Deaths Associated with Pediatric Hepatitis of Unknown Etiology, United States, October 2021-June 2023.

During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus.

Safety and Efficacy of 12-Month Intra-gastric Balloon-Series of over 1100 Patients.

BACKGROUND: Intra-gastric balloons (IGB) are a mainstay of endoscopic treatment of overweight and obesity. In recent years, an IGB which can remain in situ for 12 months has been developed. The current study aimed to analyse the safety and efficacy of this 12-month IGB. METHODS: Consecutive patients receiving the Orbera 365TM IGB (Apollo Endosurgery, TX, USA) between September 2017 and August 2021 were included in a prospective database. Patients received regular follow-up consultations followed by endoscopic removal at 12 months. Demographic data along with weight loss data were collected. All adverse events were recorded. RESULTS: In total, 1149 patients were included in the study. A majority of the patients were female (87.13%). Median body mass index (BMI) prior to insertion was 36.30 kg/m2 (IQR 32.60-40.00 kg/m2). Median absolute weight loss for all patients was 11.36 kg (IQR 6.70-16.82 kg). There was ongoing sustained weight loss until device removal at week 52. For patients with a weight recording at point of IGB removal, median weight loss was greater (15.88 kg, IQR 10.43-21.72) with percentage total body weight loss of 15.38% (IQR 10.99-21.77) and excess weight loss of 53.99% (IQR 32.44-76.30). Increased patient engagement with post-procedural follow-up was associated with increased weight loss (p<0.001). There were 60 total complications (5.22%). Fifty patients required balloon removal due to intolerance. There were eight cases of balloon rupture. There were only two severe complications (0.17%). CONCLUSION: The current study has confirmed safety of this IGB at 12 months with adverse events comparable to published literature. Weight loss increased up until the point of removal at 12 months.

Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022.

BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None.

Non-traditional data sources in obesity research: a systematic review of their use in the study of obesogenic environments.

BACKGROUND: The complex nature of obesity increasingly requires a comprehensive approach that includes the role of environmental factors. For understanding contextual determinants, the resources provided by technological advances could become a key factor in obesogenic environment research. This study aims to identify different sources of non-traditional data and their applications, considering the domains of obesogenic environments: physical, sociocultural, political and economic. METHODS: We conducted a systematic search in PubMed, Scopus and LILACS databases by two independent groups of reviewers, from September to December 2021. We included those studies oriented to adult obesity research using non-traditional data sources, published in the last 5 years in English, Spanish or Portuguese. The overall reporting followed the PRISMA guidelines. RESULTS: The initial search yielded 1583 articles, 94 articles were kept for full-text screening, and 53 studies met the eligibility criteria and were included. We extracted information about countries of origin, study design, observation units, obesity-related outcomes, environment variables, and non-traditional data sources used. Our results revealed that most of the studies originated from high-income countries (86.54%) and used geospatial data within a GIS (76.67%), social networks (16.67%), and digital devices (11.66%) as data sources. Geospatial data were the most utilised data source and mainly contributed to the study of the physical domains of obesogenic environments, followed by social networks providing data to the analysis of the sociocultural domain. A gap in the literature exploring the political domain of environments was also evident. CONCLUSION: The disparities between countries are noticeable. Geospatial and social network data sources contributed to studying the physical and sociocultural environments, which could be a valuable complement to those traditionally used in obesity research. We propose the use of information available on the Internet, addressed by artificial intelligence-based tools, to increase the knowledge on political and economic dimensions of the obesogenic environment.

Epidemia de obesidad: evidencia actual, desafíos y direcciones futuras / Obesity epidemic: current evidence, challenges and future directions

Resumen La epidemia de obesidad es un fenómeno amplia mente estudiado en las últimas décadas, pero aun así incompletamente comprendido, cuyo control se encuen tra lejos del nivel deseable si consideramos las cifras crecientes de prevalencia observadas a nivel mundial. El presente trabajo realiza una revisión narrativa con el propósito de aportar evidencia actualizada sobre la epidemia de la obesidad en el mundo, y en particular en la región latinoamericana y Argentina, identificando además los principales desafíos y direcciones futuras para el abordaje de esta problemática de salud pública. Se describe primeramente la carga actual y tendencias crecientes de la prevalencia de obesidad, general y por grupos poblacionales, y su posible relación con aspec tos genéticos y epigenéticos. Se resumen también las consecuencias socioeconómicas directas e indirectas de esta epidemia, y las estrategias e iniciativas recientes orientadas a la prevención de la obesidad, con especial atención en aquellas reportadas como las más eficientes en el contexto latinoamericano. En función de la revisión realizada, se identifican como desafíos pendientes en esa región, el abordaje integrado de la doble carga de malnutrición así como el creciente sobrepeso infantil; se apuntan también algunos enfoques emergentes, como el sindémico, potencialmente útiles para comprender y abordar esta compleja problemática en el contex to actual. Concluyendo, se destaca la importancia de implementar estrategias renovadas, más eficientes y basadas en evidencia, para controlar la creciente pre valencia de obesidad, lo cual impactaría también en la carga de las enfermedades crónicas relacionadas, y con ello, en la economía y bienestar de las sociedades latinoamericanas.

