REVIEW

CURRENT
OPINION Leishmaniasis: treatment updates and clinical
practice guidelines review
Nathanial K. Copeland a,b and Naomi E. Aronson a,b

Purpose of review
This review summarizes recent important and interesting articles investigating the challenging treatment of
the parasitic infection, leishmaniasis. In addition, it compares and contrasts leishmaniasis clinical practice
treatment guidelines.
Recent findings
Studies show that, in contrast to experience in India, visceral leishmaniasis in East Africa requires higher
doses of liposomal amphotericin for effective treatment results and that pentavalent antimonial drugs remain
efficacious. A retrospective study of visceral leishmaniasis in organ transplant patients suggests that there
may be a role for secondary prophylaxis after treatment akin to HIV coinfection recommendations. The
pros and cons of oral therapy with miltefosine, which cuts across leishmaniasis syndromes in its spectrum,
are discussed. Cutaneous leishmaniasis clinical practice guidelines vary, although the recent European
guidelines favor species-directed therapy.
Summary
Leishmaniasis remains a neglected tropical disease, with a need for additional clinical trials with better
design and reported endpoints to lead evidence-based treatment recommendations – especially in
cutaneous leishmaniasis and leishmaniasis in the immunocompromised host.
Keywords
cutaneous leishmaniasis, Leishmania, practice guidelines, treatment, visceral leishmaniasis

INTRODUCTION To date, there is no single effective treatment for

Leishmania parasites – comprising more than 20
species known as human pathogens – cause diverse
clinical syndromes (e.g., visceral, mucosal, cuta-
neous) shaped by the balance between parasite fac-
tors (e.g., tropisms, virulence, resistance, species) and
the host–immune response. The overall treatment
priorities vary by syndrome; for visceral leishmania-
sis, treatment is given to save lives, and for cutaneous
leishmaniasis to prevent morbidity such as disfigure-
ment, relapse, and, in some species, metastatic infec-
tion.
Clinical practice guidelines vary (especially for
cutaneous leishmaniasis) with standardization
being difficult in part because of the limitations of
the evidence base for treatment. Poor study design
and reporting were summarized in comments of
recent Cochrane reviews as ‘there is a need for more
evidence of effectiveness and safety of different anti-
Leishmania drugs compared with placebo. . .authors
also need to standardize the measurements used to
judge success’ [1–3]. Results obtained in trials in one
geographic area and species may not apply in other
clinical situations.
all Leishmania species and syndromes. Additionally,
the current treatment modalities usually do not
result in parasitologic cure; relapse in the setting
of immunosuppression (i.e., HIV) is an emerging
focus that requires more exploration. Recently,
the details of current treatment of cutaneous leish-
maniasis in US travelers have been reviewed in this
journal including details of drug dosages [4]. Our
review summarizes recent treatment study findings
in visceral leishmaniasis and cutaneous leishmania-
sis, and compares several leishmaniasis clinical prac-
tice treatment guidelines.
a
Walter Reed National Military Medical Center and bUniformed Services
University of the Health Sciences, Bethesda, Maryland, USA
Correspondence to Dr Naomi E. Aronson, Infectious Diseases Division,
Department of Medicine, Room A3060, USUHS 4301, Jones Bridge Rd,
Bethesda, MD 20814, USA. Tel: +1 301 295 3621;
e-mail: Naomi.aronson@usuhs.edu
Curr Opin Infect Dis 2015, 28:426–437
DOI:10.1097/QCO.0000000000000194

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KEY POINTS

Therapeutic effectiveness varies by region, excellent
efficacy is seen using L-AmB treatment in Indian visceral
leishmaniasis with low associated rates of post kala-
azar dermal leishmaniasis and relapse, whereas
treatment of visceral leishmaniasis in East Africa
generally results in less-effective responses to L-AmB but
pentavalent antimonials are associated with continued
efficacy.

The wider availability of molecular diagnostic
techniques that allow for rapid species identification
has changed treatment of cutaneous leishmaniasis,
allowing a more tailored approach.

Leishmaniasis clinical practice guidelines cannot be
standardized; management of this diverse set of
diseases varies by host, geographic area, species,
clinical presentation, available treatments, and cost
considerations.
VISCERAL LEISHMANIASIS
Treatment of visceral leishmaniasis in the
immunocompetent host
The evidence basis for visceral leishmaniasis treat-
ment in immunocompetent patients has previously
been reviewed, and there are known regional treat-
ment differences [5]. An editorial summarizes
amphotericin B (AmB) treatment trials by region [6].
Liposomal amphotericin B (AmBisome, Astellas
Pharma, Northbrook Illinois, USA; L-AmB) is a well
studied and well tolerated option for the treatment
of visceral leishmaniasis [5]. It is the WHO’s treat-
ment of choice (TOC) in the Indian subcontinent [7]
and is part of India’s plan for visceral leishmaniasis
elimination [8]. Médecins Sans Frontières (MSF)
reported results of L-AmB visceral leishmaniasis
&&
treatment in 8749 patients in India [9 ]. All patients
received L-AmB 20 mg/kg over 4–10 days resulting
in more than 99% initial clinical cure and a good
&&
safety profile [9 ]. Although passive follow-up
was poor, parasitologically confirmed relapse was
observed in 119 (1.4%) patients with the median
time to relapse being 10.1 (interquartile range,
&
7.1–13.8) months [10 ]; in the actively followed
subset, cumulative probability of relapse was 2.3%
&&
at 12 months [9 ]. Post kala-azar dermal leishma-
niasis, considered a marker of ineffective therapy,
was diagnosed in 0.3% of those undergoing initial
treatment for visceral leishmaniasis [11]. Addition-
ally, the MSF programme utilized the existing rural
primary healthcare centers to treat 1397 (16.0%)
patients, achieving equivalent results to the larger
cohort while demonstrating a cost-effective cold
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Leishmaniasis Copeland and Aronson
chain and a shorter time to therapy from symptom
onset [9 ].
&&
Unfortunately, evidence supporting the use of
L-AmB for visceral leishmaniasis in East Africa is not
as robust [5–7]. Underscoring this, a trial of L-AmB
in Ethiopia and Sudan was stopped early because of
poor efficacy in the reference arm of multiple dose
L-AmB treatment with a dose greater than what is
effective in India (initial clinical cure 85.5%, para-
sitological cure 54.1%); efficacy was even lower in
&&
the single-dose arms [12 ]. However, patients from
this study treated in southern Ethiopia (rather than
northern Ethiopia or Sudan) had 100% parasitolog-
ical cure with both the multiple and 10 mg/kg single
&&
L-AmB dose arms [12 ], suggesting that potential
regional differences in treatment efficacy exist
within Africa, a concept supported by others
&
[5,13 ]. In a highly endemic region of eastern Sudan,
MSF showed a more than 90% initial clinical cure
with L-AmB totaling 30–50 mg/kg in 379 hospital-
ized complicated visceral leishmaniasis cases –
defined as age 2 or less or at least 45 years, advanced
disease, pregnancy, pentaviral antimonial drug
(SbV) contraindication, HIV coinfection (only nine
&
patients), or prior relapse [14 ]. Less than 10%
relapsed and the death rate was 5.5% compared with
&
30% in similar studies using SbV [14 ], suggesting
that L-AmB may be superior in this setting.
Trial results and clinical experience support
using L-AmB as first-line therapy for Leishmania
infantum visceral leishmaniasis, although most data
are from prior Mediterranean region studies [5,7]. A
multicenter Italian study of 119 immunocompetent
patients demonstrated good efficacy and safety in
clinical practice [15]. Published efficacy data for
L-AmB in visceral leishmaniasis treatment in Brazil
are limited [5].
Used for visceral leishmaniasis treatment since
the 1940s, SbV continues to show ample efficacy;
apart from India where high levels of resistance are
present [5,7]. One hypothesis is that in India, SbV
resistance may be a result of chronic exposure to the
&
arsenic present in regional ground water [16 ,17]. A
small, retrospective study showed a nonsignificant
trend toward higher arsenic levels in the wells of
those who failed treatment along with a significant
increase in visceral leishmaniasis specific mortality
&
in those with higher arsenic exposure [16 ]. In con-
trast, effective SbV treatment in East Africa was
demonstrated with low rates of relapse, post kala-
azar dermal leishmaniasis, or death in over 4000
patients treated with sodium stibogluconate [18 ].
&
Miltefosine (MILT), an oral option for visceral
leishmaniasis treatment, although not recom-
mended as first-line visceral leishmaniasis therapy
by the WHO [7], has been used extensively in India
www.co-infectiousdiseases.com 427
Tropical and travel-associated diseases

