Kala-azar (Visceral Leishmaniasis)

Organism/Vector

L. donovani (Indian subcontinent, East Africa). L. infantum/chagasi (Mediterranean, Latin America — pediatric/immunocompromised predilection elsewhere). Forms: Promastigote (flagellated, sandfly/gut) vs Amastigote (non-flagellated, obligate intracellular, human macrophage — DISEASE-CAUSING form).

Vector: female sandfly (Phlebotomus argentipes, India). Dusk/night biting. India: ANTHROPONOTIC — human = reservoir (unusual among leishmaniasis regions). → case Rx = outbreak control measure.

Pathogenesis

Promastigote → dermal macrophage phagocytosis → amastigote transformation → resists killing → disseminates via blood/lymphatics → RE-rich organs (spleen, liver, marrow, LN) → progressive infection/proliferation → organomegaly + marrow suppression.

Clinical — Kala-azar PENTAD

Prolonged irregular FEVER
HEPATOSPLENOMEGALY (spleen >> liver)
WEIGHT LOSS/wasting
HYPERGAMMAGLOBULINEMIA (reversed A:G ratio)
PANCYTOPENIA (hypersplenism+marrow infiltration — anemia+leukopenia+thrombocytopenia) → bleeding + infection risk → fatal ~2yrs untreated

Skin darkening (“kala-azar”=black fever) = variable, more historical. PKDL (Post-Kala-azar Dermal Leishmaniasis): macular/papular/nodular rash, MONTHS-YEARS after successful Rx. Indian subcontinent. Epidemiologically important — PKDL patients (otherwise well) = human reservoir BETWEEN kala-azar epidemics.

Laboratory Diagnosis

Parasite demonstration (DEFINITIVE): amastigotes/LD bodies, Giemsa smear or NNN culture.

Splenic aspirate: HIGHEST sensitivity (~95%), hemorrhage risk, needs expertise
Bone marrow aspirate: safer, moderate sensitivity (60-85%), MORE PRACTICAL routine choice

Serology: rK39 ICT = STANDARD rapid field test (highly sensitive/specific, Indian subcontinent, national elimination programs). DAT + ELISA = alternatives. CAVEAT: serology stays + for YEARS post-Rx (can’t distinguish active vs past). NOT useful for cure confirmation/relapse — need parasite demonstration/antigen tests for that.

Nonspecific: pancytopenia (CBC), reversed A:G ratio, aldehyde/formol-gel test (historical, superseded).

Treatment

Liposomal Amphotericin B = DOC on Indian subcontinent. Single-dose/short-course, better safety than deoxycholate form. Miltefosine (ONLY oral antileishmanial), Paromomycin (injectable) = alternatives, combo regimens. Pentavalent antimonials (sodium stibogluconate) = OLD mainstay, fallen from 1st-line (widespread resistance, esp. Bihar).

Prevention

Vector control (IRS at sandfly resting sites, ITN), early case detection+Rx (interrupts anthroponotic cycle), PKDL management (sustains inter-epidemic transmission). India+Nepal+Bangladesh: regional elimination program, target <1 case/10,000 population/sub-district.

(Trypanosomiasis — see its own topic folder.)

The Organism and Vector

Visceral leishmaniasis (kala-azar, meaning “black fever” in Hindi, referencing the skin darkening it can cause) is caused by Leishmania donovani in the Indian subcontinent and East Africa (L. infantum/L. chagasi cause the disease elsewhere, notably the Mediterranean and Latin America, with a distinct paediatric/immunocompromised predilection). The parasite exists as a flagellated promastigote in the sandfly vector and gut, and as a non-flagellated, obligate intracellular amastigote within human macrophages — the form actually responsible for disease.

Transmission is by the bite of an infected female sandfly (Phlebotomus argentipes on the Indian subcontinent), a small, silent, weak-flying insect active mainly at dusk/night. In India, unusually among leishmaniasis-endemic regions, humans themselves serve as the reservoir (anthroponotic transmission) rather than an animal host — a fact with direct public-health weight, since it means case detection and treatment doubles as an outbreak-control measure.

Pathogenesis

Injected promastigotes are phagocytosed by dermal macrophages, transform into amastigotes, and resist intracellular killing by manipulating macrophage signalling. From the skin, infected macrophages disseminate via blood and lymphatics to the organs richest in the reticuloendothelial system — spleen, liver, bone marrow, and lymph nodes — where progressive macrophage infection and proliferation drive the disease’s defining organomegaly and marrow suppression.

Clinical Manifestations

The classic kala-azar pentad: prolonged, often irregular fever, marked hepatosplenomegaly (splenomegaly typically far more pronounced than hepatomegaly), progressive weight loss/wasting, hypergammaglobulinemia (a polyclonal B-cell response, with a characteristically reversed albumin:globulin ratio), and pancytopenia (from hypersplenism plus marrow infiltration) — anaemia, leukopenia, and thrombocytopenia together, which is what drives the bleeding tendency and secondary infection risk that make untreated kala-azar fatal within roughly 2 years in most cases.

Skin darkening (the literal “kala-azar”) is a variable finding, more classically described in earlier reports than commonly seen today. Post-kala-azar dermal leishmaniasis (PKDL) is a distinct, important sequela — a macular, papular, or nodular skin rash appearing months to years after apparently successful treatment, seen particularly on the Indian subcontinent, and epidemiologically significant because PKDL patients (though otherwise well) can serve as a human reservoir sustaining transmission between kala-azar epidemics.

Laboratory Diagnosis

Demonstration of the parasite (definitive): amastigotes (“LD bodies”) seen on Giemsa-stained smear or culture (NNN medium) from splenic aspirate (highest sensitivity, ~95%, but carries real haemorrhage risk given splenomegaly and needs experienced hands) or bone marrow aspirate (safer, moderately sensitive, ~60–85%, the more practical routine choice).

Serology: the rK39 antigen-based immunochromatographic test (ICT) is the standard rapid, field-deployable test — highly sensitive and specific on the Indian subcontinent, now central to national elimination programmes; the direct agglutination test (DAT) and ELISA are alternatives. A caveat worth remembering: serology can remain positive for years after successful treatment (it doesn’t distinguish active from past infection), so it isn’t useful for confirming cure or diagnosing relapse — parasite demonstration or antigen-based tests are needed for that.

Nonspecific supportive findings: pancytopenia on CBC, reversed albumin:globulin ratio, and the historical (now largely superseded) aldehyde/formol-gel test.

Treatment

Liposomal amphotericin B is now the treatment of choice on the Indian subcontinent — highly effective as a single-dose or short-course regimen, with a far better safety profile than conventional amphotericin B deoxycholate. Miltefosine (the only oral antileishmanial) and paromomycin (injectable) are alternatives, sometimes used in combination regimens to shorten treatment and limit resistance. Pentavalent antimonials (sodium stibogluconate), once the mainstay, have fallen out of first-line use across much of the Indian subcontinent because of widespread acquired resistance, particularly in Bihar.

Prevention

Vector control (indoor residual insecticide spraying targeting sandfly resting sites, insecticide-treated bed nets), early case detection and treatment (particularly important given the anthroponotic transmission cycle in India — treating patients directly interrupts transmission), and PKDL case management, since PKDL patients sustain transmission between epidemics. India, Nepal, and Bangladesh have run a coordinated regional kala-azar elimination programme targeting incidence below 1 case per 10,000 population at the sub-district level.