Overview
Vector-borne parasitic disease transmitted by sandflies. Three main forms: cutaneous (skin sores), mucocutaneous (destroys mucous membranes), and visceral (kala-azar — affects internal organs, fatal if untreated).
Symptoms
Symptoms | Frequency | Severity | Onset |
|---|---|---|---|
| Fatigue | 85% | Mild | Early |
| Fever | 95% | Moderate | Early |
| Nasal congestion | 90% | Moderate | Early |
| Loss of appetite | 70% | Mild | Early |
| Malaise | 80% | Mild | Early |
| Swollen lymph nodes | 30% | Mild | Early |
| Edema | 20% | Mild | Early |
| Skin ulcer | 85% | Moderate | Peak |
| Splenomegaly | 95% | Severe | Peak |
| Hepatomegaly | 80% | Moderate | Peak |
| Weight loss | 90% | Moderate | Peak |
| Dysphagia | 30% | Moderate | Peak |
| Hemorrhage | 60% | Moderate | Peak |
| Night sweats | 40% | Mild | Peak |
| Cough | 15% | Mild | Peak |
| Diarrhea | 20% | Mild | Peak |
| Itching | 15% | Mild | Peak |
| Petechiae | 25% | Moderate | Peak |
| Hypotension | 5% | Moderate | Late |
| Jaundice | 10% | Moderate | Late |
Transmission
Overview
Leishmaniasis is a vector-borne parasitic disease caused by protozoa of the genus Leishmania, transmitted through the bites of infected female phlebotomine sandflies (genera Phlebotomus in the Old World and Lutzomyia in the New World). Over 20 Leishmania species are pathogenic to humans.
The disease manifests in three principal clinical forms: visceral leishmaniasis (VL, also known as kala-azar), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). Visceral leishmaniasis is the most severe form and is almost always fatal if left untreated. Cutaneous leishmaniasis is the most common form globally, while mucocutaneous disease, primarily caused by L. braziliensis, leads to progressive destruction of the nasal and oropharyngeal mucosa.
An estimated 700,000 to 1 million new cases occur annually across 98 endemic countries, with 26,000 to 65,000 deaths per year. The disease disproportionately affects the poorest populations, and malnutrition, displacement, poor housing, and immunosuppression (particularly HIV co-infection) are major risk factors. Leishmaniasis is classified by the WHO as one of the neglected tropical diseases (NTDs) prioritized for control and elimination.
Overview
Leishmaniasis encompasses a spectrum of diseases caused by obligate intracellular protozoan parasites of the genus Leishmania. The parasites are transmitted to humans by the bite of infected female sandflies, which are small (2–3 mm) nocturnal insects that breed in organic-rich soil, rubble, and animal burrows.
Key facts:
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Causative agents: Over 20 Leishmania species, including L. donovani, L. infantum, L. major, L. tropica, L. braziliensis, and L. mexicana
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Vector: Phlebotomine sandflies (~70 of 800+ species are proven vectors)
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Reservoir hosts: Humans (anthroponotic VL caused by L. donovani), dogs (zoonotic VL caused by L. infantum), and various rodents (zoonotic CL)
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Incubation period: Visceral: 2–6 months (range: 10 days to years); Cutaneous: 2–8 weeks (range: days to months)
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Global burden: 700,000–1 million new cases/year; 12 million people currently affected; 350 million at risk
The three clinical forms have distinct geographic distributions, causative species, and prognoses. Visceral leishmaniasis accounts for roughly 50,000–90,000 new cases annually, with over 90% occurring in Brazil, Ethiopia, India, Kenya, Somalia, South Sudan, and Sudan. Cutaneous leishmaniasis accounts for the largest burden, with hotspots in Afghanistan, Algeria, Brazil, Colombia, Iran, Iraq, Pakistan, Peru, Saudi Arabia, Syria, and Tunisia.
