RESUMO
An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.
Assuntos
Infecções por Adenovirus Humanos , Dependovirus , Hepatite , Criança , Humanos , Doença Aguda/epidemiologia , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/genética , Infecções por Adenovirus Humanos/virologia , Alelos , Estudos de Casos e Controles , Linfócitos T CD4-Positivos/imunologia , Coinfecção/epidemiologia , Coinfecção/virologia , Dependovirus/isolamento & purificação , Predisposição Genética para Doença , Vírus Auxiliares/isolamento & purificação , Hepatite/epidemiologia , Hepatite/genética , Hepatite/virologia , Hepatócitos/virologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Fígado/virologiaRESUMO
BACKGROUND: We hypothesised that the clinical characteristics of hospitalised children and young people (CYP) with SARS-CoV-2 in the UK second wave (W2) would differ from the first wave (W1) due to the alpha variant (B.1.1.7), school reopening and relaxation of shielding. METHODS: Prospective multicentre observational cohort study of patients <19 years hospitalised in the UK with SARS-CoV-2 between 17/01/20 and 31/01/21. Clinical characteristics were compared between W1 and W2 (W1 = 17/01/20-31/07/20,W2 = 01/08/20-31/01/21). RESULTS: 2044 CYP < 19 years from 187 hospitals. 427/2044 (20.6%) with asymptomatic/incidental SARS-CoV-2 were excluded from main analysis. 16.0% (248/1548) of symptomatic CYP were admitted to critical care and 0.8% (12/1504) died. 5.6% (91/1617) of symptomatic CYP had Multisystem Inflammatory Syndrome in Children (MIS-C). After excluding CYP with MIS-C, patients in W2 had lower Paediatric Early Warning Scores (PEWS, composite vital sign score), lower antibiotic use and less respiratory and cardiovascular support than W1. The proportion of CYP admitted to critical care was unchanged. 58.0% (938/1617) of symptomatic CYP had no reported comorbidity. Patients without co-morbidities were younger (42.4%, 398/938, <1 year), had lower PEWS, shorter length of stay and less respiratory support. CONCLUSIONS: We found no evidence of increased disease severity in W2 vs W1. A large proportion of hospitalised CYP had no comorbidity. IMPACT: No evidence of increased severity of COVID-19 admissions amongst children and young people (CYP) in the second vs first wave in the UK, despite changes in variant, relaxation of shielding and return to face-to-face schooling. CYP with no comorbidities made up a significant proportion of those admitted. However, they had shorter length of stays and lower treatment requirements than CYP with comorbidities once those with MIS-C were excluded. At least 20% of CYP admitted in this cohort had asymptomatic/incidental SARS-CoV-2 infection. This paper was presented to SAGE to inform CYP vaccination policy in the UK.
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COVID-19 , Infecções por Coronavirus , Humanos , Criança , Adolescente , SARS-CoV-2 , COVID-19/epidemiologia , Pandemias , Estudos Prospectivos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Rotavirus vaccine efficacy is reduced in low-income populations, but efforts to improve vaccine performance are limited by lack of clear correlates of protection. Although plasma rotavirus (RV)-specific immunoglobulin A (IgA) appears strongly associated with protection against rotavirus gastroenteritis in high-income countries, weaker association has been observed in low-income countries. We tested the hypothesis that lower RV-specific IgA is associated with rotavirus vaccine failure in Malawian infants. METHODS: In a case-control study, we recruited infants presenting with severe rotavirus gastroenteritis following monovalent oral rotavirus vaccination (RV1 vaccine failures). Conditional logistic regression was used to determine the odds of rotavirus seronegativity (RV-specific IgA < 20 U/mL) in these cases compared 1:1 with age-matched, vaccinated, asymptomatic community controls. Plasma RV-specific IgA was determined by enzyme-linked immunosorbent assay for all participants at recruitment, and for cases at 10 days after symptom onset. Rotavirus infection and genotype were determined by antigen testing and reverse transcription-polymerase chain reaction, respectively. RESULTS: In 116 age-matched pairs, infants with RV1 vaccine failure were more likely to be RV-specific IgA seronegative than controls: odds ratio, 3.1 (95% confidence interval [CI], 1.6-5.9), P=.001. In 60 infants with convalescent serology, 42/45 (93%; 95% CI. 81-98) infants seronegative at baseline became seropositive. Median rise in RV-specific IgA concentration following acute infection was 112.8 (interquartile range, 19.1-380.6)-fold. CONCLUSIONS: In this vaccinated population with high residual burden of rotavirus disease, RV1 vaccine failure was associated with lower RV-specific IgA, providing further evidence of RV-specific IgA as a marker of protection. Robust convalescent RV-specific IgA response in vaccine failures suggests differences in wild-type and vaccine-induced immunity, which informs future vaccine development.
