Please select the eligibility criteria that correspond to the clinical trial below.
Title: Case-control Study of the Association Between Pertussis Vaccination in Infancy and the Risk of IgE-mediated Food Allergy
Brief Summary: Aim To assess the possible food allergy-preventive benefit of using whole cell pertussis(wP) vaccination compared with acelluar pertussis vaccine(aP) for whooping cough vaccination in childhood.

Background Whooping cough, caused by the bacteria, Bordetella pertussis, represents a significant public health burden in Australia and around the world. Acellular pertussis vaccination (aP) replaced whole cell vaccination against pertussis (wP) in the late 1990s. This replacement coincides temporally in an observed rapid rise in the occurrence of severe food allergy responses. Previous research has suggested that acellular pertussis vaccination results in the development of immunity that may predispose children to allergic responses. A retrospective case-controlled trial design, targeting cases of previously diagnosed allergy, and comparing case vaccination history to that of the whole population, is a powerful means of assessing the association between immunisation and allergy.

Participant Groups 1000 allergy cases, 10,000 controls

Project Design This is a retrospective individually-matched case-control study of Australian children born during the period of transition from use of wP vaccines to aP vaccines (year of birth 1997-1999 inclusive) and who are registered on the Australian Children Immunisation Register. Cases will be drawn from allergy clinics associated with tertiary teaching hospitals around Australia.

Methods Cases: will be retrospectively identified from patient lists from allergy clinics around Australia, born during the period of pertussis vaccine changeover, and be confirmed to have IgE-mediated food allergy on the basis of 1) a documented history of consistent clinical symptoms following ingestion of an implicated food, and 2) evidence of sensitisation to that food via laboratory testing.

Controls: Controls will be sampled from a de-identified database of children born during the transition from wP to aP vaccination appearing on the ACIR. Cases and controls will be matched by date of birth (+/-7 days), jurisdiction and socioeconomic decile.

Expected outcomes: Following the study, investigators will be able determine if there is an association between the type of vaccination received and development of IgE mediated food allergy. If whole cell vaccination is found to have a protective association against the development of allergy, this will have profound impact on health policy in Australia and around the world.


Options:
A: Inclusion Criteria:

* Healthy adults aged 18 to 45 years inclusive on the day of screening
* Fully conversant in the English language
* Able to communicate easily by both mobile telephone and text messaging
* Able and willing (in the investigator's opinion) to comply with all study requirements
* Written informed consent to participate in the trial
* Willingness to take a curative antibiotic regimen after inoculation with B. pertussis according to the study protocol
* Agreement to be admitted to the National Institute for Health Research (NIHR)-Clinical research facility (CRF) Southampton for 17 days for phase A (from inoculation until two days after the eradication therapy is given) and for the duration necessary for phase B, depending on phase A results
* Able to answer all questions on the informed consent quiz correctly

Exclusion Criteria:

* Individuals who have inviolable commitments within 3 months of discharge from the inpatient phase of the study to make contact with:

  1. unimmunised or partially immunised children and infants aged \< 1 year
  2. pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
* Individuals who have household contacts working with

  1. unimmunised or partially immunised children and infants aged \< 1 year
  2. pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
* Phase A only: Volunteers will be excluded from this study if they have evidence of recent exposure to B. pertussis, as determined by anti-PT IgG ELISA (\>20 IU/mL)
* B. pertussis detected on nasopharyngeal swab taken before the challenge
* Individuals who have a signs of a current infection at the time of inoculation with B. pertussis
* Individuals who have participated in other interventional clinical trials in the last 12 weeks
* Individuals who have a history of receiving B. pertussis vaccination in the last 5 years
* Individuals who have a history of never being vaccinated against B. pertussis
* Current smokers defined as having had a cigarette/cigar in the last week.
* Use of systemic antibiotics within 30 days of or during the challenge
* Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
* Use of immunoglobulins or blood products within 3 months prior to enrolment
* History of allergic disease or reactions likely to be exacerbated by any component of the inoculum
* Contraindications to the use of azithromycin or macrolides
* Pregnancy, lactation or intention to become pregnant during the study
* Any clinically significant abnormal finding on biochemistry, haematology, toxicology or serological blood tests, urinalysis or clinical examination - in the event of abnormal test results, confirmatory repeat tests will be requested
* Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data, for example recent surgery to the nasopharynx
B: Inclusion Criteria:

