REVIEWS OF ANTI-INFECTIVE AGENTS • CID 2006:43 (1 October) • 917
R E V I E W S O F A N T I - I N F E C T I V E A G E N T SI N V I T E D A R T I C L E
Louis D. Saravolatz, Section Editor
Liposomal Amphotericin B for the Treatment
of Visceral Leishmaniasis
Caryn Bern,1Jill Adler-Moore,2Juan Berenguer,3Marleen Boelaert,5Margriet den Boer,6Robert N. Davidson,7
Concepcion Figueras,4Luigi Gradoni,8Dimitris A. Kafetzis,10Koert Ritmeijer,6Eric Rosenthal,11Catherine Royce,12Rosario Russo,9
Shyam Sundar,14and Jorge Alvar13
1Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia;
Maran ˜o ´n, Madrid, and
University of Nice, Nice, France;
Organization, Geneva, Switzerland; and
2California State Polytechnic University, Pomona;
6Me ´decins sans Frontie `res–Holland, Amsterdam,
8Istituto Superiore di Sanita `, Rome,
11Archet Hospital and Equipes de Recherche sur les Leishmanioses,
13Communicable Diseases, Neglected Tropical Diseases Control, World Health
14Banaras Hindu University, Vanarasi, India
4Hospital Vall D’Hebro ´n, Barcelona, Spain;
7Department of Infection and Tropical Medicine, Northwick Park Hospital, Harrow, Middlesex, United Kingdom;
9Istituto Malattie Infettive, Catania, Italy;
12Drugs for Neglected Diseases Initiative and
5Institute for Tropical Medicine, Antwerp, Belgium;
10Kyriakou Children’s Hospital, Athens, Greece;
During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis
(VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for
liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia,
the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferentialpricing
for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal
amphotericin B (total dose, 20 mg/kg) in immunocompetent patientswithVL.Combinationtrialsinareaswithantileishmanial
drug resistance, and treatment and secondary prophylaxis trials in VL–human immunodeficiency virus–coinfected patients,
are important to safeguard the current armamentarium and to optimize regimens. The public health community should
work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.
Over the past decade, liposomal amphotericin B (i.e., Am-
Bisome; Gilead Sciences) has been increasingly used to treat
visceral leishmaniasis (VL). Liposomal amphotericin B has the
highest therapeutic index of current antileishmanial drugs.The
major obstacle to the drug’s wider use is its high cost, which
is beyond the range of affordability in developing countries
with the highest burden of disease. World Health Organization
(WHO) policy precludes the recommendation of therapiesthat
are impossible to implement as a result of a lack of affordability.
However, recent successful clinical trials to identify the mini-
mum effective total dose and preferential pricing provided by
the manufacturer for patients with VL treated in the public
sector in East Africa have raised the possibility that liposomal
amphotericin B use could become economically feasible for
Received 29 September 2005; accepted 18 January 2006; electronically published28August
Reprints or correspondence: Dr. Jorge Alvar, Communicable Diseases, Neglected Tropical
Diseases Control, World Health Organization, Avenue Apia 1211, Geneva, 27 Switzerland
Clinical Infectious Diseases 2006;43:917–24
? 2006 by the Infectious Diseases Society of America. All rights reserved.
first-line treatment, even in resource-poorcountries.Moreover,
there are few new antileishmanial drugs in the pipeline, and
drug resistance is on the rise. Combination therapy is now the
standard of care for such diseases as malaria and tuberculosis,
for which drug resistance is an important challenge. For these
reasons, there is growing interest in combination regimens for
VL. The WHO convened a consultative meeting at the Istituto
Superiore di Sanita ´ (Rome, Italy) on 16 April 2005 to discuss
current knowledge of and experience with liposomal ampho-
tericin B for the treatment of VL. The major goal of the work-
shop was to produce a consensus document with clear guide-
lines for liposomal amphotericin B dosing and clinical use for
VL. Attendees included 15 experts with specialtiesrangingfrom
basic research to clinical medicine and drug access who rep-
resented a wide variety of regions where VL is endemic.
VL causes an estimated 500,000 new cases of disease and
60,000 deaths each year. Ninety percent of cases occur in just
5 countries: India, Bangladesh, Nepal, Sudan, and Brazil .