Emergency Signs
Seek immediate medical attention if you develop any of the following signs or symptoms, particularly if you have traveled to or reside in a leishmaniasis-endemic area:
Visceral leishmaniasis emergencies:
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High fever persisting for more than 2 weeks with no identified cause
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Rapidly enlarging abdomen (hepatosplenomegaly) with abdominal discomfort
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Severe anemia — extreme pallor, tachycardia, dyspnea on exertion
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Bleeding — epistaxis, gingival bleeding, petechiae, or ecchymoses indicating thrombocytopenia
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Jaundice or signs of hepatic dysfunction
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Secondary bacterial infections — pneumonia, septicemia, or enteritis (leading cause of death in VL)
Cutaneous/mucocutaneous emergencies:
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Non-healing skin ulcer persisting beyond 2–3 months, especially after travel to endemic areas
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Nasal obstruction with bloody discharge following past cutaneous leishmaniasis
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Progressive facial swelling or destruction of nasal/oral tissue
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Difficulty breathing or swallowing suggesting laryngeal or pharyngeal involvement
Important: Visceral leishmaniasis has a case fatality rate exceeding 95% if left untreated. Early diagnosis and treatment are critical. Individuals with HIV co-infection have significantly worse outcomes and should be treated as a medical emergency.
Detailed Symptoms
Most common signs and symptoms
The clinical presentation of leishmaniasis varies considerably depending on the infecting Leishmania species and the host immune response.
Visceral leishmaniasis (kala-azar):
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Insidious onset with prolonged irregular fever (often double-spiking daily)
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Progressive hepatosplenomegaly — the spleen can become massively enlarged
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Weight loss and progressive cachexia
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Pancytopenia (anemia, leukopenia, thrombocytopenia) due to bone marrow infiltration
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Hypergammaglobulinemia and hypoalbuminemia
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Darkening of the skin (the Hindi term "kala-azar" means "black fever")
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Post-kala-azar dermal leishmaniasis (PKDL) may develop months to years after apparent cure, presenting as macular, papular, or nodular rash
Cutaneous leishmaniasis:
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Begins as a small papule at the sandfly bite site, progressing over weeks to a nodule
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Central necrosis develops, forming a characteristic painless ulcer with raised, indurated borders and a granulating base
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Lesions are typically on exposed skin — face, arms, legs
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Most CL lesions self-heal in 6–12 months but leave disfiguring scars
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Diffuse cutaneous leishmaniasis (DCL) produces widespread non-ulcerating nodules resembling lepromatous leprosy
Mucocutaneous leishmaniasis:
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Occurs months to years after an initial cutaneous lesion (primarily L. braziliensis in Latin America)
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Nasal mucosal involvement begins with stuffiness, epistaxis, and crusting
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Progressive destruction of the nasal septum, palate, lips, pharynx, and larynx
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Can lead to severe facial disfigurement ("espundia"), difficulty swallowing, and aspiration pneumonia
Knowing the symptoms is the first step to a quick response.
Course of Disease
The natural history of leishmaniasis is determined by the infecting species and host immune response, and follows distinct trajectories for each clinical form.
Visceral leishmaniasis:
- Incubation period: Typically 2–6 months (range: 10 days to several years; reactivation may occur decades after initial infection in immunosuppressed individuals)
- Onset: Insidious, with low-grade fever, malaise, and gradual weight loss
- Progressive phase: Over weeks to months — fever becomes persistent and irregular (often double quotidian), the spleen and liver enlarge progressively, and pancytopenia worsens
- Advanced disease: Severe cachexia, massive splenomegaly, edema, hemorrhagic manifestations, and darkened skin
- Terminal phase (untreated): Death from secondary bacterial infections (pneumonia, tuberculosis, dysentery), severe anemia, or hemorrhage — typically within 1–2 years of symptom onset
- Post-treatment: PKDL may develop 6 months to several years after apparent cure
Cutaneous leishmaniasis:
- Incubation: 2–8 weeks (range: days to months)
- Initial lesion: Small erythematous papule at the bite site
- Progression: Papule enlarges to a nodule, then develops central necrosis forming an ulcer over 2–6 weeks
- Chronic phase: Ulcer persists for months with a characteristic "volcano-like" morphology
- Resolution: Spontaneous healing in 6–12 months (Old World CL) to 6–18 months (New World CL), leaving an atrophic depressed scar
Mucocutaneous leishmaniasis:
- Latency: Months to years (even decades) after the initial cutaneous lesion has healed
- Mucosal onset: Nasal congestion, crusting, and epistaxis
- Progressive destruction: Over months to years, erosion of nasal septum, palate, uvula, and pharynx
- Complications: Facial collapse, aspiration pneumonia, and secondary infections
Diagnosis
How this disease is identified
Definitive diagnosis of leishmaniasis requires demonstration of the parasite or its DNA, combined with clinical and epidemiological assessment.
