Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Trial of Azithromycin + Artesunate v Artemether-lumefantrine in Uncomplicated Malaria in Tanzanian Children.
Brief Summary: This trial sets out to determine whether the combination of azithromycin and artesunate (AZ+AS) is as good as the current standard treatment for uncomplicated malaria in Tanzania, artemether-lumefantrine (AL). There are two reasons this is important

1. there are only a limited range of drug combinations which work against malaria in this area of Tanzania
2. azithromycin has antimalarial properties, but is also a broad-spectrum antibiotic, so if the combination is an effective antimalarial it might have a place where there are no diagnostic facilities as syndromic treatment for fever.

Artesunate and azithromycin have both been used alone or in combination with other drugs in children in Tanzania for many years, and are considered safe. There is trial evidence for the effectiveness of this combination in adults in Asia, as well as in-vitro (laboratory) evidence that it works against the malaria parasite.

The trial randomizes children with non-severe malaria to the new combination AZ+AS or the standard care arm AL. The primary outcome is the parasitological failure rate by day 28- meaning do malaria parasites get cleared, and stay cleared for at least 28 days. Secondary outcomes include safety.


Options:
A: Inclusion Criteria:

1. Acute symptomatic falciparum malaria infection with a parasite density of 100 to 100,000 asexual parasites/uL as determined on the screening smear with fever (defined as ≥37.5ºC), or reported history of fever within the last 48 hours.
2. Age: 8-65 years old
3. Males or females. All females over the age of 12 are required to have a negative human chorionic gonadotropin (hCG) pregnancy test (urine). All females of childbearing potential (not surgically sterile, or less than two years menopausal) are required to use an acceptable method of contraception, such as implant, injectable, oral contraceptive(s) with additional barrier contraception, intrauterine device, sexual abstinence, or vasectomized partner, throughout the study
4. Written informed consent obtained
5. Willing to stay under close medical supervision for the study duration
6. Otherwise healthy outpatients

Exclusion Criteria:

1. Pregnant women, nursing mothers, or women of childbearing potential who do not use an acceptable method of contraception (as described in Inclusion Criteria, #3)
2. Mixed malaria infection on admission by malaria smear
3. A previous history of intolerance or hypersensitivity to the study drugs artesunate, azithromycin, or lumefantrine or to drugs with similar chemical structures
4. Malaria drug therapy administered in the past 30 days by history
5. Previous participation in this trial, or participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study
6. History of significant cardiovascular, liver or renal functional abnormality or any other clinically significant illness, which in the opinion of the investigator would place them at increased risk.
7. Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
8. Signs or symptoms of severe malaria (as defined by WHO 2003)
9. Unable and/or unlikely to comprehend and/or follow the protocol
B: Inclusion Criteria:

Children with symptoms suggestive of malaria and

1. P.falciparum of at least 2000 parasites per microL of blood
2. are able to take study drugs by the oral route
3. are able to attend stipulated days for follow up clinic and provide specimens
4. have a parent or guardian who can give informed written/verbal consent to participate in the study
5. aged 6-59 months.

Exclusion Criteria:

1. severe and complicated forms of malaria (WHO, 2000)
2. a mixed plasmodial infection
3. a concomitant disease masking assessment of the treatment response (cases in whom advanced HIV infection is suspected will lead to be referred for HIV counseling).
4. recent effective full dose antimalarial treatment (within 7 days), excluding chloroquine, SP and AQ which have \>70% failure in this district, or combinations of these.
5. known hypersensitivity to any of the trial drugs.
6. live too far away for reliable follow-up
C: Inclusion Criteria:

* peripheral malaria parasitemia
* signed informed consent
* age 15-49 years
* mother has felt the movements of the foetus (quickening)
* fetal age of at least 14 but not more than 26 completed gestation weeks
* maternal availability for follow-up during the entire period of the study

Exclusion Criteria:

* known maternal tuberculosis, diabetes, kidney disease, or liver disease
* mental disorder that may affect comprehension of the study or success of follow-up
* twin pregnancy
* pregnancy complications evident at enrollment visit (moderate to severe oedema, blood Hb concentration \< 7 g / dl, systolic blood pressure (BP) \> 160 mmHg or diastolic BP \> 100 mmHg)
* prior receipt of azithromycin during current pregnancy
* receipt of any antimalarial within 28 days before enrollment
* known allergy to drugs containing sulfonamides, macrolides or pyrimethamine
* history of anaphylaxis
* history of any serious allergic reaction to any substance, requiring emergency medical care
* history of hepatitis or jaundice
* concurrent participation in any other clinical trial
D: Inclusion Criteria:

* Girls and boys ≥5 years to ≤12 years (Cohort 1); and ≥6 to ≤59 months of age (Cohort 2) with uncomplicated, symptomatic malaria as indicated by the presence of the following:
* Blood smears positive for monoinfection with P. falciparum and asexual parasitemia between 1000 -100,000 parasites/µL;
* Documented fever (38.0°C/100.4°F rectal or tympanic; 37.2°C/99.0°F axillary or 37.5°C/99.5°F oral) or history of fever (as reported by the legally acceptable representative) within the prior 24 hours;
* Appropriate for outpatient treatment;
* Blood glucose ≥60 mg/dL;
* Hemoglobin ≥6 g/dl or hematocrit ≥18% without signs of anemia-induced Congestive Heart Failure (CHF);
* Negative urine pregnancy test for females ≥10 years of age (and of child bearing potential)

Exclusion Criteria:

* Peripheral blood smear positive for mixed infection with multiple Plasmodium spp.
* Severe or complicated malaria including subjects with any of the following:
* Impaired consciousness (eg, obtundation, unarousable coma), seizures or abnormal neurologic exam suggestive of severe or complicated malaria;
* Known hemoglobinuria;
* Jaundice;
* Respiratory distress;
* Persistent vomiting;
* Gross hematuria, as reported by the subject's legally acceptable representative;
* Recent history of convulsions;
* Inability to drink or breastfeed;
* Unable to sit or stand as appropriate for age;
* Known pregnancy or breast-feeding or positive urine pregnancy test (females ≥10 years of age and of child bearing potential);
* History of allergy to or hypersensitivity to azithromycin, any macrolide, chloroquine, artemether, any artemisinin derivative, lumefantrine;
* Any contraindication to any study drug including AZ, CQ and AL;
* History of treatment with any antimalarial drug (such as halofantrine, chloroquine, quinine, mefloquine, Malarone, SP, artemisinin compounds) or antibacterial with known antimalarial activity (macrolides, doxycycline, clindamycin) within 2 weeks prior to enrollment of a subject (and/or of the mother of a subject who is being breastfed) into the study;
* Known or suspected cardiovascular, hepatic or renal abnormality that in the opinion of the investigator would place the subject at increased risk to participate in the study.

Answer: B