In South Asia and the Horn of Africa, the predominant mode
of transmission is anthroponotic . In these areas, humans
with kala-azar or post–kala-azar dermal leishmaniasis provide
918 • CID 2006:43 (1 October) • REVIEWS OF ANTI-INFECTIVE AGENTS
the major reservoir for ongoing transmission [3, 4], and in-
complete or irregular treatment leads to drug pressure and the
rapid development of drug-resistant parasites . In the Med-
iterranean, the Middle East, and Brazil, the disease is zoonotic,
with the domestic dog as the most important reservoir host
sustaining transmission . In these regions, most human VL
disease occurs in children or immunocompromised adults.
In addition to the distinctive epidemiology of anthroponotic
VL versus zoonotic VL, key factors that influence the ability to
control VL include poverty and its many effects, poor nutri-
tional status of the population, armed conflict and population
movements, ecological changes that alter human contact with
the sand fly vector, the prevalence of HIV infection, parasite
resistance to antileishmanial drugs, and access to health care
and antileishmanial drug treatment . In nearly all resource-
poor regions of endemicity, access to antileishmanial drugs is
constrained by the economic burden that VL care imposes.
ACCESS TO ANTILEISHMANIAL TREATMENT
South Asia has a very high anthroponotic VL disease burden
that is characterized by a poorly controlled, endemic situation
and superimposed large outbreaks, such as the one in Bihar
State, India, in the early 1990s. The region also suffers from
heterogeneous, poorly standardized systems of private health
care. The cost of VL diagnosis and treatment is largely borne
by the patient’s family. Irregular and incomplete VL treatment
courses are common and have led to a 160% rate of primary
unresponsiveness to pentavalent antimonial drugs (SbV) in
northern Bihar . In southern Bihar, where the rate of SbV
resistance is lower than in northern districts, SbVis generally
available through the government health system and is still in
use. Alternative drugs, such as conventional amphotericin B,
are only available through a few nongovernmental organiza-
tions and the private sector, severely limiting effective antil-
eishmanial drug access in northern Bihar, where the disease
burden is highest. Overall antileishmanial drug access in Bihar
is, therefore, rather poor, and policies to address primary and
secondary unresponsiveness to SbVare urgently needed .
Substantial levels of SbVresistance are also reported in the
districts of Nepal adjacent to northern Bihar . However,
Nepal has a public provision of SbVand conventional ampho-
tericin B, and current antileishmanial drug access is better than
in India or Bangladesh. In Bangladesh, the prevalence of SbV
resistance still appears to be low, but access to affordable VL
treatment is extremely poor [3, 9]. A limited supply of SbVwas
available through the Bangladesh government health care sys-
tem until 2003, when the only licensed manufacturer in the
country ceased production. Since then, antileishmanial drug
access in Bangladesh has been in a state of crisis, alleviated
temporarily by emergency procurements of SbVthrough the
WHO. Neither conventional amphotericin B nor othersecond-
line drugs are provided or sold in districts whereVLisendemic.
In a study in Bangladesh in 2004, the median direct cost of
health care for 1 patient with VL totaled 80% of the yearly per
capita income, representing a catastrophic economic burden
for affected households .
The Indian government is currently reviewing guidelines to
set specific levels of SbVunresponsiveness (10%–20% in the
draft guidelines) as a threshold for changing the first-line drug
recommendation . Review and coordination of existing VL
treatment guidelines are urgently needed for all countries of
the South Asian region. To effectively implement a rational
anthroponotic VL–control policy, health authorities must play
a major role in ensuring access to antileishmanial drugs.
In East Africa, care is provided free of charge by nongov-
ernmental organizations in some areas and through fee-for-
service by the private sector in other areas. However, access is
difficult for the majority of patients with VL who reside in
remote regions. In the Horn of Africa, war and population
displacements have contributed to explosive VL epidemicswith
extremely high mortality rates, often in association withfamine
and high rates of severe acute malnutrition . Treatment in
many areas has been in the hands of nongovernmental orga-
nizations, especially Me ´decins sans Frontie `res (MSF). Current
needs include treatment of vulnerable populations, establish-
ment of sentinel surveillance as populations again shift follow-
ing recent peace accords, and validation of protocols and reg-
imens used in emergency situations.
