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Leishmaniasis-2

7 min read

Visceral Leishmaniasis

Dr. Eatimad Mahgoub Osheik

Learning Objectives

By the end of this lecture, you should be able to:

  • Describe the epidemiology and life cycle of Leishmania
  • Classify different types of leishmaniasis
  • Understand pathogenesis of visceral leishmaniasis
  • Recognize clinical features and complications
  • Discuss diagnosis, treatment, and prevention

Introduction

Leishmaniasis is a protozoal disease with the following characteristics:

  • Caused by Leishmania species
  • Transmitted by the bite of female sandfly
  • An important neglected tropical disease
  • Affects skin, mucosa, or internal organs

Global Epidemiology

Geographic Distribution:

  • Endemic in tropical and subtropical regions
  • Found in Asia, Africa, South America, and Mediterranean regions
  • 90% of Visceral Leishmaniasis cases occur in:
    • India
    • Bangladesh
    • Sudan
    • Brazil
    • Ethiopia

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Disease Burden

  • Prevalence: Around 12 million people infected globally
  • Incidence: ~0.7–1.2 million Cutaneous Leishmaniasis cases and 0.2–0.4 million Visceral Leishmaniasis cases annually
  • Mortality: VL is fatal if untreated (>95% of cases)

Risk Factors

Socioeconomic:

  • Poverty
  • Malnutrition
  • Poor housing
  • Lack of resources

Environmental:

  • Rainforests
  • Peri-urban areas
  • Proximity to animal reservoirs (rodents)

Immune Status:

  • Compromised immunity
  • HIV co-infection (especially significant)

Human Behaviour:

  • Population movement
  • Lack of awareness

Causative Organism

Leishmania is an obligate intracellular protozoa that belongs to the Kinetoplastida class.

Old World Species (Africa, Asia, Europe)

  • L. tropica, L. major, L. aethiopica → Cutaneous leishmaniasis
  • L. donovani, L. infantum → Visceral leishmaniasis

New World Species (Americas)

  • L. mexicana, L. amazonensis → Cutaneous / diffuse cutaneous leishmaniasis
  • L. braziliensis → Mucocutaneous leishmaniasis
  • L. chagasi (= L. infantum) → Visceral leishmaniasis

Life Cycle of Leishmania Parasite

Overview: The Leishmania parasite’s life cycle involves two hosts: a sandfly vector and a mammalian host. The parasite alternates between flagellated promastigotes (in the fly) and non-flagellated amastigotes (in the mammal).

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Vector

Female Sandfly characteristics:

  • Phlebotomus (Old World)
  • Lutzomyia (New World)
  • Small, silent, night-biting insect
  • Breeds in:
    • Cracks in walls
    • Cattle sheds
    • Organic waste

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Leishmania Parasite Reservoir

Natural reservoirs include:

  • Dogs
  • Rodents
  • Humans
  • Wild animals (e.g., Foxes, Jackals)

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Life Cycle Steps

  1. Sandfly bites infected human → ingests amastigotes
  2. In sandfly gut → transform into promastigotes
  3. Promastigotes multiply and migrate to mouth
  4. Sandfly bites human → injects promastigotes
  5. Promastigotes enter macrophages → become amastigotes
  6. Multiply intracellularly → cell rupture → systemic spread

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Target Organs

The parasite primarily targets:

  • Spleen
  • Liver
  • Bone marrow
  • Lymph nodes

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Clinical Classification of Leishmaniasis

Based on Clinical Manifestations

  1. Visceral Leishmaniasis (VL)
  2. Cutaneous Leishmaniasis (CL)
  3. Mucocutaneous Leishmaniasis (MCL)
  4. Post-Kala-azar Dermal Leishmaniasis (PKDL)

Cutaneous Leishmaniasis

Causative Organisms:

  • L. tropica
  • L. major

Clinical Features:

  • Localized to skin
  • Lesion progression: Papule → nodule → ulcer
  • Usually painless
  • Heals with scarring
  • Known as “Oriental sore”

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Diffuse Cutaneous Leishmaniasis

Characteristics:

  • Rare form
  • Associated with poor cell-mediated immunity
  • Multiple nodular lesions
  • Resembles lepromatous leprosy
  • Difficult to treat

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Mucocutaneous Leishmaniasis

Causative Organism:

