Leishmaniasis - Causes, Symptoms and Treatment

Definition:

Prevalent on four continents, leishmaniasis refers to various clinical syndromes caused by a vector-borne protozoan and characterized by cutaneous lesions, weight loss, cough, fever, diarrhea, lethargy, and splenomegaly. It's endemic to subtropical countries, particularly those undergoing economic development and man-made environmental changes. Previously regarded as a rural disease, outbreaks of leishmaniasis have been reported in large cities and suburbs of Brazil due to favorable epidemiological conditions, malnutrition, poor sanitation, and population migration.

While leishmaniasis is associated with low mortality, it has a high morbidity rate. It is estimated that 350 million people are exposed to the disease and approximately 12 million are afflicted worldwide. The global annual incidence is estimated at 1.5 to 2 million new cases per year; however, it's now generally accepted that leishmaniasis is grossly underreported. It's considered to be an emerging disease in developed countries, where Leishmaniasis/human immunodeficiency virus (HIV) co-infection is becoming more prevalent due to the acquired immunodeficiency syndrome (AIDS) pandemic and expanded international travel.

Causes of Leishmaniasis

Leishmania, responsible for human leishmaniasis, is a genus of protozoan's that have a dimorphic life cycle. They occur in mononuclear phagocytes in the body's defense system and multiply intracellularly, resulting in lysis of host cells and infection of other phagocytes. Leishmania has also been located in macrophages throughout the reticuloendothelial system in cases of visceral leishmaniasis. Macrophages in skin lesions reveal Leishmania in cutaneous leishmaniasis.

Leishmaniasis is transmitted by small, biting sand flies, which are infected with Leishmania and inhabit moist soil, forests, caves, and rodent burrows. Although small rodents and mammals, dogs, foxes, chickens, horses, and humans serve as host reservoirs, the domestic dog is considered to be the principal reservoir. The protozoan is transmitted from one mammalian host to another by the bite of the sand fly, an avid feeder. It strikes humans primarily at night. Fast urbanization, invasion of primary forests, dramatic reductions in the vector's natural ecological space, drought, famine, poor sanitation, overcrowding, and the practice of harboring animal hosts, particularly dogs, close to human domiciles are among the main causes of exposure to and subsequent infection by the Leishmania vector.

Signs and Symptoms of Leishmaniasis

Leishmaniasis can be divided into four major clinical forms: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (ML), diffuse cutaneous leishmaniasis (DCL), and visceral leishmaniasis (VL). Additionally, the first three forms are further classified as New World or Old World, depending on the clinical presentation, species of infective parasite, and geographic location.

Cutaneous leishmaniasis, the most common form of infection, manifests as single or multiple ulcerating papules which heal after a few weeks or months, leaving flat, atrophic scars. Regional lymphadenopathy usually accompanies the lesions; fever, malaise, anorexia, and weight loss may also occur. The incubation period for CL may range from two weeks to several months. Resistance to re-infection by the same species of protozoa often occurs.

Mucocutaneous leishmaniasis begins with simple cutaneous lesions which progress to form hideously disfiguring lesions of the nose, mouth or pharynx months or years after primary cutaneous infection. ML is responsible for soft tissue, cartilage, and bone destruction, which can lead to nasal obstruction, congestion, discharge, or epistaxis.

Diffuse cutaneous leishmaniasis, which closely resembles leprosy and is the most difficult to treat, is the anergic variant of CL. It is characterized by large numbers of parasites in multiple, ulcerating nodules found on the face and extremities. The syndrome may persist for more than 20 years, as the body fails to mount a cellmediated immune response.

Left untreated, visceral leishmaniasis is the deadliest form of Leishmania. VL leishmaniasis symptoms include diarrhea, hepatosplenomegaly, lethargy, weight loss, cough, and fever. Some or all of these symptoms may be present, giving the disease a wide range of presentations. In general, symptoms manifest in three to eight months; however, incubation may occur in as little as ten days or extend as long as 34 months. Onset of symptoms may be sudden or gradual.

Diagnosis for Leishmaniasis

Diagnosis of all forms of leishmaniasis is most accurately accomplished via staining and identification of the parasite from specimens obtained from skin punch biopsy or scrapings from the base of an ulcer, spleen and bone marrow aspirates, and lymph node biopsy. Specific antibodies may be detected via the indirect immunofluorescent test(IFAT), the enzyme linked immunosorbent assay (ELISA), and the direct agglutination test (DAT). Occasionally, skin testing with leishmanial antigens may be employed. Polymerase chain reaction has proven to be highly sensitive and specific as well. Staining tissue with monoclonal antibodies is species­specific; however, it is available only in research laboratories.

The differential diagnoses to consider include: sporotrichosis, chromomycosis, lobomycosis, cutaneous tuberculosis, atypical mycobacterial infection, syphilis, yaws, leprosy, sarcoidosis, neoplasm, malaria, typhoid fever, typhus, acute Chagas' disease, acute schistosomiasis, miliary tuberculosis, amebic liver abscess, brucellosis, histoplasmosis, infectious mononucleosis, leukemia, lymphoma, agnogenic myeloid metaplasia, hepatosplenic schistomiasis, prolonged Salmonella bacteremia, and tropical splenomegaly from chronic malaria. Leishmaniasis can be safely excluded from those who are not international travelers or immigrants of endemic areas.

Treatment for Leishmaniasis

Pentavalent antimonial compounds are the drugs of choice for treating visceral and cutaneous leishmaniasis. The drug must be obtained from the Drug Service of the Centers for Disease Control and Prevention (CDC). It is administered I.M. or I.V. over a 5- to 28-day period, depending on the type of leishmaniasis as well as the presence of drug-related signs of toxicity. Amphotericin B is employed in cases of resistant strains of VL. Pentamidine is considered a second-line agent, due to increasing resistance and prolonged course of therapy.

Special Considerations and Prevention Tips for Leishmaniasis

In the absence of prophylactic drug treatment for leishmaniasis, the best treatment is prevention. Instruct travelers to endemic areas to minimize sand fly exposure by avoiding outdoor activities when sand flies are most active (dusk to dawn); covering all exposed skin with netting; applying repellants such as DEET, lemon essential oils, or 2% neem oil to the skin and under the edges of clothing; and using permethrin-impregnared clothing.

Some more Tips:

• Monitor skin lesions for signs and symptoms of bacterial infection.
• Utilize appropriate personal protective gear.
• Instruct patients to avoid touching skin lesions to avoid complications.
• Monitor for adverse effects of pentavalent antimonial agents, such as arthralgia, myalgia, nausea, vomiting, abdominal pain, headache, rash, pancreatitis, anemia, leukopenia, thrombocytopenia, and renal insufficiency.
• Monitor weekly transaminase, lipase, complete blood count (CBC), and creatinine levels. Transaminase levels greater than or equal to 4 to 5 times the upper limits of normal necessitate discontinuation of pentavalent anti monial therapy.
• Monitor weekly electrocardiograms for QT interval prolongation, T-wave inversions, or significant dysrhythmia with pentavalent antimonials.
• Observe for adverse effects of amphotericin therapy, which include nausea, vomiting, malaise, anemia, hypokalemia, hypomagnesemia, and nephrotoxicity. Be prepared to monitor frequent CBCs, potassium and magnesium levels, and blood urea nitrogen and creatinine levels.
• Monitor the patient for side effects of pentamidine therapy, which include hypoglycemia followed by diabetes, hypotension with too rapid infusion, nausea, vomiting, abdominal pain, and headache.
• Be prepared to provide emotional support for coinfected HIV/VL patients as their prognosis is poor.