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Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Estudos de Casos e Controles , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Humanos , Imunoglobulina A , Lactente , Malaui/epidemiologia , Rotavirus/genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas AtenuadasRESUMO
On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.
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COVID-19 , Hepatite A , Criança , Pré-Escolar , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Escócia/epidemiologiaRESUMO
Quantifying rotavirus shedding among vaccinated individuals will aid understanding of vaccine indirect effects. Serial stool samples were collected from 196 children who presented with rotavirus gastroenteritis to health facilities in Blantyre, Malawi, and were tested for rotavirus using a VP6 semi-quantitative, real-time polymerase chain reaction. The median duration of fecal shedding was 28 days (95% CI, 19-28). The median copy numbers for peak shedding were 1.99 × 107 (interquartile range, 3.39 × 106 to 6.37 × 107). The fecal viral load was positively associated with disease severity and negatively associated with serum anti-rotavirus immunoglobin A. High and persistent rotavirus shedding among vaccinated children with breakthrough disease may contribute to ongoing transmission in this setting.
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Gastroenterite/virologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Carga Viral , Eliminação de Partículas Virais , Fezes/virologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Malaui/epidemiologia , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Rotavirus/prevenção & controle , Proteínas não Estruturais ViraisRESUMO
Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8-10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi.
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Infecções por Rotavirus/imunologia , Infecções por Rotavirus/transmissão , Rotavirus/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Transmissão de Doença Infecciosa , Características da Família , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Malaui , Masculino , Estudos Prospectivos , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Adulto JovemRESUMO
Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens.
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Diarreia/etiologia , Diarreia/imunologia , Infecções por Rotavirus/imunologia , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Estudos de Casos e Controles , Criança Hospitalizada , Criptosporidiose/complicações , Cryptosporidium/patogenicidade , Diarreia/microbiologia , Diarreia/virologia , Escherichia coli/patogenicidade , Fezes/microbiologia , Fezes/virologia , Feminino , Gastroenterite/complicações , Humanos , Lactente , Malaui , MasculinoRESUMO
BACKGROUND: Histo-blood group antigen (HBGA) Lewis/secretor phenotypes predict genotype-specific susceptibility to rotavirus gastroenteritis (RVGE). We tested the hypothesis that nonsecretor/Lewis-negative phenotype leads to reduced vaccine take and lower clinical protection following vaccination with G1P[8] rotavirus vaccine (RV1) in Malawian infants. METHODS: A cohort study recruited infants receiving RV1 at age 6 and 10 weeks. HBGA phenotype was determined by salivary enzyme-linked immunosorbent assay (ELISA). RV1 vaccine virus shedding was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in stool collected on alternate days for 10 days post-immunization. Plasma rotavirus-specific immunoglobulin A was determined by ELISA pre- and post-immunization. In a case-control study, HBGA phenotype distribution was compared between RV1-vaccinated infants with RVGE and 1:1 age-matched community controls. Rotavirus genotype was determined by RT-PCR. RESULTS: In 202 cohort participants, neither overall vaccine virus fecal shedding nor seroconversion differed by HBGA phenotype. In 238 case-control infants, nonsecretor phenotype was less common in infants with clinical vaccine failure (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.20-0.75). Nonsecretor phenotype was less common in infants with P[8] RVGE (OR, 0.12; 95% CI, 0.03-0.50) and P[4] RVGE (OR, 0.17; 95% CI, 0.04-0.75). Lewis-negative phenotype was more common in infants with P[6] RVGE (OR, 3.2; 95% CI, 1.4-7.2). CONCLUSIONS: Nonsecretor phenotype was associated with reduced risk of rotavirus vaccine failure. There was no significant association between HBGA phenotype and vaccine take. These data refute the hypothesis that high prevalence of nonsecretor/Lewis-negative phenotypes contributes to lower rotavirus vaccine effectiveness in Malawi.
Assuntos
Antígenos de Grupos Sanguíneos , Imunoglobulina A/sangue , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Vacinação , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Gastroenterite/epidemiologia , Genótipo , Humanos , Lactente , Estudos Longitudinais , Malaui/epidemiologia , Fenótipo , Risco , Infecções por Rotavirus/sangue , Infecções por Rotavirus/epidemiologia , Soroconversão , Vacinas Atenuadas/imunologiaRESUMO
Atypical DS-1-like G1P[8] rotaviruses emerged in 2013 in Malawi after rotavirus vaccine introduction. Vaccine effectiveness among infants hospitalized with acute DS-1-like G1P[8] rotavirus gastroenteritis was 85.6% (95% CI 34.4%-96.8%). These findings suggest that vaccine provides protection against these strains despite their emergence coinciding with vaccine introduction.
