Leishmaniasis, trypanosomiasis and Chagas disease

• Leishmaniasis, human African trypanosomiasis (HAT, also called sleeping sickness) and Chagas disease are three vector-borne protozoal diseases of the tropics and subtropics. All three begin as often mild or unnoticed illness, and all three can become life-threatening or permanently disabling if the diagnosis is missed.
• Leishmaniasis comes in three main forms. Visceral leishmaniasis (VL), or kala-azar, is the most serious form and is fatal if untreated in over 95% of cases; cutaneous leishmaniasis is the most common and leaves scars; mucocutaneous leishmaniasis destroys the mucous membranes of the nose, mouth and throat. ^[1]
• Sleeping sickness is caused by Trypanosoma brucei and occurs in two stages: a mild, febrile, haemolymphatic stage 1, followed, if the parasite crosses the blood-brain barrier, by a meningoencephalitic stage 2 with neurological and sleep-wake disturbance that is fatal without treatment. ^[3]
• Chagas disease is caused by Trypanosoma cruzi. In the acute phase it is often mild or unnoticed; in the chronic phase, one to three decades later, about a third of patients develop cardiac disorders and one in ten develop digestive, neurological or mixed complications. ^[2]
• All three are treatable. The drugs differ by region and form, and every suspected or confirmed case needs a clinician who knows the local species and guidelines. Treatment, screening and prevention are as much a matter of public health as of the bedside. ^[1][2][5]

By the end of this page you should be able to:

1. Classify leishmaniasis, HAT and Chagas disease and describe how each is transmitted, in a few sentences for each.
2. Recognise the typical clinical picture of VL, cutaneous leishmaniasis, HAT stage 1 and 2, and acute and chronic Chagas disease. ^[3]
3. Plan investigations for suspected VL, suspected HAT and suspected chronic Chagas disease, and know which tests confirm the diagnosis. ^[4]
4. State the main drug regimens, doses, routes and durations for VL, CL, HAT and Chagas disease, and name their important toxicities.
5. Explain the staging rule that decides fexinidazole versus nifurtimox-eflornithine in HAT, and the screening strategy for Chagas disease.
6. Outline prevention, low-resource management and the red flags that require urgent referral.

Leishmaniasis is usefully classified by where the parasite ends up. In VL, Leishmania species spread throughout the reticuloendothelial system and the disease is generalised. In CL the parasite is confined to the skin. In MCL (sometimes called mucocutaneous leishmaniasis) the parasite of the Viannia subgenus, common in the Americas, has spread from a cutaneous lesion to mucous membranes. The mucous disease can appear years after the skin lesion if the latter was never, or inadequately, treated. ^[5]

Leishmaniasis is an estimated 700,000 to 1 million new cases every year, most of them cutaneous. About 95% of cutaneous leishmaniasis occurs in the Americas, the Mediterranean basin, the Middle East and Central Asia. ^[1] The WHO estimated that almost 13,000 cases of VL were documented in 2020 in just seven countries, Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan, and an estimated 50,000 to 90,000 cases occur worldwide each year, of which only 25 to 45% are reported. ^[1][5] By contrast, cutaneous disease is estimated at 600,000 to 1 million new patients annually, of whom only around 200,000 are reported. ^[1]

The regional picture explains why the same disease is managed differently in different wards:

• In east Africa, all forms of leishmaniasis occur and VL outbreaks are common.
• In the WHO Eastern Mediterranean Region about 80% of the world's reported cutaneous cases occur.
• In Europe most cases are imported, mainly from Africa and the Americas.
• In South-East Asia VL predominates; the region is the only one with an elimination programme, defined as fewer than one case per 10,000 inhabitants at district level in Nepal and sub-district level in Bangladesh and India. ^[1]

Malnutrition increases the risk that infection progresses to disease, and outbreaks follow displacement. Good housing, sanitation and vector control reduce transmission because sandflies rest close to humans. ^[1]

