Visceral and Cutaneous Leishmaniasis

Visceral Leishmaniasis (VL)

• VL, also known as kala-azar ("black fever"), is caused by the Leishmania donovani complex.
• This complex includes L. donovani and Leishmania infantum (L. chagasi in the New World).
• L. donovani causes anthroponotic transmission.
• L. infantum causes zoonotic transmission.
• India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil account for 90% of the global VL burden.
• Human leishmaniasis is increasing worldwide, except in India, Nepal, and Bangladesh due to a VL elimination program.
• These three countries have achieved the elimination target in over 90% of program sites.

Cutaneous Leishmaniasis (CL)

• Lymphatic spread and lymph gland involvement may occur, sometimes before skin lesions appear.
• Satellite lesions may be present, especially in L. major and L. tropica infections.
• Lesions usually heal spontaneously within 2–15 months.
• L. major and L. mexicana lesions tend to heal faster than L. tropica and Viannia subspecies lesions.
• Leishmaniasis recidivans, characterized by new lesions around a healed sore's center or periphery, can occur with L. tropica.
• L. mexicana and L. (Viannia) peruviana lesions resemble those in the Old World.
• Lesions on the ear's pinna are common, chronic, and destructive in L. mexicana infections.
• L. mexicana causes chiclero’s ulcer in Mexico.
• CL lesions on exposed body parts, scar formation, and social stigmatization can lead to psychological distress.
• Treatment is advised if lesions spread or persist.
• Topical agents can treat small lesions from self-healing species.
• Systemic treatment is needed for facial, hand, or joint lesions; multiple lesions; large ulcers; lymphatic spread; New World CL with potential for Mucosal Leishmaniasis (ML); and CL in HIV-co-infected patients.
• Pentavalent antimonial is the first-line drug for all forms of CL at 20 mg/kg for 20 days.
• CL caused by L. (Viannia) guyanensis is treated with pentamidine isethionate.
• CL due to L. aethiopica responds to paromomycin.
• Relapses usually respond to a second course of treatment.
• Topical imiquimod plus parenteral antimonials can cure CL faster than antimonials alone in Peru.
• Oral fluconazole has demonstrated higher cure rates than a placebo for L. major infections.
• Ketoconazole is effective against CL due to L. (V.) panamensis and L. mexicana in Panama and Guatemala.
• Miltefosine is effective against L. major and L. (V.) panamensis infections.
• L. (V.) braziliensis infections have shown inconsistent results with miltefosine.
• Intralesional injections of pentavalent antimonial can treat small lesions.
• Paromomycin sulfate ointment can treat lesions due to L. major.
• Heat therapy and cryotherapy have also been used successfully.

Diffuse Cutaneous Leishmaniasis (DCL)

• DCL is a rare form of leishmaniasis caused by L. amazonensis and L. mexicana in South and Central America and by L. aethiopica in Ethiopia and Kenya.
• DCL is characterized by a lack of cell-mediated immune response, leading to uncontrolled parasite multiplication.
• Patients do not develop a DTH response, and lymphocytes do not respond to leishmanial antigens in vitro.
• DCL patients exhibit immunosuppression with high levels of IL-10, TGF-β, and IL-4, and low concentrations of IFN-γ.
• Lesions may spread over months or years to other skin areas.
• Lesions do not ulcerate and are filled with parasites which are therefore easy to recover.
• The skin overlying lesions is often erythematous in pale-skinned patients.
• DCL does not heal spontaneously and treatment should be continued after lesions have healed
• Repeated courses of pentavalent antimonials, miltefosine, or a combination of paromomycin and sodium stibogluconate may be used for treatment.

Mucosal Leishmaniasis (ML)

• The Viannia subgenus causes deep sores and ML.
• ML is typically caused by L. (V.) braziliensis and rarely by L. amazonensis, L. (V.) guyanensis, and L. (V.) panamensis.
• Young men with chronic CL lesions are at higher risk, and not all patients have a prior CL history.
• ML is almost entirely confined to the Americas but may rarely be caused by Old World species.
• ML typically presents with nasal stuffiness and bleeding, leading to destruction of nasal cartilage, perforation of the nasal septum, and collapse of the nasal bridge.
• Involvement of the pharynx and larynx can cause difficulty in swallowing and phonation.
• Secondary bacterial infection is common, and aspiration pneumonia may be fatal.
• ML does not heal spontaneously.
• Diagnosis requires tissue biopsy for parasite identification, often using PCR.
• A positive DTH response cannot distinguish between past and present infection.
• Treatment regimen of choice is pentavalent antimonial agent, and patients require long-term follow-up.
• With failure of therapy or relapse, patients may receive another course of an antimonial but then become unresponsive,.
• AmB or miltefosine may be used in cases unresponsive to antimonials.
• The more extensive the disease, the worse the prognosis.

Prevention of Leishmaniasis

• There is no vaccine available, but several candidates are in early phases of development.
• Leishmanization is still practiced in Iran with a high percentage of recipients protected according to one report.
• Anthroponotic leishmaniasis is controlled by case finding, treatment, and vector control using insecticide-impregnated bed nets and residual insecticide spraying.
• Zoonotic leishmaniasis is more difficult to control.
• Insecticide-impregnated collars for dogs, treatment of infected dogs, and culling of street dogs have been used with uncertain efficacy to prevent L. infantum transmission.
• Canine vaccines have been found to decrease human and canine incidence of zoonotic VL in Brazil.
• Personal prophylaxis with bed nets and repellents may reduce the risk of CL infections in the New World.

Visceral Leishmaniasis (VL), or kala-azar, is caused by the Leishmania donovani complex. Cutaneous Leishmaniasis (CL) may involve lymphatic spread, sometimes preceding skin lesions. Lesions can heal spontaneously, with variations in healing time depending on the specific Leishmania species.