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BACKGROUND: Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. METHODS AND FINDINGS: CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. CONCLUSIONS: COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.
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COVID-19 , Criança , Humanos , Adolescente , Pré-Escolar , SARS-CoV-2 , Teste para COVID-19 , Estudos Prospectivos , Inglaterra/epidemiologiaRESUMO
Introduction: The GAIA (Global Alignment on Immunisation Safety Assessment in Pregnancy) consortium was established in 2014 with the aim of creating a standardised, globally coordinated approach to monitoring the safety of vaccines administered in pregnancy. The consortium developed twenty-six standardised definitions for classifying obstetric and infant adverse events. This systematic review sought to evaluate the current state of adverse event reporting in maternal vaccine trials following the publication of the case definitions by GAIA, and the extent to which these case definitions have been adopted in maternal vaccine safety research. Methods: A comprehensive search of published literature was undertaken to identify maternal vaccine research studies. PubMed, EMBASE, Web of Science, and Cochrane were searched using a combination of MeSH terms and keyword searches to identify observational or interventional studies that examined vaccine safety in pregnant women with a comparator group. A two-reviewer screening process was undertaken, and a narrative synthesis of the results presented. Results: 14,737 titles were identified from database searches, 435 titles were selected as potentially relevant, 256 were excluded, the remaining 116 papers were included. Influenza vaccine was the most studied (25.0%), followed by TDaP (20.7%) and SARS-CoV-2 (12.9%).Ninety-one studies (78.4%) were conducted in high-income settings. Forty-eight (41.4%) utilised electronic health-records. The majority focused on reporting adverse events of special interest (AESI) in pregnancy (65.0%) alone or in addition to reactogenicity (27.6%). The most frequently reported AESI were preterm birth, small for gestational age and hypertensive disorders. Fewer than 10 studies reported use of GAIA definitions. Gestational age assessment was poorly described; of 39 studies reporting stillbirths 30.8% provided no description of the gestational age threshold. Conclusions: Low-income settings remain under-represented in comparative maternal vaccine safety research. There has been poor uptake of GAIA case definitions. A lack of harmonisation and standardisation persists limiting comparability of the generated safety data.
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In 2014, the Global Alignment on Immunization safety Assessment in pregnancy consortium (GAIA) was formed, with the goal of developing a harmonized, globally-concerted approach to actively monitor the safety of vaccines in pregnancy. A total of 26 standardized definitions for the classification of adverse events have been developed. The aim of this review was to identify and describe studies undertaken to assess the performance of these definitions. A literature search was undertaken to identify published studies assessing the performance of the definitions, and reference lists were snowballed. Data were abstracted by two investigators and a narrative review of the results is presented. Four studies that have evaluated 13 GAIA case definitions (50%) were identified. Five case definitions have been assessed in high-income settings only. Recommendations have been made by the investigators to improve the performance of the definitions. These include ensuring consistency across definitions, removal of the potential for ambiguity or variations in interpretation and ensuring that higher-level criteria are acceptable at lower levels of confidence. Future research should prioritize the key case definitions that have not been assessed in low- and middle-income settings, as well as the 13 that have not undergone any validation.
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Vacinas , Gravidez , Feminino , Humanos , Vacinas/efeitos adversos , Vacinação , Imunização/efeitos adversos , Família , RendaRESUMO
OBJECTIVES: To assess disease trends, testing practices, community surveillance, case-fatality and excess deaths in children as compared with adults during the first pandemic peak in England. SETTING: England. PARTICIPANTS: Children with COVID-19 between January and May 2020. MAIN OUTCOME MEASURES: Trends in confirmed COVID-19 cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity rates in children compared with adults; community prevalence of SARS-CoV-2 in children with acute respiratory infection (ARI) compared with adults, case-fatality rate in children with confirmed COVID-19 and excess childhood deaths compared with the previous 5 years. RESULTS: Children represented 1.1% (1,408/129,704) of SARS-CoV-2 positive cases between 16 January 2020 and 3 May 2020. In total, 540 305 people were tested for SARS-COV-2 and 129,704 (24.0%) were positive. In children aged <16 years, 35,200 tests were performed and 1408 (4.0%) were positive for SARS-CoV-2, compared to 19.1%-34.9% adults. Childhood cases increased from mid-March and peaked on 11 April before declining. Among 2,961 individuals presenting with ARI in primary care, 351 were children and 10 (2.8%) were positive compared with 9.3%-45.5% in adults. Eight children died and four (case-fatality rate, 0.3%; 95% CI 0.07% to 0.7%) were due to COVID-19. We found no evidence of excess mortality in children. CONCLUSIONS: Children accounted for a very small proportion of confirmed cases despite the large numbers of children tested. SARS-CoV-2 positivity was low even in children with ARI. Our findings provide further evidence against the role of children in infection and transmission of SARS-CoV-2.
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Teste para COVID-19/estatística & dados numéricos , COVID-19 , Transmissão de Doença Infecciosa/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/virologia , Teste para COVID-19/métodos , Criança , Estudos Transversais , Inglaterra/epidemiologia , Humanos , Lactente , Saúde Pública/tendênciasRESUMO
Group B Streptococcus (GBS) is estimated to have caused 319,000 cases of neonatal disease resulting in 90,000 infant deaths globally in 2015. It is also associated with maternal sepsis, preterm births, stillbirths and neonatal encephalopathy. There is a significant burden of neurologic impairment among survivors of infant GBS disease. Intrapartum antibiotic prophylaxis strategies have reduced the incidence of newborn early-onset GBS (occurring days 0-6) in some settings, but they are not feasible in many low and middle-income countries. A maternal vaccine given to pregnant women to stimulate passive transplacental transfer of protective antibodies has the potential to reduce maternal disease, adverse pregnancy outcomes and newborn disease. Phase I and II vaccine studies are occurring, but conducting phase III efficacy studies of a GBS vaccine candidate would require very large numbers due to the relatively low incidence of invasive GBS disease. It has therefore been proposed that alternative pathways to vaccine licensure should be explored, for example, through use of a regulatory approved correlate of protection and safety evaluation in mothers, fetuses and infants. These studies would then be followed-up with post-licensure phase IV studies in which vaccine effectiveness is evaluated.
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Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae/imunologia , Fatores Etários , Antibioticoprofilaxia , Análise Custo-Benefício , Feminino , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/epidemiologia , Sepse Neonatal/imunologia , Sepse Neonatal/microbiologia , Sepse Neonatal/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Vacinas Estreptocócicas/administração & dosagem , Vacinas Estreptocócicas/imunologia , VacinaçãoRESUMO
Cholera is an acute secretory diarrhoeal infection caused by the bacterium Vibrio cholerae. It is likely to have originated in the Indian sub-continent; however, it spread to cause six worldwide pandemics between 1817-1923. The ongoing seventh worldwide pandemic of cholera began in 1961. The intensity, duration and severity of cholera epidemics have been increasing, signaling the need for more effective control and prevention measures. The response to the cholera pandemics of the 19th century led to the development of safe and effective sanitation and water systems which have effectively removed the risk of cholera in many settings. However, such systems are not in place to protect billions of people worldwide. Although some progress has been made in expanding access to water in recent years, achieving optimal infrastructure will, in the most optimistic scenario, take decades. Climate change, extreme weather events and rapid urbanisation suggests that alternatives to the current paradigm of providing large centralised water and sanitation systems should be considered, including smaller decentralised systems. The aim of this review paper is to provide an overview of current knowledge regarding management of cholera with a focus on prevention measures including vaccination and water and sanitation interventions.