Visceral Leishmaniasis Symptoms and Treatment

The World Health Organization has placed Visceral leishmaniasis (VL) on the WHO’s list of “neglected tropical diseases”. It stems from a parasite that distributes to humans through the bite of infected Phlebotomus sandflies causing the disease.

The disease is prevalent in regions with temperate climate alongside being a feature in tropical countries of Central and South America (New World), the Middle East, East Africa, and East Asia (Old World). In other regions, such as the United States and Europe, travelers from affected areas may be infected.

The most visible form of this disease is cutaneous leishmaniasis. The parasites would infect the tissues of major organs, particularly the liver, spleen, and bone marrow. In this piece, we examine visceral leishmaniasis, symptoms, and treatment.

This has been termed a “vector-borne” infection. It means that an insect from another host or “reservoir” (disease carrier) transmits it. This vector switches from household pets to farm animals.

Typically, the disease navigates from various animals, including dogs, rats, sloths, cattle, and humans, who can act as hosts for Leishmania parasites. It then spreads to people through the bite of over 30 Phlebotomus genus of sand flies.

These flies are only up to 2 mm long, they make no sound, and their bite can be painless. The females need this blood meal to lay their eggs. Phlebotomine flies that spread this disease reside in the warm tropical and subtropical areas of the world.

As climate changes and temperatures shift, tropical diseases are shifting, as well.

Visceral leishmaniasis symptoms and treatment go side by side. Usually, the effects may be mild or severe. Some patients might not show signs of the disease and will not realize that they carry the parasite. The symptoms would appear in weeks to months after the bite of the sandfly.

Less commonly, symptoms could also arise only years later when a person’s immune system becomes suppressed. The five classic symptoms of more severe disease are; Severe or mild weight loss; Low blood counts (pancytopenia); Enlargement of the liver and spleen (hepatosplenomegaly), which may distend the abdomen; Fever, which is usually intermittent; and High levels of immune globulin in the blood (hypergammaglobulinemia).

In very advanced disease, the skin may become dark (hyperpigmentation). In India, this made the disease to be referred to as “kala-azar,” which means “black fever” in Hindi. The hyper-pigmentation is due to increased melanin in the skin.

Inflammatory products due to the disease stimulate the pituitary gland to make high levels of adrenocorticotropic hormone, which increases melanin production. Hyper-pigmentation usually relapses with the prescribed treatment of VL. It would no longer appear as often if treated early.

It also affects the kidney, which may lead to renal failure, although some of the anti-leishmanial drugs may also be responsible for kidney toxicity. Leishmaniasis may affect other organs, including the bowel and the lung.

The site of the sandfly bite would usually become a raised papule that expands and ulcerates, with a heaped-up border on the edges. The disease begins to show over several weeks. There may be only one lesion, or multiple lesions may appear over time.

The skin lesions would appear in a variety of appearances and may look like acne, warts, or psoriasis. They may resemble large scaly, ulcerated plaques, or form shallow ulcerated nodules. The lesions may be dry or leaking and are not usually painful unless secondarily infected by bacteria.

Sores occur mainly on the extremities and face. They heal over months to years, leaving scars that often resemble old burns. In severe cases, such as diffuse cutaneous leishmaniasis, nodular lesions may occur widely and last for years or even for life.

Due to the diversity of species and manifestations, and lack of extensive data, there is no universal drug or treatment of choice for the disease. By the IDSA guideline and CDC recommendations, medical professionals must isolate treatment based on the species, type of syndrome, and geographic area.

The only FDA-approved anti-leishmanials in the U.S. are liposomal amphotericin B and oral miltefosine. Amphotericin B has frequent side effects, including renal toxicity, and is FDA-approved for VL. Generally, patients tolerate miltefosine (Impavido) well, and it is FDA-approved for CL, VL, and ML caused by Leishmania braziliensis, L. panamensis, and L. guyanensis. It is the first highly active oral agent for VL. Ketoconazole and fluconazole are azole antifungals that may be effective against certain species.

Patients often resort to traditional agents based on antimony, called pentavalent antimonial (SbV) compounds, intravenously or intramuscularly. Sodium stibogluconate (Pentostam) is available in the U.S. for VL through the CDC Drug Service under an investigational new drug (IND) protocol.

Some areas, such as the Indian state of Bihar, report high rates of drug-resistant VL. Short-course amphotericin B or even single-dose liposomal amphotericin B has been successful in Bihar. Pentamidine has been used second-line for VL and has a number of toxicities.

Moreover, when the disease is in a person with normal immunity, it, oftentimes, does not require any treatment, depending on the severity of the lesion, since it will resolve on its own in several weeks, because of the immunity.

Health care providers sometimes simply monitor cases with few lesions that are small and appear to be healing. More cases of the disease are treated with medications, but treatment recommendations vary with where the disease is acquired and the species of leishmania when it is known.

Possible treatments for cases arriving in the U.S. include oral ketoconazole (Nizoral, Extina, Xolegel, and Kuric) or topical compound of 15% paromomycin (Leshcutan). Other treatments include local heat therapy (requires local anesthesia) or repeated cryotherapy with liquid nitrogen over several weeks.

Finally, although there is no vaccine, some countries have practiced leishmanization in the recent past, using leishmaniasis major to produce self-limited cases that relapsed with immunity.

While successful in reducing disease, it was stopped as a result of the cases of non-healing lesions; ongoing research into non-live or milder strains seeks to revive safer options. Yet, while considering the visceral leishmaniasis symptoms and treatment, the best way to prevent it is to avoid the bite of the sandfly.