>200 cells/ml for >6 months; AIDS

as part of the national eradication programme [8].
Regrettably, use in India has met with increasing

Lip-AmB, L-AmB, SbV, or pentami-

Maintenance therapya and

defining: initiate/optimize ART

ART for HIV coinfection
disappointment: a recent study showed only 86.6%

dine; until CD4þ cell count

cure with 12.8% relapse at 12 months in the per
protocol analysis of over 1000 patients from India
&
and Nepal [19 ]. Pharmacokinetic data show failure

–
with MILT treatment correlates with low plasma
drug concentrations over time and that children
often had low concentrations with typical dosing
&&
regimens [20 ]; the latter corresponding to rela-

Table 1. Selected international and national visceral leishmaniasis treatment guidelines in both immunocompetent and HIV-coinfected persons
tively more clinical failures seen in children younger
&
than 15 years [19 ]. Despite the drawbacks of mono-
therapy, MILT has an expanding role in combi-
nation therapy [5,7].

Combinations of single dose

SbV; L-AmB (30 mg/kg total

Ongoing clinical research in visceral leishma-

AmB; MILT or PRM; SbVb

L-AmB, MILT, and PRM;
a
Alternative regimen(s)
niasis treatment includes trials on combination
therapy and potential new therapeutics. Although

dose); AmB; MILT

SbVc, possibly MILT

MILTe; SbVf; AmBg

recent experience supports combination therapy
[5], this has yet to be adopted by guideline recom-
mendations apart from SbV and paromomycin in

SbV; AmB
East Africa [7]. A Brazilian trial with 378 patients
with visceral leishmaniasis followed for 6 months
compared SbV (meglumine antimoniate), AmB,
L-AmB, and SbV and L-AmB with the AmB arm being

3–5 days up to 15 mg/kg; or L-

intermittently for 10 doses up to

L-AmB 3 mg/kg i.v. daily on days

AmB 10 mg/kg i.v. as a single

3–6 days up to 18–21 mg/kg

and PRM 15 mg/kg i.m. daily
SbV 20 mg/kg i.m. or i.v. daily

1–5, 14, 21 (21 mg/kg total

stopped early due to increased toxicity; the results

L-AmB 3–5 mg/kg i.v. daily for

L-AmB 3–5 mg/kg i.v. daily for

L-AmB 3–5 mg/kg i.v. daily or

should be presented in 2015, but have led to an
expanded role for L-AmB in Brazil (personal com-
munication; Fabiana Alves PA, written communi-
Preferred regimen

cation, DNDi, Geneva, Switzerland, March 2015;

[21]). Combination regimens should become the

for 17 days

40 mg/kg
mainstay of therapy as a result of a shortened

dose)
duration of therapy, lower cost, and theoretically
dose

increased barrier to resistance.

A summary of selected guidelines for the treat-
ment of visceral leishmaniasis in the immunocom-
L. donovani in Indian subcontinent

L. infantum in all endemic regions

petent and immunosuppressed host is found in

L. donovani in East Africa and

Table 1. Because of a stronger evidence base, these

HIV coinfected (worldwide)

visceral leishmaniasis guidelines are fairly similar in

Relevant population

their recommendations in contrast to cutaneous

leishmaniasis treatment guidelines (Tables 2 and 3).
United States
Yemen

Treatment of visceral leishmaniasis in the

immunosuppressed host
Conditions affecting cell-mediated immune
responses complicate visceral leishmaniasis man-
agement, posing diagnostic challenges and signifi-
&
cantly decreasing treatment responses [29 ]. The
most common immunocompromising condition
is HIV, and coinfection leads to increased treatment
&
failure, relapse, drug toxicity, and mortality [29 ].
North Americand

Visceral leishmaniasis–HIV coinfection is becoming

Organization

an increasingly recognized problem globally, with

WHO [7]

HIV seen in up to 5.5% of visceral leishmaniasis

&
patients in India [30 ] and estimated to occur in
8.5% in Brazil [31].

