Flu Vaccine Against Childhood Pneumonia, Bangladesh
Condition: Pneumonia; Laboratory Confirmed Influenza
MeSH terms: Influenza, Human; Pneumonia
Study type: Interventional
Phase: Phase 3

Summary: 
      Pneumonia is the leading cause of child death worldwide. Data from Bangladesh indicates that
      influenza has a substantial association with pneumonia among children less than two years
      old. This study will use commercially available trivalent inactivated vaccine (killed
      vaccine) to see if it can prevent early childhood pneumonia among children less than two
      years old. The study will vaccinate children across three seasons (3 years), and look at the
      effect on the attack rate of pneumonia, as well as its effects on laboratory-confirmed
      influenza. It will also look at the effect on laboratory-confirmed influenza illness among
      the non-vaccinated household contacts of all ages of these children.
    

Detailed description: 
      Pneumonia is the primary cause of child mortality worldwide. The global community is
      considering interventions to reduce pneumonia burden, including vaccines. Most attention is
      focused on bacterial vaccines. Influenza vaccine has not received attention due to lack of
      influenza burden data from high pneumonia endemic settings, and poor understanding of how
      influenza contributes, independently and with other pathogens, to childhood pneumonia burden.
      Data from Bangladesh indicate that influenza has a high incidence of over 10% per year among
      children < 5 years, and that among children who get influenza infection, 28% develop
      pneumonia, including severe pneumonia. Influenza-infected children who develop pneumonia are
      significantly younger (< 2y) than those who do not. Due to the high influenza incidence, and
      the high proportion of influenza-infected children who develop pneumonia, influenza is a
      major contributor to childhood pneumonia, not only in Bangladesh, but likely throughout the
      pneumonia endemic tropical and sub-tropical belt. Although trials have been conducted to
      examine influenza vaccine impact on influenza, none have been conducted specifically to
      determine the effect on childhood pneumonia, particularly among those < 2 years who are at
      highest pneumonia risk. We propose to conduct such a trial.

      The project goal is to determine whether influenza vaccine (trivalent inactivated vaccine or
      TIV) can reduce childhood pneumonia burden including: influenza-associated, other
      aetiology-mediated, and overall pneumonia incidence. The specific objectives are to determine
      influenza vaccine efficacy on 1) early childhood pneumonia (children < 2 years), 2)
      laboratory-confirmed influenza and 3) the rates of influenza-specific complications including
      severe disease, hospitalisation, and otitis media. Secondary objectives include determining
      the effect of influenza vaccine on household transmission and associated complications among
      all age groups, the effect on proven non-influenza viral and bacterial invasive diseases, the
      occurrence of adverse events associated with the vaccine, and to measure immune
      responsiveness to influenza vaccine in these young children.

      Critical milestones include comparison between vaccinated and vaccine-controlled children of
      1) pneumonia incidence (vaccine efficacy against pneumonia), 2) influenza incidence (vaccine
      efficacy against influenza) 3) rates of other clinical syndromes (vaccine efficacy against
      other childhood morbidity). Milestones related to secondary objectives include comparison
      between vaccinated and vaccine-controlled children of 1) rates of laboratory-confirmed
      infection and clinical illness among household contacts and 2) rates of other invasive
      bacterial and viral diseases, and 3) rates of adverse events. We will also measure childhood
      immune responsiveness to influenza vaccine and relate that to observed rates of infection and
      clinical illness.
    

Intervention name(s): Trivalent inactivated influenza vaccine
Intervention type(s): Biological
Intervention description(s): Two doses of 0.25 ml vaccine delivered IM at least 4 weeks apart.
Other intervention name(s): Vaxigrip Junior
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Pneumonia; Influenza; Child; Respiratory; Pathogen