Please select the eligibility criteria that correspond to the clinical trial below.
Title: Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: a Phase 2 Study in the Old World
Brief Summary: This study is to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic.


Options:
A: Inclusion Criteria:

* The subject was age 5 years or older, but less than 65 years.
* The subject was able to understand the information provided to him/her and give written informed consent. Consent was obtained from the parent/guardian of subjects who were \< 18 years old. Children 12 to \< 18 years old were asked to sign the written assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.
* The subject was a male or female who was generally healthy.
* The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by: (1) the identification of promastigotes in a culture of an aspirated lesion, or (2) the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa stained smear obtained from a lesion scraping.
* The subject had five or fewer cutaneous lesions.
* The subject had one lesion, which would be designated as the index lesion, that was ≥ 1 and \< 5 cm in its greatest diameter and primarily ulcerative, ie, not purely verrucous or nodular.
* The subject was willing to forego other forms of treatment for CL, including other investigational treatment during the study.
* In the opinion of the principal investigator, the subject or subject's parent/guardian was capable of understanding and complying with the protocol

Exclusion Criteria

* The subject received previous treatment for leishmaniasis (including WR 279,396) within the last 6-months, with the exception of mercurochrome.
* The subject had difficulty complying with instructions on maintaining the dressing, eg, due to life style activities or age.
* The subject had only a single lesion whose characteristics included any of the following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, \< 1 cm or located on the ear, or other location that in the opinion of the principal investigator would be difficult to maintain application of study drug topically.
* The subject had a lesion due to Leishmania that involved the mucosa.
* The subject had signs or symptoms of disseminated disease, ie, clinically significant lymphadenitis with nodules that were painful and \> 1 cm in the lymphatic drainage of the ulcer.
* The subject was a female with a positive urine pregnancy test, or who was breast feeding or lactating.
* The subject had an active malignancy or had a history of a solid, metastatic or hematologic malignancy, with the exception of a basal or squamous cell carcinoma of the skin that had been removed.
* The subject had a significant organ abnormality or chronic disease that, in the opinion of the investigator, would warrant exclusion of the subject from the study or would prevent the subject from completing the study.
* The subject was receiving any of the following medications: any medication containing pentavalent antimony, including stibogluconate sodium (Pentostam®) and meglumine antimoniate (Glucantime®); amphotericin B, including liposomal amphotericin B and amphotericin B deoxycholate; other medications containing paromomycin (administered IV or topically); methylbenzethonium chloride, fluconazole, ketoconazole, itraconazole; pentamidine; or allopurinol.
* The subject or the subject's parent/guardian was unable to understand verbal and/or written Arabic, English, or French (languages in which certified translations of the informed consent were available).
* The subject presented with an immuno-compromising condition, including recidivant leishmaniasis (during the past 2 years), or diabetes.
* The subject had a history of known or suspected idiosyncratic reactions or hypersensitivity to aminoglycosides.
B: Inclusion Criteria:

* Age 5-75 years
* Lesions must measure at least 1 cm and be primarily ulcerative
* Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
* Must have given written informed consent to participate in the study

Exclusion Criteria:

* Known drug intolerance to aminoglycosides in the patient or immediate family
* Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
* Patients with tuberculosis under treatment
* Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
* Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, or a lesion in the face that, in the opinion of the attending dermatologist could potentially cause significant disfigurement
* Location of disease: mucosal involvement
* Disseminated disease: clinically significant lymphadenitis with nodules that are painful and greater than 1 cm in size in the lymphatic drainage of the ulcer
* Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
* Hearing abnormality
* Ongoing pregnancy or have plans to become pregnant
* Females of child bearing age (Tunisia Only)
* Signs or symptoms of peripheral neuropathy

Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.

Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory
C: Inclusion Criteria:

1. Present a suspected Old World Cutaneous Leishmaniasis lesion confirmed by Giemsa stained wound smears with no other skin diseases or infections and who
2. Have never been previously treated with antimonial injections or any other form of anti-leishmanial medication.

Exclusion Criteria:

1. Patients with more than one lesion are excluded.
2. Patients with a lesion age of \> 3 months are also excluded. The experience of the Kabul trial shows that patients presenting themselves for the first time with a lesion, which is older than three months, have either been pre-treated somewhere else and/or show a poor compliance during the trial.
3. Patients below 12 years of age have to be excluded from the trial, because they cannot fill in the EQ-5D and Skindex questionnaire part of the health economic evaluation.
4. Intralesional antimony injections are too painful for lesions located on the nose, lips or eyes. Therefore, patients presenting these lesions are excluded from the trial.
5. For compliance reasons addicted patients and patients not available for follow-up are exclude from the trial.
6. Patients with major uncontrolled diseases as tuberculosis, diabetes or HIV are excluded from the trial, since their management requires additional co-medications, which may affect wound healing.
D: Inclusion Criteria:

* Department of Defense (DOD) Healthcare beneficiary
* Parasitologic diagnosis of cutaneous Leishmania infection

(Inclusion criteria for randomization includes that must be Leishmania major species)

* Willing to locate to WRAMC area during treatment and perform subsequent follow-up visits if needed

(If not active duty on orders, then the participant will bear the cost of food and lodging during the initial 10-day outpatient treatment period at Walter Reed Army Medical Center)

* Able to provide informed consent
* 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 sodium stibogluconate

Exclusion Criteria:

* Unable to provide informed consent
* Pregnancy (females of child bearing potential must have negative urine human chorionic gonadotropic hormone \[HCG\] within 48 hours of the start of infusion period)
* History of hypersensitivity to pentavalent antimonials
* Serious medical illness:

  1. QTc interval \>/= 0.5 sec
  2. severe cardiac disease
  3. history of current pancreatitis
  4. liver failure or active hepatitis with transaminases \>3X normal
  5. renal failure or creatinine \>2.5
  6. thrombocytopenia (platelets \<75,000)
  7. white blood cell count \<2000
  8. hematocrit \<25
  9. absence of palpable extremity pulses in the limb requiring treatment
* History of serious allergic reaction to local anesthetics
* Location of lesion not amenable to local therapy (such as close to eye, mucous membranes, face, cartilage)
* Presence of pacemaker and/or other implanted metallic devices
* Breast feeding
* Men unwilling to avoid fathering a child during and/or in the two months following receiving the treatment
* Women unwilling to avoid pregnancy for at least two months after receiving the treatment
* More than 20 lesions, or multiple lesions which in the opinion of the investigator would not be well treated with heat therapy

Answer: B