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AIDSinfo [22]
NVBDCP (guideline) [23]
NVBDCP (National Roadmap
for visceral leishmaniasis
Elimination) [8]
Ministry of Health [24,25]
HIV coinfected (USA) L-AmB 4 mg/kg i.v. daily on days Combination L-AmB and MILT L-AmBh; although CD4þ cell count
1–5, 10, 17, 24, 31, 38 up to <200 cells/mm3, monitored until
40 mg/kg immune reconstitution; initiate/
optimize ART during or soon after
visceral leishmaniasis treatment
HIV coinfected (USA) L-AmB 2–4 mg/kg i.v. daily or Lip-AmB, AmB, SbV, MILT L-AmB or Lip-AmB, SbV; until CD4þ
intermittently for up to cell count >200–350 cells/mm3
20–60 mg/kg for 3–6 months or indefinitely;
initiate/optimize ART as soon as
tolerable
India SSGi 20 mg/kg i.m. or i.v. daily AmB; MILT –
for 20–30 days
India L-AmB 10 mg/kg i.v. as a single Combination therapiesj; AmB –
dose emulsion; MILT; AmB
Brazil Meglumine antimoniatei L-AmBk –
20 mg/kg i.m. or i.v. daily
for 20–30 days

AmB, amphotericin B deoxycholate; ART, antiretroviral therapy; IDSA-ASTMH, Infectious Diseases Society of America and American Society of Tropical Medicine & Hygiene; i.m., intramuscularly; i.v., intravenously;
L-AmB, liposomal amphotericin B; Lip-AmB, amphotericin B lipid formulation; MILT, miltefosine; NVBDCP, National Vector Borne Disease Control Programme; PRM, paromomycin; SbV, pentavalent antimonial; SSG,
sodium stibogluconate.

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a
For specifics on alternative regimen dosing and route, refer to the published guideline.
b
In areas where they remain susceptible.
c
Only in areas without significant resistance.
d
Personal communication (Aronson NE, Draft North American leishmaniasis practice guidelines).
e
If disease was acquired in the Indian subcontinent and patient is 12 years, 30 kg, and is not pregnant or breastfeeding.
f
For those who cannot tolerate L-AmB or MILT and disease acquired in area of SbV resistance prevalence <10%.
g
Only for those who develop liposome-induced complement activation-related pseudoallergy while on L-AmB.
h
Optimal agents/dosage not established.
i
Dose based on SbV component.
j
Details of these regimens not specified.
k
This has replaced AmB because of the latter’s toxicity profile and is the preferred regimen for complicated visceral leishmaniasis (age <1 or >50 years; elevated clinical or laboratory severity score; renal insufficiency;
hepatic impairment; heart failure; heart, liver, or kidney transplant; QTc >450 ms; concomitant use of QT altering drug; hypersensitivity to SbV; HIV infection; immune compromising comorbidities; immunosuppressive
medications; treatment failure with SbV; pregnancy).

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Leishmaniasis Copeland and Aronson

429
Tropical and travel-associated diseases

Table 2. Comparison of selected clinical guideline recommendations for the treatment of Old World cutaneous leishmaniasis
Guideline Clinical parameters L. major L. tropica
&&
LeishMan [26 ] 3 lesions
Not disfiguring Wound care Wound care
Immunocompetent

<3 lesions SbV-IL R cryo SbV-IL R cryo

<30 mm Topical PRM Topical PRM
Not disfiguring thermotherapy thermotherapy

>3 lesions MILTa L-AmB

>30 mm Fluconazole MILTa
Delicate location L-AmB SbV-S þ allopurinol
Failed prior local treatment SbV-S þ pentoxifylline
&
Hodiamont et al. [27 ] Not complex TOC: SbV-IL þ cryo TOC: SbV-IL þ cryo
ALT 1: SbV-IL ALT 1: SbV-IL
ALT 2: thermotherapy ALT 2: thermotherapy
Complex (>5 lesions, disfiguring, TOC: MILTa TOC: SbV-S
lesion at site not amenable to ALT: SbV-S ALT: MILTa
local treatment)
Morizot et al. [28] <4 cm Wound care SbV-IL þ cryo
Healing Topical PRM

<4 cm SbV-IL R cryo SbV-IL R cryo

Patient wishes treatment Topical PRM Topical PRM

>4 cm, SbV-S SbV-S

Age <55
Not amenable to local treatment
Not pregnant
No major organ dysfunction

>4 cm MILTa MILTa

Age >55 L-AmB L-AmB
Immunosuppressed
Major organ dysfunction
Pregnant
WHO [7] <4 lesions Wound care Topical PRM
<50 mm SbV-IL þ cryo
Not disfiguring thermotherapy
Immunocompetent SbV-IL
Available for follow-up Cryotherapy

Local treatment Topical PRM Topical PRM

SbV-IL R cryo SbV-IL R cryo
thermotherapy thermotherapy
SbV-IL SbV-IL
Cryotherapy Cryotherapy

Systemic treatment Fluconazole SbV-S

SbV-S SbV-S þ allopurinol
SbV-S þ pentoxifylline

ALT, alternate treatment; cryo, cryotherapy; L-AmB, liposomal amphotericin B; MILT, miltefosine; PRM, paromomycin; SbV-IL, intralesional pentavalent antimonial;
SbV-S, systemic pentavalent antimonial; TOC, treatment of choice.
a
Not used in pregnancy.

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 Table 3. Comparison of selected clinical guideline recommendations for the treatment of New World cutaneous leishmaniasis
Guideline L. mexicana L. (V.) panamensis L. (V.) guyanensis L. (V.) braziliensis
&&
LeishMan [26 ] 3 lesions Wound care Single or few lesions Topical PRM Single lesion No recommendation Single or few lesions SbV-IL  cryo
Not disfiguring <30 mm Thermotherapy Not from Bolivia <30 mm Topical PRM
No lymphatics No lymphatics Not from Bolivia TT
No lymphatics

>3 lesions SbV-IL W cryo Multi ple lesions or MILTa All others Pentam All others SbV-S
large lesions
<30 mm Topical PRM Pentam MILTa AmB
Keto L-AmB
SbV-S

>3 lesions Keto – – – – – –

>30 mm size MILTa
Delicate location SbV-S
Refractory to
local treatment
Hodiamont All TOC: SbV-IL All TOC: SbV-IL All TOC: Pentam All TOC: SbV-S
&
et al. [27 ] þ cryo þ cryo ALT 1: SbV-IL ALT 1: L-AmB
ALT 1: thermotherapy ALT 1: SbV-S ALT 2: MILTa ALT 2: MILTa
ALT 2: SbV-S ALT 2: MILTa

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ALT 3: Pentam
Morizot et al. [28] <4 cm Wound care <4 lesions SbV-IL þ cryo <4 lesions SbV-IL þ cryo <4 lesions SbV-IL þ cryo
Not disfiguring <4 cm Topical PRM <4 cm Topical PRM <4 cm Topical PRM
Immunocompetent Not from SA Not from SA Not SA L. (V.)
braziliensis
Immunocompetent Immunocompetent Immunocompetent
Lesion site amenable Lesion site amenable