Visceral leishmaniasis:
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rK39 rapid diagnostic test (RDT): Immunochromatographic strip detecting antibodies to the rK39 antigen; sensitivity >95% and specificity >90% in South Asia; lower sensitivity in East Africa (~85%). Recommended as first-line diagnostic in endemic areas
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Splenic aspiration: Highest sensitivity (~95%) but carries a risk of hemorrhage; requires trained personnel and monitoring facilities
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Bone marrow aspirate: Sensitivity of 60–85%; safer than splenic aspirate and widely used
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PCR: Highly sensitive and specific; can be performed on blood, bone marrow, or tissue; increasingly available but costly
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Direct agglutination test (DAT): High sensitivity and specificity; requires laboratory infrastructure; useful in East Africa where rK39 sensitivity is lower
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Serology limitations: Antibodies persist after cure, so serology cannot distinguish active from past infection
Cutaneous leishmaniasis:
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Skin biopsy or scraping from the ulcer margin with Giemsa staining for amastigotes — sensitivity 50–70%
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PCR from biopsy/scraping — sensitivity >90%, also allows species identification
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Culture in NNN (Novy-MacNeal-Nicolle) medium — gold standard for species identification but slow (1–4 weeks)
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Leishmanin skin test (Montenegro test): Indicates prior exposure; positive in CL, negative in active VL
Mucocutaneous leishmaniasis:
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Biopsy of affected mucosa — parasites are often scarce, reducing microscopy sensitivity to 20–30%
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PCR is the preferred modality for MCL diagnosis (sensitivity >90%)
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Serology is usually positive and supports the diagnosis
Treatment
Available treatment methods
Treatment of leishmaniasis depends on the clinical form, infecting species, geographic region, and patient factors (age, pregnancy, HIV status).
Visceral leishmaniasis:
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Liposomal amphotericin B (AmBisome) — WHO-recommended first-line for VL in most settings. Regimen: 3–5 mg/kg total dose over 3–6 days in South Asia; 18–21 mg/kg total in East Africa/Mediterranean
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Miltefosine — the first oral drug for VL; 2.5 mg/kg/day for 28 days. Effective in South Asia (cure rate ~94%); teratogenic, contraindicated in pregnancy
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Sodium stibogluconate or meglumine antimoniate (pentavalent antimonials) — 20 mg Sb⁵⁺/kg/day for 28–30 days; cardiotoxicity risk; declining use due to resistance in Bihar, India
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Combination therapy: Single-dose liposomal amphotericin B + miltefosine (or paromomycin) — WHO-recommended in South Asia for shorter, safer treatment
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Paromomycin — 15 mg/kg/day IM for 21 days; used as monotherapy in East Africa or in combination
Cutaneous leishmaniasis:
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Many CL lesions self-heal without treatment, but treatment is recommended for large, multiple, or cosmetically sensitive lesions
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Intralesional sodium stibogluconate — first-line for localized Old World CL
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Thermotherapy or cryotherapy — non-pharmacological alternatives with ~70% cure rates
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Oral miltefosine — for New World CL (especially L. braziliensis, L. guyanensis)
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Systemic pentavalent antimonials — for multiple lesions or mucocutaneous risk
Mucocutaneous leishmaniasis:
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Always requires systemic therapy due to risk of progressive tissue destruction
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Liposomal amphotericin B or systemic pentavalent antimonials for 28 days
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Reconstructive surgery may be needed for severe facial deformity
Most cases are effectively treated with early diagnosis.
Prevention Details
How to protect yourself
There is currently no vaccine available for human leishmaniasis, although several candidates are in clinical development. Prevention relies on reducing human-sandfly contact and controlling reservoir hosts.
Personal protective measures for travelers:
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Insecticide-treated bed nets with fine mesh (sandflies are small enough to pass through standard mosquito nets unless mesh size is <0.6 mm or nets are permethrin-impregnated)
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DEET-based insect repellents (20–30% concentration) applied to exposed skin during dusk and nighttime hours when sandflies are most active
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Permethrin-treated clothing — particularly effective as sandflies bite through thin fabric
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Avoiding outdoor activities at night in endemic areas, especially near rubble, old walls, animal shelters, and forests
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Sleeping in air-conditioned or screened rooms — sandflies are weak fliers and cannot navigate well in airflow
Public health interventions:
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Indoor residual spraying (IRS) with pyrethroids — effective in reducing sandfly density, particularly for VL control in South Asia
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Reservoir control: Culling or insecticide-collaring of infected domestic dogs (zoonotic VL); rodent control for zoonotic CL
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Environmental management: Reducing sandfly breeding sites by clearing rubble, waste, and organic matter near homes
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Active case detection and treatment — reducing the human reservoir (especially VL and PKDL cases) interrupts anthroponotic transmission
Note: Travelers to endemic areas should be aware that sandfly bites are often painless and may go unnoticed. Any non-healing skin lesion developing weeks to months after travel should prompt evaluation for cutaneous leishmaniasis.
