Design
Using the methods described by Murray and Lopez (5), we estimated the DALYs for RSV infection. DALYs were calculated for the most important health outcomes of this infection: RSV no complicated, RSV with or without acute mild or moderate complications (hypoxemia, atelectasis, and pneumonia), RSV with severe acute complications (PICO admission, pneumothoraxes, pleural effusions, sepsis) and RSV infection with long term complications (recurrent wheezing). The study protocol was reviewed and approved by the Institutional Review Board of the University of Antioquia (No 18/2015).
Model Parameters and Data Sources
To estimate the PQ burden of disease we use incidences and mortality rates from comprehensive data reported by the national epidemiological surveillance system (SIVIGILA) during 2019(7). RSV is one of the notifiable diseases and it is mandatory for health providers, hospitals and laboratories to report cases. The mortality data was validated with the data reported by the National Department of Statistics during the same time period. Informed consent was not required because we used surveillance data without personal identifiers, Table I.
To estimate the ranges of incidence and mortality rates, as well as and guarantee the external validity in the sensitivity analysis , this information was supplemented with search for studies previously published with Colombian patients. This search was performed in February 2019 and was limited to published primary literature in the English or Spanish language, human subjects, and children (birth to 5 years). The following engines were searched for the periods specified: MEDLINE from 1950 on, EMBASE from 1974 on, BIREME from 1980 on. To avoid missing any articles published we performed a search using Google search engine and we reviewed the first 100 results returned. Terms for these database searches included keywords closely matching the relevant medical field headings: respiratory syncytial virus, and respiratory syncytial pneumovirus. The authors (JAB, JPS) reviewed all potentially relevant references independently and selected relevant publications. The inclusion criteria were observational studies, systematic reviews that reported the incidence or frequencies of clinical outcomes of a patient younger than 2 years with RSV infection, which included the Colombian or Latin American population. 27 studies were obtained of which 5 were included(8-12).
Statistical analysis
The years of life lost by premature mortality were estimated, per outcome, by multiplying the number of deaths due to this outcome -in children with RSV under 2 years - by the number of years of expected remaining life at the age of death according to reference life tables of the global burden of disease study as recommended the manual of GBD studies(5) .All estimates used the Colombian population in 2017 (13). Next, the YLD per outcome was obtained by multiplying the number of cases –per outcome in children under 2 years with RSV infection - by both: the average duration of this outcome obtained from the literature (14), and respective disability weight derived from the 2015 GBD study, table 1. The internal consistency of each parameter was evaluated using the DISMOD II program (15) following the recommendations of manual for national studies of the WHO disease burden (5). To estimate the confidence Interval around YLD, YLL, and DALYs calculated before, we made 10 000 iterations in a Monte Carlo simulation, using a bootstrapped technique of DALY calculator package in R to obtain each confidence interval, with a discount rate of 3% and weighting by age. The DALYs was expressed both in absolute value and per 1000 person-years. Multi-way probabilistic sensitivity analysis was made using the standardized regression coefficient method (16). In this analysis was evaluated the percentage of change in the total estimate of DALYs, evaluating each of the variables within its range, (table 1) as well as with a discount rate of 0 and 5%.