  • Leishmania braziliensis

Affected Structures:

  • Nasal septum
  • Oral cavity
  • Pharynx

Consequences:

  • Severe tissue destruction
  • Facial disfigurement
  • Common in South America

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Post-Kala-azar Dermal Leishmaniasis (PKDL)

Timing:

  • Occurs after treatment of VL
  • Develops months to years post-treatment

Clinical Manifestations:

  • Hypopigmented macules
  • Papules
  • Nodules
  • No systemic symptoms

Epidemiological Significance:

  • Serves as reservoir of infection
  • Important in disease transmission

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Visceral Leishmaniasis (VL) - “Kala-azar” (The Black Fever)

Overview:

  • Severe, potentially fatal disease
  • Caused by Leishmania donovani and Leishmania infantum (chagasi)
  • Targets internal organs (spleen, liver, and bone marrow)
  • High mortality if untreated

Pathogenesis of Visceral Leishmaniasis (Kala-azar)

Incubation Period:

  • 2–6 months, but can extend up to 2 years

Mechanism of Spread:

  • Amastigotes multiply within macrophages
  • Spread via blood and lymphatics
  • Parasites primarily invade the reticuloendothelial system (spleen, liver, bone marrow, and lymph nodes)

Systemic Manifestations:

  • Splenomegaly
  • Hepatomegaly
  • Lymphadenopathy
  • Anemia
  • Leukopenia
  • Thrombocytopenia

Immune Consequences:

  • Progressive immune suppression occurs due to macrophage dysfunction

Effects of Visceral Leishmaniasis on the Immune System

Cellular Immunity Suppression:

  • The parasite infects macrophages and suppresses protective cell-mediated (Th1) immunity
  • Leads to reduced IFN-Îł and IL-12 production

Immunosuppressive Response:

  • Increased immunosuppressive cytokines (IL-10) which allow parasite survival
  • Immune response shifts toward ineffective humoral (Th2) response - causing polyclonal B-cell activation and hypergammaglobulinemia

Clinical Presentation of Visceral Leishmaniasis

Fever:

  • Irregular, prolonged bouts

Constitutional Symptoms:

  • Progressive and severe weight loss
  • General weakness
  • Malaise
  • Anorexia
  • Fatigue

Physical Examination Findings:

  • Hepatosplenomegaly: Enlarged, non-tender spleen and liver causing abdominal swelling

Laboratory Abnormalities:

  • Pancytopenia: Anemia, leucopenia, thrombocytopenia

Dermatologic Manifestations:

  • Skin darkening or spots

Hemorrhagic Manifestations:

  • Bleeding: Petechiae or bruising

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Diagnostic Studies

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1. Parasitological Diagnosis (Gold Standard)

Detection Method: Detects Leishmania amastigotes (Leishman Donovan LD bodies)

Splenic Aspirate Microscopy:

  • Sensitivity: ~95%
  • Risk: Bleeding (needs expertise)

Bone Marrow Aspirate:

  • Sensitivity: 60–85%
  • Advantages: Safer, commonly used

Lymph Node Aspirate:

  • Lower sensitivity

Culture:

  • Confirms species identity
  • Slow process

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2. Serological Tests (Antibody Detection)

Useful for screening and diagnosis in endemic areas

rK39 Immunochromatographic Test (ICT):

  • Rapid, field-friendly
  • High sensitivity & specificity

Direct Agglutination Test (DAT):

  • Highly sensitive
  • Quantitative

ELISA:

  • Sensitive
  • Lab-based

IFA (Indirect Fluorescent Antibody Test):

  • Specialized laboratory test

Limitations of Serological Tests:

  • Cannot distinguish past vs. active infection
  • Lower sensitivity in HIV co-infection
  • Antibodies persist after cure

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3. Antigen Detection

KAtex (Urine Latex Agglutination Test):

  • Detects leishmanial antigen in urine
  • Useful for treatment monitoring
  • Lower sensitivity than rK39

4. Molecular Tests

PCR (Polymerase Chain Reaction):

  • Performed on blood, bone marrow, splenic aspirate
  • Very high sensitivity & specificity
  • Useful in HIV-VL, relapse, and low parasite load scenarios
  • Limitations: Expensive, limited availability