Preparation is the best protection.
Travel Advice
Risk assessment for travelers: Leishmaniasis risk is generally low for most short-term tourists staying in urban hotels, but can be significant for adventure travelers, researchers, military personnel, and long-term residents in endemic rural areas. The risk is highest during the rainy season when sandfly populations peak.
High-risk destinations:
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Visceral leishmaniasis: Indian subcontinent (Bihar state), East Africa (South Sudan, Sudan, Ethiopia, Kenya, Somalia), Brazil (northeast), Mediterranean basin
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Cutaneous leishmaniasis: Afghanistan, Iran, Iraq, Syria, Saudi Arabia, Algeria, Tunisia, Peru, Colombia, Brazil, Central Asia
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Mucocutaneous leishmaniasis: Bolivia, Brazil, Peru, and other Amazon basin countries
Pre-travel advice:
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No chemoprophylaxis or vaccine is available
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Pack fine-mesh insecticide-treated bed nets and DEET-based repellent
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Discuss risk with a travel medicine specialist if visiting highly endemic rural areas for extended periods
During travel:
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Avoid outdoor activities between dusk and dawn in endemic areas
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Sleep under permethrin-treated nets or in screened/air-conditioned rooms
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Minimize time near animal shelters, old stone walls, and forest edges
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Wear long sleeves and treated clothing in the evenings
Post-travel:
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Any non-healing skin ulcer appearing weeks to months after travel to an endemic area should be evaluated for CL — inform your physician of your travel history
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Unexplained prolonged fever with splenomegaly after travel to VL-endemic areas warrants urgent investigation
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Incubation can be prolonged (months to years), so maintain awareness even long after return
How common is it?
Statistics and geographic data
Leishmaniasis is endemic in 98 countries across tropical and subtropical regions, with an estimated 12 million people currently infected and 350 million at risk.
Global burden estimates (WHO, 2024):
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Visceral leishmaniasis: 50,000–90,000 new cases annually; ~95% of cases reported from Brazil, Ethiopia, India, Kenya, Somalia, South Sudan, and Sudan
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Cutaneous leishmaniasis: 600,000–1,000,000 new cases annually; ~85% of cases from Afghanistan, Algeria, Brazil, Colombia, Iran, Iraq, Pakistan, Peru, Saudi Arabia, Syria, and Tunisia
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Mucocutaneous leishmaniasis: ~5,000 cases annually, primarily in Bolivia, Brazil, Ethiopia, and Peru
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Deaths: 26,000–65,000 per year, predominantly from VL
Regional epidemiology:
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South Asia: India (Bihar), Bangladesh, and Nepal historically bore the heaviest VL burden; the Kala-Azar Elimination Programme has reduced cases by >95% since 2005
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East Africa: South Sudan and Sudan remain major hotspots; conflict and displacement drive outbreaks
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Americas: Brazil reports >90% of New World VL and significant CL burden; CL extends from Texas to northern Argentina
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Mediterranean: L. infantum causes sporadic zoonotic VL (dog reservoir); southern Europe, North Africa, and the Middle East
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Central Asia: CL caused by L. major (zoonotic) and L. tropica (anthroponotic); conflict zones in Syria, Iraq, and Afghanistan have experienced massive CL outbreaks
Trends:
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Climate change is expanding sandfly habitats to higher altitudes and latitudes (cases now reported in northern Italy, southern Germany)
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Urbanization and deforestation are creating new foci
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HIV-VL co-infection is an emerging problem in East Africa and southern Europe
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The WHO NTD Roadmap 2021–2030 targets elimination of VL as a public health problem (incidence <1/10,000 at district level)
Risk Factors
Who is most at risk
Multiple host, environmental, and socioeconomic factors influence the risk of acquiring leishmaniasis and the severity of disease.
