Leishmaniasis

Leishmaniasis is a parasitic disease caused by protozoans of the Leishmania genus, which are transmitted by infected phlebotomine sand flies. Depending on the parasite subtype and the strength of the host's immune system, the disease manifests in a cutaneous or visceral form. Cutaneous leishmaniasis is characterized by skin ulcers. The most important clinical manifestation of visceral leishmaniasis is kala-azar (Hindi for “black fever”), which presents with fever, weight loss, hepatosplenomegaly, and immunosuppression. Leishmaniasis is diagnosed by microscopic visualization of macrophages containing amastigotes in blood smears or tissue. Local treatment (cryotherapy, topical paromomycin) suffices for most cases of cutaneous leishmaniasis. Visceral leishmaniasis requires systemic treatment with amphotericin B.

• Distribution: endemic in the Mediterranean region, Africa, India, southwest and central Asia, South and Central America
• Incidence (worldwide):
  • Visceral: 50,000– 90,000 infections/year
  • Cutaneous: 600,000–1,000,000 infections/year

References:^[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Leishmania donovani (protozoan) ^[2]
  • Cutaneous leishmaniasis
    • Americas: L. mexicana, L. braziliensis, L. guyanensis, L. panamensis (L. braziliensis, L. guyanensis, L. panamensis can also cause mucosal leishmaniasis) ^[4][5]
    • Asia/Africa: L. major, L. tropica. L. aethiopica
  • Visceral leishmaniasis: L. donovani, L. infantum
• Transmission
  • Vector: phlebotomine sandflies
  • Reservoir: mammals (especially dogs, humans, and rodents)

Clinical features ^[6][7]

• Localized cutaneous leishmaniasis
  • Incubation period: weeks to months
  • Manifestation: solitary or multiple reddish macules/papules around the sandfly bite that quickly increase in size and develop central ulceration
• Mucosal leishmaniasis
  • Some Leishmania subtypes (e.g., L. braziliensis, L. guyanensis, L. panamensis) cause mucosal leishmaniasis, which can develop months to years after cutaneous leishmaniasis that was not treated properly ^[5]
  • Manifestation: commonly affects the nasopharynx (mucosal bleeding, nasal blockage)

Diagnostics

• Detection of the pathogen in skin biopsy
  • Microscopy: macrophages that contain amastigotes, the intracellular, nonmotile form of Leishmania (appear as ovoid inclusions)
  • PCR
  • Culture (Novy-Nicolle-McNeal medium)

Treatment ^[8]

The objective of treatment is to manage clinical symptoms.

• Uncomplicated disease (no immunosuppression, small lesions, no mucosal involvement)
  • No systemic treatment
  • Local treatment (cryotherapy, thermotherapy, or topical paromomycin) for skin lesions that do not heal spontaneously.
• Complicated disease (mucosal involvement, numerous lesions, immunosuppression)
  • See treatment of visceral leishmaniasis

Prognosis

Treatment reduces the recurrence rate of cutaneous leishmaniasis, accelerates the healing of lesions, and reduces the risk of dissemination and incidence of mucosal leishmaniasis.

Without treatment, localized cutaneous leishmaniasis heals over months to years with a scar or keloid. Reactivation may occur years after initial symptoms resolve.

Clinical features ^[6][9]

• Incubation period: 2–6 months
• Many patients are asymptomatic.
• Kala-azar (Hindi for “black fever,” in reference to the darkening of the skin it can cause)
  • Usually insidious progression
  • Flu-like symptoms, spiking fevers
  • Weight loss
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Ascites and edema
  • Pancytopenia
  • Possible darkened or gray skin color (especially on the palms and soles)
  • Immunosuppression may lead to secondary bacterial infections in advanced disease

Diagnostics

• Laboratory tests
  • Hemolytic anemia
  • Neutropenia, eosinopenia, thrombocytopenia
• Detection of pathogen
  • Microscopy of tissue biopsy (e.g., bone marrow) with visualization of macrophages with amastigotes
  • PCR

Treatment ^[10]

• Amphotericin B is the preferred monotherapy in Europe, North America, and South America.
• Other drugs that may be used include:
  • Sodium stibogluconate
  • Miltefosine
  • Paromomycin

Kala-azar is highly fatal without treatment!