Leishmaniasis

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Basics

A clinically diverse group of infections caused by protozoa of the genus Leishmania (transmitted by a bite from an infected female sandfly), ranging from a single self-healing ulcer (cutaneous) to destructive mucocutaneous disease or potentially lethal visceral disease

Description

  • Cutaneous leishmaniasis (CL)
    • Papules appear ~6 weeks after sandfly bites, enlarging to ulcerate (each up to 5 cm) with a firm, indurated border; most heal slowly without treatment, leaving residual scarring.
    • Consider treatment if lesions are large (>4 cm), multiple (>3), limit function (hands, feet, joints, eye), or affect cosmesis (face, ear).
    • Divided into Old World (OWCL) and New World (American; NWCL)
  • Visceral leishmaniasis (VL)
    • Most severe form; 90% fatal if untreated
    • Infects lymph nodes, spleen, liver, and bone marrow
    • Insidious presentation 3 to 8 months after inoculation
    • Various regional forms (e.g., African, Mediterranean, and Indian kala-azar)
    • Signs and symptoms: fever (usually two spikes per day), abdominal pain, weight loss, decreased appetite, diarrhea, weakness, nonproductive cough, headache, peripheral edema, organomegaly, lymphadenopathy, bleeding diathesis
  • Mucocutaneous leishmaniasis (MCL)
    • Presents months to years after primary CL; primarily due to Leishmania braziliensis
    • CL spreads via lymphatics; infects mucosa of nose, palate, pharynx, larynx
    • Begins as erythema/ulceration of the nasal septum; progresses to painful erosions
  • Synonym(s): OWCL (oriental sore, Delhi boil, Aleppo boil); NWCL (American CL, chiclero ulcer [ear], espundia [severe MCL], bush yaws, uta, Picatura de pito; VL (kala-azar, black fever, Dumdum fever)
  • System(s) affected: skin/exocrine; pulmonary; hematopoietic; lymphatic; immunologic; hepatic

Epidemiology

  • Found in 88 countries (72 of them developing)
    • >90% of VL cases occur in India, Bangladesh, Sudan, South Sudan, Brazil, and Ethiopia.
    • ~1/3 of CL cases occur in three regions: America, Mediterranean Basin, Middle East to Central Asia (10 countries account for ~70% of incidence) (1).
  • VL/CL are increasing in many parts of the world due to migration, malnutrition, and development.

Incidence
  • ~350 million at risk worldwide (2)
  • Average annual worldwide incidence of CL: 0.7 to 1.2 million; VL: 0.2 to 0.4 million (1)
  • Accounts for 2.4 million disability-adjusted life years and an estimated 20,000 to 40,000 deaths per year (1)
  • Hundreds of CL (and several VL) cases reported in the U.S. military returning from Afghanistan/Iraq
Prevalence
  • Worldwide prevalence ~12 million (1)
  • Cases may go unreported due to misdiagnosis, limited access to care/diagnosis, lack of overt illness; not a notifiable disease in all countries

Etiology and Pathophysiology

  • Sandfly meal from an infected host ingests macrophages; mastigotes transform into promastigotes and reproduce in sandfly gut and then migrate to sandfly proboscis where they are injected with next bite, repeating the cycle.
  • Bite of infected female sandfly (70 of the 800 known species carry Leishmania) injects Leishmania promastigotes (10 to 15 μm flagellated forms) into mammalian host (humans, canines, rodents). Promastigotes are phagocytized by macrophages and transform into round amastigotes (2 to 3 μm nonflagellated forms) that divide until macrophage ruptures, spilling amastigotes to infect other macrophages and further divide.
  • >30 different Leishmania species, varying by region and by organ/disease predilection

Risk Factors

  • In endemic areas, children > young adults
  • Malnutrition
  • Incomplete therapy
  • HIV/AIDS
  • Migrating to, or working in, endemic areas (e.g., military deployments, urban construction)

General Prevention

  • Use pesticides (especially synthetic pyrethroids) against sandflies and their habitat (3).
  • Avoid outdoor activities from dusk to dawn, wear long sleeves and pants whenever possible (even thin, light clothing is protective), apply insect repellant to exposed skin (3).
  • Use permethrin-impregnated bed netting (mesh size 0.6 mm × 0.6 mm; sandflies fit through standard mosquito netting) while sleeping (3)[A].
  • Diagnose and treat human cases promptly (3).
  • Control animal reservoirs (especially dogs) (3).
  • No vaccine available currently for human use (3)

Commonly Associated Conditions

  • Fulminant kala-azar described in association with AIDS and malnutrition
  • Diffuse CL, due to defective cell-mediated immune response, causes disseminated lesions (resembling leprosy) that fail to heal spontaneously and relapse after treatment.
  • Post–kala-azar dermal leishmaniasis (PKDL), a chronic cutaneous form, may develop after VL recovery, requiring prolonged treatment.

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