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      Mathematical modelling of respiratory syncytial virus (RSV) in low- and middle-income countries: A systematic review

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          Abstract

          Background:

          Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.

          Methods:

          We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies.

          Findings:

          Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries.

          Interpretation:

          The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.

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          Most cited references 41

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          Using data on social contacts to estimate age-specific transmission parameters for respiratory-spread infectious agents.

          The estimation of transmission parameters has been problematic for diseases that rely predominantly on transmission of pathogens from person to person through small infectious droplets. Age-specific transmission parameters determine how such respiratory agents will spread among different age groups in a human population. Estimating the values of these parameters is essential in planning an effective response to potentially devastating pandemics of smallpox or influenza and in designing control strategies for diseases such as measles or mumps. In this study, the authors estimated age-specific transmission parameters by augmenting infectious disease data with auxiliary data on self-reported numbers of conversational partners per person. They show that models that use transmission parameters based on these self-reported social contacts are better able to capture the observed patterns of infection of endemically circulating mumps, as well as observed patterns of spread of pandemic influenza. The estimated age-specific transmission parameters suggested that school-aged children and young adults will experience the highest incidence of infection and will contribute most to further spread of infections during the initial phase of an emerging respiratory-spread epidemic in a completely susceptible population. These findings have important implications for controlling future outbreaks of novel respiratory-spread infectious agents.
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            Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study

            Summary Background We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. Methods We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. Findings We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population. Interpretation Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. Funding The Bill & Melinda Gates Foundation.
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              Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection.

              Respiratory syncytial virus (RSV) infection is the most frequent reason for hospitalization of infants in developed countries. Premature birth without or, especially, with chronic lung disease of prematurity, congenital heart disease, and T-cell immunodeficiency are conditions that predispose to more severe forms of RSV infection. Incomplete development of the airway, damage to the airway, and airway hyperreactivity underlie the increased morbidity of RSV infection in prematurely born infants. Pulmonary hypertension and cyanosis are associated with worse outcomes in infants with congenital heart disease, and prolonged viral replication accounts for more severe illness in immunocompromised individuals.
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                Author and article information

                Journal
                101484711
                36817
                Epidemics
                Epidemics
                Epidemics
                1755-4365
                1878-0067
                16 June 2021
                22 February 2021
                June 2021
                07 July 2021
                : 35
                : 100444
                Affiliations
                [a ]Department of Medicine, University of British Columbia, Vancouver, BC, Canada
                [b ]Institute for Disease Modeling, Seattle, WA, United States
                [c ]Department of Medicine, University of British Columbia, Vancouver, BC, Canada
                [d ]Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
                [e ]Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, MA, United States
                Author notes

                Author statement

                AM, AP, JC, and JA were involved in the design of this research study. AM, MR, and AP performed the literature search. AM wrote the manuscript. AM and MR created the tables and figures. All authors critically assessed data interpretation, reviewed and revised the manuscript, and approved the final manuscript as submitted.

                [* ]Corresponding author at: UBC Department of Medicine, 2775 Laurel Street, 10th Floor, Vancouver, BC, V5Z 1M9, Canada. alexmezei@ 123456alumni.ubc.ca (A. Mezei).
                Article
                NIHMS1714505
                10.1016/j.epidem.2021.100444
                8262087
                33662812

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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