Please select the eligibility criteria that correspond to the clinical trial below.
Title: Does Vaccinating Health Hutterite Children Against Influenza Prevent Influenza in Other Hutterite Colony Members: A Randomized Cluster Trial
Brief Summary: The goal of this randomized clinical trial is to determine whether immunizing children in Hutterite colonies with inactivated influenza vaccine can prevent influenza and its complications in other colony members. Furthermore, the study will assess the indirect benefit to Hutterites at high risk of complications. The study is a blinded, cluster randomized controlled trial among Hutterite colonies to test the hypothesis that high immunization rates (\>70%) of healthy children with inactivated influenza vaccine reduces transmission of influenza to other colony members. Randomization of these homogeneous, moderately sized colonies where there is regular spread facilitated by a communal lifestyle, but limited re-introduction because of relative isolation from outside community, represents a unique opportunity to test the hypothesis of indirect benefit under close to ideal conditions. The primary outcome will be laboratory-confirmed influenza. Secondary outcomes include influenza-like illness, otitis media, physician visits, antimicrobial prescriptions, absenteeism, lower respiratory tract infection, hospitalizations, and death.


Options:
A: Group A:

Inclusion Criteria:

* Hutterites other than the healthy children who will be immunized. Although this category as a whole will be used to assess indirect benefit of the vaccine in the main analysis, Hutterites at high risk for influenza complications within this category will be assessed in a separate analysis. These are defined as anyone in one or more of the following groups:
* individuals aged ≥ 65 years
* children 23 months of age or less
* anyone with ≥ 1 of the following conditions severe enough to require regular medical follow-up or hospital care:

  * chronic cardiac or pulmonary disorders (including bronchopulmonary dysplasia, cystic fibrosis, and asthma)
  * diabetes mellitus and other metabolic diseases
  * cancer
  * immunodeficiency
  * immunosuppression (due to underlying disease and/or therapy)
  * renal disease
  * anemia
  * hemoglobinopathy
  * any condition that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk of aspiration.

Exclusion Criteria:

* There are no exclusion criteria for this category of participants.

Group B:

Inclusion Criteria:

* Healthy children aged 36 months to 15 years who will be immunized as part of the intervention.

Exclusion Criteria:

* Anaphylactic reaction to a previous dose of influenza vaccine
* Anaphylactic reaction to hepatitis A vaccine
* Anaphylactic reaction to neomycin
* Known IgE-mediated hypersensitivity to eggs manifested as hives
* Swelling of the mouth and throat, difficulty in breathing, hypotension, or shock
* Guillain-Barré syndrome within eight weeks of a previous influenza vaccine.
B: Inclusion Criteria:

* Male or female, 18 to 49 years of age (not yet reached their 50th birthday) at the time of randomization
* Healthy by medical history and physical examination
* Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act \[HIPAA\] in the United States of America \[USA\], European Union \[EU\] Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
* Females of childbearing potential, (ie, unless surgically sterile \[eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\], has sterile male partner, is at least 1 year post menopause, or practices abstinence) must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 60 days after the second dose of investigational product. In addition, the subject must also have a negative urine or blood pregnancy test at screening and, if screening and Day 1 do not occur on the same day, on the day of vaccination prior to randomization.
* Males, unless not sexually active, must use an effective method of birth control with a female partner and must agree to continue using such contraceptive precautions for at least 30 days after the second dose of investigational product (from Day 1 through Day 59 of the study)
* Subject is available by telephone
* Subject is able to understand and comply with the requirements of the protocol, as judged by the investigator
* Subject is able to complete follow-up period of 180 days after Dose 2 as required by the protocol

Exclusion Criteria:

