Leishmaniasis¶
Chapter 233 | Harrison's 22e · Part 5 – Infectious Diseases: Parasitic · Chapter 233
Key Clinical Points¶
- Caused by ~20 species of the genus Leishmania in the Kinetoplastida family.
- Three clinical syndromes: visceral (VL), cutaneous (CL), and mucosal (ML).
- Transmission via sandfly bites (Phlebotomus in Old World; Lutzomyia in New World).
- Global burden: 30,000 VL cases/year; 1 million CL cases/year.
- HIV co-infection significantly increases mortality risk (e.g., 30% in Ethiopia).
- VL is characterized by hepatosplenomegaly (pathognomonic), pancytopenia, and hyperglobulinemia.
- PKDL occurs in 5–20% of VL survivors and serves as a parasite reservoir.
- Diagnosis involves leishmanin skin tests, Giemsa-stained microscopy (amastigotes with kinetoplasts), and PCR.
- Treatment for VL: Liposomal AmB or Miltefosine; Treatment for CL: Sodium stibogluconate.
- No vaccine available; prevention focuses on vector control and personal protection.
1. DEFINITION & OVERVIEW¶
Leishmaniasis is a complex group of diseases caused by unicellular eukaryotic protozoa of the genus Leishmania, primarily affecting the reticuloendothelial system.
• Pathogen Diversity: ◦ Caused by ~20 species in the Kinetoplastida family.
• Clinical Syndromes: ◦ Visceral leishmaniasis (VL) → often fatal if untreated; caused by L. donovani complex. ◦ Cutaneous leishmaniasis (CL) → characterized by self-healing ulcers; caused by Viannia subspecies and L. major. ◦ Mucosal leishmaniasis (ML) → limited to South America; causes destruction of nasal mucosa and palate; caused by L. braziliensis.
1.1 Etiology & Life Cycle¶
Leishmania species have complex life cycles involving sandfly vectors and mammalian hosts:
• Vector Transmission: ◦ Old World: Phlebotomus species ◦ New World: Lutzomyia species
• Life Cycle Stages: ◦ Promastigotes: Flagellated form in sandfly midgut → multiply by binary fission. ◦ Transmission: Occurs via sandfly proboscis during blood meal. ◦ Amastigotes: Non-flagellated intracellular form → infect macrophages. ◦ Replication: Macrophage rupture releases amastigotes → infect new cells. ◦ Cycle Completion: Sandflies acquire amastigotes from hosts → transform into promastigotes.
2. EPIDEMIOLOGY¶
Leishmaniasis occurs in 99 countries across tropical and temperate regions.
• Global Burden: ◦ 30,000 VL cases/year; 1 million CL cases/year.
• Regional Distribution: ◦ VL: Highest incidence in East Africa, Brazil, and the Indian subcontinent. ◦ CL: Prevalent in South America, Africa, and Asia. ◦ ML: Restricted to South America.
• Transmission Dynamics: ◦ Zoonotic: Common in Middle East, Pakistan, China (often involving dogs/foxes). ◦ Anthroponotic: Dominates in Sudan/South Sudan.
• Impact of Co-infection: ◦ HIV co-infection → increased mortality risk (30% in Ethiopia).
• Public Health Success: ◦ 98.7% decline in Indian VL incidence following elimination programs.
2.1 Geographic Distribution (Table 233-1)¶
• Leishmania donovani Complex: ◦ Regions: South Asia, Africa, Mediterranean, Middle East, Central Asia, China. ◦ Syndromes: VL, PKDL; also some cases of CL. ◦ Vectors: Phlebotomus species.
• Viannia Subspecies (e.g., L. braziliensis, L. guyanensis): ◦ Regions: Central and South America. ◦ Syndromes: CL, ML. ◦ Vectors: Lutzomyia species.
• L. major: ◦ Regions: Western/Central Asia, North/Sub-Saharan Africa; Kazakhstan, Turkmenistan, Uzbekistan. ◦ Syndrome: CL.
• L. tropica: ◦ Syndromes: CL, leishmaniasis recidivans.
• L. aethiopica: ◦ Syndromes: CL, DCL.
2.2 Post-Kala-Azar Dermal Leishmaniasis (PKDL) (Table 233-2)¶
• East Africa (Sudan/South Sudan): ◦ Incidence: ~50% of patients with VL. ◦ Timing: During VL to 6 months. ◦ Treatment: Sodium stibogluconate for 2–3 months → spontaneous cure in majority.
• Indian Subcontinent (Bangladesh): ◦ Timing: 6 months to 3 years after VL. ◦ Treatment: Miltefosine for 12 weeks.
3. CLINICAL MANIFESTATIONS¶
Clinical presentations vary by Leishmania species and host immune response:
• Visceral leishmaniasis (Kala-azar): ◦ Systemic Symptoms: Prolonged fever, weight loss. ◦ Organ Involvement: Hepatosplenomegaly (pathognomonic). ◦ Laboratory Findings: Hypoglycemia, pancytopenia, hyperglobulinemia.
• Cutaneous leishmaniasis: ◦ Presentation: Ulcerated plaques on exposed skin (face, hands). ◦ Progression: May progress to post-kala-azar dermal leishmaniasis (PKDL).
• Mucosal leishmaniasis: ◦ Site: Destruction of nasal mucosa and palate. ◦ Pathogen: L. braziliensis.
3.1 Complications¶
• PKDL: ◦ Prevalence: 5–20% of VL survivors. ◦ Presentation: Hypopigmented nodules on face and extremities. ◦ Impact: Social stigma and disfigurement.
• HIV Co-infection: ◦ Risk: Increased risk of disseminated disease and treatment failure.