5. Skin Test

Montenegro (Leishmanin) Skin Test:

  • Negative in active VL
  • Becomes positive after cure
  • Not useful for diagnosis of active disease

6. Supportive Laboratory Findings (Non-specific)

  • Pancytopenia (anemia, leukopenia, thrombocytopenia)
  • Hypergammaglobulinemia
  • Elevated ESR (Erythrocyte Sedimentation Rate)
  • Hypoalbuminemia

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Management

Supportive Care

  • Adequate nutrition
  • Correction of anemia
  • Treatment of secondary infections
  • Antipyretics for fever
  • Management of bleeding and thrombocytopenia

Treatment

WHO-Approved Medications for Visceral Leishmaniasis

Several medicines have been approved by the World Health Organization (WHO) to treat VL cases:

  • Pentavalent antimony
  • Amphotericin B deoxycholate
  • Lipid formulation of amphotericin B (e.g., liposomal amphotericin B)
  • Paromomycin
  • Miltefosine

Note: Pentavalent antimony has been used for several decades and remains effective against VL.

Drugs Registered in Saudi Arabia:

  • Pentavalent antimonials (sodium stibogluconate & meglumine antimoniate)
  • Ambisome (liposomal amphotericin B)

Pentavalent Antimonials

Formulations:

  • Sodium stibogluconate solution: 100 mg/ml
  • Meglumine antimoniate solution: 81 mg/ml

Dosage:

  • 20 mg/kg/day Ă— 30 days
  • Route: Intramuscular or intravenous infusion

Side Effects:

  • Cardiotoxicity
  • Fatal arrhythmia

Contraindications:

  • Elderly patients
  • Significant heart, liver, or kidney disease
  • Pregnancy

Ambisome (Liposomal Amphotericin B)

Advantages:

  • Similar efficacy to amphotericin B
  • Significantly less toxic than standard formulation

Side Effects:

  • Transient nephrotoxicity
  • Thrombocytopenia
  • Hypokalemia

Dosage:

  • 3 mg/kg/day
  • Route: Intravenous

Clinical Use:

  • Recommended for resistant cases
  • Use when pentavalent antimony’s are contraindicated

Complications of Visceral Leishmaniasis (Kala-azar)

  • Overwhelming bacterial infections (most common cause of death)
  • Severe bleeding
  • Extreme weight loss
  • Anemia
  • Hepatosplenomegaly leading to organ failure
  • Disfiguring skin issues (PKDL)
  • Disease relapse

Prevention & Control

Individual Level

  • Early diagnosis and treatment
  • Use of bed nets
  • Personal protection

Vector Control

  • Indoor residual spraying (DDT / pyrethroids)
  • Environmental sanitation

National Programs

  • Kala-azar Elimination Programme
  • Target: <1 case per 10,000 population

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Vaccination Against Leishmaniasis

Current Status:

  • No licensed vaccine available for human leishmaniasis
  • Several candidates are in various stages of development
  • Some showing promising results in animal models and early human trials
  • DNA vaccines (e.g., LEISHDNAVAX) showing potential

Case Scenario

Clinical Presentation

A 32-year-old male farmer from Sudan presents to the outpatient department with the following complaints:

Chief Complaints:

  • Prolonged fever for the past 8 weeks
  • Fever is intermittent, associated with chills and night sweats
  • Progressive weakness
  • Significant weight loss
  • Loss of appetite
  • Increasing abdominal fullness

Physical Examination (O/E)

General Appearance:

  • Looks ill, pale, and emaciated
  • Temperature: 38.5°C
  • Pulse: 98 beats/min
  • Blood Pressure: 110/70 mmHg

Abdominal Examination:

  • Spleen: Palpable 8 cm below the left costal margin
  • Moderate hepatomegaly

Systemic Examination:

  • Generalized lymphadenopathy
  • Hyperpigmentation of the skin

Laboratory Investigations

Hematologic Parameters:

  • Hemoglobin: 8.5 g/dL
  • Total leukocyte count: 2,500/mmÂł
  • Platelet count: 90,000/mmÂł

Serological & Parasitological Testing:

  • rK39 rapid test: Positive
  • Bone marrow aspiration: Presence of LD bodies

Biochemical Parameters:

  • Liver function tests: Mildly elevated

Thank you

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