Wednesday, February 1, 2012


"The various clinical forms of leishmaniasis are also on the rise; the number of reported cases has tripled over the last 10 years."  I read this in a 2008 Pan American Health Organization (PAHO) report on Healthcare in Nicaragua. 

Leishmaniasis, I thought.
I don't know anything about leishmaniasis.  

So, learning about leishmaniasis became a learning project. Below is a summary of my reading.  

Leishmaniasis is caused by a protozoa transmitted to mammals via the bite of the female sandfly of the genus Phlebotomus in the Old World and Lutzomyia in the New World.
Female Sandfly
For most species of Leishmania, an animal reservoir is required for endemic conditions to persist. Common New World hosts include sloths, anteaters, opossums, and rodents. Humans are considered incidental hosts.
Leishmaniasis can be divided into cutaneous, mucocutaneous, visceral, and viscerotropic forms.
Parasites exist in the promastigote stage in sandflies and transform to the amastigote form in animal and human hosts.
Female sandflies can transmit the parasite 7-10 days after feeding on an infected host. The promastigotes migrate from the gut to the proboscis and are regurgitated during the next meal into the new host's tissue.
After inoculation, parasites infect the reticuloendothelial system and live in the intracellular lysosomal organelles of macrophages.
Parasites may incubate for weeks to months before presenting as skin lesions or as a disseminated systemic infection involving the liver, spleen, and bone marrow.
Pathogenesis appears related to T-cell cytotoxicity. The extent and presentation of disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence of the infecting species, and the parasite burden.
Infections might heal spontaneously or might progress to chronic disease, often resulting in death from secondary infection.

New World leishmaniasis exists throughout the Americas, with the exception of Canada, Chile, and Uruguay.
Cutaneous Leishmaniasis
      Inoculation occurs after a sandfly bites an exposed part of the body, usually the legs, arms, neck, or face.
      Incubation occurs over weeks to months followed by the appearance of a solitary erythematous papule, which can evolve into a plaque or ulcer.
      The skin lesion begins as a nontender, firm, red papule several centimeters in size at the site of the sandfly bite.
      In time, the lesion widens with central ulceration, serous crusting, and granuloma formation.
      The border often has a raised erythematous rim known as the volcano sign.
      Lesions can be wet or dry and become fibrotic or hyperkeratotic with healing.
      Satellite lesions might be present.
      Wound progression occurs over time and might exhibit localized lymphangitic spread.
      Lesions are usually without pain or pruritus, although secondary bacterial infection can complicate the wound.
      Systemic symptoms are absent.
      Healing can occur spontaneously over 2-12 months and is followed by scarring and changes in pigmentation.
      New World disease can progress to mucocutaneous leishmaniasis.

Mucocutaneous Leishmaniasis
  Most commonly caused by New World species.
  Can arise after inadequate treatment of certain Leishmania species.
      Initial infection is characterized by a persistent cutaneous lesion that eventually heals, although as many as 30% of patients report no prior evidence of leishmaniasis.
      The initial skin lesion is often notable for its prolonged healing time and large size. In most cases, a healed scar can be identified based on careful examination.
      Oral and respiratory mucosal involvement occurs months to years later and causes inflammation and mutilation of the nose, mouth, oropharynx, and trachea.
      Patients develop rhinorrhea, epistaxis, and nasal congestion.
      Examination reveals excessive tissue that obstructs the nares, septal granulation, and perforation.
      Nose cartilage might be involved, giving rise to external changes known as parrot's beak or camel's nose.
      The palate, uvula, lips, pharynx, and larynx might exhibit granulation, erosion, and ulceration with sparing of the bony structures.
      Hoarseness might be a sign of laryngeal involvement.
      With prolonged infection, death occurs from respiratory compromise, malnutrition due to dysphagia, and secondary infection.
Visceral Leishmaniasis
      The most devastating and fatal form, classically known as kala-azar or black fever.
      The incubation period varies after infection and might depend on the patient's age and immune status and the species of Leishmania.
      Results from systemic infection of the liver, spleen, and bone marrow.
      Pentad of fever, weight loss, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia.
      Patients present with recurrent high fevers, wasting, anorexia, night sweats, diarrhea, and malaise.
      Patient is thin and cachetic with abdominal distension and protuberance due to massive hepatosplenomegaly.
      Epistaxis and petechiae from severe thrombocytopenia.
      Melanocyte stimulation and xerosis causes characteristic skin hyperpigmentation.
      A progressive disease with the mortality rate ranging from 75-95% if untreated. With appropriate therapy and supportive care, the mortality rate is 5%.
      Death usually occurs from malnutrition, immunosuppression, and secondary infection.

Always treat visceral, mucocutaneous, and severe forms of cutaneous leishmaniasis. Given its potential to progress into mucocutaneous leishmaniasis, treat New World cutaneous leishmaniasis.
Therapies available are limited.
The mainstays are the pentavalent antimony compounds, sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime), which have similar efficacy. Cure rates of 80-100% have been reported.
Other therapies include amphotericin B (AmBisome) and pentamidine.
Orally administered ketoconazole, itraconazole, fluconazole, allopurinol, and dapsone have been examined internationally, but none is as effective as the pentavalent antimony compounds. However, given their minimal adverse effect profile, these agents might be useful to accelerate the cure in patients with cutaneous leishmaniasis that does not progress to mucosal disease and tends to self-resolve.

The recent discovery of an affordable, orally administered, and well-tolerated therapy for visceral leishmaniasis has made mass treatment in the developing world a reality. Miltefosine is a phosphocholine analogue originally developed as an antineoplastic agent that interacts with membrane synthesis and signal production.
Insect repellent, protective clothing, and permethrin-impregnated mosquito nets offer some protection for visitors to endemic areas. The female sandfly is small enough to pass through standard mosquito nets, thus requiring specially designed netting.