01Approach to the Critical Patient/attcp51

Immediate priorities

›Recognize the life-threatening course

›Rhodesiense pattern (acute, days to weeks)

›Severe sepsis-like presentation

›Death possible before neurological signs appear

›Gambiense pattern (chronic, months to years)

›Insidious progression to meningoencephalitis

›Mean disease duration about 3 years untreated

›Fatal if untreated regardless of subspecies

›Neglected tropical disease, WHO-notifiable

›Early definitive treatment is curative

›Airway, breathing, circulation

›Airway protection in advanced second-stage coma

›Depressed consciousness

›Seizure-related compromise

›Circulatory threats in rhodesiense

›Myocarditis with cardiogenic shock

›Pericardial effusion with tamponade physiology

›If hemodynamic instability, treat as cardiac involvement until excluded

›IV access and continuous monitoring

›Bedside echocardiography

›Concurrent tropical co-infection

›Empiric malaria evaluation in every febrile returned traveler

›Thick and thin films for Plasmodium

›Treat malaria if confirmed

›Fever not responding to antimalarials is a key trypanosomiasis clue

›No typical malaria periodicity

›Persistent recurrent fever despite therapy

02History/hx58

Travel and exposure

›Travel history is paramount

›Sub-Saharan Africa, rural or forested areas

›Tsetse fly (Glossina) habitat near rivers and woodland

›Specific country, duration, urban versus rural

›Region predicts subspecies

›Gambiense in West and Central Africa

›Rhodesiense in East and Southern Africa

›Democratic Republic of the Congo accounts for over 80% of gambiense cases

›Remote travel still relevant given long incubation

›Safari, aid work, research, fieldwork

›High-exposure activities

›Farming and water collection

›Riverine and forest edge work

›Daytime tsetse biting

›Hunting, fishing, wood gathering

›Bushland entry

›Lack of protective clothing

Symptom timeline

›Incubation and tempo

›Gambiense incubation months to years

›Insidious chronic course

›Often misdiagnosed as malaria

›Rhodesiense incubation days to 3 weeks

›Rapid progression

›Fatal within days to weeks if untreated

›Stage 1 symptoms

›Intermittent fever (irregular pattern)

03Physical Exam/exam54

Vitals and general

›Stability snapshot

›Temperature

›Intermittent irregular fever

›Hypothermia as severe sepsis marker

›Heart rate and blood pressure

›Tachycardia with cardiac involvement

›Hypotension in rhodesiense

›Mental status

›Somnolence

›Confusion and behavioral change

Classic findings

›Lymphatic and skin signs

›Winterbottom's sign

›Painless soft posterior cervical lymphadenopathy

›Classic for gambiense HAT

›Trypanosomal chancre

›Painful erythematous lesion 2 to 5 cm at bite site

›No necrosis, larger than typical eschar

›Trypanosomal rash

›Circinate or serpentine outline

›Transient and migratory

›Visceral findings

›Hepatosplenomegaly

›Common in systemic disease

›Mimics other tropical infections

›Facial and peripheral edema

›Soft tissue swelling

04Differential Diagnosis/ddx44

Life-threatening and infectious mimics

›Must-not-miss infections

›Malaria

›Most common misdiagnosis

›ICD-10 B54

›Bacterial meningitis or viral encephalitis

›Altered mental status and CSF pleocytosis

›ICD-10 A87.9 for viral encephalitis

›Severe sepsis from other source

›Overlaps rhodesiense presentation

›ICD-10 A41.9

›Chronic febrile mimics

›HIV infection

›Lymphadenopathy, weight loss, neuropsychiatric features

›ICD-10 B20

›Tuberculosis

›Chronic fever, weight loss, lymphadenopathy

›ICD-10 A15.9

›Typhoid fever and brucellosis

›Prolonged fever, hepatosplenomegaly, arthralgias

›Undulant fever pattern in brucellosis

Parasitic and neoplastic differentials

›Other tropical parasites

›Visceral leishmaniasis

›Hepatosplenomegaly, fever, pancytopenia

›ICD-10 B55.0

›Toxoplasmosis

›CNS involvement in immunocompromised

05Laboratory Tests/lt48

Parasitological confirmation

›Direct parasite detection

›Giemsa-stained thick and thin blood films

›Gold standard for rhodesiense (high parasitemia)

