Leishmaniasis¶
Chapter 233 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Leishmaniasis is caused by Leishmania species transmitted via sandfly bites, with three main clinical forms: visceral (VL), cutaneous (CL), and mucosal (ML).
- VL is caused by Leishmania donovani complex, with high mortality if untreated, while CL and ML have varied presentations and complications.
- Diagnosis relies on microscopy, PCR, serology, and clinical context, with treatment varying by region and parasite species.
- Antimonial compounds, amphotericin B, and miltefosine are key therapies, though resistance and drug toxicity pose challenges.
- Special considerations include HIV co-infection, pregnancy, and drug safety in immunocompromised patients.
1. DEFINITION & OVERVIEW¶
Leishmaniasis is a complex group of disorders caused by Leishmania protozoa, transmitted via sandfly vectors. It affects the reticuloendothelial system and presents as visceral (VL), cutaneous (CL), or mucosal (ML) forms. VL is the most severe, with high mortality if untreated.
Table 233-1 Geographic Distribution and Characteristic Epidemiology of Leishmaniases¶
| ORGANIS M, ENDEMIC REGION | CLINICAL SYNDROM E | SPECIES | VECTOR | RESERVOI R | TRANSMIS SION | SETTING | |
|---|---|---|---|---|---|---|---|
| Leishmania donovani Complex | South Asia | VL, PKDL | L. donovani | Phlebotomu s argentipes | Humans | Anthropono tic | Rural, domestic |
| Sudan, South Sudan, Somalia, Ethiopia, Kenya, Uganda | VL, PKDL | L. donovani | P. orientalis, P. martini | Humans, rodents in Sudan, canines | Anthropono tic, occasio nally zoonotic | Majority per idomestic, o ccasionally sylvatic | |
| Mediterrane an basin, Middle East, Central Asia, China | VL, CL | L. infantum | P. perniciosus, P. ariasi | Dogs, foxes, jackals | Zoonotic | Domestic, p eridomestic |
| ORGANIS M, ENDEMIC REGION | CLINICAL SYNDROM E | SPECIES | VECTOR | RESERVOI R | TRANSMIS SION | SETTING | |
|---|---|---|---|---|---|---|---|
| Middle East, Saudi Arabia, Yemen | VL | L. donovani | P. perniciosus, P. ariasi | Dogs, foxes, jackals | Zoonotic | Domestic, p eridomestic | |
| Central and South America | VL, CL | L. infantum | Lutzomyia longipalpis | Foxes, dogs, opossums | Zoonotic | Domestic, p eridomestic , periurban | |
| Azerbaijan, Armenia, Georgia, Ka zakhstan, Kyrgyzstan, Tajikistan, Turkmenist an, Uzbekistan | VL | L. infantum | P. turanicus | Humans, dogs, foxes | Anthropono tic, zoonotic | Domestic | |
| L. tropica | Western India to Turkey, parts of North and East Africa | CL | L. tropica | P. sergenti | Humans | Anthropono tic | Urban domestic, p eridomestic |
| Western and Central Asia, North and sub-Sa haran Africa | CL | L. major | P. papatasi, P. duboscqi | Nile rats, rodents | Zoonotic | Sylvatic, pe ridomestic | |
| Kazakhstan , Turkmenis tan, Uzbekistan | CL | L. major | P. papatasi, P. duboscqi | Gerbils | Zoonotic | Rural | |
| L. aethiopica | Ethiopia, Uganda, Kenya | CL, DCL | L. aethiopica | P. longipes, P. pedifer | Hyraxes | Zoonotic | Sylvatic, pe ridomestic |
| Subspecies Viannia | Peru, Ecuador | CL, ML | L. (V.) peruviana | Lutzomyia verrucarum, L. peruensis | Wild rodents | Zoonotic | Andean Valleys |
| Guyana, Surinam, French Guyana, Ecuador, Brazil, Colombia, Bolivia | CL, ML | L. (V.) guyanensis | L. umbratilis | Sloths, arboreal anteaters, opossums | Zoonotic | Tropical forest | |
