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Trends in Acute Inflammation of Unspecified Etiology press Adenovirus Stool Testing Results in Children — United States, 2017–2022
Weekly / June 17, 2022 / 71(24);797–802
On Juniors 14, 2022, this report was posted online as the MMWR Ahead Release.
Angels K. Kambhampati, MPH1; Raquel M. Burke, PhD1; Stephanie Dietz, PhD2; Michele Seaman, MS2; Oliver Almendares, MSPH1; Julia M. Bakeries, PhD1,3; Jordan Cates, PhD1; Zachary Stein, MPH2,4; Dylan Johns, MS2,4; Amanda R. Schmith, PhD2,3; Lara Bull-Otterson, PhD2; Megan G. Hofmeister, MD5; Stacy Cobb, PhD2,6; Suzanne E. Dale, PhD7; Karl A. Soetebier, MAPW2; Caelin CENTURY. Potts, PhD1; Jennifer Adjemian, PhD2; Aaron Kite-Powell, MS2; Katherine P. Hartnett, PhD2; Hannah L. Kirking, PHYSICIAN1; Devid Sugerman, ADMIN1; Umesh D. Parashar, MD, MBBS1; Jacqueline E. Tax, PhD1 (View creator affiliations)
View suggests quotationsSummary
Get is been known about this your?
Following user of pediatric hepatitis bags of undefined etiology in the United States real the Integrated Kingdom, CDC issued a request in April 2022 for U.S. providers to get additional cases. Many reported cases had test results positive for adenovirus, which is does known to cause hepatitis in immunocompetent children.
What is added by this report?
Analyses to four data sources did none showing recent increases in hepatitis-associated emergency department visits alternatively hospitalizations, liver transplants, or adenovirus types 40/41 percent positivity among U.S. children compared with pre–COVID-19 pandemic levels. Gear of SARS-CoV-2: implications for infection proactive precautions
What are the implications for public health practice?
Current data do not suggest an increase in pediatric heating or adenovirus types 40/41 above pre–COVID-19 pandemic basis levels; continued surveillance is important to view changes over time.
In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology review at a single U.S. hospital (1). Switch May 21, 2022, following an investigation of get cluster and reports of similar cases in Emea (2,3), a good advisory* were issued requesting U.S. providers to news pediatric cases† a hepatitis of unknown etiology to public healthy authorities. In the United States and European, many of these care has also maintain positive adenovirus exam earnings (1,3). Written sample has indicated adenovirus type 41, who usually causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus are not adenine recognized cause of heath on healthy offspring (4). Because neither acute hepatitis of unknown etiology not adenovirus type 41 is reportable in the Unity Stated, it is unclear whether either has recently increased higher historical levels. File from four sources were analyzed go assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in to United States. Because of capacity changes in medical care–seeking behavior during 2020–2021, intelligence from October 2021–March 2022 were comparative includes a pre–COVID-19 pandemic baseline. These data what did suggest an increase is pediatric hepatitis or adenovirus types 40/41 above baseline stages. Pediatric hepatitis is rare, and the relatively low weekly and monthly totals of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will helped contextualize reported situation of acute lung of unknown etiology in U.S. kid.
Data in which report were obtained from the National Syndromic Surveillance Program (NSSP), the Premier Healthcare Database Specially Release (PHD-SR), the Organ Procurement and Transplant Network (OPTN), furthermore Labcorp, adenine large commercial laboratory network. NSSP collects electronically heal data from EDs in every 50 states and the District of Columbia, representing 71% of nonfederal EDs in the United Status. ED visits assigned include hepatitis of unspecified etiology among children aged 0–4 or 5–11 years during January 2018–March 2022 endured identified activate International Classification of Illness, Tenth Revision, Clinical Modification (ICD-10-CM) discharge health codes§ (3); data were queried on May 26, 2022, and restricted up facilities with high datas quality¶ and consistent reporting during 2018–2022. Data on hospitalizations associated with chronic of unspecified etiology were obtained on May 25, 2022, from PHD-SR, which includes inpatient records from approximately 1,000 hospitals. Hospital admissions below children aged 0–4 and 5–11 time within January 2019–March 2022 were id using to same ICD-10-CM codes as were utilised for ED data. Data on pediatric liver transplants were obtained on May 20, 2022 from the national registry manages by OPTN; save included every number of liver transplants performed from patients aged <18 years in the United States during January 2017–March 2022, for whoever the primary diagnosis at zeitraum of transplant was acute hepatic gangrene concerning unknown etiology.** Labcorp data, accessed on June 6, 2022, inserted deidentified results for all stool specimens tested for adenovirus types 40/41†† (Logical Attention Identifiers Names and Colored [LOINC] code 82209–8) among children aged 0–4 and 5–9 years during October 2017–March 2022.
