Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Assess the Efficacy and Safety of a Pentavalent Rotavirus Vaccine (BRV-PV) Against Severe Rotavirus Gastroenteritis Among Infants in Niger
Brief Summary: The study is a double-blinded, randomized, placebo-controlled, trial with two groups of infants receiving vaccine or placebo to assess the efficacy and safety of BRV-PV. Three doses of BRV-PV containing ≥ Log10 5.6 FFU/Dose of each serotype G1, G2, G3, G4 and G9 will be administered at 4 week intervals between doses. The first administration will occur at 6-8 weeks of age.

We hypothesize a difference in vaccine efficacy of three doses of BRV-PV vaccine vs. placebo against severe rotavirus gastroenteritis in healthy infants in Niger.

Active surveillance for gastroenteritis episodes will be conducted throughout the trial. Surveillance for adverse events will be carried out among all children from the time of first vaccination and 28 days post-Dose 3. Surveillance for all serious adverse events, including intussusception and death, will be conducted on all participants until they each reach two years of age.

To assess the effect of prenatal nutrition supplementation on infant immune response to the BRV-PV vaccine, study villages in the immunogenicity sub-cohort will be randomized in a 1:1:1 ratio to provide pregnant women with daily iron-folate, multiple micronutrients or a lipid-based nutrition supplement. Infants of participating women, if eligible at 6-8 weeks of age, will be randomized in a 1:1 ratio to receive three doses of vaccine or placebo and enter the main trial as part of the immunogenicity sub-cohort.


Options:
A: Inclusion Criteria:

1. aged 6-8 weeks at the time of inclusion
2. able to swallow and no history of vomiting within 24 hours
3. resident in Madarounfa Health District and within the catchment area of the central health facility
4. intending to remain in the study area for 2 years
5. parent/guardian providing written informed consent

Exclusion Criteria:

Any of the following will exclude an infant from randomization in the study:

1. known history of congenital abdominal disorders, intussusception, or abdominal surgery
2. receipt of intramuscular, oral, or intravenous corticosteroid treatment within 2 wks
3. receipt or planned administration of a blood transfusion or blood products, including immunoglobulins
4. any known immunodeficiency condition
5. any serious medical condition
6. any other condition in which, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or the parent/guardian's ability to give informed consent
B: Inclusion Criteria:

* Healthy infants, aged from 6 weeks through full 7 weeks,
* Consent form signed by at least one parent or by the legal representative properly informed about the study,
* Parent(s) / legal representative able to understand the protocol requirements and to fill in the Diary Card.

Exclusion Criteria:

* History of congenital abdominal disorders, congenital malformation of the gastrointestinal tract that could predispose to intussusception, or abdominal surgery,
* Congenital fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency,
* Known or suspected impairment of immunological function,
* Known hypersensitivity to any component of RotaTeq® (e.g. sucrose) or of NeisVac-C® (including tetanus toxoid),
* Prior administration of any rotavirus vaccine,
* Prior administration of any vaccine within the 28 days prior to randomisation,
* Fever (rectal temperature ≥38.1°C) and/or acute diarrhoea and/or vomiting at randomisation,
* History of known prior rotavirus gastroenteritis, chronic diarrhoea, or failure to thrive,
* Any severe thrombocytopenia or any other coagulation disorder that would contraindicate intramuscular injection,
* Clinical evidence of active gastrointestinal illness,
* Receipt of intramuscular, oral, or intravenous corticosteroid treatment within the 14 days prior to randomisation. Note: Infants on inhaled and/or topical steroids may participate in the study,
* Infants residing in a household with an immunocompromised person,
* Prior receipt of a blood transfusion or blood products, including immunoglobulins.
C: Inclusion Criteria:

* Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
* A male or female between, and including 6 and 10 weeks of age at the time of the first vaccination.
* Written informed consent obtained from the parents or guardians of the subject
* Documented HIV status of the subject as confirmed by PCR.
* HIV asymptomatic and HIV mildly symptomatic; Stages I and II disease according to WHO's most recent classification for HIV stages in infants and children.
* Born after a gestation period of 36 to 42 weeks.

Exclusion Criteria:

* Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Previous routine vaccination except OPV, BCG and HBV vaccination at birth
* Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract or other serious medical condition as determined by the investigator.
* History of allergic disease or reaction likely to be exacerbated by any component of the vaccine.
* Acute disease at time of enrolment.
* Gastroenteritis within 7 days preceding the study vaccine administration.
* Previous confirmed occurrence of RV gastroenteritis.
* Other conditions which in the opinion of the investigator may potentially interfere with interpretation of study outcomes.
* HIV moderately and severely symptomatic: stages III and IV according to WHO's recent classification.
* Administration of immunoglobulins and/or blood products since birth or planned administration during the study period.
D: Inclusion Criteria:

* Male or female infants who are at least 6 weeks of age and no more than 14 weeks, 6 days of age at Visit 1.
* Parent(s)/legal guardian(s) have signed informed consent documents.
* Children who will be available for the entire study period and whose parents/legal guardians can be reached by telephone.
* Healthy infants as determined by medical history and by a baseline physical examination with no clinically significant abnormal findings within 14 days before the first dose.
* Parents/legal guardians able to complete all relevant study procedures during study participation.

Exclusion Criteria:

* Any clinically significant history of gastrointestinal disease including abdominal surgery or liver disease or other serious medical conditions as determined by the site investigator.
* Any history of immunodeficiency in the infant (e.g., the infant is known to be human immunodeficiency virus (HIV) positive, to have hypogammaglobulinemia, or to have an underlying malignancy), or any infant with any unvaccinated household contact who is immunocompromised such as:

  * Any malignancies or are otherwise immunocompromised;
  * Primary immunodeficiency; or
  * Receiving immunosuppressive therapy.
* Known sensitivity to any vaccine components, such as latex in the Rotarix® applicator.
* Previous receipt of a rotavirus vaccine.
* Acute illness at the time of vaccine administration, such as any of the following within the past 48 hours:

  1. Axillary temperature of 100.4 degrees Fahrenheit or higher, or
  2. More than 3 grossly watery stools, or
  3. Any episodes of vomiting (forceful expulsion of partially digested milk/food). Infants with previous diagnoses of gastroesophageal reflux whose regurgitation episodes have not changed in the 48-hour period prior to the first vaccination may be enrolled.

If these symptoms clear within 48 hours and the subject meets the other inclusion/exclusion criteria, then the subject may be enrolled.

* The subject is currently participating in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study.
* Less than 37 weeks gestation at birth.
* Receipt of blood and/or blood products (including immunoglobulin) within 4 weeks before vaccine administration.
* Receipt of live vaccine within the past 30 days or a nonreplicating, inactivated, or subunit vaccine within the last 14 days, although planned licensed trivalent inactivated influenza vaccine that may be administered to children over 6 months of age during a routine clinic visit is permitted and would not be exclusionary.
* The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Answer: A