>4 cm SbV-S >4 lesions SbV-S >4 lesions SbV-S >4 cm SbV-S
Age <55 >4 cm L-AmB >4 cm L-AmB Age <55
Not pregnant Immunosuppressed MILTa Immunosuppressed MILTa Not pregnant
No major organ Not amenable to Not amenable to No major organ
dysfunction or failed local or failed local Rx dysfunction
treatment

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> 4 cm L-AmB – – – – >4 cm L-AmB
Age 55 MILTa Age 55 MILTa

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Pregnant Pregnant

(Continued )
Leishmaniasis Copeland and Aronson

431
Tropical and travel-associated diseases

The role and timing of antiretroviral therapy (ART)

ALT, alternate treatment; AmB, amphotericin B deoxycholate; cryo, cryotherapy; Keto, ketoconazole; L-AmB, liposomal amphotericin B; MILT, miltefosine; Pentam, pentamidine isethionate; PRM, paromomycin; SbV-IL,
and/or secondary prophylaxis for visceral leishma-

L-AmB
SbV-S
None
niasis remains poorly explored in East African and

AmB
L. (V.) braziliensis Indian populations with HIV, but extrapolating
from European data both should be implemented
Major organ dysfunction &
whenever feasible [5,29 ]. In India, L-AmB mono-
therapy (without secondary prophylaxis) was not as
effective in coinfected patients, with high rates of

Systemic Rx
&
relapse and mortality in more than 20% [32 ]. How-
not renal

Local Rx

ever, with initiation of ART immediately following

treatment for visceral leishmaniasis, one study
showed a 64–66% reduction in mortality compared
&
with those not on ART [32 ]. In Brazil, poor efficacy
was reported regardless of treatment used, but one
study using predominantly SbV had a much higher
mortality than another wherein AmB formulations
L. (V.) guyanensis

Pentam

&
were utilized (19.4% compared with 8.7%) [33,34 ].
SbV-S
MILTa
None

In a recent multiregional systematic review of a total

of 920 visceral leishmaniasis–HIV, SbV was associ-
ated with three times higher mortality than AmB
formulations (18.4 vs. 6.1%); additionally, lipid
formulations showed better clinical improvement
Systemic Rx

with less adverse events [35]. Limited data suggest

Local Rx

that combination L-AmB and MILT may be an

effective visceral leishmaniasis treatment option
&
[13 ]. Currently, the AfriCoLeish Consortium is con-
ducting trials in Ethiopian patients with visceral
leishmaniasis–HIV evaluating combination L-AmB
Pentam

and MILT as well as monthly pentamidine prophy-

SbV-S
MILTa
None
L. (V.) panamensis

laxis [36,37].
intralesional pentavalent antimonial; SbV-S, systemic pentavalent antimonial; TOC, treatment of choice.

Table 1 also summarizes selected guidelines for

the treatment of visceral leishmaniasis–HIV coin-
fection. There are significantly less data supporting
Local treatment

these recommendations relative to those for immu-

treatment

nocompetent patients. Additionally, the WHO

Systemic

recommendation of L-AmB 40 mg/kg has not been

&
studied in East Africa [7,13 ].
Other immunocompromising conditions, such
as organ transplantation, have been less well
studied. Data predominantly from case studies
thermotherapy

and series suggested that treatment response and

Topical PRM

relapse rates were somewhere between visceral leish-

L. mexicana

SbV-IL

MILTa
Keto

maniasis–HIV coinfected and immunocompetent

&
patients [29 ]. A retrospective case–control study
of more than 25 000 solid organ transplant recipi-
ents from Brazil and Spain demonstrated 91.7% cure
Local treatment
dysfunction
Major organ

in 36 patients with visceral leishmaniasis, with most

treatment
not renal

Systemic

&&
using L-AmB (61.1%) or SbV (25.0%) [38 ]. Relapse
was common, but seen less frequently in patients
Table 3 (Continued)

receiving secondary prophylaxis compared those

Not used in pregnancy.

with no prophylaxis (rate: 8.3 vs. 34.8%, P ¼ 0.19)

&&
[38 ]. L-AmB is the best option in the organ trans-
plant (especially renal) population because of better
Guideline

WHO [7]

safety and fewer drug interactions, but further

studies are needed on the role of secondary prophy-
laxis. Immunosuppressing medications (e.g., tumor
a

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 Leishmaniasis Copeland and Aronson

Size of cutaneous
leshmaniasis lesion

<4 cm >4 cm

Patient wishes Age <55; no

L. major, cardiac,
treatment,
L. mexicana, renal or liver
not L. (V). braziliensis*,
or healing lesions disease;
and lesion site accessible
not pregnant

Wound Care: Local Therapy:

SbV-IL plus cryotherapy Yes No
wash, dress,
Topical paromomycin if L.
follow-up
major

Systemic
Systemic SbV miltefosine or
L-AmB

FIGURE 1. Management algorithm for cutaneous leishmaniasis. The French guidelines for the treatment of cutaneous
leishmaniasis are simplified in this diagram, as applied to patients managed by the French Leishmaniasis Reference Center
and modified from [28]. L-AmB, liposomal amphotericin B; SbV-IL, intralesional pentavalent antimonial.

necrosis factor-a inhibitors) may have similar dec-
rements in efficacy with visceral leishmaniasis treat-
ment, but limited data are available addressing
specific management.
CUTANEOUS LEISHMANIASIS
New treatment guidelines
In the past 18 months, several European guidelines
for the management of cutaneous leishmaniasis
have suggested a new species-directed approach
&& &
[26 ,27 ]; an approach made possible by more avail-
able molecular techniques for species determination
[39]. Globally, geographic region experience has
generally informed initial therapy, such as Old
World and New World approaches to treatment.
The WHO guidelines 2010 [7] were primarily tar-
geted to endemic countries and provide syndromic
treatment options for Old World cutaneous leish-
maniasis (OWCL, L. major and L. tropica) and New
World cutaneous leishmaniasis (NWCL), specifying
preferences for management of a few selected Leish-
mania species (Tables 2 and 3).
The European leishmaniasis treatment guide-
&&
line, LeishMan guidelines [26 ], employed the
Oxford evidence grading system and provided ranked
treatment options for Leishmania major, Leishmania
tropica, Leishmania(V). panamensis, Leishmania(V).
guyanensis, Leishmania(V). braziliensis, and Leishma-
nia mexicana, etc. In their recommendations, they
account for the severity measures of infection (e.g.,
risk of mucosal spread, size, number, location of
lesions) and recommended observation or topical
therapy for simple cutaneous leishmaniasis and
oral or parenteral systemic treatment for complex
cutaneous leishmaniasis. Tables 2 and 3 compare
published European and WHO cutaneous leishma-
niasis treatment guidelines.
Another species-directed treatment guideline
for cutaneous leishmaniasis, mucosal leishmaniasis,
&
and visceral leishmaniasis [27 ] varied this approach
using an expert panel to rank treatment options
that were provided based on pooled efficacy and
practical considerations. This analysis permitted up
to 50% lost to follow-up cutaneous leishmaniasis
studies to be included and the authors stated that
37% of the analyses were based on observational
studies only. Treatment was divided into clinical
categories, 13 OWCL and 12 NWCL categories.
In less than 50% the TOC recommendation was
supported by medical literature, 13 categories were