In the areas of Europe and Brazil where zoonotic VL is
endemic, VL disease burdens are lower than in Asia and Africa,
and access to treatment is generally much better . Never-
theless, cost constraints impede liposomal amphotericin B
availability for HIV-VL–coinfected patients in Brazil. In addi-
tion, questions remain regarding optimal dosing for children
 and for HIV-infected patients. In Europe, the incidence
of VL as an opportunistic infection in HIV-infected patients
has decreased substantially as a result of widespread introduc-
tion of HAART [14, 15]. However, for HIV-infected patients
with incomplete immune reconstitution, data are insufficient
to make firm recommendations regarding the best regimens
for primary treatment and secondary prophylaxis of VL [16,
PHARMACOLOGY AND PHARMACOKINETICS
OF LIPOSOMAL AMPHOTERICIN B
Liposomal amphotericin B is a formulation of amphotericin B
in which the drug is packaged with cholesterol and other phos-
pholipids within a small unilamellar liposome. The drug binds
to parasite ergosterol precursors, causing disruption of the par-
asite membrane. The specialized formulationhascharacteristics
that increase efficacy while minimizing toxicity: effective pen-
etration and sustained levels in tissue, especially liver and
REVIEWS OF ANTI-INFECTIVE AGENTS • CID 2006:43 (1 October) • 919
spleen; high transition temperature leading tostabilityinblood,
macrophages, and tissues; presence of cholesterol in the lipo-
some, which minimizes drug interaction with mammalian cell
membranes and decreases toxicity; and high affinity for ergos-
terol and its precursors ensuring antimicrobial efficacy .
Higher initial doses (?5 mg/kg) provide better penetrationand
longer tissue persistence than do frequent low doses. Although
transient increases in the creatinine level can occur, acute and
chronic toxicity is uncommon even with doses up to 15 mg/
kg . Exposure to temperatures 125?C or !0?C will alter the
liposome’s characteristics and may increase toxicity or decrease
CLINICAL TRIALS AND OTHER EXPERIENCE
WITH LIPOSOMAL AMPHOTERICIN B FOR VL
Thirteen clinical trials of liposomal amphotericin B for the
treatment of VL have been published; most were open-label,
dose-finding studies or randomized, open-label comparisons
with other antileishmanial drugs (table 1). At least 10 different
regimens have been tested in India; one objective of these stud-
ies has been to find the lowest total dose with acceptable ef-
ficacy. A single dose of 7.5 mg/kg yielded a 90% cure rate at
6 months in a fairly large trial (
20 mg/kg in various dosing schedules yielded cure rates 195%,
whereas a single dose of 3.75 mg/kg led to a cure rate of 89%
in a limited number of patients (
demonstrated that liposomal amphotericin B caused substan-
tially lower rates of toxicity than conventional amphotericin B
desoxycholate or amphotericin B lipid complex (ABLC) [27,
31]. Three randomized, comparative trials for the treatment of
fungal infections in neutropenic patients also confirmed sig-
nificantly lower rates of renal toxicity for liposomal ampho-
tericin B than for conventional amphotericin B desoxycholate
or ABLC .
In the Horn of Africa, clinical trial data are sparse. However,
MSF has extensive clinical experience in VL treatment under
emergency conditions [11, 33]. In Sudan, MSF developed a
protocol to triage the highest-risk patients to a more intensive
regimen, including initial liposomal amphotericin B treatment
with a shift to other antileishmanials afterimprovement,aswell
as aggressive nutritional and medical supportive therapy .
These protocols, applied on a compassionate use basis, have
substantially reduced case-fatality rates in MSF VL-treatment
In Europe, clinical trials demonstrated 90%–98% efficacy
with a total dose of 18–21 mg/kg in immunocompetentpatients
(table 2). A variety of regimens are currently in use. In Italy,
the standard regimen consists of 3 mg/kg on days 1–5 and 10,
for a total dose of 18 mg/kg . For imported cases in the
United States, the US Food and Drug Administration recom-
mends 3 mg/kg on days 1–5, 14, and 21, for a total dose of 21
). Total doses of 10–n p 203
). Indian experiencen p 28
mg/kg . In New Zealand, the recommended regimen is 1–
1.5 mg/kg for 21 days or 3 mg/kg for 10 days. Published case
series and current pediatric practice in southernEuropesuggest
good efficacy with a total dose of 20 mg/kg. Many pediatricians
currently use a regimen of 10 mg/kg/day for 2 consecutive days
LIPOSOMAL AMPHOTERICIN B IN HIV-VL
There have been no formal, randomized, clinical trials of li-
posomal amphotericin B treatment or secondary prophylaxis
regimens involving HIV-VL–coinfectedpatients,andtherehave
been only 2 open-label, dose-finding studies (table 2). In pa-
tients with severe immunosuppression, relapse rates after an-
tileishmanial treatment are extremely high . A randomized
trial of ABLC versus SbVshowed comparable efficacy but lower
toxicity for ABLC . The efficacy of SbVand liposomal am-
photericin B were comparable in most case studies, but the
lower rate of toxicity for liposomal amphotericin B has caused
most clinicians to consider it to be the antileishmanial drug of
choice in VL-HIV–coinfected patients.