Abstract The obesity epidemic is a phenomenon that has been widely studied in recent decades but is still incompletely understood, and its control is far from the desirable level in view of the increasing prevalence figures observed worldwide. This paper conducts a narrative review with the aim of providing updated evidence on the global obesity epidemic, and particularly on the situation in Latin America and Argentina, identifying the main chal lenges and future directions for addressing this public health problem. It first describes the current burden and increasing trends in the prevalence of obesity, in the overall population and by population groups, and its pos sible association with genetic and epigenetic aspects. It also summarizes the direct and indirect socioeconomic consequences of this epidemic, as well as recent strate gies and initiatives focused on obesity prevention, with special attention to those reported as the most efficient in the Latin American context. This review identified some pending challenges in the region, the integrated approach to the double burden of malnutrition and the growing childhood overweight; and it points out some emerging approaches, such as the syndemic approach, as potentially useful to understand and address this complex problem in the current context. In conclusion, it highlights the importance of implementing renewed, more efficient and evidence-based strategies to control the growing prevalence of obesity, which would also impact on the burden of related chronic diseases, and thus on the economy and well-being of Latin American societies.

[Obesity epidemic: current evidence, challenges and future directions]. / Epidemia de obesidad: evidencia actual, desafíos y direcciones futuras.

The obesity epidemic is a phenomenon that has been widely studied in recent decades but is still incompletely understood, and its control is far from the desirable level in view of the increasing prevalence figures observed worldwide. This paper conducts a narrative review with the aim of providing updated evidence on the global obesity epidemic, and particularly on the situation in Latin America and Argentina, identifying the main challenges and future directions for addressing this public health problem. It first describes the current burden and increasing trends in the prevalence of obesity, in the overall population and by population groups, and its possible association with genetic and epigenetic aspects. It also summarizes the direct and indirect socioeconomic consequences of this epidemic, as well as recent strategies and initiatives focused on obesity prevention, with special attention to those reported as the most efficient in the Latin American context. This review identified some pending challenges in the region, the integrated approach to the double burden of malnutrition and the growing childhood overweight; and it points out some emerging approaches, such as the syndemic approach, as potentially useful to understand and address this complex problem in the current context. In conclusion, it highlights the importance of implementing renewed, more efficient and evidence-based strategies to control the growing prevalence of obesity, which would also impact on the burden of related chronic diseases, and thus on the economy and well-being of Latin American societies.

La epidemia de obesidad es un fenómeno ampliamente estudiado en las últimas décadas, pero aun así incompletamente comprendido, cuyo control se encuentra lejos del nivel deseable si consideramos las cifras crecientes de prevalencia observadas a nivel mundial. El presente trabajo realiza una revisión narrativa con el propósito de aportar evidencia actualizada sobre la epidemia de la obesidad en el mundo, y en particular en la región latinoamericana y Argentina, identificando además los principales desafíos y direcciones futuras para el abordaje de esta problemática de salud pública. Se describe primeramente la carga actual y tendencias crecientes de la prevalencia de obesidad, general y por grupos poblacionales, y su posible relación con aspectos genéticos y epigenéticos. Se resumen también las consecuencias socioeconómicas directas e indirectas de esta epidemia, y las estrategias e iniciativas recientes orientadas a la prevención de la obesidad, con especial atención en aquellas reportadas como las más eficientes en el contexto latinoamericano. En función de la revisión realizada, se identifican como desafíos pendientes en esa región, el abordaje integrado de la doble carga de malnutrición así como el creciente sobrepeso infantil; se apuntan también algunos enfoques emergentes, como el sindémico, potencialmente útiles para comprender y abordar esta compleja problemática en el contexto actual. Concluyendo, se destaca la importancia de implementar estrategias renovadas, más eficientes y basadas en evidencia, para controlar la creciente prevalencia de obesidad, lo cual impactaría también en la carga de las enfermedades crónicas relacionadas, y con ello, en la economía y bienestar de las sociedades latinoamericanas.

Adeno-associated virus type 2 in US children with acute severe hepatitis.

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

Nanopore adaptive sampling for targeted mitochondrial genome sequencing and bloodmeal identification in hematophagous insects.

