Transmission of Respiratory Syncytial Virus in Households: Who Acquires Infection From Whom?

Households represent a setting of frequent and intense contacts and hence are conducive to the spread of respiratory viruses, such as respiratory syncytial virus (RSV). Infants are most vulnerable to severe RSV disease but a vaccine is not yet available hence the need to explore alternate strategies of protecting them. Such strategies would require better understanding of who infects the infants. During the RSV season of 2009/2010, we undertook a prospective study in rural Kenya involving 493 members of 47 households each with a child bom after the preceding RSV epidemic and at least one elder sibling. Throughout the epidemic a nasopharyngeal swab (NPS) was collected every 3-4 days irrespective of symptoms, from all household members, and tested for a range of respiratory viruses including RSV using a molecular diagnostic assay. Partial sequencing of the attachment protein (G) gene from positive swabs was used to compare RSV strains within the household. In addition, once-a-week a specimen of oral fluid (OF) from around the gums was collected for RSV-specific antibodies screening and for assessment of sensitivity of the OF in detection of RSV using molecular diagnostics. This is the first prospective study to investigate introduction and transmission of RSV in families using molecular techniques over a complete RSV season. Analysis of RSV infection data is reported in this thesis with particular interest to identifying from where infants derive their infection, estimating the duration of RSV shedding and identity factors influencing the recovery rates, and estimating parameters of RSV susceptibility and transmission probability. In addition, data on diagnostic performance of OF in detection of RSV by molecular methods is presented. A total of 16,924 NPS were collected, representing 86% of planned. RSV was detected in 40 (85%) households and 179 (36%) of the participants. In 28 of the 44 households with complete data, there was transmission of RSV to the infants experiencing their first epidemic. The probable source of RSV infection of the naive infants was a household member in at least 54% of the cases. Co-primary infection between a household member and the RSV-naive infant was ascribed in 4 of the cases. Older children were assigned the primary case for 11 (39%) of the infant cases and 10 (91%) of these were attending school. The infants appeared to play a role transmitting the introduced infections to the other members of the household including to the mothers. These findings support vaccination strategies that target school age children and pregnant women. Both of these vaccination strategies can have profound benefits to RSV naive infants directly by augmenting neutralizing antibodies against RSV (immunization of the pregnant women) and indirectly by reducing transmission from siblings to RSV-naive infants. Results from this study provide increased confidence in the rationale for RSV vaccination of individuals who are not the key targets for protection