* 0 to 3 day old infants
* Mother seronegative for Human Immunodeficiency Virus (HIV)
* Born at full term of pregnancy (≥ 37 weeks) with a birth weight ≥ 2.5 kg
* Apgar score \>7 at 5 or 10 minutes of life
* Informed consent form signed by a parent or other legal guardian and by an independent witness if the parent or other legal guardian is illiterate
* Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

* Current or planned participation in another clinical trial during the entire duration of the present trial
* Suspected congenital or acquired immunodeficiency
* Suspected maternal acute seroconversion syndrome to HIV after 24 weeks gestation based on clinical history
* Chronic illness at a stage that could interfere with trial conduct or completion
* Blood or blood-derived products received since birth
* Any planned vaccination (except Bacille Calmette Guérin and trial vaccinations) from birth to 18 weeks of age
* Oral Poliovirus Vaccine (OPV) administration at birth
* Known maternal history of HIV, Hepatitis B (HB) (HbsAg carrier) or Hepatitis C seropositivity
* Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination
* History of seizures
* Febrile or acute illness on the day of inclusion.
C: Eligibility Criteria

1. All cases and controls must be registered on ACIR as having had a first dose of any pertussis containing vaccine before age 16 weeks and during the period of time in which the transition between aP and wP vaccine occurred; birth dates within 1st Janurary 1997 and 31st December 1999 depending on the jurisdiction.

Case Inclusion Criteria- Cases will be considered to have IgE-mediated food allergy on the basis of

1. a documented history of consistent clinical symptoms following ingestion of an implicated food, and
2. evidence of sensitisation to that food via either positive skin-prick test or elevated specific IgE to the implicated food, with onset after the first pertussis-containing vaccine but before age 15 years.

IgE-mediated food allergy is defined as BOTH:

1. The clinical notes or clinical letter arising from the allergy consult must explicitly document the presence of one or more of the following features. Onset of at least one these features must be within 1 hour of ingestion of suspected food where this can reasonably inferred from statements such as "immediate", "within x mins" where x is \<60:

   * urticaria
   * angioedema
   * emesis
   * vocal hoarseness
   * persistent cough
   * wheeze
   * stridor
   * collapse
   * hypotension

   AND
2. Documented evidence of allergic sensitisation to the implicated food through EITHER:

   * specific IgE positive (serum specific IgE \>0.35KU/l) to suspected food ), OR
   * positive skin prick test (wheal diameter \>3mm) against suspected food (SPT) Evidence of sensitisation must be at the time of consultation or the 6 months after the clinical encounter for the case to meet definition.

Exclusion Criteria- none
D: Inclusion Criteria:

* Willing to be immunized with a pertussis containing vaccine during pregnancy
* Intend to be available for follow-up visits and phone call through 19 months postpartum
* Willing to have infant immunized with a pertussis containing vaccine at 2, 4, 6 months and 18 months of age according to EPI (Expanded Programme of Immunization) and receiving (randomized) either acellular pertussis (aP) (study vaccine) or a whole cell pertussis (wP) vaccine. Consent for participation of the child is needed by both married parents or by a single unmarried other.
* At low risk for pregnancy related complications as determined by the investigator and a second trimester ultrasound with no significant abnormalities.

Exclusion Criteria:

Pregnant subjects

* Multiple pregnancies
* Serious obstetrical risk
* Serious underlying medical condition
* Significant mental illness
* History of febrile illness (greater than or equal to 38°C) within the past 72 hours before injection
* Previous severe reaction to any vaccine
* Receipt of tetanus-diphtheria toxoid immunization within the past 1 month Receipt of an pertussis containing vaccine (Tdap) in the last 5 years
* Receipt of a vaccine, blood product (excluding Rhogam) within the 4 weeks prior to injection through 4 weeks following injection and IVIG (Intravenous Immunoglobulins) within 12 weeks period. One month interval should be respected with another vaccine (except influenza) in orde to evaluate Adverse events following one or both vaccines (fever, local symptoms)
* Receipt of an experimental drug during pregnancy
* Anything in the opinion of the investigator that would prevent women from completing the study or put the woman at risk

Infants

* Preterm delivery before 37 weeks of gestation
* Serious underlying medical condition
* Children suffering from primary humoral immune disorders; suffering from primary cellular immune deficiencies and disorders from the complete cascade
* No informed consent from one or both married parents
* Severe reactions to any vaccine
* Anything in the opinion of the investigator that would prevent children from completing the study or put the child at risk

Answer: C