Sleeping sickness is now rare. Fewer than 1,000 cases have been reported annually since 2018, and the WHO targets elimination, aiming to stop gambiense transmission by 2030 and to keep rhodesiense disease below the public-health-problem threshold by the same date. ^[3] The disease is confined to sub-Saharan Africa and is found wherever humans and tsetse flies share habitat, especially rural farming, fishing, hunting and water-collection settings. ^[3]

Chagas disease is mainly a disease of continental Latin America, where it affects an estimated 8 million people and causes more than 10,000 deaths a year; more than 100 million people live at risk. It is increasingly seen outside the Americas because of human migration, congenital transmission having become the main worldwide route with over 10,000 new cases annually. Twenty-one continental Latin American countries are endemic. Interventions have already verified interruption of domiciliary vector transmission on the whole territory of Chile, Paraguay and Uruguay, and in parts of a further five countries. ^{[2] [4]}

Leishmaniasis has no modifiable host risk factor in the way hypertension has for stroke, but the social epidemiology is strong. Poverty, poor housing with wall crevices into which sandflies can rest, lack of waste management or open sewage, overcrowding, migration into endemic areas, and diets lacking protein-energy, iron, vitamin A and zinc all increase the risk that a sandfly bite will progress to disease. Only a small fraction of people infected ever develop clinical illness. ^[1] In the Americas the transmission cycle is complex: multiple reservoir animals, many sandfly species and several Leishmania species can coexist in the same area. Over 90 sandfly species transmit the parasite, and about 70 animal species, including humans, can be a source of it. ^{[1] [5]}

HAT's epidemiology is anthroponotic for gambiense and zoonotic for rhodesiense, with wild and domestic animals acting as reservoirs in the latter. Activities that take people into bush and riverside vegetation, farming, hunting, fishing, collecting water and firewood, expose adults of both sexes at all ages. ^[3]

Chagas disease risks follow vector contact and food hygiene. Triatomine bugs live in wall and roof cracks of rural and peri-urban housing and in animal shelters; they feed at night and defecate near the bite, and the parasite enters when the faeces are rubbed into mucosa or a skin break. Food or drink contaminated with vector or opossum faeces has caused outbreaks. Cardiac, digestive and neurological complications appear one to three decades after infection. ^[2]

A sandfly injects promastigotes, which are phagocytosed by macrophages and transform into amastigotes. These multiply inside macrophages and disseminate. ^[1][5]

• Visceral disease. Amastigotes flood the reticuloendothelial system. The spleen and liver enlarge, the bone marrow is infiltrated and pancytopenia follows. The characteristic hepatosplenomegaly, fever, weight loss and anaemia of kala-azar are the direct result of this macrophage infection. ^[1][5]
• Cutaneous disease. A local nodule at the bite site ulcerates over weeks and then heals slowly with a scar. Lesions are usually painless. ^[5]
• Mucocutaneous disease. Weeks to years after a skin lesion, Viannia parasites can disseminate to nasal, pharyngeal and laryngeal mucosa, producing destructive and disfiguring ulceration. ^[5]
• Post-kala-azar dermal leishmaniasis (PKDL). A macular, papular or nodular rash on the face, upper arms and trunk, usually appearing 6 months to a year or more after apparently cured kala-azar. People with PKDL can infect sandflies, so the rash matters for transmission. ^[1]
• HIV coinfection. Because Leishmania and HIV both suppress immunity, coinfected people have high parasite loads, severe disease, frequent relapses after treatment and high mortality. Antiretroviral therapy reduces the incidence of disease, delays relapse and improves survival. ^[1]

The parasite is inoculated by a tsetse fly, multiplies in the blood and lymphatic system during stage 1 (the haemolymphatic stage), and later crosses the blood-brain barrier to produce stage 2 (the meningoencephalitic stage). During stage 1 the symptoms are non-specific: swollen lymph nodes, headache, fever, weakness, joint and muscle pain. In stage 2, sleep-wake disturbance, sensory changes, abnormal muscle tone, ataxia, psychiatric symptoms, seizures, coma and death appear. ^[3]

The same parasite avoids the innate trypanolytic factors of human serum, and avoids antibody-mediated destruction through variant surface glycoproteins; when antibodies are raised the parasite switches its coat and survives. This immune evasion is why infection persists and why treatment must clear the parasite rather than rely on the host. ^[3]

