Pneumonia Research and Vaccine Impact League
Pneumonia Research and Vaccine Impact League
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.
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
PREVAIL-Pneumo:

 Inclusion criteria:

 -  Age 1-35 months

 -  Admitting diagnosis is pneumonia or lower respiratory tract illness/infection Written
 informed consent obtained from parent or legally authorized representative

 Exclusion criteria:

 -  Discharged as an PREVAIL case in the last 90 days

 PREVAIL-Community:

 Inclusion criteria:

 -  Age 1-35 months with no systemic illness (mild respiratory illness is not an exclusion
 criteria)

 -  Written informed consent obtained from parent or legally authorized representative

 Exclusion criteria:

 -  Known underlying serious disease (e.g., congenital heart diseases, immunodeficiency
 disorders, sickle cell anemia etc.) which may negatively influence the participant's
 ability to participate in the study

 PREVAIL-Econ:

 Inclusion criteria:

 -  Currently enrolled into the PREVAIL study