Leishmania

Leishmania

Introduction

The genus Leishmania is a member of the phylum Sarcomastigophora of the kingdom protista. It is a diploid, intracellular parasite with a single flagellate.

Leishmania is a parasite that affects vertebrates with the disease called Leishmaniasis. It has a complex life cycle. When an infected Phlebotomid sand fly (Phlebotomus) takes a blood meal it infects the vertebrate host with promastigote metacyclic forms. Within a short time the promastigotes are taken up by macrophages, the first line of defense of the immune system. The promastigote then loses its flagella and transforms into the amastigote form. Once internalized in a phagosome the macrophage lysosome fuses with the phagosome to from a phagolysosome containing the parasite

Epidemiology

Leishmania spp. are transmitted by flies of the genus phlebotomus in the old world and Lutzomyia in the new world 

 Life Cycle

Leishmania is a protozoan infection that is responsible for three primary diseases.

Cutaneous leishmaniasis

• 1. Cutaneous infection is caused by either Leishmania tropica or L. braziliensis

it Is the most common form of leishmaniasis in which the epidermis is the primary sight of infection. The symptoms associated with cutaneous leishmaniasis are macule or papule erthematous (small raised skin lesions), skin ulcer (extremely raw often-bleeding area of skin around sight of original infection), satellite lesions (small lesions that form a few centimeters from the original infection. Most of the time a person infected with cutaneous leishmaniasis will survive the infection without medical intervention, although in developed nations it is usually treated nonetheless to prevent disfigurement. In weak individuals cutaneous leishmaniasis can progress to visceral leishmaniasis

• 1) Sores develop where sandflies bite
• 2) Incubation period 2 weeks to 3 years
• 3) Characteristics of ulcers

o    a) Uusally singular

o    b) Begins as itching papule

o    c) Surface breaks down-discharges bloody fluid

o    d) Healing is slow (3-12 months)

Mucocutaneous Leishmaniasis (Leishmania braziliensis) (Espundia, uta, chiclero ulcer)

enlarged liver

o    a. Hosts: man, dog, wild animals, particularly rodents

o    b. Geographic distribution: Central and South America

Is the most sever of the three types of disease, in this form the parasite becomes systemic (spread through out the entire body) by infecting macrophages (immune cells) that in turn carry it to the spleen, liver and bone marrow. The typical symptoms for this form of the disease are fever, night sweats, fatigue, weakness, anorexia (appetite loss), weight loss, vomiting, diarrhea, cough, skin lesions and hair loss. If visceral leishmaniasis goes untreated it will usually result in death of the host do to liver damage, fever, weight loss and often secondary infection do to the fact that the macrophages are killed there by compromising the immune system. Visceral leishmaniasis is extremely dangerous to people already infected with HIV as the already compromised immune system is damaged even more so by the loss of macrophages. (World Health Organization, Fact sheet on Leishmania/HIV co-infection)

• Usually occurs when the original sight of infection is near mucous membrane, although it can also result from visceral or cutaneous infections. The symptoms include nasal stuffiness, runny nose, bleeding of nose, rectum and vagina, ulcers and erosions of mouth, nose, tongue, gums, lips, rectum, vagina. This form of leishmaniasis typically requires rapid treatment in order to prevent extreme deformities to the infected area. Mucocutaneous infections will often advance to visceral infections if not treated.