| Central America, Ecuador, Colombia | CL, ML | L. (V.) pana mensis | L. trapidoi | Sloths | Zoonotic | Tropical forest and deforested areas |
| ORGANIS M, ENDEMIC REGION | CLINICAL SYNDROM E | SPECIES | VECTOR | RESERVOI R | TRANSMIS SION | SETTING | |
|---|---|---|---|---|---|---|---|
| South and Central America | CL, ML | L. (V.) braziliensis | Lutzomyia spp., L. umbratilis, Psychodop ygus wellcomei | Forest rodents, per idomestic animals | Zoonotic | Tropical forest and deforested areas | |
| L. mexicana Complex | Central America and northern parts of South America | CL, ML, DCL | L. amazone nsis | L. flaviscute llata | Forest rodents | Zoonotic | Tropical forest and deforested areas |
| CL, ML, DCL | L. mexicana | L. olmeca | Variety of forest rodents and marsupials | Zoonotic | Tropical forest and deforested areas | ||
| CL, DCL | L. pifanoi | L. olmeca | Variety of forest rodents and marsupials | Zoon,otic | Tropical forest and deforested areas |
1.1 Global Distribution¶
Leishmaniasis occurs in 99 countries, predominantly in tropical and temperate regions. Over 1 billion people live in endemic areas, with 30,000 new VL cases and 1 million CL cases annually.
1.2 Pathogenesis¶
Leishmania parasites are transmitted via sandfly bites. Promastigotes enter macrophages, multiply as amastigotes, and cause tissue damage. Immune response (T1 cytokines) determines disease outcome.
2. EPIDEMIOLOGY¶
Leishmaniasis occurs in 99 countries, with 1 billion people at risk. VL is common in South Asia, East Africa, Brazil, and the Indian subcontinent. CL is prevalent in South America, Africa, and Asia. ML is limited to South America. Climate change and HIV co-infection drive disease spread.
Table 233-2 Clinical, Epidemiologic, and Therapeutic Features of Post–Kala-Azar Dermal Leishmaniasis: East Africa and the Indian Subcontinent¶
| FEATURE | EAST AFRICA | INDIAN SUBCONTINENT |
|---|---|---|
| Most affected country | Sudan and South Sudan | Bangladesh |
| Interval between VL and PKDL | During VL to 6 months | 6 months to 3 years |
| Age distribution | Mainly children | Any age |
| History of prior VL | Yes | Not necessarily |
| Rashes of PKDL in presence of active VL | Yes | No |
| Treatment | Sodium stibogluconate for 2–3 months | Miltefosine for 12 weeks |
| FEATURE | EAST AFRICA | INDIAN SUBCONTINENT |
|---|---|---|
| Natural course | Spontaneous cure in majority of patients | Spontaneous cure rarely |
2.1 Risk Factors¶
Immunocompromised individuals (e.g., HIV, IV drug users), rural/periurban dwellers, and travelers to endemic regions are at highest risk. Zoonotic transmission is common in rural areas.
2.2 Demographics¶
VL is most common in children and adults in endemic regions. CL affects all ages, while ML is more common in men aged 20–40.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Leishmania species (20+ species) are transmitted via sandfly vectors. Pathogenesis involves promastigote entry into macrophages, intracellular amastigote replication, and immune response polarization (T1 vs. T2 cytokines). IL-10 and TGF- β drive immunosuppression in VL.
3.1 Life Cycle¶
Sandflies transmit promastigotes to humans. Promastigotes are phagocytosed by macrophages, replicate as amastigotes, and are transmitted via sandfly feces. Immune response determines disease outcome.
3.2 Immune Response¶
T1 response (IFN- γ , TNF- α ) controls infection; T2 response (IL-10, TGF- β ) leads to immunosuppression and disease progression. HIV co-infection exacerbates immunosuppression.
