Respiratory syncytial virus (RSV) is a respiratory pathogen with potentially high disease
burden in Lower middle income country (LMIC). This pathogen is a potential target for
maternal immunization strategies to prevent disease and early death in young infants.
Majority of current studies estimate the burden of disease in terms of facility-based (e.g.
hospital) deaths. There is a knowledge gap regarding the proportion of community-based deaths
due to RSV. There are many challenges to generating evidence for the burden of RSV, such as
lack of resources for hospital and community surveillance and diagnostics, and difficulty in
obtaining specimens.
Parent study: In January 2018, the Community-based Infant RSV Mortality Study was initiated
in collaboration with Emory University, funded by the Bill and Melinda Gates Foundation.
Following a formative phase involving interviews with community stakeholders, in August 2018
a pilot surveillance stage was initiated, in which upon receiving death alerts from key
community partners about the recent death of an infant (<6 months) in the 4 catchment areas
of Karachi, a team of nurses and health workers mobilize to identify and approach the
household of the infant's primary caregivers. Upon obtaining verbal consent from the parents,
the nurse obtains nasopharyngeal specimens from the left and right nostrils of the recently
deceased infant. These specimens are tested for respiratory syncytial virus and Bordetella
pertussis through real-time Polymerase chain reaction (PCR) testing, and lab results are
reported to the parents along with verbal autopsy findings in a cause of death consultation.
Enrolled bereaved parents are also offered grief support home visits and grief counseling
services by the community health workers and study psychologist. The surveillance phase
continued from August 2018 to March 2020, when specimen collection was paused due to
coronavirus disease of 2019 (COVID-19) distancing measures. In 20 months, 490 nasopharyngeal
specimens were collected out of 713 households approached upon death alerts. Of these 490, 14
tested positive for RSV and 1 positive for pertussis. Following a training on disinfection,
personal protective equipment (PPE) protocols, distancing measures, as well as a
study-specific training on mental health, communication, and counseling skills June-July
2020, surveillance and specimen collection is planned to resume from August 2020.
Proposal for current study: While nasopharyngeal swab sampling with PCR testing is the gold
standard for detection of RSV, little is understood about lung morphology in relation to
upper respiratory tract infections in neonate and infant mortality. The objective of this
study is to assess and analyze the burden and determinants of RSV mortality in infants in 2
peri-urban areas of Karachi Pakistan and to provide a cause of death consultation for the
families of the recently deceased infants under 6 months of age in the catchment areas.
The RSV-MITS Study will be merged with the ongoing parent study of Community-based Infant RSV
Mortality. With the additional procedure and analysis of minimally invasive tissue sampling
(MITS) of the lungs/thorax, we aim to examine lung morphology through microbiology and
histology specimens. Designated staff (nurses) will require additional MITS training, and the
nasopharyngeal swab specimens and lung/thorax MITS specimens will be collected in the
designated study ambulance parked near the household or transported to the closest partner
hospital. The target sample size is 150 lung/thorax MITS and nasopharyngeal specimens from
deceased infants under 6 months of age; stillbirths and miscarriages excluded. This study
will be conducted in 2 Health and Demographic Surveillance System (HDSS) catchment areas:
Bhains Colony and Ali Akbar Shah Goth. The MITS Study is funded by the MITS Surveillance
Alliance.