* History of hypersensitivity to any component of the investigational product including egg or egg protein, gelatin or arginine, or serious, life-threatening, or severe reactions to previous influenza vaccinations
* History of hypersensitivity to gentamicin
* Any condition for which the inactivated influenza vaccine is indicated, including chronic disorders of the pulmonary or cardiovascular systems (eg, asthma), chronic metabolic diseases (eg, diabetes mellitus), renal dysfunction, or hemoglobinopathies that required regular medical follow-up or hospitalization during the preceding year
* Acute febrile (\> 100.0°F oral or equivalent) and/or clinically significant respiratory illness (eg, cough or sore throat) within 14 days prior to randomization
* History of asthma
* Any known immunosuppressive condition or immune deficiency disease, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy
* History of Guillain-Barré syndrome
* A household contact who is severely immunocompromised (eg, hematopoietic stem cell transplant recipient, during those periods in which the immunocompromised individual requires care in a protective environment); subject should additionally avoid close contact with severely immunocompromised individuals for at least 21 days after receipt of investigational product
* Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after the second dose of investigational product (use of licensed agents for indications not listed in the package insert is permitted)
* Expected receipt of antipyretic or analgesic medication on a daily or every other day basis from randomization through 14 days after receipt of each dose of investigational product
* Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after administration of each dose of investigational product
* Receipt of any nonstudy vaccine within 30 days before or after Dose 1 or expected receipt of any nonstudy vaccine within 30 days before or after Dose 2
* Known or suspected mitochondrial encephalomyopathy
* Subject is pregnant or a nursing mother
* Any condition (eg, chronic cough, allergic rhinitis) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
* Subject or immediate family member of subject is an employee of the clinical study site or is otherwise in involved with the conduct of the study
C: Inclusion Criteria:

* Male or female, 2 to 17 years of age (not yet reached their 18th birthday) at the time of randomization
* Healthy by medical history and physical exam
* Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act \[HIPAA\] in the United States of America \[USA\], European Union \[EU\] Data Privacy Directive in the EU and written informed assent) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
* Females of child-bearing potential, (ie, unless premenarchal, surgically sterile \[eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\], has sterile male partner, or practices abstinence) must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 60 days after the second dose of investigational product. In addition, the subject must also have a negative urine or blood pregnancy test at screening and, if screening and Day 1 do not occur on the same day, on the day of vaccination prior to randomization. Investigator judgment is required to assess the childbearing potential of a pre-adolescent or adolescent girl.
* Males, unless not sexually active, must use an effective method of birth control with a female partner and must agree to continue using such contraceptive precautions for at least 30 days after the second dose of investigational product (from Day 1 through Day 59 of the study)
* Subject's legal representative available by telephone
* Subject/subject's legal representative is able to understand and comply with the requirements of the protocol, as judged by the investigator
* Ability to complete follow-up period of 180 days after Dose 2 as required by the protocol

Exclusion Criteria:

* History of hypersensitivity to any component of the investigational product including egg or egg protein, gelatin or arginine, or serious, life-threatening, or severe reactions to previous influenza vaccinations
* History of hypersensitivity to gentamicin
* Any condition for which the inactivated influenza vaccine is indicated, including chronic disorders of the pulmonary or cardiovascular systems (eg, asthma), chronic metabolic diseases (eg, diabetes mellitus), renal dysfunction, or hemoglobinopathies that required regular medical follow-up or hospitalization during the preceding year
* Acute febrile (\> 100.0°F oral or equivalent) and/or clinically significant respiratory illness (eg, cough or sore throat) within 14 days prior to randomization
* History of asthma, or in children \< 5 years of age, history of recurrent wheezing
* Any known immunosuppressive condition or immune deficiency disease, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy
* History of Guillain-Barré syndrome
* A household contact who is severely immunocompromised (eg, hematopoietic stem cell transplant recipient, during those periods in which the immunocompromised individual requires care in a protective environment); subject should additionally avoid close contact with severely immunocompromised individuals for at least 21 days after receipt of investigational product
* Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after the second dose of investigational product (use of licensed agents for indications not listed in the package insert is permitted)
* Use of aspirin or salicylate-containing products within 30 days prior to randomization or expected receipt through 30 days after final vaccination
* Expected receipt of antipyretic or analgesic medication (non-salicylate-containing) on a daily or every other day basis from randomization through 14 days after receipt of each dose of investigational product
* Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after administration of each dose of investigational product
* Receipt of any nonstudy vaccine within 30 days before or after Dose 1 or expected receipt of any nonstudy vaccine within 30 days before or after Dose 2
* Known or suspected mitochondrial encephalomyopathy
* Adolescent subject is pregnant or a nursing mother
* Any condition (eg, chronic cough, allergic rhinitis) that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
* Subject, legal representative, or immediate family member of subject is an employee of the clinical study site or is otherwise in involved with the conduct of the study
D: Inclusion Criteria: (First Season)

* who is aged at least 6 months and less than 36 months of age at the time of enrollment;
* who is in good health as determined by medical history, physical examination and clinical judgement;
* whose parent(s)/legal guardian(s) have provided written informed consent after the nature of the study has been explained;
* who, along with their parent(s)/legal guardian(s), will be available until the completion of the first season's surveillance phase;
* whose parent(s)/legal guardian(s), can be reached by study staff for the post-vaccination contacts \[telephone, clinic or home visit\].

