The Source of Respiratory Syncytial Virus Infection In Infants: A Household Cohort Study In Rural Kenya

Abstract

Background. Respiratory syncytial virus (RSV) vaccine development for direct protection of young infants faces substantial obstacles. Assessing the potential of indirect protection using different strategies, such as targeting older children or mothers, requires knowledge of the source of infection to the infants.Methods. We undertook a prospective study in rural Kenya. Households with a child born after the preceding RSV epidemic and ≥1 elder sibling were recruited. Nasopharyngeal swab samples were collected every 3–4 days irrespective of symptoms from all household members throughout the RSV season of 2009–2010 and tested for RSV using molecular techniques.Results. From 451 participants in 44 households a total of 15 396 nasopharyngeal swab samples were samples were collected, representing 86% of planned sampling. RSV was detected in 37 households (84%) and 173 participants (38%) and 28 study infants (64%). The infants acquired infection from within (15 infants; 54%) or outside (9 infants; 32%) the household; in 4 households the source of infant infection was inconclusive. Older children were index case patients for 11 (73%) of the within-household infant infections, and 10 of these 11 children were attending school.Conclusion. We demonstrate that school-going siblings frequently introduce RSV into households, leading to infection in infants.

Risk factors and patterns of household clusters of respiratory viruses in rural Nepal

“…Studies in rural Kenya have identified school-age children as the primary introducers of RSV into households where an infant subsequently became infected [6]. These results were in agreement with a US study from the 1960s reporting older siblings aged 2-16 years as most likely to introduce RSV disease into families [11].…”

“…In many global regions where access to healthcare is limited, especially in rural areas, the true community-based burden of respiratory virus-associated ALRI remains poorly characterised [3][4][5]. In these settings, household surveillance studies can provide a more comprehensive evaluation of viral incidence, transmission and molecular epidemiology patterns in the community [4][5][6][7][8].…”

Determinants of early life immune responses to RSV infection

“…Shedding was shown to be strongly associated with age and the severity of infection [54]. Additional studies in these same cohorts revealed that older, school-aged siblings are most often responsible for transmitting RSV to within-household infants [55]. A vaccine that would induce a level of protection equivalent to natural infection (around 6 months) in school-aged children is predicted to reduce RSV occurrence in those less than one year old by 35% within 10 years.…”

Vaccines against respiratory syncytial virus: The time has finally come

“…Therefore, the likelihood of adverse events would be lower, but the direct benefit to the individual would also be lower, since by age 5 most people have achieved a level of immunity that prevents serious lower airway disease unless immunity is compromised by disease or aging. Immunization of this population would be primarily to reduce transmission to neonates and the elderly, based on RSV transmission dynamics studies (18, 19) showing that most neonatal infections come from older siblings, and the precedent in influenza showing that immunization of school-age children is more cost-effective than immunizing the elderly (20). Boosting pre-existing immunity in the elderly may reduce RSV-related disease, but immunity and pathogenesis in this population is complex, making the definition of clinical endpoints short of hospitalization difficult.…”