District of Columbia
Leishmanias is a disease caused by the bite of sandflies and is found in many parts of the
world including the Europe, Southwest Asia, Africa and the Middle East. This disease is a
threat for military soldiers in areas where this disease is found. Sodium stibogluconate
(SSG) or Pentostam (Glaxo Smith Kline, United Kingdom) is an Investigational New Drug (IND)
product used by the Department of Defense for over 20 years to treat cutaneous, mucosal and
viseral leishmanias. This drug is not licensed for commercial use in the United States
because of very limited need for the product in the U.S.A. The objective of this protocol is
to provide sodium stibogluconate for the treatment of cutaneous leishmaniasis and mucosal
leishmaniasis (pentavalent antimonials curently considered the drug of choice for these
infections) Provide sodium stibogluconate as a second line treatment for viscerotropic and
visceral leishmaniasis (liposomal amphotericin is the drug of choice for these types as it
is FDA approved for vusceral leishmaniasis).
Leishmaniasis is a protozoal disease transmitted by sandflies and is endemic in many parts
of the world including Central and South America, Europe, Southwest Asia, Africa, and the
Middle East. Infected humans may develop cutaneous (Old or New World), mucocutaneous (New
World), or visceral leishmaniasis. The disease is a medical threat for military soldiers
assigned in endemic areas and currently a major cause of morbidity in soldiers deployed to
the Middle East and a complication of military exercises in Panama, Honduras, and South
Pentavalent antimonials (Pentostam, GSK, UK, and Glucantime, Rhone-Poulenc, France) have
been used to treat leishmaniasis for more that 50 years. Neither of these drugs are licensed
for commercial use in the United States, likely because of limited use. Worldwide, there is
a great deal of experience and use of these products.
Pentostam or sodium stibogluconate is a pentavalent antimony drug complexed to carbohydrate
the exact structure and mechanism of action of which are not known. It is provided as a 100
mg antimony/ml solution that contains a preservative, m-chlorocresol. Most of the dose is
excreted by the kidneys within 24 hours.
Pentostam is presently an investigational new drug (IND) product that has been in use by the
Department of Defense (DoD) for over 20 years for the treatment of cutaneous, mucosal and
visceral leishmaniasis. In August, 1997, the FDA approved Ambisome (liposomal amphotericin)
for the treatment of visceral leishmaniasis. As a result, in the treatment of visceral and
viscerotropic leishmaniasis, the use of antimonials will now be considered a second-line
In 1984, the World Health Organization recommended that the daily dose of antimony in the
treatment of visceral leishmaniasis be increased to 20 mg/kg/day. A randomized controlled
trial of 40 subjects with American, New World, cutaneous leishmaniasis (ACL) found 100% cure
rates with 20 mg/kg/day Sb for 20 days but only a 76% cure if 10 mg/kg/day for 10 days was
used. A comparison of three treatment schedules in 36 subjects with CL (single rapid
infusion, continuous 24 hour infusion, or every eight hour doses) found no advantage over
using once daily dosing. A review of the controlled trials of SSG concludes that a
recommended course of therapy is 20 mg/kg/day with no upper limit to dose for 20 days for CL
and 20 mg/kg/day for 28 days for visceral or mucocutaneous leishmaniasis. The Pentostam®
package insert suggests that 10-20 mg/kg/day with a maximum dose of 850 mg for a minimum of
20 days be used; however, based on the Centers for Disease Control and Prevention (CDC) and
Walter Reed Army Medical Center (WRAMC) experience and their practice guidelines, 20
mg/kg/day with no upper limit to dosage is used. WRAMC recently published their CL treatment
experience primarily in New World leishmaniasis comparing SSG 20 mg/kg for 10 or 20 days and
found 100% of volunteers in the 10-day group were cured. In this study 15% were Leishmania
major infections. Comparable results are expected for Old World leishmaniasis based on
clinical experience and current literature.
Detailed toxicity data for the 20 mg/kg/day dose are provided by several studies.
Percentages from the WRAMC experience are included here. Subjective musculoskeletal
complaints are common (58%), as well as elevated hepatocellular (67%) and pancreatic enzyme
levels (97%) and nonspecific electrocardiogram (EKG) changes (T wave changes). These side
effects are usually reversible, and no deaths have been associated with SSG at WRAMC. Other
SSG toxic effects include headache (22%), rash (9%), thrombocytopenia, depression of various
hematologic cell lines (44%), phlebitis, anaphylaxis, inflammation around lesions, and
transient coughing after infusion. Other associated symptoms include anorexia, malaise,
myalgia, abdominal pain, headache, lethargy, sweating, vertigo, facial flushing, initial
worsening of skin lesions, epistaxis, jaundice and peripheral neuropathy. In our
above-mentioned 10 versus 20 days study, the adverse events (AE) were significantly
decreased in the cohort receiving the 10 days versus 20 with myalgias in 42% (versus 68%),
with less chemical pancreatitis and fewer hematologic parameter disorders. Angioedema during
SSG infusion has recently been described in two subjects at WRAMC. Both subjects responded
quickly to benadryl treatment without complications. Both subjects were subsequently skin
tested with SSG intradermally for hypersensitivity and one reacted.
Alternative heat therapies have been used to successfully treat CL. Laboratory investigation
showed that Leishmania infection is sensitive to heat. Various forms of heat application in
human CL has shown variable efficacy. The TTI Thermomed™ device has been cleared as a 510-k
device by the U.S. Food and Drug Administration (FDA) for use in the treatment of CL. This
device uses localized current field radio frequency. Other therapies that may be effective
for treating CL include topical paromomycin and oral fluconazole.
- DoD healthcare beneficiary of any age and gender.
- Clinicoepidemiologic or parasitologic diagnosis (microscopy, PCR or culture) of
- Able to provide informed consent or assent (children).
- All participants (both male and female) must agree to take precautions not to become
pregnant or father a child for at least 2 months after receiving SSG.
- Pregnancy. Females of childbearing potential must have negative urine human chorionic
gonadotropin hormone (HCG) within 96 hours start of infusion period.
- History of hypersensitivity to pentavalent antimonials.
- Any of the following on screening examination:
1. QTc interval greater or equal to 0.5 sec
2. Severe cardiac disease (disabling valvular heart disease, myopathy, or
3. History of recurrent pancreatitis
4. Liver failure or active hepatitis with transaminases > 3x upper limit of normal
5. Renal failure or creatinine > 2.5 mg/dL
6. Thrombocytopenia (platelets <100,000/mm3)
7. White blood cell count < 2000 / mm3
8. Hematocrit < 30 %