4. CLINICAL FEATURES¶
VL presents with fever, weight loss, splenomegaly, and hepatomegaly. CL causes skin ulcers, while ML leads to mucosal destruction. PKDL is a post-treatment complication with hypopigmented skin lesions.
4.1 Visceral Leishmaniasis¶
Fever, weight loss, splenomegaly, anemia, and hypoalbuminemia. Severe cases may present with ascites, thrombocytopenia, and secondary infections.
4.2 Cutaneous Leishmaniasis¶
Papules/nodules progressing to ulcers. Lesions vary in size and location, with spontaneous healing in most cases. L. tropica causes recidivans (new lesions after healing).
4.3 Mucosal Leishmaniasis¶
Progressive destruction of nasal/mucosal tissues. Often follows untreated CL. Leads to severe disability and airway obstruction.
4.4 Post-Kala-Azar Dermal Leishmaniasis (PKDL)¶
Hypopigmented macules/papules after VL recovery. Common in Indian subcontinent and East Africa. Spontaneous cure is rare.
5. DIFFERENTIAL DIAGNOSIS¶
VL must be differentiated from malaria, typhoid, tuberculosis, and brucellosis. CL may mimic cutaneous tuberculosis, fungal infections, or leprosy. ML is distinguished from sarcoidosis and other mucosal infections.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis via microscopy (splenic smears), PCR, serology (rK39 RDT), and clinical evaluation. Skin biopsy and culture confirm infection. Imaging (ultrasound) assesses splenomegaly.
6.1 Diagnostic Tests¶
Microscopy (splenic smears >95% sensitive), PCR (species identification), serology (rK39 RDT 98% sensitive in immunocompetent patients), and skin biopsy.
7. MANAGEMENT & TREATMENT¶
Treatment varies by region and parasite species. Pentavalent antimonials (SbV) are first-line in many areas, while amphotericin B and miltefosine are alternatives. Resistance and drug toxicity require careful monitoring.
Table 233-1 Geographic Distribution and Characteristic Epidemiology of Leishmaniases¶
| ORGANIS M, ENDEMIC REGION | CLINICAL SYNDROM E | SPECIES | VECTOR | RESERVOI R | TRANSMIS SION | SETTING | |
|---|---|---|---|---|---|---|---|
| Leishmania donovani Complex | South Asia | VL, PKDL | L. donovani | Phlebotomu s argentipes | Humans | Anthropono tic | Rural, domestic |
| Sudan, South Sudan, Somalia, Ethiopia, Kenya, Uganda | VL, PKDL | L. donovani | P. orientalis, P. martini | Humans, rodents in Sudan, canines | Anthropono tic, occasio nally zoonotic | Majority per idomestic, o ccasionally sylvatic | |
| Mediterrane an basin, Middle East, Central Asia, China | VL, CL | L. infantum | P. perniciosus, P. ariasi | Dogs, foxes, jackals | Zoonotic | Domestic, p eridomestic | |
| Middle East, Saudi Arabia, Yemen | VL | L. donovani | P. perniciosus, P. ariasi | Dogs, foxes, jackals | Zoonotic | Domestic, p eridomestic | |
| Central and South America | VL, CL | L. infantum | Lutzomyia longipalpis | Foxes, dogs, opossums | Zoonotic | Domestic, p eridomestic , periurban |
| ORGANIS M, ENDEMIC REGION | CLINICAL SYNDROM E | SPECIES | VECTOR | RESERVOI R | TRANSMIS SION | SETTING | |
|---|---|---|---|---|---|---|---|
| Azerbaijan, Armenia, Georgia, Ka zakhstan, Kyrgyzstan, Tajikistan, Turkmenist an, Uzbekistan | VL | L. infantum | P. turanicus | Humans, dogs, foxes | Anthropono tic, zoonotic | Domestic | |
