What is the treatment approach for leishmaniasis in children?

Leishmaniasis in Children: Signs, Symptoms, Diagnosis, and Treatment

Liposomal amphotericin B (L-AmB) is the first-line treatment for visceral leishmaniasis in children, while treatment for cutaneous leishmaniasis should be tailored based on species, location, and lesion characteristics. 1, 2

Clinical Manifestations

Visceral Leishmaniasis (VL)

• Intermittent fever
• Pallor
• Anorexia or refusal to feed
• Weight loss
• Abdominal distension
• Hepatosplenomegaly (splenomegaly more prominent)
• Lymphadenopathy
• Laboratory findings: thrombocytopenia, anemia, leukopenia, hypergammaglobulinemia 3

Cutaneous Leishmaniasis (CL)

• Chronic, painless lesion at the site of sandfly bite
• Typically begins as a papule that evolves into a nodule and may ulcerate
• Facial lesions/scars can have long-lasting social and psychological consequences 1
• Spontaneous healing may occur as cellular immunity develops, but treatment accelerates this process 2

Mucocutaneous Leishmaniasis (MCL)

• Can appear concurrently with or after CL, especially with species of the Viannia subgenus
• Destructive lesions in the nasopharyngeal/laryngeal mucosa 2

Diagnostic Approach

Multiple diagnostic approaches should be used to maximize detection:

1. Direct visualization of amastigotes:

   • Tissue aspirates or biopsy specimens
   • Bone marrow aspiration is preferred first diagnostic sample for VL
   • For CL, sample from lesion edge

2. Parasite isolation:

   • In vitro culture (contact reference laboratory before collecting specimens)

3. Molecular detection:

   • PCR-based assays (most sensitive method currently available) 1, 2

4. Serologic testing:

   • Particularly useful for VL
   • Less helpful for CL/MCL 1

5. Additional sources for sampling in VL:

   • Liver
   • Enlarged lymph nodes
   • Whole blood (buffy coat) - especially in immunocompromised patients 1

Treatment Approach

Visceral Leishmaniasis

1. First-line therapy:

   • Liposomal amphotericin B (L-AmB):
     • Dosage: 3-5 mg/kg/day IV for a total dose of 10-21 mg/kg
     • Children typically tolerate this well without need for pediatric-specific dosage regimens 1, 2
     • Monitor: Baseline and frequent (1-2x weekly) serum chemistry values and CBC

2. Alternative options:

   • Miltefosine:

     • For children ≥12 years weighing ≥30 kg: FDA-approved dosing
       • 30-44 kg: 50 mg twice daily for 28 days
       • ≥45 kg: 50 mg three times daily for 28 days 4
     • For children <12 years: Off-label use
       • Target dose ~2.5 mg/kg/day (not <2 mg/kg)
       • Young children may require adjusted dosing due to lower plasma drug exposure 1
     • Contraindicated in pregnancy and breastfeeding 4

   • Pentavalent antimonials (sodium stibogluconate or meglumine antimoniate):

     • 20 mg SbV/kg/day IM or IV for 28 days
     • Not recommended for VL acquired in India due to resistance 1
     • Young children may have lower plasma exposure and may need adjusted dosing 1

Cutaneous Leishmaniasis

Treatment decisions should consider:

• Leishmania species (risk of mucosal dissemination)
• Lesion location, size, and number
• Patient's immune status

1. Local therapy options (for simple CL):

   • Intralesional pentavalent antimonials:

     • Inject ~0.1 mL/cm² of lesion
     • Repeat every 3-7 days until healing
     • Note: May require sedation in young children 1
     • Not for use on fingers, nose, ears, eyelids, near lips

   • Cryotherapy:

     • For smaller, recent-onset lesions
     • Well-tolerated on face (avoid eyelids, lips, nose, ears)
     • Can be used during pregnancy and breastfeeding 1

2. Systemic therapy (for complex CL):

   • Liposomal amphotericin B
   • Miltefosine (for children ≥12 years weighing ≥30 kg)
   • Pentavalent antimonials

Mucocutaneous Leishmaniasis

• All cases require systemic therapy
• Complete examination of naso-oropharyngeal/laryngeal mucosa should be conducted
• Consider prophylactic corticosteroids for laryngeal/pharyngeal disease with risk of respiratory obstruction 1

Special Considerations in Children

1. Dosing challenges:

   • Young children may have lower drug exposure to miltefosine and pentavalent antimonials, potentially requiring adjusted dosing 1

2. Procedural considerations:

   • Local therapies may require sedation in young children 1

3. Monitoring:

   • Regular laboratory monitoring for drug toxicity
   • Long-term follow-up to detect recurrences or mucosal involvement

4. Education:

   • For children at risk for ML, educate caregivers about seeking medical attention for persistent nasopharyngeal/laryngeal manifestations 1

Potential Pitfalls and Caveats

1. Underdiagnosis:

   • Consider leishmaniasis in children with compatible symptoms from endemic areas

2. Drug toxicity:

   • Pentavalent antimonials: Cardiac, renal, and hematologic toxicity
   • Amphotericin B: Infusion reactions, electrolyte abnormalities, nephrotoxicity
   • Miltefosine: Gastrointestinal effects, embryo-fetal toxicity (contraindicated in pregnancy) 4

3. Treatment failure:

   • More common in immunocompromised children
   • Consider drug resistance, especially to antimonials in certain regions (India)
   • Malnutrition contributes to disease development and treatment failure 3

4. Post-treatment monitoring:

   • All children treated for leishmaniasis should have follow-up to assess for relapse
   • Children with CL caused by species associated with ML should be monitored for mucosal symptoms even after apparent cure