Environmental and behavioral risk factors:
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Living in or traveling to endemic areas — 98 countries have reported cases; risk is highest in rural and peri-urban settings
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Nighttime outdoor exposure — sandflies are crepuscular and nocturnal feeders
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Proximity to animal reservoirs — domestic dogs (VL), rodent burrows (CL)
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Poor housing conditions — mud walls, earth floors, and lack of window screens facilitate sandfly entry
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Sleeping outdoors or on the ground without bed nets
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Occupational exposure — agricultural workers, soldiers, forest workers, construction laborers
Host risk factors for severe disease:
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Malnutrition — strongly associated with progression from subclinical infection to clinical VL; odds ratio 2–9× depending on severity
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HIV co-infection — greatly increases risk of VL (10–100× higher in HIV-positive individuals in endemic areas); impairs treatment response and promotes relapse
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Immunosuppression — organ transplant recipients, patients on TNF-alpha inhibitors, and other immunocompromised states
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Age: Children under 5 years are at highest risk for VL in endemic areas
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Genetic factors: Certain HLA alleles and polymorphisms in cytokine genes influence susceptibility
Socioeconomic risk factors:
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Poverty: Leishmaniasis is strongly associated with the poorest communities — poor nutrition, inadequate housing, and limited healthcare access
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Displacement and migration — refugee camps in endemic areas experience outbreaks; non-immune populations entering endemic zones are at high risk
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Deforestation and urbanization — bring humans into contact with sylvatic transmission cycles
Complications Details
Potential complications
Leishmaniasis can lead to serious and potentially life-threatening complications across all clinical forms.
Visceral leishmaniasis complications:
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Secondary bacterial infections — the most common cause of death in VL patients; pneumonia, tuberculosis, and enteritis frequently arise due to profound immunosuppression and neutropenia
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Hemorrhage — severe thrombocytopenia leads to epistaxis, gastrointestinal bleeding, and petechiae; splenic rupture is a rare but fatal complication
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Severe anemia — hemoglobin levels can fall below 5 g/dL, requiring transfusion; anemia results from bone marrow suppression, hypersplenism, and hemolysis
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Post-kala-azar dermal leishmaniasis (PKDL) — macular, papular, or nodular skin lesions developing 6 months to years after VL treatment; more common in East Africa (up to 50%) than South Asia (5–10%); serves as a reservoir for ongoing transmission
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Drug-related toxicity — pentavalent antimonials cause cardiotoxicity (QT prolongation, fatal arrhythmias), pancreatitis, and hepatotoxicity; amphotericin B can cause nephrotoxicity and infusion reactions
Cutaneous leishmaniasis complications:
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Disfiguring scarring — even self-healed lesions leave permanent atrophic scars; facial lesions cause significant psychosocial impact
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Secondary bacterial superinfection of ulcers
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Leishmaniasis recidivans — chronic relapsing form with satellite papules around scarred lesions (usually L. tropica)
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Progression to mucocutaneous disease — 5–15% risk with L. braziliensis
Mucocutaneous leishmaniasis complications:
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Nasal septum perforation and progressive destruction of oropharyngeal structures
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Aspiration pneumonia from pharyngeal and laryngeal involvement
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Severe psychological and social consequences — facial disfigurement leads to stigma, isolation, and depression
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Treatment failure and relapse — common, particularly without prolonged follow-up
Recovery & Outlook
Expected outcomes and recovery
The prognosis of leishmaniasis varies markedly by clinical form and access to treatment.
Visceral leishmaniasis:
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Untreated: Case fatality rate (CFR) exceeds 95% within 1–2 years, typically from secondary infections, hemorrhage, or severe anemia
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Treated: Cure rates of 90–98% with liposomal amphotericin B-based regimens; relapse rates of 1–5% in immunocompetent patients
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HIV co-infection: Dramatically worsened prognosis — relapse rates of 20–60% even after adequate treatment; mortality remains high
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Post-kala-azar dermal leishmaniasis (PKDL): Develops in 5–10% of VL patients in South Asia and up to 50% in Sudan; usually non-fatal but serves as a parasite reservoir
Cutaneous leishmaniasis:
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Self-healing in 6–12 months for most Old World CL (L. major, L. tropica), but permanent scarring is universal
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Diffuse cutaneous leishmaniasis (DCL) does not self-heal and is extremely difficult to treat
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New World CL caused by L. braziliensis carries a 5–15% risk of progressing to mucocutaneous disease
Mucocutaneous leishmaniasis:
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Without treatment, progressive and irreversible destruction of nasopharyngeal tissue
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With systemic treatment, cure rates are 70–90%, though relapse is common
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Significant psychological morbidity and social stigma associated with facial disfigurement
Overall, early diagnosis and appropriate treatment yield excellent outcomes for most patients. The greatest determinant of poor prognosis is delayed presentation, particularly for visceral disease.