T. cruzi multiplies in the blood during the acute phase, produces an acute inflammatory illness in which high numbers of parasites circulate, and then persists intracellularly in tissues, mainly heart and digestive muscle. ^[2]

The cardiac damage of chronic Chagas disease is the result of years of parasite persistence together with immune and autonomic injury to heart muscle, producing arrhythmias, progressive heart failure and sudden death. Digestive disease is the result of damage to ganglia and smooth muscle, producing megaoesophagus or megacolon. Reactivation of latent infection can occur if immunity falls, for example with HIV infection, transplantation or chemotherapy. ^[2]

Gross and microscopic pathology is rarely available at the bedside but it explains the laboratory findings. In VL, bone marrow, spleen, liver and lymph node smears and biopsy specimens show abundant amastigotes of Leishmania within macrophages, and pancytopenia reflects marrow infiltration and hypersplenism. In CL, histology shows a dermal granuloma with amastigotes; well-formed granulomas may have fewer visible parasites. In chronic Chagas disease, myocarditis, cardiac fibrosis, hypertrophy and disruption of the myenteric plexus underlie the clinical cardiology and gut presentations. These pathological observations are consistent with the clinical descriptions in the cited sources above. ^[2][5]

History: a patient from an endemic area, often a child or immunosuppressed adult, presents with weeks of fever, weight loss, abdominal discomfort and fatigue. Examination shows hepatosplenomegaly, sometimes massive splenomegaly, pallor and poor general condition. Laboratory examination reveals anaemia, often pancytopenia. The disease is almost always fatal if untreated. ^[1][5]

History: a chronic, painless skin lesion at the site of a sandfly bite, on an exposed part of the body, often with no systemic symptoms. Examination finds a nodule that evolves into a shallow ulcer with a raised border; lesions can be single or multiple. Self-healing occurs in some forms, but a permanent scar can remain. ^[1][5]

History: nasal congestion, epistaxis, or painful ulceration of the nose, lips or gums months to years after an untreated or poorly treated cutaneous lesion. Examination shows erosions and ulcers around the nares and lips and, in advanced disease, perforation of the nasal septum or involvement of the pharynx and larynx. ^[5]

Stage 1 is indistinguishable clinically from many other febrile illnesses: swollen lymph nodes, headache, fever, weakness, joint and muscle pain. Posterior cervical lymphadenopathy can be striking. Stage 2 brings neurological and psychiatric change, sensory disturbance, ataxia, tremor, altered sleep, seizures, coma and death. Because most 19th and 20th century names for the disease come from this neurological picture, the absence of neurological signs essentially rules out stage 2. The patient may look well for long periods during the gambiense infection. ^[3]

Acute phase, lasting about two months: usually asymptomatic or mildly unwell with fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling and abdominal or chest pain. Characteristic signs are a skin lesion (chagoma) at the bite site or unilateral purplish swelling of the eyelid (Romaña sign). Babies can be born with signs or develop them shortly afterwards. ^[2]

Chronic phase, one to three decades later: about a third of infected people develop cardiac disorders (arrhythmias, progressive heart failure, sudden death), one in ten develop digestive, neurological or mixed disorders such as megaoesophagus or megacolon, and the remainder live with lifelong infection but no clinically obvious disease on routine examination. ^[2]

The differential follows from the clinical picture and from geography. In the table, the clue is the single feature that most usefully separates each condition from the disease above it. The list is clinical and not exhaustive.

| | Condition | Presentation it masquerades as | Feature that separates it | | --- | --- | --- | | Malaria, typhoid, brucellosis | Fever with hepatosplenomegaly | Blood film, serology, and malaria rapid test; kala-azar tests point to VL | | HIV infection and AIDS | Fever, weight loss, immunosuppression | HIV test; co-infection worsens both diseases | | Haematological malignancy | Pancytopenia, splenomegaly | Bone marrow aspiration and biopsy | | Tuberculosis | Lymphadenopathy, weight loss | Microbiology and imaging | | Sporotrichosis, cutaneous TB, tropical ulcer | Chronic skin ulcer | Biopsy and PCR for the species | | Bacterial cellulitis or erysipelas | Acute red, painful skin infection | Painful, warm, well-demarcated erythema; ulcer less typical | | Cardiomyopathy of other cause | Heart failure or arrhythmia in a migrant | Serology plus echocardiogram and ECG | | Achalasia, idiopathic megacolon | Dysphagia or chronic constipation | Serology for T. cruzi; chagasic achalasia differs in mechanism | | Viral or bacterial meningitis | Stage 2 HAT | Epidemiology; CSF trypanosomes and white cell count |

