Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Pivotal, Randomized, Double-blind, Vehicle-controlled Study to Evaluate WR 279,396 and Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)
Brief Summary: This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. This cream will be compared to the effect of a topical cream containing paromomycin alone and to a placebo cream that contains no antibiotics. Therefore, this study will have three groups of patients, and they will be assigned to one of these treatments randomly. The study will be carried out without the patient or the physician knowing which cream is being used for which patient. The goal is to determine if WR 279,396 cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than paromomycin alone.


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:

* Parasitologically proved kala-azar

Exclusion Criteria:

* HIV positive serology
C: 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
D: 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.

Answer: A