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

Scott, E. M.; Magaret, A.; Kuypers, J.; Tielsch, J. M.; Katz, J.; Khatry, S. K.; Stewart, L.; Shrestha, L.; LeClerq, S. C.; Englund, J. A.; Chu, H. Y.

contribution of older children to transmission compared to the Kenyan cohort. Over half of RSV infections in children 5-15 years in that study were asymptomatic, with a smaller proportion of asymptomatic infections in infants under 1 year and children 1-4 years at 9% and 17%, respectively [28] . However, they also reported viral shedding in symptomatic RSV infections was 14 log 10 RNA copies greater than in asymptomatic RSV cases suggesting that symptomatic episodes are more likely to transmit virus [29] . Last, we collected weekly specimens and our findings may be biased if non-infant younger children had longer shedding duration compared to older children. However, this has not been demonstrated in studies of RSV and HRV shedding duration [28, 30] . Our large cohort allowed us to use a multivariable analysis to identify the risk factors and protective characteristics associated with the incidence of transmission. While both infants and preschool children were frequently identified as the index case in a transmission event and can shed virus for prolonged periods, a preschool child index case was associated with a twofold increased risk of transmission and an infant index case was associated with a decreased risk of transmission [11, 31, 32] . Whereas infants are more likely to transmit RSV via direct contact as compared with fomites, young children may transmit infection efficiently through both methods due to differences in mobility and behaviour [33] . Coinfection as the initial infection was associated with an increased risk of transmission, including in our multivariable model. Coinfections most commonly involved HRV and a greater proportion of coinfections resulted in a secondary case compared to monoinfection of most viruses. Viral coinfection with RSV infection has been demonstrated to increase RSV viral load and shedding duration. However, this has not been consistently seen, including a study analysing seven respiratory viruses [29 31, 34] . Finally, electricity in the household, a proxy for socio-economic status and housing conditions, was negatively associated with transmission. Although an association between indoor air pollution and RSV infection has been reported in resource-limited regions, smoking and biofuel cookstove use were not associated with the risk for transmission in our model [4] . However, we had limited power to detect this association due to the use of indoor biofuel cookstoves in over 90% of households in our model and exposures were self-reported without actual measures of indoor air pollution.