Secondary prophylaxis with doses of liposomalamphotericin
B or other antileishmanials every 2–4 weeks after initial clinical
cure of VL is now the standard of care in Europe [16, 17, 41],
but data are insufficient to recommend a specific regimen. For
some authors, clinical experience to date suggests that discon-
tinuation of secondary antileishmanial prophylaxis can be con-
sidered in patients whose CD4+lymphocyte counts increase to
1200–350 cells/mL in response to HAART, but that prophylaxis
should be continued in those with counts !200 cells/mL .
However, other authors observe that HAART is not sufficient
to control the disease, despite increases intheCD4+lymphocyte
count and undetectable viral loads, suggesting that secondary
prophylaxis should be maintained indefinitely [42, 43].
LIPOSOMAL AMPHOTERICIN B PRICING
In 1992, an agreement between the WHO and Vestar led to
preferential pricing for liposomal amphotericin B for patients
with VL of $50 (in US dollars) per vial; a negotiation in 2004
led to the even more reduced price of i22.30 per vial. This
price is valid for liposomal amphotericin B for patients with
VL who are treated by not-for-profit institutions in East Africa,
but not for treatment of other diseases or for patients with VL
in other regions. An extension of this preferential pricing to
include patients with VL inIndia, Bangladesh,Nepal,andBrazil
could improve access to effective treatmentandsavemanylives.
Even with preferential pricing, liposomal amphotericin B (total
dose, 20 mg/kg) is not as cost-effective as other first-line reg-
imens (i.e., SbV, paromomycin, and conventionalamphotericin
B). Nevertheless, preferential pricing opens the prospect of li-
posomal amphotericin B as second-line treatment and for in-
Table 1.Efficacy and toxicity of various dosing regimens of liposomal amphotericin B (LAmB) in immunocompetent patients with visceral leishmaniasis.
No. of subjects
dose, mg/kg LAmB regimen
months Reported adverse eventsa
Total Per group
Brazil Open-label, dose-finding32156 2 mg/kg on day 1, 5, and 10876Fever, 41%; chills, 9%; respiratory dis-
tress, 6%; cardiac arrhythmia, 9%;
treatment was stopped for 2 subjects
Fever and chills, 7%; no discontinuations
Nonsignificant increase in BUN level; no
change in creatinine level; no discon-
tinuations of treatment
Mild adverse effects; transient increase
in BUN and creatinine levels; no dis-
continuations of treatment
No adverse events, no change in levels
of BUN, creatinine, electrolytes, or
One patient had fever, and 2 had chills;
no discontinuations of treatment
2 mg/kg on days 1–4 and 10
1–2 mg/kg on days 1–6 and 10
10 mg/kg on days 1–2
Greece Open-label with historical control 123c
4 mg/kg on days 1–5
3 mg/kg on days 1–10
1–1.4 mg/kg on days 1–21
3 mg/kg on days 1–4 and 10
Open-label, dose-finding 88f
3 mg/kg on days 1–5 and 10
4 mg/kg on days 1–5 and 10
3 mg/kg on days 1–3, 5, and
12Italy Open-label, dose-finding 106c
3 mg/kg on days 1–5 and 10
1 mg/kg on days 1–21
3 mg/kg on days 1–10
2 mg/kg on days 1, 5, and 10
2 mg/kg on days 1–4 and 10
1–2 mg/kg on days 1–6 and 10
India Randomized, open-label
3417 15 Single 15-mg/kg dose1006 Chills, 17% (65% of subjects in
ConAmB group); nausea, 6% (53% of
subjects in ConAmB group)
Fever and/or chills, 49%; vomiting, 4%;
back pain, 2%; no change in creati-
Infusion-related rigors, 44%; fever, 36%;
back pain, 10%; transient increase in
creatinine level, 8%
Fever, 10%; chills, 3%; vomiting, 4%;
back pain, 2%; no renal toxicity
Fever, 29%; rigors in 98% of subjects in
ConAmB group; no increase in creati-
nine level (but a significant increase in
the ConAmB group)
Clinical evaluation only; 4 instances of
extravasation; patients in study were
India Open-label, dose-finding 91465 Single 5-mg/kg dose 916
1 mg/kg on days 1–5
0.75 mg/kg on days 1–5
6IndiaRandomized, open-label, dose-
1.5 mg/kg on days 1–5
3 mg/kg on days 1–5
Single 7.5-mg/kg dose
6 India Open-label noncomparison203
India Randomized, open-label
15351 102 mg/kg on days 1–5 966
Open-label, dose-finding 25562 mg/kg on days 1, 5, and 10
2 mg/kg on days 1–4 and 10
1–2 mg/kg on days 1–6 and 10
3–5 mg/kg on days 1, 3, and
12 SudanOpen-label, dose-finding49 Passive
16243–5 mg/kg on days 1, 2, 6, 8,
10, and 13
aIncidence of adverse events in the LAmB group (versus comparison group, where appropriate).
