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.

Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020-2021.

Existing acute febrile illness (AFI) surveillance systems can be leveraged to identify and characterize emerging pathogens, such as SARS-CoV-2, which causes COVID-19. The US Centers for Disease Control and Prevention collaborated with ministries of health and implementing partners in Belize, Ethiopia, Kenya, Liberia, and Peru to adapt AFI surveillance systems to generate COVID-19 response information. Staff at sentinel sites collected epidemiologic data from persons meeting AFI criteria and specimens for SARS-CoV-2 testing. A total of 5,501 patients with AFI were enrolled during March 2020-October 2021; >69% underwent SARS-CoV-2 testing. Percentage positivity for SARS-CoV-2 ranged from 4% (87/2,151, Kenya) to 19% (22/115, Ethiopia). We show SARS-CoV-2 testing was successfully integrated into AFI surveillance in 5 low- to middle-income countries to detect COVID-19 within AFI care-seeking populations. AFI surveillance systems can be used to build capacity to detect and respond to both emerging and endemic infectious disease threats.

Rapid virtual training and field deployment for COVID-19 surveillance officers: experiences from Ethiopia

Rapid scale-up of surveillance activities is the key to successful coronavirus disease 2019 (COVID-19) pandemic prevention and mitigation. Ethiopia did not have a sufficient number of active surveillance officers for the public health COVID-19 response. Training of surveillance officers was needed urgently to fill the gap in the workforce needed. Subject-matter experts from the United States and Ethiopia developed applicable training modules including background on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contact investigation, and communications. The training modules were delivered live in real-time via web-based virtual presentation. Seventy-seven health surveillance officers were hired, trained, and deployed in two weeks to assist with surveillance activities in Ethiopia. Electronic capacity building is needed in order to improve Web-based training in resource-limited settings where internet access is limited or unreliable. Web-based synchronously delivered course was an effective platform for COVID-19 surveillance training. However, strengthening public and private information technology capacity, literacy, and internet availability will improve Web-based education platforms in resource-limited countries.

Seroprevalence and risk factors for SARS-CoV-2 Infection in selected urban areas in Ethiopia: a cross-sectional evaluation during July 2020.

BACKGROUND: Ethiopia reported the first case of COVID-19 on 13th March, 2020 with community transmission ensuing by mid-May. A national, population-based serosurvey against anti-SARS-CoV-2 IgG was conducted to measure the prevalence of prior COVID-19 infections and better approximate the burden across major towns in Ethiopia. METHODS: We conducted a cross-sectional, population-based serosurvey from June 24 to July 8, 2020 in 14 major urban areas. Two-stage cluster sampling was used to randomly select enumeration areas and households. All persons aged ≥15 years were enrolled. Serum samples were tested by Abbott™ ARCHITECT™ assay for SARS-CoV-2 IgG antibodies. National COVID-19 surveillance data on the median date of the serosurvey is analyzed for comparison. FINDINGS: Adjusted seroprevalence was 3.5% (95% CI: 3.2%-3.8%) after controlling for age, sex and test kit performance. Males (3.7%) and females (3.3%) were nearly equally infected, while middle-aged adults '40-65 years' had the highest (4.0%) prevalence. Gambella (7.5%), Dire Dawa (6.2%) and Jigjiga (6.1%) were the most affected towns. About 6.7% and 8.0% of seropositives had symptoms and chronic underlying illness, respectively. A surveillance system had identified 4,416 RT-PCR confirmed cases in Addis Ababa. INTERPRETATION: This serosurvey shows that a majority of urban Ethiopians remain uninfected with SARS-CoV-2. Most anti-SARS-CoV-2 IgG positive cases were asymptomatic with no underlying illness, keeping case detection to a minimum.

Rapid virtual training and field deployment for COVID-19 surveillance officers: experiences from Ethiopia.

Rapid scale-up of surveillance activities is the key to successful coronavirus disease 2019 (COVID-19) pandemic prevention and mitigation. Ethiopia did not have a sufficient number of active surveillance officers for the public health COVID-19 response. Training of surveillance officers was needed urgently to fill the gap in the workforce needed. Subject-matter experts from the United States and Ethiopia developed applicable training modules including background on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contact investigation, and communications. The training modules were delivered live in real-time via web-based virtual presentation. Seventy-seven health surveillance officers were hired, trained, and deployed in two weeks to assist with surveillance activities in Ethiopia. Electronic capacity building is needed in order to improve Web-based training in resource-limited settings where internet access is limited or unreliable. Web-based synchronously delivered course was an effective platform for COVID-19 surveillance training. However, strengthening public and private information technology capacity, literacy, and internet availability will improve Web-based education platforms in resource-limited countries.

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.