In practice, antibody tests for gambiense HAT are simple, although parasitological confirmation has historically been required because of the complexity of treatment. Serology for VL is helpful but depends on the species and the region. ^[1][3]

The point of investigation is threefold: to confirm the diagnosis, to identify the species or stage, and to choose a drug the person can actually take.

Visceral leishmaniasis. Diagnosis rests on clinical signs combined with parasitological or serological tests such as a rapid diagnostic test. Bone marrow or splenic aspiration, and culture or PCR, confirm the parasite when serology is equivocal. ^[1][5] Routine bloods usually show anaemia and, often, neutropenia and thrombocytopenia; abnormal liver enzymes can occur. ^[5]

Cutaneous and mucocutaneous leishmaniasis. Serology has limited value; diagnosis is confirmed by finding the parasite in the lesion. A punch biopsy, slit-skin smear or aspirate from the lesion border is examined by microscopy, culture and increasingly by PCR, which can identify the species and therefore the risk of mucosal disease and the most appropriate treatment. ^[1][5]

Sleeping sickness. Case-finding relies on screening antibodies (for gambiense, the card agglutination test is the most sensitive screening tool, with simplified lateral flow tests now available) followed by parasitological confirmation, because treatment is prolonged and potentially toxic. Parasites are usually found in lymph node aspirate, blood after concentration by mini-anion exchange chromatography, and, when stage 2 is suspected, CSF. In stage 1 gambiense disease parasite numbers in the blood are frequently very low. A CSF white cell count above 5 cells per microlitre, in a confirmed case, is accepted as evidence of stage 2 disease, and a further distinction between early stage 2 (below 100 white cells per microlitre) and late stage 2 (more than 100 white cells per microlitre) decides whether fexinidazole or nifurtimox-eflornithine combination therapy is used. Nucleic acid tests (PCR, LAMP and newer methods) exist but are not yet standard in the field. ^[3]

Chagas disease. Acute infection may be found by microscopy of blood or by PCR in the first weeks. Chronic infection is diagnosed serologically, ideally with two tests using different techniques and antigens; serology also underlies blood-donor screening. ^[4] In a person with chronic infection, cardiac assessment with a 12-lead ECG is the minimum; Holter monitoring, echocardiography and barium studies of the oesophagus and colon are added if symptoms or ECG abnormalities suggest organ involvement. ^[2][4]

There are no formal numerical diagnostic scores for any of these diseases in ordinary practice. The diagnosis in each case is clinical plus confirmatory parasitology or serology in an appropriate epidemiological setting.

• VL. Clinical illness consistent with VL plus a positive parasitological or serological test in an endemic area. Cure cannot be assumed to be sterile; the parasite can persist and disease can relapse if immunity falls. ^[1]
• HAT staging. Stage 1 when the parasite is confined to blood and lymph with no CSF evidence of CNS disease; stage 2 when parasites or more than 5 white cells per microlitre are found in CSF, with further separation at 100 white cells per microlitre (see flowchart below). ^[3]
• Chagas disease staging. Acute disease is the first two months after infection; latent or indeterminate chronic disease is serological positivity without cardiac, digestive or neurological disease; cardiac, digestive, neurological or mixed chronic disease is defined by organ involvement. ^[2][4]

All three diseases must be treated promptly and completely. Incomplete treatment is worse than no treatment: it cures nothing and selects resistance. ^[1][2][3] Below, drug doses are typical adult doses from the cited sources; always check the local formulary and national programme guidance.

