RESUMEN
BACKGROUND: Little information is available on the costs of respiratory syncytial virus (RSV) in Vietnam or other low- and middle-income countries. Our study estimated the costs of LRTIs associated with RSV infection among children in southern Vietnam. METHODS: We conducted a prospective cohort study evaluating household and societal costs associated with LRTIs stratified by RSV status and severity among children under 2 years old who sought care at a major pediatric referral hospital in southern Vietnam. Enrollment periods were September 2019-December 2019, October 2020-June 2021 and October 2021-December 2021. RSV status was confirmed by a validated RT-PCR assay. RSV rapid detection antigen (RDA) test performance was also evaluated. Data on resource utilization, direct medical and non-medical costs, and indirect costs were collected from billing records and supplemented by patient-level questionnaires. All costs are reported in 2022 US dollars. RESULTS: 536 children were enrolled in the study, with a median age of 7 months (interquartile range [IQR] 3-12). This included 210 (39.2%) children from the outpatient department, 318 children (59.3%) from the inpatient respiratory department (RD), and 8 children (1.5%) from the intensive care unit (ICU). Nearly 20% (105/536) were RSV positive: 3.9 percent (21/536) from the outpatient department, 15.7% (84/536) from the RD, and none from the ICU. The median total cost associated with LRTI per patient was US$52 (IQR 32-86) for outpatients and US$184 (IQR 109-287) for RD inpatients. For RSV-associated LRTIs, the median total cost per infection episode per patient was US$52 (IQR 32-85) for outpatients and US$165 (IQR 95-249) for RD inpatients. Total out-of-pocket costs of one non-ICU admission of RSV-associated LRTI ranged from 32%-70% of the monthly minimum wage per person (US$160) in Ho Chi Minh City. The sensitivity and the specificity of RSV RDA test were 88.2% (95% CI 63.6-98.5%) and 100% (95% CI 93.3-100%), respectively. CONCLUSION: These are the first data reporting the substantial economic burden of RSV-associated illness in young children in Vietnam. This study informs policymakers in planning health care resources and highlights the urgency of RSV disease prevention.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Niño , Humanos , Lactante , Preescolar , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Vietnam/epidemiología , Estrés Financiero , Virus Sincitial Respiratorio Humano/genética , HospitalizaciónRESUMEN
Background: Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. Methods: In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections. Results: Respiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/ß, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens. Conclusions: We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6.
Asunto(s)
Células Sanguíneas/patología , Perfilación de la Expresión Génica , Inmunidad Innata , Mucosa Respiratoria/patología , Infecciones por Virus Sincitial Respiratorio/patología , Virus Sincitiales Respiratorios/patogenicidad , Infecciones del Sistema Respiratorio/patología , Preescolar , Estudios de Cohortes , Resfriado Común/patología , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. METHODS: A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. RESULTS: Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. CONCLUSION: We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/etiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Preescolar , Humanos , Lactante , Virus Sincitial Respiratorio Humano/patogenicidad , Factores de Riesgo , Estaciones del Año , Vietnam/epidemiología , Carga ViralRESUMEN
Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children ,2 years of age. Little is known about RSV intra-host genetic diversity over the course of infection or about the immune pressures that drive RSV molecular evolution. We performed whole-genome deep-sequencing on 53 RSV-positive samples (37 RSV subgroup A and 16 RSV subgroup B) collected from the upper airways of hospitalized children in southern Vietnam over two consecutive seasons. RSV A NA1 and RSV B BA9 were the predominant genotypes found in our samples, consistent with other reports on global RSV circulation during the same period. For both RSV A and B, the M gene was the most conserved, confirming its potential as a target for novel therapeutics. The G gene was the most variable and was the only gene under detectable positive selection. Further, positively selected sites inG were found in close proximity to and in some cases overlapped with predicted glycosylation motifs, suggesting that selection on amino acid glycosylation may drive viral genetic diversity. We further identified hotspots and coldspots of intra-host genetic diversity in the RSV genome, some of which may highlight previously unknown regions of functional importance.