BACKGROUND: Blood-feeding insects are important vectors for an array of zoonotic pathogens. While previous efforts toward generating molecular resources have largely focused on major vectors of global medical and veterinary importance, molecular data across a large number of hematophagous insect taxa remain limited. Advancements in long-read sequencing technologies and associated bioinformatic pipelines provide new opportunities for targeted sequencing of insect mitochondrial (mt) genomes. For engorged hematophagous insects, such technologies can be leveraged for both insect mitogenome genome assembly and identification of vertebrate blood-meal sources. METHODS: We used nanopore adaptive sampling (NAS) to sequence genomic DNA from four species of field-collected, blood-engorged mosquitoes (Aedes and Culex spp.) and one deer fly (Chrysops sp.). NAS was used for bioinformatical enrichment of mtDNA reads of hematophagous insects and potential vertebrate blood-meal hosts using publically available mt genomes as references. We also performed an experimental control to compare results of traditional non-NAS nanopore sequencing to the mt genome enrichment by the NAS method. RESULTS: Complete mitogenomes were assembled and annotated for all five species sequenced with NAS: Aedes trivittatus, Aedes vexans, Culex restuans, Culex territans and the deer fly, Chrysops niger. In comparison to data generated during our non-NAS control experiment, NAS yielded a substantially higher proportion of reference-mapped mtDNA reads, greatly streamlining downstream mitogenome assembly and annotation. The NAS-assembled mitogenomes ranged in length from 15,582 to 16,045 bp, contained between 78.1% and 79.0% A + T content and shared the anticipated arrangement of 13 protein-coding genes, two ribosomal RNAs, and 22 transfer RNAs. Maximum likelihood phylogenies were generated to further characterize each insect species. Additionally, vertebrate blood-meal analysis was successful in three samples sequenced, with mtDNA-based phylogenetic analyses revealing that blood-meal sources for Chrysops niger, Culex restuans and Aedes trivittatus were human, house sparrow (Passer domesticus) and eastern cottontail rabbit (Sylvilagus floridanus), respectively. CONCLUSIONS: Our findings show that NAS has dual utility to simultaneously molecularly identify hematophagous insects and their blood-meal hosts. Moreover, our data indicate NAS can facilitate a wide array of mitogenomic systematic studies through novel 'phylogenetic capture' methods. We conclude that the NAS approach has great potential for broadly improving genomic resources used to identify blood-feeding insects, answer phylogenetic questions and elucidate complex pathways for the transmission of vector-borne pathogens.

Potential Novel N-Glycosylation Patterns Associated with the Emergence of New Genetic Variants of PRRSV-2 in the U.S.

Glycosylation of proteins is a post-translational process where oligosaccharides are attached to proteins, potentially altering their folding, epitope availability, and immune recognition. In Porcine reproductive and respiratory syndrome virus-type 2 (PRRSV-2), positive selection pressure acts on amino acid sites potentially associated with immune escape through glycan shielding. Here, we describe the patterns of potential N-glycosylation sites over time and across different phylogenetic lineages of PRRSV-2 to better understand how these may contribute to patterns of coexistence and emergence of different lineages. We screened 19,179 PRRSV GP5 sequences (2004−2021) in silico for potential N-glycosylated sites. The emergence of novel combinations of N-glycosylated sites coincided with past PRRSV epidemics in the U.S. For lineage L1A, glycosylation at residues 32, 33, 44, 51, and 57 first appeared in 2012, but represented >62% of all L1A sequences by 2015, coinciding with the emergence of the L1A 1-7-4 strain that increased in prevalence from 8 to 86% of all L1A sequences from 2012 to 2015. The L1C 1-4-4 strain that emerged in 2020 also had a distinct N-glycosylation pattern (residues 32, 33, 44, and 51). From 2020 to 2021, this pattern was responsible for 44−47% of the L1C sequences, contrasting to <5% in years prior. Our findings support the hypothesis that antigenic evolution contributes to the sequential dominance of different PRRSV strains and that N-glycosylation patterns may partially account for antigenic differences amongst strains. Further studies on glycosylation and its effect on PRRSV GP5 folding are needed to further understand how glycosylation patterns shape PRRSV occurrence.

Primary and Secondary Attack Rates by Vaccination Status after a SARS-CoV-2 B.1.617.2 (Delta) Variant Outbreak at a Youth Summer Camp-Texas, June 2021.

Children are capable of initiating COVID-19 transmission into households, but many questions remain about the impact of vaccination on transmission. Data from a COVID-19 Delta variant outbreak at an overnight camp in Texas during June 23-27, 2021, were analyzed. The camp had 451 attendees, including 364 youths aged  < 18 years and 87 adults. Detailed interviews were conducted with 92 (20.4%) of consenting attendees and 117 household members of interviewed attendees with COVID-19. Among 450 attendees with known case status, the attack rate was 41%, including 42% among youths; attack rates were lower among vaccinated (13%) than among unvaccinated youths (48%). The secondary attack rate was 51% among 115 household contacts of 55 interviewed index patients. Secondary infections occurred in 67% of unvaccinated household members and 33% of fully or partially vaccinated household members. Analyses suggested that household member vaccination and camp attendee masking at home protected against household transmission.