Systemic treatment is always required. The dose schedules below come from a 2024 review and match WHO and PAHO recommendations as discussed there. ^[5]

Oral agents such as the azoles, allopurinol and azithromycin have not shown reliable efficacy. In young children, the intravenous options are used. ^[5]

Non-drug care matters: food, fluids, treatment of intercurrent bacterial infection and blood transfusion if severe. Secondary bacterial infection is a common cause of death in late-presenting kala-azar.

Treatment is chosen by lesion number, size, site, species, immune status and patient preference. If risk of mucosal disease is low and the patient finds scarring acceptable, observation is valid; many lesions heal spontaneously, though permanently.

Local options include thermotherapy or cryotherapy for 1 to 3 sessions, intralesional pentavalent antimonial 1 to 3 millilitres under and around the lesion until the surface pales, repeated every 5 to 7 days for 2 to 5 sessions, and paromomycin-containing cream applied twice daily for 10 days, rested for 10 days and applied twice daily for a further 10 days. Local treatment is painful, needs repeat visits and can scar. ^[5]

Systemic treatment is reserved for complicated cases: multiple or facial lesions, lesions on the ear or eyelid, large or refractory lesions, immunosuppression, species capable of causing mucocutaneous disease and treatment failure. Miltefosine by mouth is the usual first oral agent, and liposomal amphotericin B intravenously is the alternative when systemic treatment is needed. ^[5]

Systemic treatment is always required because the disease can destroy nasal and laryngeal tissue over years. Pentavalent antimonials intravenously or intramuscularly, or liposomal amphotericin B intravenously, are the most used parenteral drugs, with miltefosine by mouth a useful oral option, particularly where hospitalisation is difficult. Reported cure rates with liposomal amphotericin B in mucocutaneous disease are 80 to 90%. Relapse and treatment failure are common and patients should be followed for years. ^[5]

In Leishmania-HIV coinfection, parasite loads are high and relapse is frequent. WHO has specific treatment recommendations for east Africa and South-East Asia for coinfected patients, based on liposomal amphotericin B plus miltefosine combinations, with pentamidine used for secondary prophylaxis in some settings; modern antiretroviral therapy is part of the treatment of the leishmaniasis. ^[1]

Fexinidazole is the first-line oral drug for most people. It comes as 600 mg tablets. Adults and children weighing 35 kg or more take 1,800 mg (three tablets) once daily for 4 days as a loading dose, then 1,200 mg (two tablets) once daily for 6 further days, so 10 days in total. Children aged 6 years or more weighing 20 to 34 kg take 1,200 mg for 4 days and then 600 mg daily for 6 days. Tablets must be taken whole with food and under supervision. It is not used in children under 6 years or below 20 kg, or in people with nitroimidazole hypersensitivity, hepatic impairment, significant cardiac disease, arrhythmia, QT prolongation risk, electrolyte disturbance or a family history of sudden death. Common adverse effects are nausea, vomiting, decreased appetite, headache, insomnia, tremor and dizziness; neuropsychiatric reactions including suicidal ideation can occur, and alcohol should be avoided. ^{[3] [5]}

Pentamidine 4 mg per kilogram daily for 7 days by deep intramuscular injection is the alternative for stage 1 gambiense disease in young or small patients, and for stage 1 rhodesiense disease when other drugs are not available. Patients should take a sugar-containing snack or drink before injection and lie down for at least an hour afterwards; hypotension occurs in up to three-quarters of patients given intravenous pentamidine and still in a minority given intramuscular injection. Pentamidine isethionate is supplied as 300 mg vials reconstituted with 10 millilitres of sterile water. ^[3]

Suramin is given as a test dose of 4 to 5 mg per kilogram on day 1, followed by five further intravenous injections of 20 mg per kilogram, up to a maximum of 1 gram, given weekly for 5 weeks. It requires close supervision and should not be used in severe renal disease. Hypersensitivity reactions occur in roughly 1 in 5,000 treated patients and can cause urticaria and circulatory collapse. ^[3]

