disease) |
||
− | | < 9 months |
||
|- |
|- |
||
+ | |Duration of illness |
||
− | | Lymphadenopathy |
||
+ | |months to years |
||
− | | Prominent |
||
+ | |< 9 months |
||
− | | Minimal |
||
|- |
|- |
||
+ | |Lymphadenopathy |
||
− | | Parasitemia |
||
+ | |prominent |
||
− | | Low |
||
+ | |minimal |
||
− | | High |
||
|- |
|- |
||
+ | |Parasitemia |
||
− | | Epidemiology |
||
+ | |low |
||
− | | Rural |
||
+ | |high |
||
− | | Tourists and workers in game parks/wild areas; rural |
||
+ | |- |
||
+ | |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 |
||
− | [[File:SleepingSick_LifeCycle_19.jpg|T. brucei life cycle]] |
||
+ | *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=== |
||
− | == Epidemiology == |
||
+ | *Procyclic trypomastigotes develop in the midgut then migrate to the salivary glands, where they develop into epimastigotes and then metacyclic trypomastigotes |
||
− | * Present only in sub-Saharan Africa |
||
− | * |
+ | *Metacyclic trypomastigotes are transmitted in the saliva during feeding |
+ | **Local replication in the trypanosomal chancre followed by lymphatic and hematogenous dissemination |
||
− | ** Tsetse fly exists only in Africa |
||
+ | *They multiply in the bloodstream and are thus exposed continuously to the immune system |
||
− | * Animal reservoirs include cattle and possibly wild ungulates (''T. b. rhodesiense''); non-human animals are less important for ''T. b. gambiense'' |
||
+ | **They undergo antigenic variation to periodically change their external glycoprotein structures (VATs) |
||
+ | **VAT: variant antigen type |
||
+ | ==Clinical Manifestations== |
||
− | == Pathophysiology == |
||
+ | *Almost all cases lead to death if not treated |
||
− | * 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 |
||
+ | ===West African trypanosomiasis=== |
||
− | == Clinical Presentation == |
||
+ | *Typically more chronic than East African trypanosomiasis |
||
− | * Almost all cases lead to death if not treated |
||
+ | ====Trypanosomal chancre==== |
||
− | === West African trypanosomiasis === |
||
+ | *Incubation period of 1 to 2 weeks |
||
− | * Typically more chronic than East African trypanosomiasis |
||
+ | *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 |
||
− | * Painful, indurated trypanosomal chancre, which resolves after several weeks |
||
+ | *Lymphadenopathy develops |
||
− | ** May ulcerate |
||
− | ** |
+ | **'''Winterbottom sign''': enlargement of posterior cervical lymphadenopathy |
+ | *Hepatosplenomegaly |
||
− | ** Often not present |
||
+ | *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 |
||
− | * Incubation period weeks to months |
||
+ | **Irritability, personality changes, and loss of concentration may be the earliest symptoms |
||
− | * Intermittent high fever lasting days, with intervening afebrile periods |
||
+ | **Progressive indifference with daytime somnolence and sometimes restlessness and insomnia at night |
||
− | * Lymphadenopathy develops |
||
+ | **Headache is common |
||
− | ** '''Winterbottom sign''': enlargement of posterior cervical lymphadenopathy |
||
+ | **Extrapyramidal signs with choreiform movements, tremors, fasciculations |
||
− | * Hepatosplenomegaly |
||
+ | **Ataxia |
||
− | * Transient edema in face, hands, feed, and periarticular areas |
||
+ | **Parkinsonian features |
||
− | * Pruritis, often with an irregular erythematous circinate rash on trunk, shoulders, buttocks, and thighs (5-10 cm with central clearing) |
||
+ | **Coma and death over weeks to months |
||
− | * May also have malaise, headache, weakness, weight loss/cachexia, arthralgias, and tachycardia |
||
+ | *CSF should be abnormal, with elevated protein and WBCs |
||
− | * Anemia, thrombocytopenia |
||
+ | *Extraneurological symptoms may include hypothyroidism and adrenal insufficiency (not necessarily confirmed on bloodwork) |
||
− | * Mott cells on tissue biopsy |
||
+ | ===East African trypanosomiasis=== |
||
− | ==== Stage 2 disease (meningoencephalitic) ==== |
||
+ | *Typically more acute than West African trypanosomiasis |
||
− | * Multiple neurological manifestations are possible, following months to years of infection |
||
+ | *Incubation period of days to weeks |
||
− | ** Irritability, personality changes, and loss of concentration may be the earliest symptoms |
||
+ | *In returned travelers, may present with fever, malaise, and headache |
||
− | ** Progressive indifference with daytime somnolence and sometimes restlessness and insomnia at night |
||
+ | *Fever becomes intermittent and a rash develops |
||
− | ** Headache is common |
||
+ | *Lymphadenopathy is less prominent |
||
− | ** Extrapyramidal signs with choreiform movements, tremors, fasciculations |
||
+ | *Persistent tachycardia |
||
− | ** Ataxia |
||
+ | *No clear distinction between hemolymphatic and meningoencephalitic stages |
||
− | ** Parkinsonian features |
||
+ | *Patients may die from arrhythmias or heart failure related to pancarditis |
||
− | ** Coma and death over weeks to months |
||
+ | *Untreated, death within 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) |
||
+ | ==Diagnosis== |
||
− | === East African trypanosomiasis === |
||
+ | *Diagnosis requires demonstration of parasite in tissue or fluid on microscopy, '''including CSF in all patients''' |
||
− | * Typically more acute than West African trypanosomiasis |
||
+ | **For chancre, express fluid and examine under light microscopy for motile trypanosomes |
||
− | * Incubation period of days to weeks |
||
+ | **Fix and stain with Giemsa |
||
− | * In returned travelers, may present with fever, malaise, and headache |
||
+ | **Aspiration of lymph nodes with kneading (may need multiple aspirates) |
||
− | * Fever becomes intermittent and a rash develops |
||
+ | **Thin and thick Giemsa stained blood films is most useful in hemolymphatic stage |
||
− | * Lymphadenopathy is less prominent |
||
+ | *PCR and LAMP may be sensitive and specific but is not currently well-enough developed |
||
− | * 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 |
||
− | == |
+ | ==Management== |
+ | *Treatment is more toxic in meningoencephalitic stage |
||
− | * Diagnosis requires parasite in tissue or fluid on microscopy, '''including CSF in all patients''' |
||
+ | *Monitor for side effects during treatment (common) |
||
− | ** 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 |
||
− | == |
+ | ===CDC Guidelines=== |
+ | {| class="wikitable" |
||
− | * Treatment is more toxic in meningoencephalitic stage |
||
+ | !Species |
||
− | |||
+ | !Drug |
||
− | == Side effects of treatment are many == |
||
+ | !Adult Dosage |
||
− | |||
+ | !Pediatric Dosage |
||
− | === 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 |
||
− | == Prevention == |
||
+ | *Treatment of infected humans and animals |
||
+ | *Vector avoidance with insect repellant, long-sleeve clothes, and avoiding known endemic areas |
||
+ | {{DISPLAYTITLE:''Trypanosoma brucei''}} |
||
− | * Vector control programs |
||
+ | [[Category:Protozoa]] |
||
− | * Treatment of infected humans and animals |
||
− | * Vector avoidance with insect repellant, long-sleeve clothes, and avoiding known endemic areas |
Latest revision as of 08:08, 21 August 2020
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