Leishmaniasis and trypanosomiasis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Leishmaniasis encompasses more than 20 protozoan species. Sandflies inoculate promastigotes that survive as amastigotes within macrophages. Host immunity, species and geography determine whether parasites remain in skin, spread to mucosa or disseminate through the reticuloendothelial system. A sterile cure is not assured, so later immunosuppression can permit relapse.

Human African trypanosomiasis is caused by extracellular T. brucei. Gambiense disease usually evolves over months or years and has a major human reservoir; rhodesiense disease can progress over weeks or months and has zoonotic reservoirs. Parasites multiply in blood and lymph before crossing the blood-brain barrier, making stage assessment therapeutically decisive.

American trypanosomiasis is caused by intracellular T. cruzi. The vector defecates near a bite and scratching inoculates parasites into skin or mucosa. After a brief parasitaemic phase, organisms persist within myocardium, enteric nerves and other tissues. Years later, progressive conduction, myocardial or gastrointestinal disease can appear.

These are specialist imported infections. The safe generalist role is to recognise epidemiology and organ pattern, exclude immediately treatable alternatives such as malaria, involve laboratories before sampling, assess physiological severity and connect the patient rapidly with UK tropical and reference services.

Key points

Leishmania is transmitted by infected sandflies and presents as cutaneous ulcers, destructive mucosal disease or visceral infection affecting spleen, liver and marrow.
Visceral leishmaniasis causes prolonged irregular fever, weight loss, massive splenomegaly, cytopenias and hypergammaglobulinaemia; prompt complete treatment is essential.
First-line confirmation of cutaneous or mucosal disease uses lesion scraping, aspirate or biopsy for microscopy, culture and PCR; serology is usually unhelpful for isolated skin disease.
For visceral disease, obtain specialist-directed marrow or other tissue microscopy, culture and PCR with serology; tissue parasite demonstration is definitive but sampling risk and sensitivity vary.
African trypanosomiasis follows tsetse exposure: T. b. rhodesiense is often acute in eastern or southern Africa, whereas T. b. gambiense progresses more slowly in western or central Africa.
Demonstrate African trypanosomes in blood, chancre or lymph-node material, then stage central nervous system involvement using the current WHO specialist algorithm because treatment depends on form and stage.
Chagas disease is caused by T. cruzi, transmitted by triatomine faeces, congenitally, through contaminated food, blood, organs or laboratory exposure.
Acute Chagas may cause fever, a chagoma or unilateral Romaña eyelid swelling; chronic disease causes cardiomyopathy, arrhythmia, stroke, megaoesophagus or megacolon decades later.
Confirm chronic Chagas with two different serological assays; use PCR or microscopy for acute, congenital or reactivated infection and stage every confirmed case for cardiac and digestive damage.
Treatment is never selected by syndrome name alone: Leishmania species and geography, African trypanosome form and CNS stage, or Chagas phase, pregnancy and organ function determine the regimen.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sandfly-borne Leishmania

Female phlebotomine sandflies inoculate Leishmania promastigotes acquired from human or animal reservoirs across endemic tropical and Mediterranean regions.

Tsetse-borne African disease

Glossina tsetse flies transmit T. b. gambiense in western or central Africa and T. b. rhodesiense in eastern or southern Africa.

Triatomine-borne Chagas

Infected reduviid bugs defecate near a bite; rubbing faeces into broken skin or conjunctiva inoculates T. cruzi.

Non-vector T. cruzi

Congenital, oral foodborne, transfusion, transplantation and laboratory routes allow Chagas transmission outside places containing the insect vector.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Macrophage persistence
Leishmania amastigotes multiply inside macrophages, with cellular immune response determining local containment, mucosal spread or visceral dissemination.
2
Reticuloendothelial expansion
Visceral parasites infiltrate spleen, liver and marrow, causing organ enlargement, immune activation, cytopenias and vulnerability to secondary infection.
3
Trypanosome antigen variation
African trypanosomes repeatedly alter surface glycoproteins, escaping antibodies and producing waves of parasitaemia, fever and lymphatic inflammation.
4
Blood-brain invasion
African trypanosomes cross into cerebrospinal tissues, provoking diffuse meningoencephalitis, sleep-cycle disruption, endocrine change, movement abnormalities and progressive coma.
5
Chagas tissue persistence
Intracellular T. cruzi and chronic inflammation damage myocardium, conduction tissue and enteric nerves, causing cardiomyopathy and hollow-viscus dilatation.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Cutaneous leishmaniasis

A painless papule on exposed skin enlarges into a crusted ulcer with a raised indurated edge; multiple, nodular or sporotrichoid lesions can occur.

Mucosal leishmaniasisRed flag

Progressive nasal blockage, epistaxis, septal destruction, oral ulceration or voice change can follow a remote New World skin lesion.