Melarsoprol is reserved for stage 2 rhodesiense disease in patients for whom fexinidazole cannot be used, most often children under 6 years or under 20 kg. It is given as 2.2 mg per kilogram once daily by slow intravenous injection for 10 days, with prednisolone 1 mg per kilogram daily up to 50 mg for 9 days, tapering over days 10 to 12. Reactive encephalopathy occurs in 5 to 10% of treated patients and carries a mortality up to 50%; melarsoprol injection is painful and must be given by experienced staff. ^[3]

Nifurtimox-eflornithine combination therapy (NECT) is given for late stage 2 gambiense disease, that is CSF findings above 100 white cells per microlitre. Nifurtimox is given at 15 mg per kilogram per day in three oral doses every 8 hours for 10 days; eflornithine 400 mg per kilogram per day is given intravenously in two 2-hour infusions for 7 days. It should be used in children under 6 or below 20 kg with stage 2 gambiense disease, in whom more than 5 white cells per microlitre in CSF is enough to classify disease as stage 2 and in whom fexinidazole is not approved. Cure rates are 95 to 98% with few side effects. Eflornithine alone, 400 mg per kilogram per day intravenously in four 6-hourly infusions for 14 days, remains an alternative when NECT cannot be given. ^[3]

Adverse effects shared by these drugs include gastrointestinal upset, marrow suppression, neurological symptoms and, for melarsoprol and suramin, life-threatening reactions. Access is through national sleeping sickness programmes, which receive the drugs free of charge from WHO. ^[3]

Antiparasitic treatment uses either benznidazole or nifurtimox, and the two are regarded as equally recommended by WHO; most experienced clinicians still choose benznidazole first line. ^[4]

• Benznidazole: 5 mg per kilogram per day in two or three divided doses, with a maximum of 300 mg per day, for 60 days. ^[4]
• Nifurtimox: 10 mg per kilogram per day in three divided doses, for 60 days. ^[4]

Both drugs kill the parasite and are essentially curative when given in the acute phase, including after congenital infection. Efficacy falls with increasing duration of infection, and adverse reactions become more frequent and more severe with age. Treatment is indicated also for reactivated infection, for early chronic disease, and for girls and women of childbearing age before or after pregnancy, in order to prevent congenital transmission. Adults with infection, especially those without symptoms, should be offered treatment because it can prevent or slow the progression of disease. ^[2]

When a patient is asymptomatic, the potential benefit must be weighed against the 60 day course and adverse reactions that occur in up to 40% of adults. ^[2]

Contraindications are pregnancy, kidney failure and liver failure for both drugs, and a history of neurological or psychiatric disorder for nifurtimox. ^[2] WHO donation programmes provide free nifurtimox for all ages and free benznidazole to those under 19 years of age. ^[2]

Adverse effects are frequent. In a large European observational series, 90% of adults had at least one adverse event during treatment and only about 60% completed 60 days; nifurtimox produced more events (about 6) than benznidazole (about 3) per patient, and the drug had to be interrupted or changed more often. Mucocutaneous reactions were commoner with benznidazole, digestive and neuro-psychiatric events (headache, mood change, insomnia, vertigo, memory difficulty) with nifurtimox. ^[4]

Non-antiparasitic care in chronic disease consists of long-term follow-up and organ-specific treatment for cardiac, digestive and neurological manifestations: regular ECG, antiarrhythmic and heart-failure therapy, and management of oesophageal or colonic dysfunction, as symptoms dictate. ^[2]

• Visceral leishmaniasis: untreated disease kills in over 95% of cases; malnutrition, intercurrent infection and delayed treatment drive mortality; relapse with immunosuppression. ^[1]
• Post-kala-azar dermal leishmaniasis: cosmetic and stigmatising disease and a source of transmission. ^[1]
• Mucocutaneous leishmaniasis: disfigurement and disability from tissue destruction. ^[5]
• Sleeping sickness: stage 2 neurological disease, coma and death; late drug toxicity, particularly with melarsoprol. ^[3]
• Chagas disease: arrhythmias, heart failure, sudden cardiac death; megaoesophagus and megacolon; reactivation with immunosuppression. ^[2]
• Drugs: organ toxicity, anaphylaxis, encephalopathy. ^[2][3][4][5]