4. DIAGNOSIS¶
Diagnostic approach depends on clinical suspicion and available resources:
• Leishmanin skin test (Montenegro test): ◦ Mechanism: Delayed-type hypersensitivity to leishmanial antigens. ◦ Sensitivity: Positive in 80% of exposed individuals.
• Microscopy: ◦ Method: Giemsa-stained smears (e.g., splenic smear for VL). ◦ Findings: Amastigotes (2–4 μm) with nucleus and kinetoplast. ◦ Sensitivity: <50% in VL, >90% in CL.
• Molecular methods (PCR): ◦ Use: Rapid and specific for species identification from blood or lesion samples.
• Differential Diagnosis: ◦ Cutaneous lesions may mimic: ◦ Tuberculosis ◦ Fungal infections (e.g., sporotrichosis) ◦ Leprosy ◦ Sarcoidosis ◦ Malignant ulcers.
5. TREATMENT¶
Therapeutic options vary by disease form and geographic region:
• Visceral leishmaniasis (VL): ◦ First-line: Liposomal amphotericin B (AmB) 3–5 mg/kg/day for 10–20 days. ◦ Alternative: Miltefosine 100 mg/day for 28 days. ◦ Note: HIV co-infected patients require extended treatment duration.
• Cutaneous leishmaniasis (CL): ◦ Local therapy: Cryotherapy or intralesional antimonials. ◦ Systemic: Sodium stibogluconate 20 mg/kg/day for 20–30 days.
• Mucosal leishmaniasis (ML): ◦ Combination: Systemic antimonials and surgical debridement.
6. PREVENTION & CONTROL¶
Preventive measures focus on vector control and public health initiatives:
• Personal Protection: ◦ Clothing: Permethrin-treated. ◦ Repellents: DEET-based. ◦ Behavior: Avoid outdoor activities during sandfly season (May–October).
• Public Health Strategies: ◦ Vector Control: Indoor residual spraying in endemic areas. ◦ Reservoir Management: Dog population management for zoonotic VL control. ◦ Community Action: Mass drug administration in high-risk communities.
• Vaccination: ◦ Status: No vaccine available; research ongoing.
Reference Tables¶
TABLE 233-1 Geographic Distribution and Characteristic Epidemiology of Leishmaniases¶
Harrison's 22e, p.1782
| ORGANISM, ENDEMIC REGION | CLINICAL SYNDROME |
SPECIES | VECTOR | RESERVOIR | TRANSMISSION | SETTING |
|---|---|---|---|---|---|---|
| Leishmania donovani Complex | ||||||
| South Asia | VL, PKDL | L. donovani | Phlebotomus argentipes |
Humans | Anthroponotic | Rural, domestic |
| Sudan, South Sudan, Somalia, Ethiopia, Kenya, Uganda |
VL, PKDL | L. donovani | P. orientalis, P. martini |
Humans, rodents in Sudan, canines |
Anthroponotic, occasionally zoonotic |
Majority peridomestic, occasionally sylvatic |
| Mediterranean basin, Middle East, Central Asia, China |
VL, CL | L. infantum | P. perniciosus, P. ariasi |
Dogs, foxes, jackals | Zoonotic | Domestic, peridomestic |
| Middle East, Saudi Arabia, Yemen |
VL | L. donovani | P. perniciosus, P. ariasi |
Dogs, foxes, jackals | Zoonotic | Domestic, peridomestic |
| Central and South America | VL, CL | L. infantuma | Lutzomyia longipalpis |
Foxes, dogs, opossums |
Zoonotic | Domestic, peridomestic, periurban |
| Azerbaijan, Armenia, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan |
VL | L. infantum | P. turanicus | Humans, dogs, foxes | Anthroponotic, zoonotic |
Domestic |
| L. tropica | ||||||
| CL, leishmaniasis recidivans |
L. tropica | P. sergenti | Humans | Anthroponotic | ||
| L. major | ||||||
| Western and Central Asia, North and sub-Saharan Africa |
CL | L. major | P. papatasi, P. duboscqi |
Nile rats, rodents | Zoonotic | Sylvatic, peridomestic |
| Kazakhstan, Turkmenistan, Uzbekistan |
CL | L. major | P. papatasi, P. duboscqi |
Gerbils | Zoonotic | Rural |
| L. aethiopica | ||||||
| CL, DCL | L. aethiopica | P. longipes, P. pedifer |
Hyraxes | Zoonotic | ||
| 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.) panamensis | L. trapidoi | Sloths | Zoonotic | Tropical forest and deforested areas |
| South and Central America | CL, ML | L. (V.) braziliensis | Lutzomyia spp., L. umbratilis, Psychodopygus wellcomei |
Forest rodents, peridomestic animals |
Zoonotic | Tropical forest and deforested areas |
| L. mexicana Complex | ||||||
| CL, ML, DCL | L. amazonensis | L. flaviscutellata | Forest rodents | Zoonotic | ||
| CL, ML, DCL | L. mexicana | L. olmeca | Variety of forest rodents and marsupials |
Zoonotic | ||
| CL, DCL | L. pifanoi | L. olmeca | Variety of forest rodents and marsupials |
Zoonotic |
TABLE 233-2 Clinical, Epidemiologic, and Therapeutic Features of Post–Kala-Azar Dermal Leishmaniasis: East Africa and…¶
Harrison's 22e, p.1785
| FEATURE | EAST AFRICA | INDIAN SUBCONTINENT |
|---|---|---|
| Most affected country | Sudan and South Sudan | Bangladesh |
| ~50% | ||
| Interval between VL and PKDL |
During VL to 6 months | 6 months to 3 years |
| Mainly children | ||
| History of prior VL | Yes | Not necessarily |
| Yes | ||
| Treatment | Sodium stibogluconate for 2–3 months |
Miltefosine for 12 weeks |
| Spontaneous cure in majority of patients |