Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3 Multicenter, Randomized, Controlled, Clinical Trial to Assess the Safety and Efficacy of Injectable Paromomycin in Patients With Visceral Leishmaniasis
Brief Summary: Symptomatic Visceral Leishmaniasis(VL)is fatal; Due to the increasing resistance to standard therapy with antimonials, there is a need for new safe, efficacious, low-cost therapies for the treatment of VL. Paromomycin is an off-patent aminoglycoside antibiotic with anti-leishmaniasis activity. This study will test the safety and efficacy of paromomycin in the treatment of patients with VL in India.


Options:
A: Inclusion Criteria:

* Parasitologically proved kala-azar

Exclusion Criteria:

* HIV positive serology
B: Inclusion Criteria:

* Age between 5-55 years (inclusive) of either gender.
* Newly diagnosed VL or VL treatment failure confirmed by spleen or bone marrow aspirate.
* Clinical signs and symptoms compatible with VL: fever of over two weeks duration and splenomegaly.
* Biochemical and haematological test values as follows:

  * Haemoglobin \> 5.0g/100mL
  * White blood cell count \> 1 x109/L
  * Platelet count \> 50 x 109/L
  * AST, ALT and alkaline phosphatase \< 3 times upper normal limit
  * Prothrombin time \< 5 seconds above control
  * Serum creatinine levels within normal limits
  * Serum potassium levels within normal limits
* HIV negative

Exclusion Criteria:

* A history of intercurrent or concurrent diseases (e.g. chronic alcohol consumption or drug addiction; renal, hepatic, cardiovascular or central nervous system disease; diabetes; tuberculosis or other infectious or major psychiatric diseases) that may introduce variables affecting the outcome of the study.
* Any condition which the investigator thinks may prevent the patient from completing the study therapy and subsequent follow-up.
* An abnormal baseline audiogram (presentation with 75 dB or higher at 8KHz or below) and/or a history of significant vestibular or auditory dysfunction.
* Proteinuria (\> 2+).
* A history of allergy or hypersensitivity to aminoglycosides.
* A history of major surgery within the last two weeks.
* Pregnancy or lactation. \[Note: women of childbearing age must use an adequate form of contraception (documented) or agree to a period of sexual abstinence during the treatment phase of the study.\]
* Previous treatment for VL within two weeks of enrolment into the study.
* Prior treatment failures with paromomycin or amphotericin B.
C: 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.
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: B