With prompt appropriate treatment, VL has a high cure rate and most patients recover, although cure does not eradicate every parasite. ^[1][5] Cutaneous leishmaniasis usually heals, but scarring and disfigurement can be permanent and secondary bacterial infection worsens outcomes. ^[5] Mucocutaneous disease commonly relapses and needs long follow-up. ^[5]

Sleeping sickness is almost invariably fatal if untreated, but modern regimens have transformed the prognosis: NECT cures 95 to 98% of late stage 2 gambiense disease and fexinidazole gives a cure rate comparable enough that a single oral drug now covers most cases of both forms and stages. ^[3]

Chagas disease is curable in the acute phase and infection is curable in the early chronic phase, but drug efficacy falls as infection duration increases. Long-term outcome is dominated by cardiac disease, which develops in a minority but carries serious morbidity and mortality. ^[2]

Leishmaniasis: early diagnosis and prompt treatment reduce transmission and death; vector control by insecticide spraying, treated nets and environmental management; screening and control of reservoirs where locally important; active surveillance; and skin-disease and NTD integration. In South-East Asia the elimination target remains fewer than one case per 10,000 inhabitants at district or sub-district level. ^[1]

Sleeping sickness: population screening with antibody tests (and clinical examination), treatment of confirmed cases, vector control and reduction of contact with tsetse, supported by national sleeping sickness programmes. ^[3]

Chagas disease: screening is the cornerstone of prevention because curative and partially curative treatment is most useful early. WHO key strategies are:

• screen blood donors;
• test organ, tissue and cell donors and recipients;
• screen newborns and other children of infected mothers;
• test girls and women of reproductive age and treat before or after pregnancy to prevent congenital transmission;
• improve rural housing and control triatomine vectors;
• educate health professionals. ^[2]

WHO's five targets for elimination as a public health problem are interruption of domiciliary vector transmission, transfusional transmission, organ transplantation transmission and congenital transmission, plus 75% antiparasitic treatment coverage of the eligible population. ^[2]

• Children. Dosing in children must be by weight. ^[5] Fexinidazole is only licensed from 6 years and 20 kilograms upwards; lighter children with sleeping sickness need pentamidine or melarsoprol. ^[3] Congenital Chagas should be treated. ^[2]
• Pregnancy. Antiparasitic treatment for Chagas disease is contraindicated in pregnancy, so girls and women of childbearing age are treated before or after pregnancy. ^[2] For leishmaniasis, management in pregnancy must be by experienced clinicians and each decision should be taken on its own merits, including in the case of Chagas. ^[2]
• Older adults. Adverse reactions to Chagas therapy become more frequent and severe with age. One European series withheld treatment in older patients unless individual circumstances justified it. ^{[4] [2]}
• HIV and the immunosuppressed. Coinfection worsens outcome in all three diseases; cutaneous lesions can be atypical and dissemination more likely. Antiretroviral therapy is part of VL care. ^[1]

• Visceral leishmaniasis is diagnosable with fever, splenomegaly and a cheap rapid antibody test, and treatable with sodium stibogluconate or amphotericin B deoxycholate at far lower cost than liposomal amphotericin, although with more toxicity. Where hospital capacity is minimal, structure the pathway so diagnosis and treatment happen at the same visit. ^[5]
• Sleeping sickness, active population screening and treatment campaigns historically reduced incidence from catastrophic levels, and WHO-integrated packages let programmes treat whole districts. ^[3]
• Chagas disease, the single most cost-effective measure is early treatment of young people and women of childbearing age, plus home improvement and vector control. Housing improvements, spraying and community education are inexpensive and durable. Even entry-level blood screening changes transmission. ^[2]
• Referral: any patient with suspected neurological stage HAT, severe VL, mucosal leishmaniasis, reactivation of Chagas, or adverse drug effects beyond what local care can manage should be referred quickly, because delays raise mortality. ^[2][3][5]

• Malaria.
• HIV infection and antiretroviral therapy.
• Tuberculosis.
• Anaemia and pancytopenia.
• Cardiomyopathy and heart failure.
• Gastro-oesophageal and colonic motility disorders.
• Tropical medicine and infection control in low-resource settings.