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Tropical and travel-associated diseases
primarily expert opinion, and five of 25 categories
had no evidence base identified for treatment
recommendations. This analysis excluded a signifi-
cant portion of the armamentarium available to
treat cutaneous leishmaniasis; no monotherapy
with liquid nitrogen or intralesional SbV (SbV–IL)
was considered, no azoles or topical paromomycin,
and all lipid formulations of AmB were pooled,
although differences in efficacy have been reported
in cutaneous leishmaniasis. Although this approach
highlights the limited evidence base that exists for
the treatment of cutaneous leishmaniasis, these
guidelines should be evaluated mainly as expert
opinion blinded to the full spectrum of treatment
options (Tables 2 and 3).
The French cutaneous leishmaniasis treatment
recommendations include an algorithmic approach
as follows (Fig. 1; [28]). This algorithm was applied
through consultation from the French Leishmaniasis
Reference Center in 135 parasitologically confirmed
patients with cutaneous leishmaniasis [28]. Of these
patients, 12 were immunocompromised (five HIV,
one chronic lymphocytic leukemia, six immunosup-
pressive therapy). OWCL was the majority (79%) of
the cases, and 19 of 28 NWCL were L. (V.) braziliensis
or L. (V.) guyanensis. Notably, follow-up time was
short (42–60 days). Their results suggested that the
majority of OWCL can be treated locally with a good
outcome (among those given solely wound care 92%
healed, among those with topical paromomycin or
SbV–IL 79% were healed). About 10% were con-
sidered ineligible for topical treatment, and systemic
therapy was given. The authors conclude their
recommendations by suggesting when third-gener-
ation topical paromomycin becomes readily avail-
able (e.g., WR 279 396) that it will replace watchful
waiting with no specific therapy and local treatment
with SbV–IL and cryotherapy.
The North American treatment guidelines are in
final development; if approved they should be pub-
lished in 2016. The general approach to cutaneous
leishmaniasis treatment is an individualized one.
These guidelines stratify guidance by the simple
vs. complex differentiation of leishmanial skin
lesions (complex definition includes species,
geography, host factors, and clinical factors). Avail-
able treatments that have been studied in clinical
trials, and more recently in observational series for
new therapies, are discussed, along with infor-
mation to allow a provider to weigh the individual
risk–benefit of treatment options. Management is
not species-directed as in the recent European guide-
lines, and given the limited evidence base of well
done randomized clinical trials, algorithmic care
plans were not provided (Aronson NE, personal
communication).
434 www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Wound care
The more nuanced approach to the cutaneous leish-
maniasis treatment spectrum includes wound care.
Wound management includes debridement, con-
trol of infection, and moisturizing. Three studies
[40–42] evaluated the role of adjunctive dressings.
In L. major infection, one studied an antimicrobial
silver impregnated polyester dressing and SbV-IL
compared with a plain polyester dressing and
SbV-IL vs. SbV-IL only. At 10 weeks follow-up, nei-
ther dressing added to the efficacy of SbV-IL, which
was unexpectedly low at 40% [40]. In Afghanistan
(both L. major and L. tropica), the antimicrobial
solution 0.045% DAC N-055 (alkaline sodium chlor-
ite) was studied in conjunction with moisturized
wound dressings after electrocautery debridement.
These studies [41,42] suggested that 70–90% per-
sons with cutaneous leishmaniasis treated with elec-
trocautery, followed with DAC N-055 solution and
dressings, were healed vs. 63% treated with SbV-IL
by day 75. In the study using polyacrylic hydrogel
dressings after electrocautery, there was no differ-
ence gained by adding DAC N-55 to the dressing
[42].
New topical treatments
A proof-of-concept study of 31 patients, 17 self-
administering daylight-activated photodynamic
therapy in cutaneous leishmaniasis (L. major and
L. tropica), showed healing in 70% [43]. After
curettage of the crust over lesions, a thick layer of
the photosensitizer aminolevulinate (Metvix,
Galderma, France) was applied to the lesions weekly,
covered with a dressing and foil for 30 min, then the
dressing removed, and the patient was asked to
expose the area to daylight for 2.5 h. In those
patients with multiple lesions, a control lesion
was not initially treated and none of these healed
spontaneously during the 8–10 weeks treatment
session.
Another novel topical treatment reported was
the use of intralesional AmB as a second-line treat-
ment of antimonial resistant OWCL [44]. Ninety-
three patients received AmB 2 mg/ml injected into
lesions weekly for up to 12 weeks. Adverse events
were ‘low and insignificant’ ([44], page 635).
By 12 weeks, 61% of patients with cutaneous
leishmaniasis had healed completely (>90%
reduction in size and induration) and 22% more
had a partial remission (60–90% reduction).
Although pentavalent antimonials are frequently
injected intralesionally, this study describes a
similar method using AmB – which one might think
would be very sclerotic/reactogenic based on the
phlebitis that it may cause.
Volume 28
Number 5
October 2015

