Safety and effectiveness of Amphotericin B deoxycholate for the treatment of visceral leishmaniasis in Uganda

Médecins Sans Frontières, Swiss Section, Rue de Lausanne 78, 1202 Geneva, Switzerland.
Pathogens and Global Health (Impact Factor: 1.66). 09/2008; 102(1):11-9. DOI: 10.1179/136485908X252142
Source: PubMed


Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb(V)). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) = 2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI = 1.4%-7.9%) among the 161 patients treated with Sb(V) (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI = 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI = 0.1%-4.4%) of the patients treated with Sb(V) (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.

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Available from: Sophie Couffignal, Mar 12, 2014
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    • "In fact, in Europe, lipid preparations of amphotericin B are used as first-line treatment or in those cases where antimonials have previously failed [44]. In Uganda, a cure rate of 92.4 % was obtained with amphotericin B deoxycholate at a dose of 1 mg/kg on alternate days for a period of 30 days, similar to the cure rate in a historical cohort treated with antimonials and without any difference in the occurrence of severe side effects [41]. A retrospective study of five cases of VL in Tunisia treated with amphotericin B deoxycholate at a dose of 0.5–1 mg/kg/day for an average of 25 days obtained a 100 % response rate [57]. "
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    ABSTRACT: Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.
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    • "Second-line treatment was intravenous ampB deoxycholate 1 mg ⁄ kg on alternate days for 30 days (15 doses). AmpB deoxycholate had to be introduced as first-line treatment during a 9-month shortage of GlucantimeÔ (August 2003– April 2004) (Mueller et al. 2008). Sodium stibogluconate (PentostamÔ) was then used as the first-line treatment from May 2004 until December 2005. "
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    ABSTRACT: To identify risk factors for in-hospital mortality in patients treated for visceral leishmaniasis (VL) in Uganda. Retrospective analysis of VL patients' clinical data collected for project monitoring by Médecins Sans Frontières in Amudat, eastern Uganda. Between 2000 and 2005, of 3483 clinically suspect patients, 53% were confirmed with primary VL. Sixty-two per cent were children <16 years of age with a male/female ratio of 2.2. The overall case-fatality rate during pentavalent antimonial (n = 1641) or conventional amphotericin B treatment (n = 217) was 3.7%. There was no difference in the case-fatality rate between treatment groups (P > 0.20). The main risk factors for in-hospital death identified by a multivariate analysis were age <6 years and >15 years, concomitant tuberculosis or hepatopathy, and drug-related adverse events. The case-fatality rate among patients >45 years of age was strikingly high (29.0%). Subgroups of VL patients at higher risk of death during treatment with drugs currently available in Uganda were identified. Less toxic drugs should be evaluated and used in these patients.
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    ABSTRACT: Leishmaniasis is a major health problem in many parts of the world, caused by various species of Leishmania. Amastigotes are the clinically relevant form of the parasite in the human host and reside in the parasitophorous vacuole within macrophages. Polymer-drug conjugates have been used for lysosomotropic drug delivery and have already shown potential in anticancer and antileishmanial chemotherapy. We synthesised N-(2-hydroxypropyl)methacrylamide-amphotericin B (HPMA-AmB) copolymer conjugates in which the AmB was attached to the polymer through a degradable GlyPheLeuGly linker. Antileishmanial activity was assessed in vitro against intracellular amastigotes in host macrophages [murine peritoneal exudate macrophages (PEMs), murine bone marrow-derived macrophages (BMMs) and differentiated THP-1 cells]. The most potent copolymers had 50% effective concentration (EC(50)) values of 0.03 microg/mL AmB equivalent against Leishmania donovani amastigotes in PEMs and BMMs and an EC(50) of 0.57 microg/mL AmB equivalent against L. donovani in THP-1 cells. This activity was comparable with free AmB (EC(50)=0.03-0.07 microg/mL against L. donovani in PEMs and BMMs and 0.24-0.42 microg/mL against amastigotes in THP-1 cells) and Fungizone (EC(50)=0.04-0.07 microg/mL against amastigotes in PEMs). Conjugates also showed potent in vivo activity with ca. 50% inhibition of parasite burden at 1mg/kg body weight.
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