What is the diagnosis and treatment of visceral Leishmaniasis (Kala-azar)?

From the Guidelines

Visceral leishmaniasis should be treated with liposomal amphotericin B (L-AmB) as the first-line therapy, with a recommended dosage regimen of 3 mg/kg/day IV on days 1–5,14, and 21 (total dose, 21 mg/kg) for immunocompetent persons, as per the guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) 1. The treatment of visceral leishmaniasis involves several options, including L-AmB, miltefosine, paromomycin, and pentavalent antimonials.

• The FDA-approved dosage regimen for L-AmB is 3 mg/kg/day IV on days 1–5,14, and 21 (total dose, 21 mg/kg) 1.
• Alternative regimens include miltefosine (2.5 mg/kg/day for 28 days) and pentavalent antimonials like sodium stibogluconate (20 mg SbV /kg/day IV or IM for 28 days) for immunocompetent persons with VL acquired in areas where the prevalence of antimony-resistant Leishmania species is low (<10%) 1.
• Patients require close monitoring for treatment response and potential side effects such as kidney damage, hepatotoxicity, or cardiac abnormalities.
• Diagnosis involves demonstration of the parasite in tissue samples or serological tests.
• Prevention focuses on vector control through insecticide use, bed nets, and environmental management in endemic areas.
• Immunocompromised patients may require longer treatment courses and are at higher risk for relapse, necessitating follow-up care for at least 6-12 months after treatment. The choice of treatment regimen depends on various factors, including the patient's immune status, weight, and the region where the infection was acquired.
• For example, doses of 40 mg/kg or more of L-AmB may be necessary in persons with VL acquired in East Africa 1.
• In addition, miltefosine can be used as an alternative therapy for immunocompetent persons with VL caused by L. donovani, acquired in the Indian subcontinent (South Asia), who are ≥12 years of age, weigh ≥30 kg, and are not pregnant or breastfeeding 1.

From the FDA Drug Label

One randomized, open-label, active-controlled study was conducted to evaluate the efficacy of IMPAVIDO in the treatment of visceral leishmaniasis in Bihar, India, an area where L. donovani is known epidemiologically to be the prevalent infecting species Patients ≥ 12 years of age with clinical signs and symptoms compatible with visceral leishmaniasis (fever, splenomegaly, and cytopenia) confirmed by the presence of Leishmania amastigotes in aspirates of spleen or bone marrow were randomized to receive oral IMPAVIDO or intravenous amphotericin B deoxycholate in a 3:1 ratio The final cure rates for IMPAVIDO and amphotericin B were 94% and 97%, respectively.

The treatment of visceral leishmaniasis with miltefosine (IMPAVIDO) has a final cure rate of 94% in patients ≥ 12 years of age, as compared to 97% with amphotericin B deoxycholate 2.

• Key points:
  • The study was conducted in Bihar, India, where L. donovani is the prevalent infecting species.
  • Patients received oral IMPAVIDO or intravenous amphotericin B deoxycholate.
  • The final cure rate for IMPAVIDO was lower than that of amphotericin B deoxycholate, but still 94%.
• Main idea: Miltefosine (IMPAVIDO) is effective in treating visceral leishmaniasis, with a final cure rate of 94%.

From the Research

Visceral Leishmaniasis Treatment Options

• The available treatment options for visceral leishmaniasis (VL) have problems relating to efficacy, adverse effects, and cost, making treatment a complex issue 3.
• Liposomal amphotericin B appears to be the optimal treatment for patients in resource-rich countries, while miltefosine is being used in South Asia 3.
• In Africa, the evidence to switch from SSG is not yet compelling, and there is a need to monitor and plan for evolving drug failure due to leishmania parasite resistance 3, 4.

Efficacy and Safety of Treatment Regimens

• A phase II randomized, parallel arm, open-labelled trial was conducted to assess the efficacy of miltefosine alone or in combinations with sodium stibogluconate (SSG) or liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa 4.
• The trial aimed to identify regimen(s) that are sufficiently promising for future trials in East Africa, with a primary endpoint of cure at day 28 and secondary endpoint at day 210 (6 months) 4.
• Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis, with high efficacy and low toxicity in immunocompetent patients 5.

Combination Therapy for VL-HIV Co-infection

• A retrospective cohort study was conducted to determine the initial effectiveness of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients in Ethiopia 6.
• The study found that the initial cure rate was 83.8%, with a low parasitological failure rate of 3.5%, suggesting that this regimen may be a suitable treatment option for VL-HIV co-infected patients 6.
• Predictors of poor outcome, such as tuberculosis co-infection, age >40 years, and hemoglobin ≤6.5 g/dL, may facilitate better management of VL-HIV co-infected patients 6.

Need for New Diagnostic Tools and Treatment Strategies

• There is a need for improved diagnostic tests and accurate and simple tests to identify treatment failures 7.
• New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients, particularly in poor and neglected populations in East Africa and the Indian sub-continent 7.