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, 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 burden of disease we use incidences and mortality rates from comprehensive data reported by the national report of epidemiological surveillance system during 2017 (7). RSV is one of the notifiable diseases , 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. Informed consent was not required because we used surveillance data without personal identifiers, Table I.
Table 1. Model inputs: morbidity probabilities used in base case and sensitivity analyses
Model input
|
Base case value
|
SA range for one-way sensitivity analyses
|
Source
|
Probability
|
|
|
|
Mortality by RSV in hospitalization
|
0,009
|
0,001-0,067
|
(7-12)
|
Mortality by RSV in pediatric intensive critical unit
|
0,036
|
0,021-0,052
|
Incidence of acute complications in hospitalization
|
0,131
|
0,101-0,202
|
Incidence of acute complications in pediatric intensive critical unit
|
0,153
|
0,150-0,536
|
Probability of recurrent wheeze in RSV
|
0,285
|
0,237-0,289
|
Disability weight
|
|
|
|
Mild or moderate lower respiratory infections
|
0,051
|
0,032-0,074
|
(17)
|
Severe lower respiratory infections
|
0,133
|
0,008-0.19
|
Recurrent wheeze
|
0,133
|
0,086-0,192
|
SA : sensitivity analyses
To estimate the ranges of incidence and mortality rates, systematic review of studies previously published with Colombian patients was made. 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 , we reviewed the first 100 results returned of this search. 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 recommended the manual of GBD studies(5) .All estimates used the Colombian population in 2017 (13). 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 , 10 000 iterations were made using a Monte Carlo simulation.. 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) with a discount rate of 0 and 5%.