BLOOD AND TISSUES – LEISHMANIA SPECIES

LEISHMANIA SPECIES

Definition – leishmaniasis is a protozoal disease caused by intracellular flagellates of the genus Leishmania (L. donovani complex produces visceral form).

Cause – bite of infected female sand‑fly (Phlebotomus or Lutzomyia) which injects metacyclic promastigotes.

Types (important for exams) –
→ Visceral leishmaniasis (Kala‑azar, L. donovani, L. infantum)
→ Cutaneous leishmaniasis (L. major, L. tropica)
→ Mucocutaneous leishmaniasis (L. braziliensis)
→ Diffuse cutaneous leishmaniasis (L. aethiopica)

Morphology of Leishmania donovani –
• Amastigote (intracellular “Leishman‑Donovan body”) – round‑oval, 2‑4 µm, nucleus occupies most of the cell, tiny kinetoplast, no external flagellum, seen inside macrophages.
• Promastigote (extracellular, sand‑fly stage) – elongated, spindle‑shaped, 15‑20 µm, single anterior flagellum attached to an undulating membrane, nucleus near the middle, prominent kinetoplast.

Life cycle (step‑wise, numbered) –

1. Sand‑fly takes a blood meal from an infected human → ingests amastigotes inside macrophages.
2. In the gut of the sand‑fly, amastigotes transform → promastigotes, multiply and become metacyclic (infective) forms.
3. Metacyclic promastigotes migrate to the proboscis.
4. During the next bite, promastigotes are injected into the skin of a new host.
5. Promastigotes are phagocytosed by neutrophils/macrophages → transform into amastigotes.
6. Amastigotes multiply by binary fission inside the phagolysosome of macrophages.
7. Infected macrophages disseminate → liver, spleen, bone marrow, lymph nodes (visceral spread).
8. Heavy parasitic load causes macrophage rupture → release of amastigotes into circulation → taken up by another sand‑fly → cycle repeats.

Memory trick for life cycle – “Bite‑Fly‑Promastigote‑Phagocyte‑Amastigote‑Spread‑Rupture” → B‑F‑P‑P‑A‑S‑R (pronounce “Bee‑F‑P‑P‑A‑S‑R”).

Pathogenesis (step‑wise) –

1. Metacyclic promastigotes enter skin → are engulfed by macrophages.
2. Inside the phagolysosome they change to amastigotes and evade oxidative burst (surface lipophosphoglycan).
3. Amastigotes multiply → overload macrophage → cell distension and eventual rupture.
4. Infected macrophages travel via blood and lymph to reticulo‑endothelial organs (liver, spleen, bone marrow).
5. Massive parasitism → splenomegaly, hepatomegaly, suppression of hematopoiesis, hypergammaglobulinemia.
6. Cytokine imbalance (↑IL‑10, ↓IFN‑γ) impairs cell‑mediated immunity, allowing chronic infection.

Clinical features –

Visceral leishmaniasis (Kala‑azar) –
→ Persistent fever (often evening rise)
→ Marked weight loss, anorexia, fatigue
→ Massive splenomegaly and moderate hepatomegaly (soft, non‑tender)
→ Pancytopenia → anemia, leukopenia, thrombocytopenia
→ Hypergammaglobulinemia (IgG)
→ Darkening of skin (post‑kala‑azar dermal leishmaniasis)

Cutaneous leishmaniasis –
→ Papule at bite site → enlarges to nodule → ulcer with raised indurated border, painless center
→ Heals with scar; lesions may be multiple in disseminated form

Mucocutaneous –
→ Nasal or oral mucosal ulceration after cutaneous lesion heals, destructive tissue loss

Complications –
→ Secondary bacterial infection of skin ulcers
→ Hemorrhagic manifestations due to thrombocytopenia
→ Relapse or post‑kala‑azar dermal leishmaniasis (PKDL)
→ Fatality if untreated (especially in children, pregnant women, immunocompromised)

Laboratory diagnosis –

Microscopy –
• Tissue smears/biopsies (splenic aspirate, bone‑marrow, lymph node) show intracellular amastigotes (Leishman‑Donovan bodies).

Culture –
• Novy‑McNeal‑Nicolle (NNN) medium or Schneider’s Drosophila medium; promastigotes appear in 3‑7 days.

Serology –
• rk39 rapid immunochromatographic test (high sensitivity for visceral form)
• Direct agglutination test (DAT)
• ELISA for anti‑Leishmania IgG

Molecular –
• PCR (targeting kDNA minicircle) – most sensitive, species identification possible.

Hematology –
• Pancytopenia, elevated ESR, hypergammaglobulinemia on serum protein electrophoresis.

Management (exam‑relevant drugs) –
• Sodium stibogluconate (SSG) 20 mg kg⁻¹ IV/IM for 20‑30 days (first‑line in many regions).
• Amphotericin B (deoxycholate or liposomal) – especially for resistant cases or HIV co‑infection.
• Miltefosine oral tablets (30 mg day⁻¹ for adults, 2‑3 weeks).
• Paromomycin (topical for cutaneous, IM for visceral).
• Supportive care – blood transfusion for severe anemia, nutritional support, treat secondary infections.

Key exam points to remember –
→ Leishmania is an obligate intracellular parasite of macrophages.
→ Visceral form = L. donovani complex → spleen, liver, bone‑marrow.
→ Diagnosis relies on demonstration of amastigotes or rk39 serology.
→ First‑line therapy still SSG in many endemic areas; liposomal amphotericin B is drug of choice in resistant or HIV cases.

Funny memory rhyme for pathogenesis –
“Macrophage eats, parasite beats, multiplies, spreads, spleen greets” – each word cues a step: engulf → survive → divide → disseminate → organ involvement.