›Repeat exams and concentration for gambiense

›Buffy coat preparation

›Concentrates trypanosomes

›About 50% sensitivity for gambiense

›Mini anion exchange centrifugation technique (mAECT)

›About 80% sensitivity for gambiense

›Concentration method for low parasitemia

›Aspirate microscopy

›Lymph node aspirate

›When palpable cervical nodes present

›Direct trypanosome visualization

›Chancre aspirate

›Detects trypanosomes within days of rhodesiense infection

›Early diagnostic window

Serology and molecular

›Serological screening (gambiense only)

›CATT (Card Agglutination Test for Trypanosomiasis)

›Titer at or above 1:16 considered positive

›Field screening tool

›Lateral flow rapid diagnostic tests

›HAT Sero K-SeT sensitivity about 100%

›Specificity about 94%

›Confirmatory reference assays

›Trypanolysis test specific for gambiense contact

06Diagnostic Tests/dt61

Scoring Systems

›Disease staging classification

›Stage 1 haemolymphatic

›CSF WBC at or below 5/uL

›No trypanosomes in CSF

›Stage 2 meningoencephalitic

›CSF WBC above 5/uL

›Or trypanosomes detected in CSF

›Severe stage 2 threshold

›CSF WBC at or above 100/uL

›Favors NECT over fexinidazole for gambiense

›Lumbar puncture decision

›Required in children under 6 years or under 20 kg

›Staging mandatory for drug choice

›Neurological signs present

›May be deferred in adults without neuro signs when fexinidazole planned

›Simplified staging-free pathway

›WHO 2019 to 2020 guidance

›No validated ED prognostic score

›Staging drives management

›Clinical trajectory supersedes single value

MRI

›Brain MRI role

›Second-stage findings

›White matter signal change

›Meningoencephalitic features

›Not routinely required

›Staging relies on CSF examination

07Disposition/dispo34

Level of care

›Admission indications

›All confirmed HAT cases

›Treatment initiation, monitoring, staging

›Directly observed therapy

›Fexinidazole course logistics

›10 days of observed dosing with food

›Ideally in a health facility

›NECT requirement

›Hospitalization for IV eflornithine infusions

›Nursing-intensive regimen

›ICU indications

›Rhodesiense instability

›Hemodynamic compromise

›Cardiac involvement

›Multiorgan failure

›Renal or hepatic dysfunction

›Severe encephalopathy

Coordination and follow-up

›Consultation and drug access

›Infectious disease consultation essential

›Non-endemic management expertise

›Staging interpretation

›CDC Parasitic Diseases hotline (US)

›Drug release coordination

›Management guidance

›WHO strategic drug depots

›Donated drug supply

08Treatment/t78

Initial stabilization

›Resuscitation priorities

›IV access and hemodynamic monitoring

›Especially rhodesiense

›Continuous cardiac monitoring

›Treat concurrent malaria if present

›Confirm and treat per protocol

›Do not delay HAT workup

›Rhodesiense treated without delay

›Rapid progression to multiorgan failure

›Early specialist involvement

First-line by stage gambiense

›Fexinidazole oral (first-line, most cases)