Assuntos
Criança Hospitalizada , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Vacinas contra Rotavirus/uso terapêutico , Rotavirus/isolamento & purificação , Pré-Escolar , Feminino , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Humanos , Lactente , Recém-Nascido , Malaui/epidemiologia , Masculino , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas AtenuadasRESUMO
BACKGROUND: Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. METHODS: We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)-exposed and stunted children. RESULTS: Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997-2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8-68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%-87.0%) and 31.7% (95% CI, -140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%-94.9%] in 257 well-nourished and 27.8% [95% CI, -99.5% to 73.9%] in 205 stunted children;P= .12), or by HIV exposure (60.5% [95% CI, 13.3%-82.0%] in 745 HIV-unexposed and 42.2% [95% CI, -106.9% to 83.8%] in 174 exposed children;P= .91). CONCLUSIONS: Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting.
Assuntos
Diarreia/prevenção & controle , Gastroenterite/prevenção & controle , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Saúde da População Urbana/tendências , Vacinação , Estudos de Casos e Controles , Pré-Escolar , Diarreia/epidemiologia , Diarreia/virologia , Monitoramento Epidemiológico , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Genótipo , Transtornos do Crescimento/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Lactente , Malaui/epidemiologia , Prevalência , Rotavirus/genética , Rotavirus/imunologia , Rotavirus/isolamento & purificação , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Saúde da População Urbana/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Vacinação/tendências , Potência de Vacina , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Populações Vulneráveis/estatística & dados numéricosRESUMO
BACKGROUND: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. METHODS: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. RESULTS: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. CONCLUSIONS: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.
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Providing emergency care in low resource settings relies on delivery by lower cadres of health workers (LCHW). We describe the development, implementation and mixed methods evaluation of a mobile health (mHealth) triage algorithm based on the WHO Emergency, Triage, Assessment, and Treatment (ETAT) for primary-level care. We conducted an observational study design of implementation research. Key stakeholders were engaged throughout implementation. Clinicians and LCHW at eight primary health centres in Blantyre district were trained to use an mHealth algorithm for triage. An mHealth patient surveillance system monitored patients from presentation through referral to tertiary and final outcome. A total of 209,174 children were recorded by ETAT between April 2017 and September 2018, and 155,931 had both recorded mHealth and clinician triage outcome data. Concordance between mHealth triage by lower cadres of HCW and clinician assessment was 81·6% (95% CI [81·4, 81·8]) over all outcomes (kappa: 0·535 (95% CI [0·530, 0·539]). Concordance for mHealth emergency triage was 0.31 with kappa 0.42. The most common mHealth recorded emergency sign was breathing difficulty (74·1% 95% CI [70·1, 77·9]) and priority sign was raised temperature (76·2% (95% CI [75·9, 76·6]). A total of 1,644 referrals out of 3,004 (54·7%) successfully reached the tertiary site. Both providers and carers expressed high levels of satisfaction with the mHealth ETAT pathway. An mHealth triage algorithm can be used by LCHWs with moderate concordance with clinician triage. Implementation of ETAT through an mHealth algorithm documented successful referrals from primary to tertiary, but half of referred patients did not reach the tertiary site. Potential harms of such systems, such as cases requiring referral being missed during triage, require further evaluation. The ASPIRE mHealth primary ETAT approach can be used to prioritise acute illness and support future resource planning within both district and national health system.
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Diagnosis and treatment of latent tuberculosis infection (LTBI) is important to reduce risk of progression to active tuberculosis (TB) disease. For the past century the tuberculin skin test (TST) has been used as a measure of exposure to Mycobacterium tuberculosis (MTB), but this test has limitations in test performance, sensitivity and specificity. Interferon γ release assays (IGRA), like TST, measure host immune response to MTB. IGRA are designed to be more specific for the diagnosis of LTBI than TST in patients with previous BCG or exposure to non-tuberculous mycobacteria, detecting interferon γ generated by T cells in response to antigens more specific to MTB. Although developed as an alternative to TST, recent data, particularly in children, suggest IGRA have their own limitations. Superiority to TST as a diagnostic test in children has not been demonstrated. Neither test discriminates between current or past MTB infection, or between latent infection and active disease. This article reviews the current literature on sensitivity and specificity of IGRA in the diagnosis of LTBI, and summarises current NICE recommendations for the use of IGRA in combination with TST. Although not developed for this purpose, in clinical practice IGRA have also been used as a diagnostic test for active TB. The gold standard for diagnosis of active TB disease is microbiological confirmation by culture of MTB. This article discusses the utility of IGRA as an adjunct to diagnosis of active TB disease, but emphasises that IGRA do not have sufficient sensitivity or specificity to exclude or confirm active TB disease.
