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.

Keywords: RSV; households; infants; siblings; transmission.

Figure 1.

Number of households participating and individual episodes of respiratory syncytial virus (RSV) A and B infection detected during the follow-up period (weekly delimited data) in 2009–2010.

Figure 2.

Distribution of primary cases for the 28 household episodes linked with the study infant infection in rural Kenya. Only the first household episodes/outbreaks involving the study infants are shown. The diagonal and zigzag lines shading the circles indicate outside- and within-household acquisition of the infant infections, respectively, and the area of the circle is in proportion to the number of cases in each category.

Figure 3.

A, Temporal occurrence of respiratory syncytial virus (RSV)–positive samples in a household of 5 members (household 40). Each box represent a sample collected; each circle, an RSV-positive sample. RSV was introduced by subject 4004. B, An Maximum Likelihood phylogenetic tree of 10 of 12 samples from household 40 together with 10 RSV A reference sequences from Kilifi District Hospital (KDH). All samples from household 40 (preceded by triangles on tree) had identical sequences in the G region sequenced. C, Phylogenetic relationship of the G similarity of study infant–primary case pairs for RSV A. Samples from the same household are preceded by the same symbol (filled or open). Taxon naming for the household samples follows household number with individual number and date of sampling (eg, 4703_02April2010 represents household 47, individual 3, and sample collected on 2 April 2010). The KDH RSV A reference sequences are as in B. D, Same as C, but for RSV B. An example RSV B pairing is 3803_14Feb2010 and the later infant-infecting virus sequence 3801_27Feb2010. Ten random samples from the KDH inpatient studies are included for reference, as in B and C.