What is the treatment for kala azar?

Treatment of Kala Azar (Visceral Leishmaniasis)

Miltefosine is the recommended first-line oral treatment for visceral leishmaniasis (kala azar) at a dose of 2.5 mg/kg/day for 28 consecutive days, with a maximum daily dose of 150 mg. 1

First-Line Treatment Options

Miltefosine (Oral)

• For patients weighing 30-44 kg: 50 mg twice daily (total 100 mg/day) for 28 consecutive days 1
• For patients weighing ≥45 kg: 50 mg three times daily (total 150 mg/day) for 28 consecutive days 1
• Doses should be taken with food to minimize gastrointestinal side effects 1
• Miltefosine has demonstrated excellent cure rates in visceral leishmaniasis in India, Nepal, and Bangladesh 1

Liposomal Amphotericin B (IV)

• FDA-approved for treatment of visceral leishmaniasis 2
• Recommended dosage for immunocompetent patients: 3 mg/kg/day IV on days 1-5,14, and 21 (total dose: 21 mg/kg) 3
• For immunosuppressed patients including those with HIV/AIDS: 4 mg/kg/day IV on days 1-5,10,17,24,31, and 38 (total dose: 40 mg/kg) 3
• Higher doses (≥40 mg/kg) may be necessary for VL acquired in East Africa 3

Sodium Stibogluconate (IV or IM)

• Recommended in areas with low antimony resistance (<10%): 20 mg SbV/kg/day IV or IM for 28 days 3
• Efficacy rates exceed 90-95% for both L. infantum-chagasi and L. donovani infection in East Africa, Brazil, and Greece 3
• Not recommended in areas with high resistance (northeast India, Bangladesh, Nepal, and Bhutan) 3

Combination Therapy Approaches

• Combination of liposomal amphotericin B (single dose 5 mg/kg) followed by 7-14 days of miltefosine has shown cure rates of 96-98% 1
• Paromomycin (IM) 15 mg/kg/day for 10 days + miltefosine (oral) for 10 days has shown excellent efficacy 4
• For HIV-coinfected patients in Ethiopia: Miltefosine (oral) 100 mg/day + sodium stibogluconate (IM) 20 mg/kg/day for 30 days 4
• Combination therapies may reduce treatment duration, decrease toxicity, and potentially reduce the development of drug resistance 1

Special Population Considerations

Children

• FDA approval for miltefosine is limited to patients ≥12 years of age who weigh ≥30 kg 1
• Use in children <12 years or <30 kg is considered off-label in the United States 1
• Young children (2-11 years) may have lower plasma drug exposure and potentially lower cure rates compared to adults 1

Pregnant and Breastfeeding Women

• Miltefosine is contraindicated in pregnancy due to potential fetotoxicity 1
• Breastfeeding women should not breastfeed during treatment or for 5 months after treatment 1

HIV Co-infection

• Patients with HIV co-infection may have lower cure rates and higher relapse rates 1
• Consider higher doses of liposomal amphotericin B (total dose: 40 mg/kg) 3
• Consider combination therapy (e.g., miltefosine plus sodium stibogluconate) 4
• Initiate or optimize antiretroviral therapy as soon as the patient is stable enough to tolerate it 3

Treatment Monitoring and Follow-up

• Clinical parameters correlate well with parasitologic responses and should be used to monitor treatment response 3
• For therapeutic failure, consider an alternative drug, higher dose, or longer course of treatment 3
• In cases of relapse, patients almost invariably respond to retreatment with the original regimen 5

Common Pitfalls to Avoid

• Doses of miltefosine <2 mg/kg/day are associated with lower response rates 1
• Patients weighing >60 kg receive <2.5 mg/kg/day using standard dosing, which may affect efficacy 1
• Poor compliance with the full 28-day course may lead to treatment failure and potential drug resistance 1
• Delayed diagnosis and treatment can lead to increased mortality and morbidity 6
• Ambulatory (non-supervised) treatment is associated with higher failure rates (OR=10.2) 6
• Interruption of treatment significantly increases the risk of treatment failure (OR=4.3) 6

By following these evidence-based treatment guidelines, clinicians can optimize outcomes for patients with kala azar while minimizing adverse effects and the development of drug resistance.