Safety and efficacy of liposomal amphotericin B for treatment of complicated visceral leishmaniasis in patients without HIV, North-West Ethiopia

Visceral leishmaniasis (VL), also called kala-azar, is a protozoan parasitic neglected disease that is transmitted by sand flies belonging to the genera Phlebothomus and Lutzomyia. The disease is a worldwide health problem affecting over 70 countries with annual incidence of 0.2 – 0.4 million cases. India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil account for the majority of cases [1]. It is caused by Leishmania donovani (Asia and Africa), or Leishmania infantum (Southern Europe and South America). The disease is characterized by fever, splenomegaly, anemia, weight loss, abdominal swelling, bleeding, and pancytopenia. Peripheral lymphadenopathy is common in some foci [2]. If left untreated, the disease is universally fatal.

VL is a significant public health problem in Ethiopia. Its incidence is estimated to be 3,700 – 7,400 per year [3]. The northwestern regions of Ethiopia accounts for about 60 % of the case load in Ethiopia. In this region of Ethiopia, young migrant workers are the most affected [4].

There are limited drugs available to treat VL. The currently used anti-leishmanial drugs are antimonials (sodium stibogluconate [SSG] and meglumine antimoniate [glucantime]), liposomal amphotericin B, paromomycin and miltefosine. Currently, the standard treatment in East Africa is a combination of SSG and paromomycin for 17 days. While SSG has been the mainstay of treatment for VL since 1940s, resistance has become a concern in the Indian subcontinent [5, 6].

Liposomal amphotericin B (Gilead Sciences) was first used in humans for the treatment of multidrug resistant Mediterranean VL in 1990 [7]. Since then, the drug has increasingly been used in endemic regions. Short-course regimens give cure rates of more than 90 % in the Indian subcontinent [8]. It also has good safety profile. It causes minor adverse events, commonly infusion related reactions (fever, chills, arthralgia) and rarely renal toxicity. Encouraged by its high efficacy and low toxicity, the World Health Organization (WHO) endorsed liposomal amphotericin B as a drug with the highest therapeutic index of existing anti-leishmanial dugs [9]. Nevertheless, treatment outcomes vary by geographic locations. While there was good treatment response in India, it was less efficacious and inconsistent in Brazil and East Africa [10].

There is limited experience in use of liposomal amphotericin B in East Africa due to cost implications. It was first introduced to Ethiopia in 2006 as first-line treatment for HIV-positive and severely ill immunocompetent VL patients [11]. Since then its use is primarily limited to patients with severe disease and HIV co-infection. The experience from Médecins Sans Frontière (MSF) programs in Sudan showed lower cure rate at a total dose of 20 mg/kg [12].

A study in Ethiopia involving 94 HIV negative severely ill VL patients showed 93 % initial cure and 6 % death. However, among 195 VL-HIV co-infected patients, the initial cure rate was only 60 %, with 7 % deaths, and 32 % parasitological failure [11]. Liposomal amphotericin B was even less effective in treating HIV-positive VL relapses with reports of 38 % initial cure and 56 % parasitological failure [13]. Higher doses are now recommended to treat VL in HIV positive patients [14].

In the past, low dose liposomal amphotericin B (21 mg/kg) had been in use in Ethiopia for non-HIV VL patients; but assessments of treatment outcomes from time to time were not done. In this study, we aimed to study the treatment outcomes of liposomal amphotericin B in VL patients treated under routine settings.