Visceral leishmaniasisRed flag

Persistent fever, cachexia, darkened skin, very large spleen, hepatomegaly, pancytopenia and polyclonal hypergammaglobulinaemia form the classic kala-azar pattern.

African early stageRed flag

A painful chancre, intermittent fever, headache, pruritus and lymphadenopathy follow tsetse exposure; posterior cervical nodes are especially suggestive in gambiense disease.

African neurological stageRed flag

Reversal of sleep rhythm, behavioural change, tremor, ataxia, hyperreflexia, endocrine dysfunction, seizures or coma indicate meningoencephalitic progression.

Acute Chagas disease

Fever, malaise, lymphadenopathy, hepatosplenomegaly, a local chagoma or unilateral painless eyelid oedema can accompany high parasitaemia.

Chronic Chagas diseaseRed flag

Bradyarrhythmia, bundle-branch block, apical aneurysm, ventricular tachycardia, embolic stroke, dysphagia or severe constipation may emerge decades after infection.

Red flags requiring action

Prolonged fever, weight loss, marked splenomegaly and pancytopenia after endemic residence can be untreated visceral leishmaniasis, which is usually fatal without therapy.
Confusion, abnormal sleep-wake cycle, tremor, ataxia, psychiatric change or coma after sub-Saharan exposure may indicate central nervous system human African trypanosomiasis.
Acute fever after safari travel in eastern or southern Africa with a painful tsetse chancre can represent rapidly progressive rhodesiense sleeping sickness.
Mucosal ulceration, epistaxis, nasal obstruction or destructive oral disease months or years after a Latin American skin lesion needs urgent leishmania species assessment.
Syncope, palpitations, conduction block, ventricular arrhythmia or heart failure in someone from continental Latin America may be chronic Chagas cardiomyopathy.
Immunosuppression increases visceral leishmania relapse and Chagas reactivation risk; negative antibody tests are less reassuring in these hosts.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line travel and severity screenFirst stepFirst line
Why
Define epidemiological plausibility, competing emergencies and organ injury before rare-pathogen confirmation.
Interpretation and limitations
Map lifetime residence and travel, vector and animal contact, transfusion and maternal origin; obtain malaria films, cultures, FBC, renal and liver profiles, HIV testing and syndrome-directed imaging.
02
Leishmania lesion microscopy and PCR
Why
Confirm cutaneous or mucosal infection and identify a species complex that predicts behaviour.
Interpretation and limitations
Send edge scraping, aspirate or biopsy through an experienced laboratory for microscopy, culture and PCR; ulcer swabs for ordinary bacteria cannot exclude leishmaniasis.
03
Visceral leishmania tissue testing
Why
Demonstrate amastigotes or parasite DNA in reticuloendothelial tissue.
Interpretation and limitations
Bone-marrow aspirate is commonly safer than splenic aspiration in UK practice; splenic sampling may be more sensitive but bleeding risk requires expert selection and performance.
04
African trypanosome microscopy
Why
Directly demonstrate motile parasites and establish infection before stage-directed therapy.
Interpretation and limitations
Examine chancre fluid, lymph-node aspirate or concentrated blood according to phenotype and geography; parasitaemia may be intermittent, especially in gambiense infection, so repeat expert sampling.
05
African trypanosomiasis stage assessment
Why
Determine whether central nervous system invasion changes treatment choice.
Interpretation and limitations
Use the current WHO form-specific algorithm, including lumbar puncture and CSF parasite or white-cell assessment when indicated; correct raised-pressure or imaging concerns before LP.
06
Chagas direct detection
Why
Identify high-level parasitaemia in acute, congenital or reactivated T. cruzi infection.
Interpretation and limitations
Use blood microscopy and PCR through a reference laboratory; PCR positivity in chronic infection can be intermittent and does not replace serological diagnosis.
07
Two-assay Chagas serology
Why
Confirm chronic T. cruzi infection when circulating parasites are sparse.
Interpretation and limitations
Require two assays using different antigen principles; a discordant pair needs a third reference method rather than choosing the preferred-looking result.
08
Chagas organ staging
Why
Find clinically silent cardiac or digestive damage that changes surveillance and treatment.
Interpretation and limitations
Obtain 12-lead ECG for every confirmed case, then echocardiography and ambulatory monitoring as indicated; use contrast studies, endoscopy or motility testing for dysphagia or constipation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Malaria and enteric fever

Prolonged fever and splenomegaly overlap with visceral leishmaniasis or sleeping sickness; urgent films and blood cultures identify immediately treatable alternatives.

Haematological malignancy

Lymphoma, leukaemia and myelofibrosis cause fever, weight loss, splenomegaly and cytopenias but require marrow morphology, flow cytometry and imaging.