What is new with liposomal amphotericin B
in the treatment of cutaneous leishmaniasis?
Additional experience with L-AmB for the treatment
of cutaneous leishmaniasis and mucosal leishma-
niasis continues to support off-label use for these
infections, although we advocate for a convincing
clinical trial to develop more definitive recommen-
dations. A retrospective case series reported on 24
children with cutaneous leishmaniasis caused by L.
tropica who were treated with L-AmB 3–5 mg/kg/day
for 5 days and then received an additional dose on
day 10 [45]. Seventy-five percent experienced a
complete response at 3 months; the four children
who failed L-AmB responded to systemic SbV.
The largest published case series of mucosal leish-
maniasis treated with L-AmB reported the responses
of 16 patients; 88% were healed after receiving a
mean daily dose of L-AmB of 2.5 mg/kg/day. Two
patients stopped L-AmB due to toxicity and were
&
nonresponders [46 ]. The author concluded that a
total dose of 30–35 mg/kg L-AmB yielded 100%
effective treatment of mucosal leishmaniasis in this
Brazilian cohort that had nasal>pharyngeal>oral
&
cavity>larynx involvement [46 ].
Miltefosine
In 2014, the Food and Drug Administration
approved oral MILT for the treatment of cutaneous
leishmaniasis due to L. (V.) braziliensis, L. (V.) guya-
& Financial support and sponsorship
nensis, and L. (V.) panamensis [47 ]. This drug and
the relevant clinical trial evidence base were
recently reviewed [48]. This exciting first Food
and Drug Administration approved drug indicated
for cutaneous leishmaniasis treatment should be
considered in light of two concerning develop-
ments: clinical resistance given the prolonged drug
& & &&
half-life [19 ,49 ] and data [20 ] suggesting that the
response rate is lower in persons receiving less than
2.5 mg/kg/day (this means that anyone weighing
>60 kg [132 lbs] could be underdosed).
CONCLUSION
Recent studies have highlighted the complexity of
leishmaniasis treatment. Updates in visceral leish-
maniasis management are informed by the long-
term follow-up on treatment efficacy of L-AmB
and MILT in India, to data observing the relative
ineffectiveness of L-AmB in East Africa where
SbV remains the mainstay of therapy. Advances in
our understanding of MILT monotherapy failure
pinpoint the need for more studies looking at com-
bination therapy and the need for novel drug devel-
opment. Two promising nitroimidazoles are being
evaluated, fexinidazole in phase II trials in Sudan
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Leishmaniasis Copeland and Aronson
and (R)-PA-824, an enantiomer of a new tuberculosis
&
drug [50 ]. Current treatment continues to be
disappointing in immunocompromised patients,
especially in HIV–visceral leishmaniasis coinfec-
tion, and there are new data suggesting an expanded
role of secondary prophylaxis in organ transplant
patients. Clinical practice guidelines for the treat-
ment of cutaneous leishmaniasis are not standar-
dized; a sea change in approach has occurred with
broader options considered than previously. The
North American clinical practice guidelines for
cutaneous leishmaniasis, expected in 2016, will
focus on an individualized treatment approach.
Finally, more research is needed in visceral leishma-
niasis regarding combination therapies, especially
in HIV coinfected patients, and clinical trials are
sorely needed in cutaneous leishmaniasis and
mucosal leishmaniasis to not only clarify best
approaches to treatment in an often self-healing
infection, but also to evaluate various options (such
as L-AmB) head-to-head. Unfortunately, there is
little financial incentive for the development of
effective leishmaniasis treatments and support from
governmental and nonprofit organizations such as
the Drugs for Neglected Diseases Initiative is crucial
for ongoing progress.
Acknowledgements
None.
None.
Conflicts of interest
N.E.A. receives royalties for writing leishmaniasis
chapters for UpToDate. She is also the Chair, IDSA-
ASTMH leishmaniasis clinical practice guidelines writing
committee.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Gonzalez U, Pinart M, Reveiz L, et al. Designing and reporting clinical trials on
treatments for cutaneous leishmaniasis. Clin Infect Dis 2010; 51:409–419.
2. Gonzalez U, Pinart M, Rengifo-Pardo M, et al. Interventions for American
cutaneous and mucocutaneous leishmaniasis. Cochrane Database Syst Rev
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8. NVBDCP. National road map for kala-azar elimination. Directorate of National
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Services, Minister of Health & Family Welfare, Government of India; 2014.
http://nvbdcp.gov.in/Doc/Road-map-KA_2014.pdf. [Accessed 27 March
2015]
9. Burza S, Sinha PK, Mahajan R, et al. Five-year field results and long-term
&& effectiveness of 20 mg/kg liposomal amphotericin B (Ambisome) for visceral
leishmaniasis in Bihar. India PLoS Negl Trop Dis 2014; 8:e2603.
A retrospective cohort study of 8749 patients with visceral leishmaniasis treated
with L-AmB in Bihar, India. It is the largest cohort (in this context) published to date
and demonstrated the excellent efficacy of L-AmB with low rates of relapse. With
1397 of the patients treated in community health centers, it serves as a model for
use of L-AmB in resource-limited settings.
10. Burza S, Sinha PK, Mahajan R, et al. Risk factors for visceral leishmaniasis
& relapse in immunocompetent patients following treatment with 20 mg/kg
liposomal amphotericin B (Ambisome) in Bihar, India. PLoS Negl Trop Dis
2014; 8:e2536.
This is an analysis of a large cohort of patients treated with L-AmB regarding risks
of relapse showing that, although uncommon, relapse often occurs 6–12 months
after treatment, suggesting this may be the key follow-up period.
11. Burza S, Sinha PK, Mahajan R, et al. Post kala-azar dermal leishmaniasis
following treatment with 20 mg/kg liposomal amphotericin B (Ambisome) for
primary visceral leishmaniasis in Bihar, India. PLoS Negl Trop Dis 2014;
8:e2611.
12. Khalil EA, Weldegebreal T, Younis BM, et al. Safety and efficacy of single
&& dose versus multiple doses of AmBisome1 for treatment of visceral leish-
maniasis in Eastern Africa: a randomised trial. PLoS Negl Trop Dis 2014;
8:e2613.
This is a multicenter, prospective, open-label, randomized trial attempting to find a
single-dose L-AmB regimen appropriate for East Africa; unfortunately, the multiple
dose L-AmB control arm only demonstrated 85% efficacy leading to early
termination of the study. Interestingly, although underpowered to make conclu-
sions, the study sites in southern Ethiopia showed 100% cure at 6 months of both
the multiple dose and 10 mg/kg single dose arms, suggesting possible regional
differences within Eastern Africa.
13. Diro E, Lynen L, Ritmeijer K, et al. Visceral leishmaniasis and HIV coinfection in
& East Africa. PLoS Negl Trop Dis 2014; 8:e2869.
This is a review discussing the growing challenge of visceral leishmaniasis and HIV
coinfection in East Africa. They highlight the high death rates associated with
treatment using pentavalent antimonials, the lack of data to support the WHO’s
recommended L-AmB treatment regimen, and field evidence supporting the use of
L-AmB combined with MILT. They also note a regional difference in East Africa with
northern Ethiopia and Sudan having lower cure rates than other areas.
14. Salih NA, van Griensven J, Chappuis F, et al. Liposomal amphotericin B for
& complicated visceral leishmaniasis (kala-azar) in eastern Sudan: how effective is
treatment for this neglected disease? Trop Med Int Health 2014; 19:146–152.
This is a retrospective cohort study in East Africa showing 92–94% initial clinical
cure in 379 complicated or relapsing visceral leishmaniasis cases treated with
L-AmB, but also a 7–10% observed relapse rate and nearly 40% of patients lost to
follow-up.
15. Di Masi F, Ursini T, Iannece MD, et al. Five-year retrospective Italian
multicenter study of visceral leishmaniasis treatment. Antimicrob Agents
Chemother 2014; 58:414–418.