(Second Season)

* who was enrolled into the first season of the trial and received at least one vaccination in the primary series;
* who completed the safety and efficacy evaluations during the first season surveillance phase;
* who is in good health as determined by medical history, physical examination and clinical judgement;
* whose parent(s)/legal guardian(s) have provided written informed consent for the second season of the trial after the nature of the study has been explained;
* who, along with their parent(s)/legal guardian(s), will be available until the completion of the second season's surveillance phase;
* whose parent(s)/legal guardian(s), can be reached by study staff for the post-vaccination contacts \[telephone, clinic or home visit\].

Exclusion Criteria: (First Season)

* whose parent(s)/legal guardian(s) are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;
* with any serious chronic disease (e.g., with signs of cardiac or renal failure or severe malnutrition), including progressive neurological disease;
* with Down's syndrome or other known cytogenetic disorders;
* with a known or suspected disease of the immune system or those receiving immunosuppressive therapy, including systemic corticosteroids;
* who received any blood products, including immunoglobulin, in the period from six months prior to vaccination through to the conclusion of the study;
* for whom there is intent to administer any other investigational vaccine or agent from one month prior to enrollment through to the conclusion of the study;
* have an immunosuppressed or an immunocompromised individual living in the same household;
* who, at any time prior to entry into this study, received a dose of any influenza vaccine (commercial or investigational);
* who, in the two weeks prior to entry into this study, received a dose of any influenza treatment (commercial or investigational);
* with a documented history of hypersensitivity to egg or egg protein or any other component of the assigned study vaccine;
* with a clinically confirmed respiratory illness with wheezing within two weeks prior to enrollment;
* who received aspirin (acetylsalicylic acid) or aspirin-containing products in the two weeks prior to enrollment or for which use is anticipated during the study;
* who were administered any live virus vaccine within one month prior to enrollment or expected to receive another live virus vaccine within one month of vaccination in this study;
* with any medical conditions that in the opinion of the investigator might interfere with interpretation of the study results.

If any of these criteria are met following enrolment, the subject will be excluded from subsequent vaccine dosing.

Note: Pregnancy in a household member or any person who has regular contact with the subject is not a contraindication to the enrollment or ongoing participation of the subject in the study.

(Second Season)

* whose parent(s)/legal guardian(s) are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;
* with any serious chronic disease (e.g., with signs of cardiac or renal failure or severe malnutrition), including progressive neurological disease;
* with Down's syndrome or other known cytogenetic disorders;
* with a known or suspected disease of the immune system or those receiving immunosuppressive therapy, including systemic corticosteroid of a dose equivalent to 2 mg/kg/day or greater of prednisolone or equivalent to a total of 20 mg/day or greater for children who weigh more than 10 kg, for more than 14 days duration until 2 weeks after corticosteroids have been discontinued;
* who received any blood products, including immunoglobulin, in the period from six months prior to the second season vaccination through to the conclusion of the study;
* for whom there is intent to administer any other investigational vaccine or agent from one month prior to the second season vaccination through to the conclusion of the study;
* have an immunosuppressed or an immunocompromised individual living in the same household;
* who, at any time prior to entry into this study, received a dose of any influenza vaccine (commercial or investigational) with the exception of the primary series of study vaccine (CAIV-T/placebo);
* who, in the two weeks prior to receiving the second season vaccination, received a dose of any influenza treatment (commercial or investigational);
* with a documented history of hypersensitivity to egg or egg protein or any other component of the assigned study vaccine (CAIV-T/placebo);
* with a clinically confirmed respiratory illness with wheezing within two weeks prior to receiving the second season vaccination;
* who received aspirin (acetylsalicylic acid) or aspirin-containing products in the two weeks prior to receiving the second season vaccination or for which use is anticipated during the study;
* who were administered any live virus vaccine within one month prior to receiving the second season vaccination or expected to receive another live virus vaccine within one month of receiving the second season vaccination;
* with any medical conditions that in the opinion of the investigator might interfere with interpretation of the study results.

Note: Pregnancy in a household member or any person who has regular contact with the subject is not a contraindication to the enrollment or ongoing participation of the subject in the study.

Answer: A