Chronic tropical ulcer

Mycobacteria, deep fungi, pyoderma gangrenosum and squamous carcinoma can mimic leishmania; tissue should support microbiology and histology.

Other encephalitis

Malaria, viral encephalitis, HIV-related infection and autoimmune disease can cause neurological change and require simultaneous emergency exclusion.

Other cardiomyopathy

Ischaemic, genetic, toxic and viral myocardial disease can resemble chronic Chagas and must be assessed with standard cardiac investigations.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01LEISHMANIAClassify and confirm leishmaniasisFirst stepA compatible skin, mucosal or visceral syndrome follows sandfly exposure in an endemic region.

1Classify cutaneous, mucosal or visceral disease and record lesion number, size, site, duration, mucosal symptoms, immune status and complete geography.
2Send appropriate lesion or tissue material for microscopy, culture and PCR through a tropical laboratory; add serology for visceral but not as a skin-disease rule-out.
3Admit and treat visceral disease promptly while supporting anaemia, neutropenic sepsis, bleeding and malnutrition; avoid traumatic splenic procedures outside expert hands.
4Let species, geography, lesion risk, immune status and organ involvement determine observation, local therapy or systemic antileishmanial treatment.

02HATDiagnose and stage sleeping sicknessTsetse exposure or relevant residence is followed by chancre, fever, nodes, sleep disturbance or neurological change.

1Determine whether geography favours gambiense or rhodesiense disease and urgently contact tropical infection and the Imported Fever Service.
2Demonstrate parasites using targeted chancre, node or concentrated blood microscopy, repeating samples when gambiense disease remains strongly suspected.
3Assess neurological stage using the current WHO algorithm, performing lumbar puncture only after contraindications are addressed and with expert laboratory handling.
4Obtain the WHO-supplied or specialist medicine matched to form, body weight, stage and ability to complete food-dependent oral dosing; monitor treatment in hospital.

03CHAGASConfirm and stage T. cruzi infectionLatin American residence, maternal origin or exposure accompanies acute illness, immunosuppression, cardiac disease or gastrointestinal dysmotility.

1Use PCR or microscopy for acute, congenital or reactivated infection and two independent serological assays for chronic infection.
2Stage confirmed disease with ECG and targeted echocardiography, rhythm monitoring, neurological review and gastrointestinal investigation before counselling on prognosis.
3Discuss benznidazole or nifurtimox with a Chagas-experienced service, weighing age, phase, pregnancy plans, organ function, adverse effects and expected benefit.
4Screen women before pregnancy when possible and test infants born to infected mothers through the specialist congenital pathway; do not treat during pregnancy.

04THERAPYDeliver toxic specialist medicines safelyReference testing confirms an infection for which antiparasitic treatment is indicated.

1Confirm product, weight, regimen, route and access plan with tropical pharmacy because formulations and programmes are not interchangeable.
2Record baseline FBC, renal and liver profiles, electrolytes, ECG and pregnancy status according to the chosen drug and disease phenotype.
3Monitor infusion reactions, nephrotoxicity, electrolyte loss, marrow suppression, neuropathy, rash or gastrointestinal intolerance using drug-specific thresholds.
4Define parasitological, clinical and organ follow-up before discharge because relapse, treatment failure and chronic damage are not captured by symptom resolution alone.

05PREVENTReduce vector and congenital transmissionA person will travel to an endemic setting or belongs to a population at risk of silent Chagas infection.

1Prevent sandfly bites from dusk to dawn with repellent, fine-mesh screens, clothing and insecticide-treated nets, especially when sleeping close to ground level.
2Reduce tsetse exposure with neutral-coloured thick clothing and vehicle inspection; repellents alone are less dependable against tsetse flies.
3Avoid poorly constructed triatomine-infested accommodation and potentially contaminated unpasteurised juices or foods in Chagas-endemic areas.
4Use risk-based Chagas screening before pregnancy, blood or organ donation and immunosuppression, connecting positive patients with lifelong organ surveillance.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Licensed UK treatment for visceral leishmaniasis in immunocompetent adults and children, and a core option in many specialist regimens.

Liposomal amphotericin B for visceral leishmaniasis

Use a specialist intravenous course to a total 21 to 30 mg/kg over 10 to 21 days, with exact daily or intermittent schedule selected for species, geography, immunity and product.

Liposomal and deoxycholate products are not interchangeable; monitor every infusion for anaphylaxis and check renal function, potassium, magnesium, FBC and liver tests throughout.

WHO-recommended oral option for selected gambiense and rhodesiense disease when form, neurological severity, weight and reliable food-supported adherence meet criteria.

Fexinidazole for human African trypanosomiasis

For an eligible patient weighing at least 35 kg, WHO dosing is 1,800 mg orally once daily on days 1 to 4, then 1,200 mg once daily on days 5 to 10 with a substantial meal.

