Leishmania:

## **Introduction** - Leishmania is a genus of flagellate protozoa responsible for leishmaniasis. - The disease is transmitted by the female sandfly (*Phlebotomus* species in the Old World and *Lutzomyia* species in the New World). - It is an **obligate intracellular parasite**, completing its life cycle in two hosts:**Definitive host:** Humans, dogs, and other mammals. - **Vector:** Female sandfly. - **Infective form:** Metacyclic promastigote. ## **Epidemiology** - **Global Distribution:** Leishmaniasis is widespread in the tropics and subtropics, including:Central and South America, parts of North America, Central and Southeast Asia, India, China, the Mediterranean region, and Africa. - **Risk Factors:**Affects low socio-economic groups. - Poor housing, overcrowding, poor ventilation, and organic material accumulation inside houses increase transmission risk. ## **Types of Leishmaniasis** - **Visceral Leishmaniasis (Kala-azar):**Caused by *L. donovani complex*. - Affects internal organs, mainly the liver, spleen, and bone marrow. - **Cutaneous Leishmaniasis:**Caused by *L. tropica complex, L. aethiopica, L. major,* and *L. mexicana complex*. - Characterized by skin ulcers. - **Mucocutaneous Leishmaniasis:**Caused by *L. braziliensis complex*. - Affects mucous membranes of the nose, mouth, and throat. # **Leishmania donovani: Visceral Leishmaniasis (Kala-azar)** ## **Morphology** - Exists in **two forms**:**Amastigote form** (Leishman-Donovan [LD] bodies) – found inside macrophages of the reticuloendothelial system. - **Promastigote form** – found in the sandfly vector and in artificial culture. ## **Life Cycle** ### **1. Transmission to Humans** - Humans acquire the infection through the bite of an infected **female sandfly**. - Other transmission routes:Vertical (mother-to-fetus). - Blood transfusion. - Laboratory inoculation (accidental). ### **2. Infection in Humans** - Promastigotes enter the wound via sandfly bite. - Phagocytosed by **macrophages, monocytes, and polymorphonuclear leukocytes**. - Transform into **amastigotes** within the macrophages. - Multiply by **binary fission**, eventually lysing the macrophages. - Spread to **spleen, liver, bone marrow, lymph nodes, and intestinal mucosa**. ### **3. Transmission to Sandfly** - When a sandfly bites an infected person, it ingests **amastigotes**. - In the sandfly's **midgut**, amastigotes transform into **promastigotes**. - Multiply by **longitudinal binary fission**, forming **rosettes**. - Migrate to the **pharynx and hypostome**, where they accumulate and block passage. - When the sandfly bites another person, **infective promastigotes** are regurgitated into the wound. ### **4. Extrinsic Period (In Vector)** - Takes about **10 days** for promastigotes to develop in the sandfly before transmission. ## **Pathogenesis and Organ Involvement** - **L. donovani** infects the **reticuloendothelial system (RES)**, leading to widespread infection. - **Spleen**:Most affected organ, **massive splenomegaly**. - Soft, friable, dark chocolate/red cut surface due to engorged vascular spaces. - Microscopically, reticulum cells contain **numerous LD bodies**. - **Liver**:Enlarged liver with **Kupffer cell** parasitization. - Hepatocytes are **not affected**. - Nutmeg appearance on cut section. - **Bone Marrow**:**Suppression of hematopoiesis** due to infiltration with infected macrophages. - Causes **pancytopenia** (anemia, leukopenia, thrombocytopenia). ## **Clinical Features of Kala-azar** - **Incubation Period**: 2–6 months (can range from 10 days to 2 years). - **Symptoms**:Insidious onset of **irregular, remittent fever**. - **Progressive massive splenomegaly** (hallmark sign). - **Hepatomegaly** (less prominent than spleen). - **Lymphadenopathy** (not always present). - **Severe anemia** due to bone marrow suppression and hypersplenism. - **Darkening of skin** ("Kala-azar" means "black fever"). - **Cachexia, weight loss, and emaciation**. - **Bleeding tendencies** (epistaxis, gum bleeding). - **Fatality** in untreated cases within **2 years** due to opportunistic infections. ## **Post-Kala-azar Dermal Leishmaniasis (PKDL)** - Occurs **1–2 years after recovery** from visceral leishmaniasis. - Seen mainly in **India and East Africa**. - **Types of Skin Lesions**:**Depigmented macules** – resemble tuberculoid leprosy. - **Erythematous patches** – occur on the face in a **butterfly distribution**. - **Nodular lesions** – non-ulcerative granulomatous nodules. - **Parasites can be demonstrated in lesions**. ## **Diagnosis of Visceral Leishmaniasis** ### **1. Microscopy (Gold Standard)** - **Demonstration of amastigotes (LD bodies)** in smears from:**Peripheral blood** - **Bone marrow aspirate** - **Splenic aspirate (most sensitive but risky due to bleeding complications)** - **Enlarged lymph node aspirate** - Staining: **Leishman, Giemsa, or Wright’s stain**. ### **2. Culture** - *Novy-MacNeal-Nicolle (NNN) medium* for promast