Visceral Leishmaniasis (Kala-Azar) Complete Lecture Notes for Medical Students

Visceral Leishmaniasis (Kala-Azar)

1. Definition & Synonyms

Visceral Leishmaniasis (VL), also called Kala-azar or dum-dum fever, is a systemic protozoal disease caused by the Leishmania donovani complex. Multiplication in reticulo-endothelial cells leads to fever, cachexia, hepatosplenomegaly, pancytopenia & hyper-gammaglobulinemia.

2. Epidemiology & Life Cycle

Global hot-spots: India, Bangladesh, Sudan, South Sudan, Ethiopia, Brazil.
Agents: L. donovani (Old World), L. infantum / chagasi (New World).
Vector: Female sandfly (Phlebotomus, Lutzomyia).
Reservoir:
- Indian subcontinent – humans (anthroponotic).
- Mediterranean & Latin America – dogs & wild canids (zoonotic).
Transmission: Sandfly bite; rarely trans-placental, transfusion, needle sharing.

3. Morphology

Promastigote (in sandfly): flagellated, infective.
Amastigote (LD body) (in human macrophage): 2–4 µm oval body with nucleus & kinetoplast.

4. Pathogenesis & Immunity

Parasite survives in macrophage by blocking oxidative burst (LPG, gp63).
Spreads to spleen, liver, bone marrow → RE-cell hyperplasia.
Immunosuppression: ↓ IL-2, IFN-γ; ↑ IL-10 → anergy to leishmanin skin test.
Post-cure immunity is lifelong; HIV co-infection increases relapse risk.

5. Clinical Features

Incubation	2–6 months (range 10 days – 2 years)
Systemic	Prolonged irregular fever (double-quotidian). Marked weight loss & cachexia. Hepatosplenomegaly – spleen firm, non-tender. Pallor, petechiae, epistaxis (pancytopenia). Lymphadenopathy common in Sudan strain.
Laboratory	Pancytopenia (anemia, leukopenia, thrombocytopenia). Hyper-gammaglobulinemia (polyclonal IgG). Reversed A:G ratio.

5.1 Complications

Secondary bacterial infections (pneumonia, TB).
Hemorrhage (epistaxis, GIT).
Post-kala-azar dermal leishmaniasis (PKDL): hypopigmented macules → nodules/plaques 6-36 months after cure.

6. Diagnosis

A. Parasitological (gold standard)

Splenic / bone-marrow / lymph-node aspirate – Giemsa stain shows LD bodies.
Culture (NNN medium) or qPCR (species identification & quantitation).

B. Serological (field screening)

Test	Sensitivity	Remarks
rK39 Rapid test (dipstick)	~97 %	Point-of-care, no cold chain
DAT	95 %	Field lab friendly
ELISA / IFAT	90–100 %	Good for surveillance

C. Molecular

qPCR on blood/buffy-coat – >95 % sensitive, useful for monitoring.

D. Leishmanin (Montenegro) skin test

Negative during active disease, positive 6–8 weeks after cure.

7. Treatment

Drug	Dose & Duration	Region / Notes	Side-effects
Liposomal Amphotericin B (LAMB)	3–5 mg/kg/day × 5–10 days (total 20 mg/kg)	First-line India, Europe, USA	Infusion reactions, nephrotoxicity
Sodium Stibogluconate (SSG)	20 mg Sb⁵⁺/kg/day IM/IV × 28–30 days	East Africa, Nepal	Pancreatitis, cardiotoxicity
Miltefosine (oral)	2.5 mg/kg/day (max 100 mg) × 28 days	India, Bangladesh, Nepal	Teratogenic, GI upset
Paromomycin (IM)	15 mg/kg/day × 21 days	Africa combination therapy	Ototoxicity, nephrotoxicity
Pentamidine	4 mg/kg every other day × 8–10 doses	Second-line South America	Diabetes, cardiotoxicity

Special situations

HIV co-infection: LAMB 40 mg/kg total + monthly secondary prophylaxis.
Pregnancy: LAMB safest; avoid miltefosine & SSG.
PKDL: miltefosine 12 weeks or LAMB 20 mg/kg.

8. Prevention & Control

Early case detection & complete treatment.
Vector control: long-lasting insecticidal nets, indoor residual spraying.
Canine reservoir management (collars, testing, culling).
Surveillance for PKDL.
No licensed vaccine yet.

9. Prognosis

Untreated mortality >90 %.
With therapy: >95 % cure if no resistance.

10. High-Yield Exam Points

Fever + splenomegaly + pancytopenia = think VL.
Diagnostic smear: LD body inside macrophage.
Best field test: rK39 dipstick.
Drug of choice India: single-dose LAMB 10 mg/kg.
Pregnancy safe: Liposomal Amphotericin B.

References: WHO 2022 VL guidelines, CDC Yellow Book, StatPearls, NIH review articles.