16. Perry MR, Prajapati VK, Menten J, et al. Arsenic exposure and outcomes of
& antimonial treatment in visceral leishmaniasis patients in Bihar, India: a
retrospective cohort study. PLoS Negl Trop Dis 2015; 9:e0003518.
This is a retrospective cohort study evaluating whether water arsenic exposure
correlates to treatment failure with pentavalent antimonials. This was the first
clinical study evaluating this question and showed a 1.78 odds of treatment failure
if exposed to higher arsenic levels, but this failed to attain statistical significance
(confidence interval: 0.7–4.6, P ¼ 0.23).
17. Perry MR, Wyllie S, Raab A, et al. Chronic exposure to arsenic in drinking
water can lead to resistance to antimonial drugs in a mouse model of visceral
leishmaniasis. Proc Natl Acad Sci U S A 2013; 110:19932–19937.
18. Mueller YK, Kolaczinski JH, Koech T, et al. Clinical epidemiology, diagnosis
& and treatment of visceral leishmaniasis in the Pokot endemic area of Uganda
and Kenya. Am J Trop Med Hyg 2014; 90:33–39.
This is a retrospective analysis of nearly 5000 patients with visceral leishmaniasis
in East Africa utilizing primarily pentavalent antimonials demonstrating their con-
tinued efficacy with relatively low rates of relapse or death.
19. Ostyn B, Hasker E, Dorlo TP, et al. Failure of miltefosine treatment for visceral
& leishmaniasis in children and men in South-East Asia. PLoS One 2014;
9:e100220.
This is a prospective observational study looking at patients treated with oral MILT
showing a more than 9% relapse and identifying age less than 15 in particular to be
associated with relapse, postulating that a factor such as pharmacokinetics could
be responsible rather and not likely parasite resistance.
20. Dorlo TP, Rijal S, Ostyn B, et al. Failure of miltefosine in visceral leishmaniasis
&& is associated with low drug exposure. J Infect Dis 2014; 210:146–153.
This is a pharmacokinetics–pharmacodynamics study showing that failure with
MILT is associated with shorter duration of time spent 10 times above the half
maximal effective concentration and that, with standard dosing regimens, children
are less exposed to MILT than adults, likely explaining the higher rate of relapse and
treatment failure in children seen in other studies.
436 www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
21. University of Brasilia; Ministry of Health, Brazil; Drugs for Neglected Diseases;
Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico. Efficacy
and safety study of drugs for treatment of visceral leishmaniasis in Brazil.
ClinicalTrials.gov. Bethesda, MD: National Library of Medicine (US). 2000.
http://clinicaltrials.gov/show/NCT01310738. [Accessed 23 March 2015]
22. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents.
Guidelines for the prevention and treatment of opportunistic infections in HIV-
infected adults and adolescents. Centers for Disease Control and Prevention,
the National Institutes of Health, and the HIV Medicine Association of the
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gov/contentfiles/lvguidelines/adult_oi.pdf. [Accessed 15 March 2015]
23. NVBDCP. Diagnosis & treatment. Directorate of National Vector Borne
Disease Control Programme, Directorate General of Health Services, Minister
of Health & Family Welfare, Government of India. http://nvbdcp.gov.in/doc/
guidelines-diagnosis-treatment-ka.pdf. [Accessed 16 March 2015]
24. Ministério da Saúde [Ministry of Health]. Manual de Vigilância e Controle da
Leishmaniose Visceral [Surveillance control manual of leishmaniasis in
health]. Departamento de Vigilância Epidemiológica, Secretaria de Vigilância
em Saúde, Ministério da Saúde, Brasil; 2006. http://bvsms.saude.gov.br/bvs/
publicacoes/manual_vigilancia_controle_leish_visceral_2006.pdf. [Acces-
sed 28 March 2015]
25. Grupo Técnico das Leishmanioses [Technical Group of Leishmanioses]. MS
amplia indicação de medicamento para o tratamento da leishmaniose visceral
[MS expands indications of drugs for treatment of visceral leishmaniasis].
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Saúde, Ministério da Saúde, Brasil; 2014. http://portalsaude.saude.gov.br/
index.php/o-ministerio/principal/leia-mais-o-ministerio/726-secretaria-svs/
vigilancia-de-a-a-z/leishmaniose-visceral-lv/13058-ms-amplia-indicacao-de-
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March 2015]
26. Blum J, Buffet P, Visser L, et al. LeishMan recommendations for treatment of
&& cutaneous and mucosal leishmaniasis in travelers. J Travel Med 2014;
21:116–129.
This comprehensive European clinical guideline for cutaneous leishmaniasis and
mucosal leishmaniasis treatment in travelers proposes a species-directed approach
and uses a formal grading system to evaluate the evidence base. The limitations of the
underlying studies confound this simplified regimen, but until further studies are
completed this is a good start for a clinician to use as a reference.
27. Hodiamont C, Kager P, Bart A, et al. Species-directed therapy for leishma-
& niasis in returning travellers: a comprehensive guide. PLoS Negl Trop Dis
2014; 8:e2832.
A Dutch guideline using species-directed treatment recommendations for travelers.
Final ranking was done by expert opinion and several categories have little or no
evidence base to be considered TOC. This study may be useful to point out research
gaps.
28. Morizot G, Kendjo E, Mouri O, et al. Travelers with cutaneous leishmaniasis
cured without systemic therapy. Clin Infect Dis 2013; 57:370–380.
29. van Griensven J, Carrillo E, Lopez-Velez R, et al. Leishmaniasis in immuno-
& suppressed individuals. Clin Microbiol Infect 2014; 20:286–299.
This is a review of leishmaniasis in immunosuppressed patients, particularly of
interest is discussion of the treatment of visceral leishmaniasis in HIV coinfected
patients, supporting the use of L-AmB despite limited data and role of secondary
prophylaxis. Authors deal minimally with treatment and prophylaxis in non-HIV
immunosuppressed patients, again recommending L-AmB as first-line and dis-
cussing the lack of a clear role of prophylaxis in this group.
30. Burza S, Mahajan R, Sanz MG, et al. HIV and visceral leishmaniasis coinfec-
& tion in Bihar, India: an underrecognized and underdiagnosed threat against
elimination. Clin Infect Dis 2014; 59:552–555.
This study screening 2077 patients with visceral leishmaniasis from Bihar, India, for
HIV found a prevalence of 5.6% for coinfection, supporting the need for increased
screening and not just of those who have visceral leishmaniasis relapse.
31. Lindoso JA, Cota GF, da Cruz AM, et al. Visceral leishmaniasis and HIV
coinfection in Latin America. PLoS Negl Trop Dis 2014; 8:e3136.
32. Burza S, Mahajan R, Sinha PK, et al. Visceral leishmaniasis and HIV co-
& infection in Bihar, India: long-term effectiveness and treatment outcomes with
liposomal amphotericin B (AmBisome). PLoS Negl Trop Dis 2014; 8:e3053.
This is a subgroup analysis of the retrospective study of a larger cohort of patients
with visceral leishmaniasis treated with L-AmB by the same authors focusing on
HIV coinfection; whereas initial effectiveness was excellent at 96%, not unexpect-
edly relapse was nearly 20% at 1 year and 23% of coinfected patients died at a
median of 11 months. They also found that starting ART immediately after initiating
treatment for visceral leishmaniasis was associated with a more than 60%
reduction in mortality.
33. Albuquerque LC, Mendonça IR, Cardoso PN, et al. HIV/AIDS-related visceral
leishmaniasis: a clinical and epidemiological description of visceral leishma-
niasis in northern Brazil. Rev Soc Bras Med Trop 2014; 47:38–46.
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Dis 2014; 8:e2816.
This is a small prospective cohort study of visceral leishmaniasis and HIV-coin-
fected patients in Brazil compared with noncoinfected patients all treated with
mostly AmB formulations showing similar initial response rates, but a 37% relapse
rate in the coinfected group compared with only 3% in the immunocompetent
patients.
Volume 28
Number 5
October 2015