bMulticenter trial in Brazil, India, and Kenya.
cAll subjects were children.
dStudy population included 15 immunocompetent children, 5 immunocompetent adults, and 11 immunocompromised adults.
eStudy included 83 cases from Italy, 3 cases from Brazil, and 2 cases treated in the United Kingdom.
fStudy population included 56 children and 32 adults.
gPatients who did not respond to or relapsed after treatment with pentavalent antimonial drugs.
BUN, blood urea nitrogen; ConAmB, conventional AmB desoxycholate.
922 • CID 2006:43 (1 October) • REVIEWS OF ANTI-INFECTIVE AGENTS
Findings of published studies of liposomal amphotericin B (LAmB) treatment in HIV-visceral leishmaniasis–coinfected
Country ReferenceStudy design
dose, mg/kg Regimen Initial response
SpainCase series (relapse
222.51.5 mg/kg per day for
Good clinical response,
parasite free at 3– 6
211 mg/kg per day for 21
1 mg/kg per day for
days 1–7 and 1.5
mg/kg per day for
0.75 mg/kg per day for
days 1–7 and 1.5
mg/kg per day for
4 mg/kg per day for
days 1–5, 10, 17, 31,
100 mg per day for 21
GreeceCase series2 40
Good clinical response;
no relapse at 10–16
Spain Case series5 40
Parasites cleared in
80% of subjects
Open-label, dose-finding11 29–39Partial clinical response
in 9 of 11 subjects;
negative for para-
sites at day 21
Partial clinical response
in 7 of 8 subjects;
negative for para-
sites at day 45
3 of 5 subjects were
relapse free at
ItalyOpen-label, dose-finding10 404 mg/kg per day for
days 1–5, 10, 17, 31,
France  Case series, secondary
5 60–86 by day 302.9–4.1 mg/kg per day
for 5–24 days, fol-
lowed by 2.7–3.8
mg/kg every 15 days
to prevent relapse
aRelapses at 4 and 20 months.
bNine subjects from Italy, 1 from France, and 1 from Portugal.
cTwo deaths due to other causes, 8 relapses, and 1 cure.
dSeven subjects experienced relapses at 2–7 months, 2 were lost to follow-up, and 1 was listed as “leishmanina positive.”
eTwo patients had relapse at 42 and 270 days and were re-treated with high-dose liposomal LAmB followed by prophylaxis, with good response in 1 of the
SBV, pentavalent antimonial drugs.
clusion of lower total doses in combination regimens. To file
for an extension of the preferential pricing scheme, figures de-
tailing the projected annual uptake will be compiled under the
leadership of the WHO.
Zoonotic VL (the Mediterranean Basin, the Middle East, and
A total liposomal amphotericin B dose of 20 mg/kg is ad-
equate to treat immunocompetent children and adults in
The exact dosing schedule can beflexible(dividedintodoses
of 10 mg/kg on 2 consecutive days or in smaller divided
doses), but liposomal amphotericin B pharmacokinetics
suggest that the initial dose will provide better tissue levels
if at least 5 mg/kg is given.
The schedule of 10 mg/kg/day on 2 consecutive days needs
to be validated in adults with zoonotic VL.
Veterinary use of liposomal amphotericin B and other new
antileishmanial drugs (e.g., miltefosine and paromomycin)
should be avoided to prevent the development of resistance.
