This study is a global multicenter randomized factorial double-blind, placebo-controlled trial designed to evaluate (i) efficacy and safety of nitazoxanide 600 mg administered orally twice daily for five days compared to a placebo in the treatment of acute uncomplicated influenza and (ii) efficacy and safety of combination therapy with nitazoxanide 600 mg plus Oseltamivir 75 mg co-administered orally twice daily for five days compared to nitazoxanide monotherapy (600 mg b.i.d. for 5 days) and Oseltamivir monotherapy (75 mg b.i.d. for 5 days) in the treatment of acute uncomplicated influenza.

Inclusion Criteria:

1. Age 13 to 65 years

2. Presence of clinical signs and/or symptoms consistent with acute illness compatible with influenza infection (each of the following is required):

   1. oral temperature of ≥100.4 °F or ≥38 °C (obtained in office or self-measured within 12 hours prior to screening - if self-measured, subject must also have taken an antipyretic within 4 hours prior to screening) AND
   2. at least one of the following respiratory symptoms (cough, sore throat, nasal obstruction) that is considered by the patient to be moderate or severe (greater than mild severity) AND
   3. one of the following constitutional symptoms (fatigue, headache, myalgia, feverishness) that is considered by the patient to be moderate or severe (greater than mild severity).

3. Confirmation of influenza A or B infection in the local community by one of the following means:

   1. the institution's local laboratory, or
   2. the local public health system, or
   3. the national public health system, or
   4. a laboratory of a recognized national or multinational influenza surveillance scheme.

4. Onset of illness no more than 48 hours before enrollment in the trial.

   Note: Time of onset of illness is defined as either the earlier of:

   1. the time when the temperature was first measured as elevated, OR
   2. the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.

5. Willing and able to provide written informed consent (including assent by legal guardian if under 18 years of age) and comply with the requirements of the protocol, including completion of the patient diary.

Exclusion Criteria:

1. Severity of illness requiring or anticipated to require in-hospital care or subject defined as being at high risk of complications from influenza infection according to the Infectious Diseases Society of America (IDSA) guidelines for seasonal influenza in adults and children (Committee of Infectious Diseases (CID) 2009:48) or current Centers for Disease Control and Prevention (CDC) criteria. Current criteria for persons 13-65 years of age who are at risk of influenza complications include (list to be reviewed and updated as required prior to initiation of the study and at least monthly during the study):

   1. Persons with asthma or other chronic pulmonary diseases, such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults.
   2. Persons with hemodynamically significant cardiac disease.
   3. Persons who have immunosuppressive disorders or who are receiving immunosuppressive therapy.
   4. HIV-infected persons.
   5. Persons with sickle cell anemia or other hemoglobinopathies.
   6. Persons with diseases requiring long-term aspirin therapy, such as rheumatoid arthritis or Kawasaki disease.
   7. Persons with chronic renal dysfunction.
   8. Persons with liver disorders.
   9. Persons with cancer.
   10. Persons with chronic metabolic disease, such as diabetes mellitus, inherited metabolic disorders and mitochondrial disorders.
   11. Persons with neuromuscular disorders, seizure disorders or cognitive dysfunction that may compromise the handling of respiratory secretions.
   12. Residents of any age of nursing homes or other long-term care institutions.
   13. Persons who are morbidly obese (Body Mass Index ≥40)
   14. American Indians (seemed to be at higher risk of complications last flu season)
   15. Alaskan natives (seemed to be at higher risk of complications last flu season)

2. Females of childbearing potential who are either pregnant, breast-feeding or are sexually active without the use of birth control. Female patients of child-bearing potential that are sexually active must have a negative baseline pregnancy test and must agree to continue an acceptable method of birth control for the duration of the study and for 1 month post-treatment. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an intrauterine device (IUD), or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. Female subjects are considered of childbearing potential unless they are postmenopausal (absence of menstrual bleeding for 1 year - or 6 months if laboratory confirmation of hormonal status), or have had a hysterectomy, bilateral tubular ligation or bilateral ovariectomy.

3. Vaccination for seasonal influenza on or after i. August 1, 2012 in the case of subjects enrolled during the 2012/2013 flu season in the United States, ii. February 1, 2013 in the case of subjects enrolled during the 2013 flu season in Australia or New Zealand, or iii. August 1, 2013 in the case of subjects enrolled during the 2013/2014 flu season in the United States, Canada, Europe, or other countries in the Northern Hemisphere, or iv. February 1, 2014 in the case of subjects enrolled during the 2014 flu season in Australia or New Zealand, or v. August 1, 2014 in the case of subjects enrolled during the 2014/2015 flu season in the United States, Canada, Europe, or other countries in the Northern Hemisphere.

4. Receipt of any dose of nitazoxanide, oseltamivir, zanamivir, amantadine, or rimantadine within 30 days prior to screening.

5. Prior treatment with any investigational drug therapy within 30 days prior to screening.

6. Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies.

7. Known sensitivity to Nitazoxanide or any of the excipients comprising the Nitazoxanide tablets.

8. Known sensitivity to Oseltamivir or any of the excipients comprising the Oseltamivir capsules.

9. Subjects unable to take oral medications.

10. Subject has chronic kidney or liver disease (including Hepatitis A,B or C) or known impaired hepatic and/or renal function.

11. Presence of any other pre-existing chronic infection that is undergoing or requiring medical therapy.

12. Presence of any pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study.

13. Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.