35. Cota GF, de Sousa MR, Fereguetti TO, Rabello A. Efficacy of antileishmania
therapy in visceral leishmaniasis among HIV infected patients: a systematic
review with indirect comparison. PLoS Negl Trop Dis 2013; 7:e2195.
36. Institute of Tropical Medicine, Belgium; Addis Ababa University; University of
Gondar; et al. Prophylaxis of visceral leishmaniasis relapses in HIV co-infected
patients with pentamidine: a cohort study. ClinicalTrials.gov. Bethesda, MD:
National Library of Medicine (US). 2000. NLM Identifier: NCT01360762.
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37. Drugs for Neglected Diseases; Médicins Sans Frontières; London School of
Hygiene and Tropical Medicine; et al. Efficacy trial of AmBisome given alone
and AmBisome given in combination with miltefosine for the treatment of VL
HIV positive Ethiopian patients. ClinicalTrials.gov. Bethesda, MD: National
Library of Medicine (US). 2000. NLM Identifier: NCT02011958. http://
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38. Clemente W, Vidal E, Girao E, et al. Risk factors, clinical features and
&& outcomes of visceral leishmaniasis in solid-organ transplant recipients: a
retrospective multicenter case-control study. Clin Microbiol Infect 2015;
21:89–95.
This is a large retrospective case–control study identifying 36 visceral leishmaniasis
cases out of over 25 000 solid organ transplant recipients demonstrating an initial
cure rate of 94% with mostly AmB formulations used for therapy. Interestingly,
patients who used some sort of prophylaxis had only 8% relapse rate compared with
35% in those with none; although the number of cases is too low to draw any firm
conclusions, this study suggests a role for secondary prophylaxis in non-HIV-related
immunosuppression that needs to be further studied prospectively.
39. Van der Auwera G, Dujardin J. Species typing in dermal leishmaniasis. Clin
Microbiol Rev 2015; 28:265–294.
40. Khatami A, Talaee R, Rahshenas M, et al. Dressings combined with injection
of meglumine antimoniate in the treatment of cutaneous leishmaniasis: a
randomized controlled clinical trial. PLoS One 2013; 8:e66123.
41. Stahl H-C, Faridullah Ahmadi, Schleicher U, et al. A randomized controlled
phase IIb wound healing trial of cutaneous leishmaniasis ulcers with 0.045%
pharmaceutical chlorite (DAC N-055) with and without bipolar high frequency
electro-cauterization versus intralesional antimony in Afghanistan. BMC Infect
Dis 2014; 14:619.
42. Jebran A, Schleicher U, Steiner R, et al. Rapid healing of cutaneous leishma-
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without DAC N-055:a randomized controlled phase IIa trial in Kabul. PLoS
Negl Trop Dis 2014; 8:e2694.
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Leishmaniasis Copeland and Aronson
43. Enk C, Nasereddin R, Alper M, et al. Cutaneous leishmaniasis responds to
daylight-activated photodynamic therapy: proof of concept for a novel self-
administered therapeutic modality. Br J Dermatol 2015; 172:1364–1370.
44. Goyonlo V, Vosoughi E, Kiafar B, et al. Efficacy of intralesional amphotericin B
for the treatment of cutaneous leishmaniasis. Indian J Dermatol 2014; 59:631.
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& for the treatment of mucosal leishmaniasis in HIV-negative patients. Trans R
Soc Trop Med Hyg 2014; 108:176–178.
A retrospective review of 16 patients with mucosal leishmaniasis treated with
L-AmB, this is the largest series published to date and gives a reasonable sense
of what dose and duration to use. In addition, this obliquely supports the use of
L-AmB in L.(V). braziliensis cutaneous leishmaniasis because it suggests that
adequate concentrations will accumulate in the nasopharynx in the event of
metastatic infection.
47. FDA, Center for Drug Evaluation and Research. Application Number:204684-
& Orig1s000 Application Review. 2014. http://www.accessdata.fda.gov/drug
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Drug Administration to approve MILT for the treatment of cutaneous leishmaniasis,
mucosal leishmaniasis, and visceral leishmaniasis in the United States.
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Parasite isolates from patients with cutaneous leishmaniasis who failed therapy,
obtained before and after MILT treatment, found two of six had resistance, one a
high-effective concentration more than 32, and one developed a decreased
expression of MILT transporter LbMT. These findings raise concern that MILT
monotherapy may select for drug-resistant cutaneous leishmaniasis parasites.
50. Sundar S, Chakravarty J. Investigational drugs for visceral leishmaniasis.
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of particular interest are the nitroimidazoles, fexinidazole, and (R)-PA-824.
www.co-infectiousdiseases.com 437