Pneumonia Research and Vaccine Impact League
Condition: Pneumonia
MeSH terms: Pneumonia
Study type: Observational

Summary: 
      The leading cause of severe respiratory disease and death in young children is Streptococcus
      pneumoniae (pneumococcus). An estimated one-fifth of global childhood pneumococcal-related
      deaths occurred in India. The pneumococcal conjugate vaccine (PCV) is a primary prevention
      tool against pneumococcal disease that is safe and effective and has been in use in many
      countries. In alignment with the Government of India's rollout of PCV sub-nationally in
      selected districts and states, this two-year observational study will use a
      non-interventional, observational prospective study design to evaluate the impact of PCV in 7
      sites in India (5 hospitals and 2 community sites) by assessing clinical and
      serotype-specific outcomes that include hospitalized pneumonia and community pneumococcal
      carriage. A sub-study to assess the cost of illness of pneumonia will also be conducted. This
      study is anticipated to provide data to support sustainability of PCV expansion and disease
      surveillance in India.
    

Detailed description: 
      Streptococcus pneumoniae (pneumococcus) is the leading cause of severe respiratory disease
      and death in young children, and is also responsible for other serious diseases such as
      meningitis and sepsis. Global disease burden models for the year 2015, estimate that 20
      percent of global childhood pneumococcal deaths occurred in India. Data from India indicate
      that available pneumococcal conjugate vaccines (PCV) include serotypes that account for 66 to
      74 percent of invasive pneumococcal disease (IPD) in young children. The 2017 PCV launch into
      the national immunization schedule in selected high-burden states was poised to successfully
      combat the pneumococcal disease burden in the country once scale-up of vaccine coverage takes
      place. The Government of India has recommended robust evaluation of PCV impact to facilitate
      national rollout and sustained use of PCV.

      This study aims to evaluate the impact of PCV introduction to the national immunization
      program. The investigators propose to quantify the impact of PCV on pneumonia and other acute
      respiratory infections resulting in hospitalization and on community carriage of pneumococci.
      Hereafter, in reference to the proposed study, the investigators use the term 'pneumonia' to
      denote to a group of physician-based diagnoses representing a range of acute respiratory
      illness including pneumonia. Specifically, the investigators propose to measure differences
      in the proportion of pneumonia hospitalizations in children 1-35 months colonized with
      vaccine-serotype (VT) pneumococcus, as well as differences in VT pneumococcal nasopharyngeal
      (NP) colonization in the community, comparing children enrolled at sites where PCV has been
      introduced (PCV sites) to children at sites where PCV has not yet been introduced (non-PCV
      sites). The health economic aims will consist of assessing the cost of illness of
      pneumococcal disease, and economic cost of pneumococcal disease and pneumonia
      hospitalization. The investigators have designed this portfolio of PCV impact evaluations
      within the context of PCV introduction and rollout in six selected states in India, mindful
      of the need for baseline data, the staggered plan for PCV roll-out, variance of
      cost-generating events, and the inherent biases of non-interventional studies with outcomes
      that are not specific for pneumococcal disease and that may be subject to secular trends and
      possible confounders. The study sites are located in New Delhi and within three of the six
      states that were included in the PCV rollout plan starting in 2017. The investigators plan
      this as a two-year study that will include data from both PCV sites and non-PCV sites, the
      comparison of which will allow an assessment of vaccine impact. Active study sites will be
      located in Delhi; Agra in Uttar Pradesh state (non-PCV-using); Bhopal in Madhya Pradesh
      state; and Jaipur in Rajasthan state (PCV-using). Community enrollment will take place in two
      demographic survey sites in Bhopal and Delhi, and economic assessment will take place in four
      hospital sites. Sites will use a common protocol to identify and recruit children, obtain
      nasopharyngeal swabs for colonization studies, and run validated laboratory tests. A
      reference laboratory will provide pneumococcal serotyping results, nasopharyngeal
      quantification of pneumococcus, and provide site laboratory oversight.

      These data will provide evidence to policy makers on changes in pneumococcal disease burden
      in young children, pneumococcal community transmission changes as a result of PCV
      introduction, that can help policy makers support, optimize, and advocate for the expansion
      of the PCV immunization program in India and in other countries.

      The primary objectives of PREVAIL are as follows:

        1. Quantify the difference in the proportion of hospitalized pneumonia cases 1-35 months of
           age carrying a vaccine-type pneumococcus in the nasopharynx in cases enrolled at sites
           that have introduced PCV into the national immunization program compared to cases
           enrolled at sites that have not introduced PCV

        2. Quantify the difference in the proportion of children in the community 1-35 months who
           are colonized with vaccine-type pneumococcus enrolled at a site that has introduced PCV
           into the national immunization program compared to the proportion of children colonized
           with vaccine-type pneumococcus enrolled at a site that has not introduced PCV

        3. Determine the overall economic impact of PCV by: (i) Estimating the total cost of
           hospitalized pneumonia in children 1-35 months from the healthcare system and household
           perspectives; and (ii) Estimating the proportion of households facing catastrophic
           health spending and medical impoverishment from out-of-pocket health expenses due to
           hospitalized pneumonia in children 1-35 months.

      Secondary objectives are evaluated within each of the four groups, and are;

        1. Assess the difference in mortality and occurrence of illnesses within 3 months of
           hospital discharge among children aged 1-35 months presenting with pneumonia in
           PCV-using sites compared to children at non-PCV sites.

        2. Quantify the difference in proportion among hospitalized cases aged 1-35 months with
           alveolar consolidation detected on radiography in PCV-using sites compared to children
           at non-PCV sites.

        3. Quantify the difference in proportion among hospitalized cases aged 1-35 months with
           hypoxemia (oxygen saturation<90%) in PCV-using sites compared to children at non-PCV
           sites.

        4. Quantify the difference in proportion of hospitalized cases aged 1-35 months that are
           vaccinated at PCV-using sites (indirect cohort method to assess vaccine effectiveness)
           between the following groups:

             1. Carrying a VT vs. carrying a non-VT serotype

             2. With vs. without alveolar consolidation

             3. With vs. without hypoxemia
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        There are three cohorts/groups that are recruited:

        PREVAIL-Pneumo: Cases aged 1-35 months of age hospitalized with physician-diagnosed
        pneumonia or lower respiratory tract infection.

        PREVAIL-Community: Children 1-35 months of age residing in the community with no systemic
        illness and randomly selected for inclusion into this group

        PREVAIL-Econ: A subset of cases enrolled into the PREVAIL-Pneumo study
      
Biospecimen description: 
      Nasopharyngeal swab
    
Keywords: pneumococcal conjugate vaccine; vaccine impact; radiographic pneumonia; hospitalization; nasopharyngeal swab; India; cost of illness; pneumococcal carriage; pneumococcal serotypes; pneumonia