Diffuse, anergic cutaneous leishmaniasis (keloid or leproid leishmaniasis

o    a. Hosts: Man --other animals?

o    b. Geographic Distribution: Ethiopia, Sudan, kenya, Tanzania,Venezuela, Brazil and Mexico

o    c. Clinical Features

§  1. Begins as single nodule

§  2. Resembles leprosy

§  3. Nodules do not ulcerate nor do granulomas form

§  4. ID skin test remains negative, indicating a deficient immune response

Diagnosis of mucocutaneous leishmaniasis

Leishmanin (Montenegro test - ID test for delayed hypersensitivity

for cutaneous mucocutaneous infections skin biopsy fallowed by culturing of biopsy material is the most common way to check for Leishmania infections. For visceral infections spleen or bone marrow biopsies are possible, and the most accurate tests, but are also very expensive and require invasive surgery. The more common test is to draw blood, and test the blood with florescent antibodies to check for the presence of Leishmania. Complementary tests that can be performed include CBC (shows decreased cellularity of blood), hemoglobin (shows signs of anemia), serum protein (decreased), serum albumin (decreased) and immunoglobulins (increased).

Clinical features

     a. Incubation period 2 to 4 months

     b. Symptoms include fever, malaise, lassitude

     c. Five cardinal features of established disease

§  1). Hepatosplenomegaly

§  2). Generalized lymphadenopathy

§  3) Pancytopenia

§  4) Fever

§  5) Cachexia

    d. Other signs include peripheral edema, dry brittle hair, ecchymoses.

    e. Patients usually die from severe cachexia and intercurrent infection.

Post kala-azar dermal leishmaniasis

o    a. Occurs in small percentage of patients who recover from visceral leishmaniasis

o    b. Macules, papules, and nodules are disfiguring.

o    c. Caused by inadequate cell-mediated immune response

 Diagnosis of visceral leishmaniasis

o    a. Smears and biopsy specimens

o    b. Skin biopsies for dermal leishmaniasis

Treatments for Leishmania

The most commonly used cheapest and most effective chemotherapies for Leishmania infections are antimony-containing compounds such as Meglumine or Amphotericin B7. However many people have rather severe allergies to these compounds, plus they have been shown to be dangerous to those who are pregnant, breast feeding, or likely to become pregnant in the next year. Another option in the case of allergy to the antimony compounds is Sodium stibogluconate, however this drug is less effective and has been shown to more often result in drug immune Leishmania. In the case of cutaneous Leishmania infections Paromomycin that is an antimony topical ointment is an option. In sever cases were drug immunity is present it may be necessary to remove the spleen; this however is not always effective, and often not possible in developing nations.

(The Medical Letter)

Prevention of Leishmania

So far all attempts to create a preventative vaccine have been unsuccessful. However there is some evidence that people who have had cutaneous infections have heightened resistance to future visceral or cutaneous infections so some researchers are looking into the possibility of infection with an attenuated strain in the epidermis to cause a mild cutaneous infection. At present the only effective preventative measure is to prevent sand fly bites either by killing them with pesticides or by using insect repellents. 

(National Institute of Health)

Control of Leishmaniasis

Since 1993, regions that are Leishmania-endemic have expanded significantly; this is most likely due to development, like the massive rural-urban migration in many developing nations. Also man-made projects with environmental impact, like dams contribute to the spread of Leishmaniasis.

(World Health Organization)

Leishmaniasis currently threatens 350 million men, women and children in 88 countries around the world. (CDC)

It is found in Africa, Asia, Europe, North America and South America. 

In endemic areas such as Bangladesh and India sand fly control is often combined with malaria control. Mass spraying with chemicals such as DDT, Malathion, Fenitrothion, Propoxur and Diazinon is used to controle sand fly populations. Self-protection is important; several methods are available to avoid being bitten by sand flies including repellents such as diethyltoluamide (DEET) applied to the exposed areas of the body and clothing. Fine mesh screens can be applied to doors and windows and bed nets should be used impregnated with insecticides such as permethrin and deltamethrin. Mosquito nets are not effective since sand flies can get through the holes.

There is no vaccines or drugs discovered yet to prevent the infection of Leishmania. The best way to prevent infection is to prevent being bit by an infected sand fly. Sand flies are controlled in many courtiers such as Bangladesh and India by mass spraying of chemicals such as DDT, Malathion, Fenitrothion, Propoxur and Diazinon.

Screening and treatment of domestic animals especially dogs is recommended