›Indication

›Age at or above 6 years and at least 20 kg

›No severe neurological signs

›Dosing schedule

›Loading dose once daily for 4 days

›Maintenance dose once daily for 6 days

›Total 10-day directly observed course

›Administration

›Must be taken with a substantial meal

›Fasting compromises absorption and risks failure

›Pentamidine IM for early gambiense in young children

›Indication

›Under 6 years or under 20 kg, stage 1

›When fexinidazole unsuitable

›Dosing

09Special Populations/sp33

Pregnancy

›Pregnancy considerations

›Treatment urgency

›Untreated HAT is fatal and harms the fetus

›Specialist-guided therapy

›Drug safety

›Limited fexinidazole pregnancy data, weigh risk and benefit

›Pentamidine used when benefit outweighs risk

›Monitoring

›Fetal surveillance when viable gestation

›Maternal glucose and blood pressure with pentamidine

Geriatric

›Older adult features

›Comorbidity burden

›Cardiac and renal impairment affect drug choice

›Suramin nephrotoxicity risk higher

›Drug interaction risk

›Polypharmacy and QT-prolonging agents

›Heightened neuropsychiatric sensitivity

›Atypical presentation

›Confusion may dominate

›Lower physiologic reserve

Pediatrics

›Pediatric approach

›Weight and age thresholds drive therapy

›Fexinidazole for at least 6 years and 20 kg

›Alternative agents below threshold

›Stage 1 alternatives below threshold

10Background/b51

Epidemiology

›Global burden and distribution

›Caused by Trypanosoma brucei subspecies

›Gambiense about 95% of cases, chronic

›Rhodesiense about 5% of cases, acute

›Geographic concentration

›DRC accounts for over 80% of gambiense cases

›Rhodesiense in Uganda, Malawi, Tanzania, Zambia

›Transmission and prevention

›Vector tsetse fly (Glossina) bite

›No vaccine or chemoprophylaxis available

›Outcome and elimination

›Fatal if untreated

›Mean gambiense duration about 3 years

›Rhodesiense fatal within days to weeks

›WHO elimination target

›Elimination as a public health problem by 2030

›Declining global case counts

Pathophysiology

›Disease mechanism

›Two-stage progression

›Stage 1 haemolymphatic dissemination

›Stage 2 CNS invasion (meningoencephalitis)

›Immune evasion

›Antigenic variation of variant surface glycoprotein

›Evades host antibody response

›CNS and sleep disruption

›Crossing blood-brain barrier

11Patient Discharge Instructions/pdi19

copy discharge instructions

›African sleeping sickness care plan

›Take all medication exactly as prescribed until finished

›Take fexinidazole with a full meal every day

›Keep every follow-up appointment, even if you feel well

›Relapse can occur up to 12 to 24 months after treatment

›Warning signs to return to the ER

›Return of fever, headache, or sleep problems

›New confusion, tremor, unsteady walking, or seizures

›Mood changes, hallucinations, or thoughts of self-harm

›Chest pain, shortness of breath, or swelling

›Severe vomiting or inability to keep fluids down

›Follow-up schedule

›Clinic review at the times your specialist sets

›Repeat testing to confirm cure

›Bring this record to every visit

›Prevention for future travel

›Wear long sleeves and neutral-colored clothing

›Use insect repellent in endemic areas

›Avoid bushland during peak tsetse biting hours

12References/r12

Guidelines and key sources

›Guideline sources

›WHO guidelines for treatment of human African trypanosomiasis

›WHO 2024 update on rhodesiense HAT and fexinidazole

›CDC parasitic diseases guidance on African trypanosomiasis

›Landmark evidence

›Mesu et al, pivotal fexinidazole trial for late-stage gambiense HAT, Lancet 2018

›Lejon, Lindner, Franco, Human African Trypanosomiasis review, Lancet 2025

›Betu Kumeso et al, acoziborole phase 2/3 trial, Lancet Infectious Diseases 2023

›Coding standards

›ICD-10 B56.0 gambiense trypanosomiasis

›ICD-10 B56.1 rhodesiense trypanosomiasis

›ICD-10 B56.9 African trypanosomiasis unspecified

Evidence & Review

Evidence & Review