Leishmaniasis

Leishmaniasis is a zoonosis (a disease transmitted from animal to human) caused by more than 20 species of parasites of the genus Leishmania, hemophagellated (i.e., equipped with a flagellum that moves through the bloodstream) asexual and dixenes (whose vire cycle takes place within two separate hosts. The parasite has different stages of evolution during its life cycle. In promastigote form, in which it has an elongated shape and a flagellum, it penetrates the host during the blood meal of the vector insect, reaching the bloodstream where it is attacked by macrophages. Within these it transforms into the amastigote stage, in which the shape becomes oval and the flagellum retracts into the membrane, preventing its autonomous mobility. It is at this stage that replication occurs, which continues until it causes lysis (destruction) of the cell, resulting in the release of the amastigotes into the bloodstream, where they can infect new cells. Remaining present in the bloodstream, it is then able to infect new insects during the blood meal, which transports it to the gut of the vector where it returns to the promastigote stage, multiplies by binary cleavage, and emigrates to the salivary glands of the vector for a new cycle of transmission.

Vectors are more than 90 species of phlebotomus, or pappatacs, small mosquito-like gnats whose females feed on blood as their eggs mature and are therefore at risk of receiving and transmitting the parasite. It is estimated that more than 70 different animal species (including dogs and rodents) serve as intermediate hosts of the parasite, capable of infecting the parasites.
Direct human-to-human transmission of the disease from blood transfusions or through the use of infected syringes is also possible, although rare.

Leishmaniasis is endemic in nearly 90 countries in Asia, tropical North Africa and Africa, Mediterranean Europe (including Italy, France, and Spain), and Central and South America, with some cases even in the southern US. It is most common in rural areas, where the parasites tend to live, but it can also be found on the borders of urban regions, and there is a real risk that climate change will lead to a significant enlargement of endemic regions, creating suitable habitats for the parasites.

Leishmaniasis has three main forms in which it can manifest itself:

Cutaneous leishmaniasis, the most common form, causes skin lesions such as papules and nodules, which can develop into ulcers and scabs, usually concentrated in exposed areas such as the legs, arms and face. It may be accompanied by swelling of glands near the lesions. Lesions can appear in considerable numbers (even more than 200 individual lesions) and leave scars after healing.

Mucocutaneous leishmaniasis, which causes lesions that can lead to destruction of the mucous membranes of the nose, mouth and throat, and surrounding tissues, also leading to severe disfiguration. It is also known as "espundia."

Visceral leishmaniasis, or kala azar, is the most severe form, manifested by periods of irregular fever, malaise, weight loss, anemia, leukopenia and thrombocytopenia (deficiency of red, white and platelet cells), abdominal pain with enlargement of the liver and spleen. If untreated, it has a mortality rate of up to 100%.

Five to 10 percent of cases of patients (usually in the Indian subcontinent and East Africa) with visceral leishmaniasis may develop a cutaneous form that typically appears between 6 months and 1 year after apparent recovery. Of particular concern is Leishmania/HIV coinfection, particularly in cases of visceral leishmaniasis. On the one hand, the parasite speeds infection with HIV (and also with other diseases such as tuberculosis and pneumonia); on the other hand, HIV increases the risk of contracting leishmaniasis 100 to 1000 times more. Co-infection contributes to weakening the immune system (both virus and parasite target the same cells), increasing the chances of developing a severe form, with high mortality rates and numerous relapses.

Diagnosis is made by observing clinical symptoms combined with confirmatory tests. In the case of visceral leishmaniasis, a serologic test for antibodies can also be used in support, while for cutaneous and mucocutaneous forms it is necessary to resort to parasitologic tests on samples taken from the lesions (cutaneous form) or bone marrow (visceral form), such as detection of amastigotes under a microscope or with polymerase chain reaction (PCR) tests.

Several drugs are available for the treatment of leishmaniasis, the choice of which depends largely on the characteristics of the patient, the form of the disease, the geographic region of infection, and the species of parasite responsible, which should be identified following careful case analysis.
For the cutaneous form, which is able to heal spontaneously, control therapies can be used in the case of small lesions. If the lesions are small and simple, topical treatments based on injections of sodium stibogluconate or topical paromomycin, cryotherapy, or thermotherapy may be used.
In more severe cases, or in the presence of the other forms, systemic treatments with liposomal amphotericin EV or miltefosine orally, or amphotericin B deoxycholate EV or pentavalent antimonials (sodium stibogluconate, meglumine antimoniate) EV or IM are used if the infecting species is susceptible to such treatments.
Particular attention should be paid to cases of coinfection, where immunodepression reduces the efficacy of treatment and increases the risk of recurrence. Retroviral drugs for the management of AIDS can assist in restoring immune system function and promote recovery.
In the case of the visceral form, supportive therapies such as blood transfusions, administration of antibiotics for secondary infections, and dietary control are often necessary.

No vaccines are currently available against human leishmaniasis, so careful behavioral prophylaxis is essential to reduce the risk of being stung by parasites. In endemic areas, care should be taken to cover up with thick clothing, apply repellents, and avoid exposure at dusk and at night. It is advisable to treat clothing and equipment (such as mosquito nets) with permethrin.
Plans to control phlebotomus populations and reservoir animals (particularly dogs and rodents) can assist in reducing the risk of infection, but their effectiveness depends largely on the specific characteristics of the region.