Anthroponotic VL (South Asia and the Horn of Africa)
When unresponsiveness to antimonial drugs exceeds a
threshold to be determined in each specific region, policy
makers should strongly consider a shift to an alternative
first-line regimen. An Indian expert committee has sug-
gested using thresholds of 10%–20% unresponsiveness.Two
possible alternative regimens are an amphotericin B for-
mulation (for example, liposomal amphotericin B at a total
dose of 20 mg/kg) or a combination regimen that does not
REVIEWS OF ANTI-INFECTIVE AGENTS • CID 2006:43 (1 October) • 923
Use of combination antileishmanial drug regimens should
be promoted to prevent the development of resistance to
existing drugs. Well-conducted trials of specific combina-
tions are urgently needed. A regimen would be considered
effective if it produces an initial parasitologic and clinical
cure in ?95% of patients and a definitive cure at 6 months
in ?90% of patients.
With respect to liposomal amphotericin B, the following
combinations should be tested: liposomal amphotericin B
plus miltefosine, liposomal amphotericin B plus paromo-
mycin, and (in areas with !10% primary unresponsiveness
to SbV) liposomal amphotericin B plus SbV.
If SbVor other monotherapy is used for anthroponotic VL,
it is imperative that the regimen fulfills WHO guidelines
for adequacy (currently, ?30 days of SbVat 20 mg/kg/day
administered once per day) and that all efforts are made to
ensure compliance with complete treatment courses.
To promote access for all patients, to ensure completeness
of treatment, and to delay development of drug resistance,
the public health community should work in concert with
governments and drug companies to provide antileishman-
ial drugs gratis or at the lowest possible price. To ensure
quality of and access to care, patients with VL should pref-
erably be treated within or in close coordination with an
appropriately structured and monitored public health
The governments of the countries where VL endemicity is
major should facilitate the clinical trials outlined above and
accelerate registration of liposomal amphotericin B and
other antileishmanial drugs. Emphasis should be placed on
areas where resistance is a problem or where HIV-Leish-
mania coinfection is a major issue.
Access to HAART is high priority for HIV-VL–coinfected
Multicenter trials of first-line treatment and secondary pro-
phylaxis of VL in HIV-infected patients are needed, and
liposomal amphotericin B regimens should be included in
these trials. Because of stark epidemiologic and clinical dif-
ferences, results from trials in European settings should not
be extrapolated to apply to low-income countries, and vice
An alternative route of liposomal amphotericin B admin-
istration that is more easily employed in peripheral health
care settings (intramuscular, subcutaneous, or intrarectal)
would be extremely useful. Preclinical work to develop such
formulations is encouraged.
Research is needed to investigate the stability of liposomal
amphotericin B in field settings where the cold chain may
be suboptimal, and to investigate it especially in extreme
conditions (temperatures 145?C).
The current price of liposomal amphotericin B is prohibi-
tively high for VL treatment in resource-poor countries.
Therefore, the WHO and others will work with its manu-
facturer to make it available at a preferential and more
affordable price for the public sectors in India, Bangladesh,
and Nepal and for programs that treat HIV-VL–coinfected
patients in Brazil.
We thank the Istituto Superiore di Sanita `, Rome for kindly providing
the meeting facilities.
The consultative meeting on which this article is
based was supported by Communicable Disease Control, Prevention and
Eradication, WHO (Geneva, Switzerland), and the Italian Cooperation.
Potential conflicts of interest.
J.A.-M. has served as consultant to, is
a member of the speakers’ bureau of, and has received research grants
from manufacturers of liposomal amphotericin B (Gilead Sciences and
Fujisawa Healthcare [now Astella]). J.B. has servedas aconsultanttoGilead
in relation to antiretroviral compounds. R.N.D. has receivedresearchfund-
ing from the manufacturers of liposomal amphotericin B (Gilead Sciences)
and has acted as a consultant for a nonprofit company developing paro-
momycin (Institute of OneWorld Health). S.S. has received support for
clinical trials and presentation of data at scientific meetings from the man-
ufacturers of liposomal amphotericin B (Nextar Pharmaceuticals[nowGil-
ead Sciences]). J.A. received institutional support for clinical trials from
the manufacturers ofamphotericinBlipidcomplex(PENSA,GrupoEsteve)
and is a member of the scientific board of Microbisome, a journal funded
by Vestar. All other authors: no conflicts.
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