Association Between Rotavirus Vaccination and Antibiotic Prescribing Among Commercially Insured US Children, 2007-2018.

Background: Vaccines may play a role in controlling the spread of antibiotic resistance. However, it is unknown if rotavirus vaccination affects antibiotic use in the United States (US). Methods: Using data from the IBM MarketScan Commercial Database, we conducted a retrospective cohort of US children born between 2007 and 2018 who were continuously enrolled for the first 8 months of life (N = 2 136 136). We followed children through 5 years of age and compared children who completed a full rotavirus vaccination series by 8 months of age to children who had not received any doses of rotavirus vaccination. We evaluated antibiotic prescriptions associated with an acute gastroenteritis (AGE) diagnosis and defined the switching of antibiotics as the prescription of a second, different antibiotic within 28 days. Using a stratified Kaplan-Meier approach, we estimated the cumulative incidence for each study group, adjusted for receipt of pneumococcal conjugate vaccine, provider type, and urban/rural status. Results: Overall, 0.8% (n = 17 318) of participants received an antibiotic prescription following an AGE diagnosis. The 5-year adjusted relative cumulative incidence of antibiotic prescription following an AGE diagnosis was 0.793 (95% confidence interval [CI], .761-.827) among children with complete rotavirus vaccination compared to children without rotavirus vaccination. Additionally, children with complete vaccination were less likely to switch antibiotics (0.808 [95% CI, .743-.887]). Rotavirus vaccination has averted an estimated 67 045 (95% CI, 53 729-80 664) antibiotic prescriptions nationally among children born between 2007 and 2018. Conclusions: These results demonstrate that rotavirus vaccines reduce antibiotic prescribing for AGE, which could help reduce the growth of antibiotic resistance.

A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

Epidemiology beyond its limits.

In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged <10 Years - United States, October 2021-June 2022.

On April 21, 2022, CDC issued a health advisory† encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.§ A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.¶ Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children - United States, 2017-2022.

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases† of hepatitis of unknown etiology to public health authorities. In the United States and Europe, many of these patients have also received positive adenovirus test results (1,3). Typed specimens have indicated adenovirus type 41, which typically causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus is not a recognized cause of hepatitis in healthy children (4). Because neither acute hepatitis of unknown etiology nor adenovirus type 41 is reportable in the United States, it is unclear whether either has recently increased above historical levels. Data from four sources were analyzed to assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in the United States. Because of potential changes in health care-seeking behavior during 2020-2021, data from October 2021-March 2022 were compared with a pre-COVID-19 pandemic baseline. These data do not suggest an increase in pediatric hepatitis or adenovirus types 40/41 above baseline levels. Pediatric hepatitis is rare, and the relatively low weekly and monthly counts of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will help contextualize reported cases of acute hepatitis of unknown etiology in U.S. children.

Acute Hepatitis and Adenovirus Infection Among Children - Alabama, October 2021-February 2022.

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.

SARS-CoV-2 B.1.1.529 (Omicron) Variant Transmission Within Households - Four U.S. Jurisdictions, November 2021-February 2022.

The B.1.1.529 (Omicron) variant, first detected in November 2021, was responsible for a surge in U.S. infections with SARS-CoV-2, the virus that causes COVID-19, during December 2021-January 2022 (1). To investigate the effectiveness of prevention strategies in household settings, CDC partnered with four U.S. jurisdictions to describe Omicron household transmission during November 2021-February 2022. Persons with sequence-confirmed Omicron infection and their household contacts were interviewed. Omicron transmission occurred in 124 (67.8%) of 183 households. Among 431 household contacts, 227 were classified as having a case of COVID-19 (attack rate [AR] = 52.7%).† The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively. The AR was lower among household contacts of index patients who isolated (41.2%, 99 of 240) compared with those of index patients who did not isolate (67.5%, 112 of 166) (p-value <0.01). Similarly, the AR was lower among household contacts of index patients who ever wore a mask at home during their potentially infectious period (39.5%, 88 of 223) compared with those of index patients who never wore a mask at home (68.9%, 124 of 180) (p-value <0.01). Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are critical to reducing Omicron transmission in household settings.

Association of enteropathogen detection with diarrhoea by age and high versus low child mortality settings: a systematic review and meta-analysis.

BACKGROUND: The odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting. METHODS: We did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea. FINDINGS: 1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I2) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2-0·6) for Giardia lamblia to 54·1 (95% CI 7·4-393·5) for Vibrio cholerae. INTERPRETATION: Incorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates. FUNDING: WHO, Bill & Melinda Gates Foundation, and National Institutes of Health.