Successive Respiratory Syncytial Virus Epidemics in Local Populations Arise from Multiple Variant Introductions, Providing Insights into Virus Persistence

Abstract

Respiratory syncytial virus (RSV) is a global respiratory pathogen of humans, with infection occurring characteristically as recurrent seasonal epidemics. Unlike influenza viruses, little attention has been paid to the mechanism underlying worldwide spread and persistence of RSV and how this may be discerned through an improved understanding of the introduction and persistence of RSV in local communities. We analyzed 651 attachment (G) glycoprotein nucleotide sequences of RSV B collected over 11 epidemics (2002 to 2012) in Kilifi, Kenya, and contemporaneous data collected elsewhere in Kenya and 18 other countries worldwide (2002 to 2012). Based on phylogeny, genetic distance and clustering patterns, we set out pragmatic criteria to classify local viruses into distinct genotypes and variants, identifying those newly introduced and those locally persisting. Three genotypes were identified in the Kilifi data set: BA (n = 500), SAB1 (n = 148), and SAB4 (n = 3). Recurrent RSV epidemics in the local population were composed of numerous genetic variants, most of which have been newly introduced rather than persisting in the location from season to season. Global comparison revealed that (i) most Kilifi variants do not cluster closely with strains from outside Kenya, (ii) some Kilifi variants were closely related to those observed outside Kenya (mostly Western Europe), and (iii) many variants were circulating elsewhere but were never detected in Kilifi. These results are consistent with the hypothesis that year-to-year presence of RSV at the local level (i.e., Kilifi) is achieved primarily, but not exclusively, through introductions from a pool of variants that are geographically restricted (i.e., to Kenya or to the region) rather than global.IMPORTANCE The mechanism by which RSV persists and reinvades local populations is poorly understood. We investigated this by studying the temporal patterns of RSV variants in a rural setting in tropical Africa and comparing these variants with contemporaneous variants circulating in other countries. We found that periodic seasonal RSV transmission at the local level appears to require regular new introductions of variants. However, importantly, the evidence suggests that the source of new variants is mostly geographically restricted, and we hypothesize that year-to-year RSV persistence is at the country level rather than the global level. This has implications for control.

Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment

“…Recent epidemiological reports have suggested that there may be virological interactions such as competition (234) between influenza virus and RSV infections (233,234). The early onset of an influenza season and the 2009 H1N1 influenza pandemic coincided with the delayed onset of RSV and hMPV epidemics (233,234). It was suggested that epidemiological studies such as these support a hypothesis of viral competition and/or virological interaction (234).…”

“…In further support of a meteorological influence on respiratory viruses, RSV and influenza seasons occur at discordant times of the year in Australia, coinciding more with the rainy and winter seasons, respectively (229). Recent epidemiological reports have suggested that there may be virological interactions such as competition (234) between influenza virus and RSV infections (233,234). The early onset of an influenza season and the 2009 H1N1 influenza pandemic coincided with the delayed onset of RSV and hMPV epidemics (233,234).…”

“…5). Enterovirus infections peak in the summer in temperate regions, whereas influenza virus, RSV, and human metapneumovirus (hMPV) infections peak in the winter months (233,234). This pattern of outbreaks is suggestive of a sociological and/or a meteorological effect on the timing of virus outbreaks.…”

“…There have been a few good reports on whole-genome sequences of RSVA and RSVB that describe the transmission of RSV genotypes derived from these two groups (233,243,(250)(251)(252). The current working model of RSV transmission is that yearly outbreaks of RSV are the result of variants that grow out of locally evolved clades, not necessarily viruses that have been introduced from distant locations (233).…”

“…Genome sequencing has refined our knowledge of the clades and strains of RSVA and RSVB that circulate worldwide (15,233,250). There have been a few good reports on whole-genome sequences of RSVA and RSVB that describe the transmission of RSV genotypes derived from these two groups (233,243,(250)(251)(252).…”