Estimation of the national disease burden associated with respiratory viruses
We reported mean annual estimates over the study period for any SRI and ILI as well as those associated with the respiratory viruses investigated in this study. Estimates were obtained overall and within the following age categories: <1, 1-4, 5-24, 25-44, 45-64, ≥65, <5 and ≥5 years of age. Rates were reported per 100,000 population. The details of the estimation approach are provided in Supplementary Material and summarized below.
Medically-attended illness
To estimate the national number of respiratory viruses-associated SRI hospitalizations we used a four-step approach. In Step 1 we estimated the SRI hospitalizations rates at the two hospitals mentioned above (data source 1) during 2013-2015 as previously described [11Tempia S, Walaza S, Moyes J, et al. Quantifying How Different Clinical Presentations, Levels of Severity, and Healthcare Attendance Shape the Burden of Influenza-associated Illness: A Modeling Study From South Africa. Clin Infect Dis.2019 ;69(6):1036-1048. doi: 10.1093/cid/ciy1017.] and we used the SRI hospitalization rates at the two sites as proxy for the corresponding provinces (considered to be the base provinces in our estimation approach). In Step 2 we estimated the SRI hospitalizations rates for the other 7 provinces from the base provinces using a previously described methodology that leverages provincial differences in the prevalence of known risk factors for pneumonia and healthcare seeking behavior (data source 3). In Step 3 we estimated the respiratory viruses-associated SRI hospitalizations rates using available virological surveillance data (data source 1) (i.e. detection rate of individual viruses adjusted for the estimated AF for each virus). In Step 4 we obtained the number of respiratory viruses-associated SRI hospitalizations using the estimated respiratory viruses-associated rates and the population at risk in each province (data source 4).
To estimate the national number of respiratory viruses-associated ILI outpatient consultations we used an approach similar to those used for SRI cases, but we did not adjust for the provincial level risk factors for pneumonia [18].
Non-medically attended illness
To estimate the national number and rates of respiratory viruses-associated non-medically attended ILI and SRI we used the four-step approach described above in conjunction with HUS data (data source 2) [18].