Asunto(s)
Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/inmunología , Virus Sincitiales Respiratorios/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19 , Preescolar , Ensayos Clínicos Fase III como Asunto , Aprobación de Drogas , Femenino , Humanos , Inmunidad Materno-Adquirida/inmunología , Lactante , Recién Nacido , Inflamación/inmunología , Embarazo , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/virología , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Vacunas contra Virus Sincitial Respiratorio/química , Virus Sincitiales Respiratorios/química , Proteínas Virales de Fusión/química , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/metabolismo , Internalización del Virus , Vacunas de ARNm/administración & dosificación , Vacunas de ARNm/inmunologíaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and a key driver of childhood mortality. Previous RSV burden of disease estimates used hospital-based surveillance data and modelled, rather than directly measured, community deaths. Given this uncertainty, we conducted a 3-year post-mortem prevalence study among young infants at a busy morgue in Lusaka, Zambia-the Zambia Pertussis RSV Infant Mortality Estimation (ZPRIME) study. METHODS: Infants were eligible for inclusion if they were aged between 4 days and less than 6 months and were enrolled within 48 h of death. Enrolment occurred mainly at the University Teaching Hospital of the University of Zambia Medical School (Lusaka, Zambia), the largest teaching hospital in Zambia. We extracted demographic and clinical data from medical charts and official death certificates, and we conducted verbal autopsies with the guardian or next of kin. RSV was identified using reverse transcriptase quantitative PCR and stratified by age, time of year, and setting (community vs facility deaths). By combining the PCR prevalence data with syndromic presentation, we estimated the proportion of all infant deaths that were due to RSV. FINDINGS: The ZPRIME study ran from Aug 31, 2017, to Aug 31, 2020, except for from April 1 to May 6, 2020, during which data were not collected due to restrictions on human research at this time (linked to COVID-19). We enrolled 2286 deceased infants, representing 79% of total infant deaths in Lusaka. RSV was detected in 162 (7%) of 2286 deceased infants. RSV was detected in 102 (9%) of 1176 community deaths, compared with 10 (4%) of 236 early facility deaths (<48 h from admission) and 36 (5%) of 737 late facility deaths (≥48 h from admission). RSV deaths were concentrated in infants younger than 3 months (116 [72%] of 162 infants), and were clustered in the first half of each year and in the poorest and most densely populated Lusaka townships. RSV caused at least 2·8% (95% CI 1·0-4·6) of all infant deaths and 4·7% (1·3-8·1) of community deaths. INTERPRETATION: RSV was a major seasonal cause of overall infant mortality, particularly among infants younger than 3 months of age. Because most RSV deaths occurred in the community and would have been missed through hospital-based surveillance, the global burden of fatal RSV has probably been underestimated. FUNDING: Bill & Melinda Gates Foundation.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio/mortalidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Vigilancia en Salud Pública/métodos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitial Respiratorio Humano , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Zambia/epidemiologíaRESUMEN
The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34-2.06-fold lower in males than females (P = 0.018 - < 0.001). IFN-ß, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.
Asunto(s)
Imidazoles/inmunología , Inmunidad Innata , Oligodesoxirribonucleótidos/inmunología , Infecciones por Picornaviridae/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Rhinovirus/inmunología , Adolescente , Cohorte de Nacimiento , Estudios de Cohortes , Femenino , Humanos , Interferones/inmunología , Interferones/metabolismo , Leucocitos Mononucleares/inmunología , Masculino , Infecciones por Picornaviridae/mortalidad , Infecciones por Picornaviridae/virología , Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/virología , SARS-CoV-2 , Factores SexualesRESUMEN
Respiratory syncytial virus (RSV) infections result in significant morbidity and mortality for young children worldwide. The development of preventive strategies for RSV has faced different challenges, including the legacy of the first vaccine attempt, and an incomplete understanding of the host immune response to the virus. However, promising preventive strategies against RSV are in the pipeline and their development has advanced rapidly in the past decade due in part to our improved knowledge about the structural conformation of key RSV proteins. These strategies include monoclonal antibodies and different vaccines platforms directed towards the main target populations.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Niño , Humanos , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/mortalidad , Infecciones por Virus Sincitial Respiratorio/terapia , Proteínas Virales/inmunología , Proteínas Virales/metabolismoRESUMEN
Objectives: To compare the clinical characteristics and outcomes of patients hospitalized with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza infections.Methods: This study prospectively enrolled 594 patients hospitalized with influenza-like illness (ILI) and laboratory-confirmed RSV, hMPV, or influenza infections over three consecutive influenza seasons at a tertiary hospital in China.Results: While certain clinical features were of value as predictors of infection type, none exhibited good predictive performance as a means of discriminating between these three infections (area under the receiver-operating characteristic curve < 0.70). After controlling for potential confounding variables, RSV infections in pneumonia patients were found to be associated with a 30-day mortality risk comparable to that of influenza patients [odds ratio (OR) 1.016, 95% confidence interval (CI) 0.267-3.856, p = 0.982], whereas hMPV infection was associated with a reduced risk of mortality (OR 0.144, 95% CI 0.027-0.780, p = 0.025). Among those without pneumonia, the 30-day mortality risk in patients with influenza was comparable to that in patients infected with RSV (OR 1.268, 95% CI 0.172-9.355, p = 0.816) or hMPV (OR 1.128, 95% CI 0.122-10.419, p = 0.916).Conclusion: Disease severity associated with these three types of viral infection was inconsistent when comparing patients with and without pneumonia, highlighting the importance of etiologic testing.