| L. tropica | Western India to Turkey, parts of North and East Africa | CL | L. tropica | P. sergenti | Humans | Anthropono tic | Urban domestic, p eridomestic |
| Western and Central Asia, North and sub-Sa haran Africa | CL | L. major | P. papatasi, P. duboscqi | Nile rats, rodents | Zoonotic | Sylvatic, pe ridomestic | |
| Kazakhstan , Turkmenis tan, Uzbekistan | CL | L. major | P. papatasi, P. duboscqi | Gerbils | Zoonotic | Rural | |
| L. aethiopica | Ethiopia, Uganda, Kenya | CL, DCL | L. aethiopica | P. longipes, P. pedifer | Hyraxes | Zoonotic | Sylvatic, pe ridomestic |
| Subspecies Viannia | Peru, Ecuador | CL, ML | L. (V.) peruviana | Lutzomyia verrucarum, L. peruensis | Wild rodents | Zoonotic | Andean Valleys |
| Guyana, Surinam, French Guyana, Ecuador, Brazil, Colombia, Bolivia | CL, ML | L. (V.) guyanensis | L. umbratilis | Sloths, arboreal anteaters, opossums | Zoonotic | Tropical forest | |
| Central America, Ecuador, Colombia | CL, ML | L. (V.) pana mensis | L. trapidoi | Sloths | Zoonotic | Tropical forest and deforested areas | |
| South and Central America | CL, ML | L. (V.) braziliensis | Lutzomyia spp., L. umbratilis, Psychodop ygus wellcomei | Forest rodents, per idomestic animals | Zoonotic | Tropical forest and deforested areas |
| ORGANIS M, ENDEMIC REGION | CLINICAL SYNDROM E | SPECIES | VECTOR | RESERVOI R | TRANSMIS SION | SETTING | |
|---|---|---|---|---|---|---|---|
| L. mexicana Complex | Central America and northern parts of South America | CL, ML, DCL | L. amazone nsis | L. flaviscute llata | Forest rodents | Zoonotic | Tropical forest and deforested areas |
| CL, ML, DCL | L. mexicana | L. olmeca | Variety of forest rodents and marsupials | Zoonotic | Tropical forest and deforested areas | ||
| CL, DCL | L. pifanoi | L. olmeca | Variety of forest rodents and marsupials | Zoonotic | Tropical forest and deforested areas |
7.1 Visceral Leishmaniasis¶
Pentavalent antimonials (20 mg/kg for 28–30 days), amphotericin B (0.75–1.0 mg/kg alternate days), or miltefosine (2.5 mg/kg for 28 days). LAmB preferred in Mediterranean regions.
7.2 Cutaneous Leishmaniasis¶
Topical paromomycin, intralesional antimonials, or systemic miltefosine. Localized lesions may respond to imiquimod cream.
7.3 Mucosal Leishmaniasis¶
Long-term antimonial therapy, AmB, or miltefosine. Surgical intervention may be required for severe airway obstruction.
7.4 PKDL¶
Prolonged antimonial therapy (up to 120 days) or miltefosine. No curative treatment exists for PKDL.
8. PROGNOSIS & COMPLICATIONS¶
VL has high mortality without treatment. Complications include secondary infections, anemia, and organ failure. PKDL may persist for years. ML leads to severe disfigurement and airway obstruction.
9. SPECIAL CONSIDERATIONS¶
HIV co-infection increases VL severity and resistance. Pregnancy requires caution with antimonials. Children and elderly may need adjusted dosages. Travelers to endemic regions should use repellents and avoid sandfly bites.
10. KEY POINTS & CLINICAL PEARLS¶
- Leishmaniasis is a vector-borne disease with three main forms (VL, CL, ML).
- Diagnosis requires microscopy, PCR, and clinical context.
- Treatment varies by region and parasite species.
- HIV co-infection worsens prognosis.
- PKDL is a common post-treatment complication.
- Miltefosine and amphotericin B are key therapies in resistant cases.