Assuntos
Interferon gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Criança , Humanos , Interferon gama/imunologia , Mycobacterium tuberculosis/imunologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Multimorbidity is one of the greatest challenges facing health and social care systems globally. It is associated with high rates of health service use, adverse healthcare events, and premature death. Despite its importance, little is known about the effects of contextual determinants such as household and area characteristics on health and care outcomes for people with multimorbidity. This study protocol presents a plan for the examination of associations between individual, household, and area characteristics with important health and social care outcomes. METHODS: The study will use a cross-section of data from the SAIL Databank on 01 January 2019 and include all people alive and registered with a Welsh GP. The cohort will be stratified according to the presence or absence of multimorbidity, defined as two or more long-term conditions. Multilevel models will be used to examine covariates measured for individuals, households, and areas to account for social processes operating at different levels. The intra-class correlation coefficient will be calculated to determine the strength of association at each level of the hierarchy. Model outcomes will be any emergency department attendance, emergency hospital or care home admission, or mortality, within the study follow-up period. DISCUSSION: Household and area characteristics might act as protective or risk factors for health and care outcomes for people with multimorbidity, in which case results of the analyses can be used to guide clinical and policy responses for effective targeting of limited resources.
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Multimorbidade , Humanos , Análise Multinível , Fatores de RiscoRESUMO
OBJECTIVES: To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections. DESIGN: Population-based cohort study. SETTING AND POPULATION: All live births in Scotland, 1 March 2020-31 January 2022. RESULTS: There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection. IMPLICATIONS AND RELEVANCE: Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.
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COVID-19 , Complicações Infecciosas na Gravidez , Gravidez , Recém-Nascido , Lactente , Criança , Humanos , Feminino , COVID-19/diagnóstico , COVID-19/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , SARS-CoV-2 , Estudos de Coortes , Escócia/epidemiologia , Resultado da Gravidez/epidemiologiaRESUMO
INTRODUCTION: SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs. METHODS AND ANALYSIS: We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection. ETHICS AND DISSEMINATION: This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.
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COVID-19 , Criança , Humanos , Adolescente , COVID-19/epidemiologia , SARS-CoV-2 , Teste para COVID-19 , Estudos de Coortes , País de Gales/epidemiologia , Atenção à Saúde , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. METHODS: In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. FINDINGS: Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06-1·30) and disease (1·28 [1·08-1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16-57). INTERPRETATION: Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. FUNDING: Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases.
Assuntos
Características da Família , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/transmissão , Vacinas contra Rotavirus/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Diarreia/virologia , Fezes/virologia , Feminino , Humanos , Imunoglobulina A , Incidência , Malaui , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rotavirus , Vacinação , Adulto JovemRESUMO
A 13-year-old girl presented to the emergency department with acute onset of chest pain, nausea and tremor. The patient denied drug ingestion, and urine toxicology was negative. ECG demonstrated sinus tachycardia, prolonged QTc (541 ms) and ST depression. Laboratory testing demonstrated metabolic acidosis, hypokalaemia, hypophosphataemia and hyperglycaemia. She was commenced on continuous cardiac monitoring and treated with intravenous fluids and electrolyte replacement. Presenting features and laboratory abnormalities resolved within 48 hours. The National Poisons Information Service and Clinical Biochemistry were integral to her management, advising the clinical team on the likeliest aetiology. Five weeks after discharge, urine toxicology, using mass spectrometry, identified clenbuterol. Clenbuterol is an oral ß2-agonist with anabolic and lipolytic effects that is misused as a performance and image enhancing drug. Clinicians must be aware of the increasing availability of these drugs and their potential for causing harm in children and adolescents.
Assuntos
Acidose/induzido quimicamente , Agonistas Adrenérgicos beta/toxicidade , Clembuterol/toxicidade , Taquicardia Sinusal/induzido quimicamente , Acidose/terapia , Adolescente , Agonistas Adrenérgicos beta/urina , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Clembuterol/urina , Diagnóstico Diferencial , Eletrocardiografia/métodos , Serviço Hospitalar de Emergência , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hipopotassemia/induzido quimicamente , Hipofosfatemia/induzido quimicamente , Náusea/diagnóstico , Náusea/etiologia , Taquicardia Sinusal/fisiopatologia , Resultado do Tratamento , Tremor/diagnóstico , Tremor/etiologiaRESUMO
OBJECTIVE: To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). DESIGN: Prospective observational cohort study with rapid data gathering and near real time analysis. SETTING: 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). PARTICIPANTS: 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. MAIN OUTCOME MEASURES: Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. RESULTS: Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group. CONCLUSIONS: Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). STUDY REGISTRATION: ISRCTN66726260.