Use only through a tropical centre and WHO access pathway; vomiting, poor food intake, severe CNS disease, pregnancy, hepatic impairment and interacting medicines may require an alternative.

Provides effective treatment when fexinidazole eligibility, absorption or disease-stage criteria are not satisfied.

Alternative African trypanosomiasis therapy

Use the exact WHO form-, stage- and weight-specific protocol supplied by the tropical centre, such as pentamidine, suramin or nifurtimox-eflornithine combination therapy when indicated.

These medicines have major renal, neurological, marrow, pancreatic, cardiovascular or infusion toxicities and require inpatient specialist administration, monitoring and international supply coordination.

Antiparasitic treatment for acute, congenital, reactivated and selected chronic T. cruzi infection after individual benefit-harm assessment.

Benznidazole or nifurtimox for Chagas disease

Use a specialist weight-based oral protocol, usually lasting 60 days for benznidazole or 60 to 90 days for nifurtimox, with product access and divided dosing confirmed before initiation.

Do not use during pregnancy; review renal, hepatic, neurological and psychiatric disease, monitor FBC and liver tests, and stop urgently for severe rash, neuropathy or marrow toxicity.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Kala-azar death

Untreated visceral leishmaniasis leads to profound wasting, bleeding, severe anaemia and overwhelming bacterial infection, with very high mortality.

Mucosal destruction

New World leishmania can erode nasal, oral and laryngeal structures, causing disfigurement, secondary infection and airway compromise.

Sleeping sickness coma

Progressive meningoencephalitis causes psychiatric disturbance, endocrine dysfunction, seizures, aspiration, immobility, coma and death without effective treatment.

Chagas cardiomyopathy

Conduction block, ventricular arrhythmia, apical aneurysm, intracardiac thrombus and pump failure cause syncope, embolic stroke and sudden death.

Chagas megasyndromes

Enteric denervation produces megaoesophagus with aspiration and weight loss or megacolon with severe constipation, volvulus and perforation.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

For visceral leishmaniasis, follow fever, spleen size, weight and blood counts; assess relapse clinically and parasitologically when immune suppression or recurrent features raise concern.
Photograph and measure cutaneous lesions consistently, then review epithelialisation and signs of mucosal spread for the species-appropriate period.
During liposomal amphotericin, check renal function, potassium and magnesium before repeated doses and monitor each infusion for hypersensitivity.
After African trypanosomiasis therapy, complete WHO-defined parasitological and neurological follow-up because relapse can precede obvious symptoms.
For chronic Chagas, arrange lifelong cardiac review with ECG frequency matched to stage; investigate palpitations, syncope, embolic symptoms, dysphagia or constipation promptly.
During benznidazole or nifurtimox, review rash, peripheral sensation, weight, gastrointestinal tolerance, mood, FBC and liver tests at specialist-defined intervals.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Geography predicts treatment

Identical-looking leishmania ulcers may have different mucosal risk and drug susceptibility, making species complex and acquisition country clinically decisive.

Splenic aspiration is not routine

Its sensitivity for visceral leishmania is high, but haemorrhage risk means an expert may choose safer marrow or other tissue sampling.

Sleep disturbance is late biology

The name sleeping sickness reflects brain invasion; earlier haemolymphatic disease can present only with fever, chancre, pruritus or nodes.

Chagas needs two antibodies

No single chronic serological assay is sufficiently definitive across parasite strains, so concordant tests using different antigens are required.

Parasite cure is not organ cure

Antiparasitic treatment does not reverse established Chagas conduction disease, megaoesophagus or leishmania-related tissue destruction, which need parallel care.

Scope boundary

Recognition and initial specialist pathways are presented here; definitive rare-drug procurement and dosing remain tied to species, stage and national reference services.

11Common pitfallsFrequent interpretation and management errors.

01
Do not label every tropical ulcer as cutaneous leishmaniasis; obtain lesion-edge material and exclude bacterial, fungal, mycobacterial and malignant causes.
02
Do not use negative leishmania serology to exclude cutaneous disease or visceral infection in a substantially immunosuppressed patient.
03
Do not begin a generic leishmania regimen before establishing geography, clinical form and immune status; inappropriate local therapy can miss mucosal risk.
04
Do not treat African trypanosomiasis without defining parasite form and CNS stage through a specialist pathway, because medicines and toxicity differ.
05
Do not diagnose chronic Chagas from one screening antibody result; require a second method and resolve discordance through a reference laboratory.
06
Do not give benznidazole or nifurtimox during pregnancy, and do not omit congenital testing for an infant born to an infected mother.
07
Do not assume that successful parasite treatment removes the need for Chagas cardiac surveillance or leishmania relapse monitoring.