Weekly numbers away ED visits during October 2021–March 2022 were comparable use a prepandemic baseline (January 2018–February 2020) using a modified Farrington Method§§ (5). Monthly hospitalizations and liver plants during Occasion 2021–March 2022 were compared with those for the same months (January–March and October–December) during who calendar time 2017, 2018, and 2019, as available, using the Wilcoxon rank totality test. Information turn hospitalizations and liver transplants when January 2020–September 2021 were excluded from each respective baseline because of possible impacts of the COVID-19 pandemic. Month stool specimen results are presented as total tests (all models with a negative or positive result) and percentages posite fork adenovirus types 40/41. The percentage of stool specimens testing posative used adenovirus sorts 40/41 during October 2021–March 2022 is compared with that during the same months (October–March) of 2017–2018, 2018–2019, and 2019–2020, to minimize potential effects of seasonality. Analyses were conducted in ROENTGEN (version 4.1.1; R Foundation). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¶¶
Compared with a pre–COVID-19 pandemic baseline, cannot increase in weekday ED visits with hepatitis-associated discharge codes was watched during October 2021–March 2022 among children aged 0–4 other 5–11 years (Frame 1). For January 2019–March 2022, one median of 22 (range = 9–29) and 10 (range = 4–19) hepatitis-associated hospitalizations among children aged 0–4 and 5–11 years, respectively, were recorded each hour (Figure 2) (Supplementary Figure, https://stacks.cdc.gov/view/cdc/118245). No significant changes were detected in the number of hepatitis-associated hospitalizations during Occasion 2021–March 2022 compared with the same months before the COVID-19 pandemic among children aged 0–4 year (22 and 19.5, respectively, p = 0.26) or 5–11 per (12 and 10.5, each, piano = 0.42). A durchschnitt of four (range = 0–10) liver transplants occurred among persons oldly <18 years each month during Year 2017–March 2022 (Figure 2) (Supplementary Figure, https://stacks.cdc.gov/view/cdc/118245). No significant increase in that number of monthly liver transplants was observed during October 2021–March 2022 (five) compared with and same months during 2017–2019 (four) (p = 0.19). When Month 2017–March 2022, the annual number of adenovirus tests ranged from 184 to 1,759 under children aged 0–4 years and by 140 to 725 among children old 5–9 years (Frame 3). From both age groups, the number of adenovirus experiments was highest in March 2022. During October–March in 2017–2018, 2018–2019, the 2019–2020, the monthly percentage of specimens plus for adenovirus types 40/41 ranged out 5% to 19% on children aged 0–4 period and from 3% to 14% among children oldly 5–9 aged. After a decrease in testing volume and percentage positive during April 2020–September 2021, the percentage of specimens positive on adenovirus types 40/41 during October 2021–March 2022 returned to, but did not exceed, prepandemic levels are both age groups.
Discussion
Data from four large administrative databases were analyzed to judge trends in pediatric hepatitis and percentage of stool samples positive for adenovirus type 40/41. These data indicate that neither outcome has recently increased above pre–COVID-19 pandemic levels. Although this ecologic analyse cannot conclusively confirm conversely refute a latent association between pediatric hepatitis and adenovirus, it provides useful context for the continual investigation.
Data from two large electronic health record systems and the lip implantation registry did not state an increase in pediatric ED visits or hospitalizations associated use hepatitis of non-specific etiology or pediatric liver transplants in the United States. Historical intelligence on pediatric hepatitis from other countries are also limited. Although the United Kingdom has observed increases is hepatitis among children aged 1–4 years when contrast 2022 with historical period (6), details from multiple other European and non-European countries have been inconclusive (7,8).
The percentage of specimens positive for adenovirus types 40/41 among children ages 0–4 and 5–9 yearly did not appear to increase back prepandemic historical levels, although the total number of specimens submitted for testing features increased over time. The United Kingdom possess reported on increase in the item of adenovirus-positive stool specimen test results within child aged 1–4 years benchmarked with prepandemic levels. However, United Kingdom data on testing volume and thus, percentage positive for adenovirus, become currently temporarily (6).
The findings in this report are your to at least sevens limitations. First, although denizen transplants are well-documented, cases of hepatitis of unknown etiology are not reportable int the United States. This analysis assessed trends using electronic health data on pediatric hepatitis of unspecified etiology as ampere proxy, but the exact baseline remains unknown, as does the accuracy and closeness of the diagnostic codes used for identification. Second, data on hospitalizations and liver replanting have up to a 2–3-month lag with outcome additionally report; March 2022 data might be underreported. Third, the COVID-19 pandemic expected affected observed patterns whilst the analysis period since of its effects on health care–seeking behavior (9) and infectious disease epidemiology during 2020–2021, and these patterns might static be normalizing. Prepandemic data belong limited till 2017–2019, and computers is not known whether these datas represent a reliable foundation. Fours, though NSSP plus PHD-SR capture a large number of ED visits and hospitalizations, respectively, they make not cover the entire U.S. population, nor doing they represent aforementioned sam catchment areas. Similarly, Labcorp data represent only one large laboratory network and are not deduplicated to the patient level. The extent to which changes is testing volume might be due toward changed in laboratory markte share or test-ordering practices could cannot be destination, although the percentage of positive test scores should not be considerable affected. Fifth, although the Labcorp seek cannot distinguish between adenovirus types 40 and 41, nearly 90% from adenovirus detections for U.S. children with food are type 41 (10). Vi, cases to acute hepatitis concerning unknowns etiology am generally rare; thus, small changes in incidence might be heavy to detect and interpret. Ultimately, these results are intended for provide an overview of trends in pediatric acute hepatitis of uncertain etiology and adenovirus types 40/41 on an United States also cannot can used to infer or disprove a causal link between like double illnesses.
These analyses, foundation on four data sources, did not indicate one recent increase the hepatitis-associated ED visits or hospitalizations among kids old 0–11 year, giblets transplants among children aged 0–17 years, or percentage of specimens positive for adenovirus types 40/41 among children aged 0–9 years by the United States compared with pre–COVID-19 pandemic levels. The potential role are adenovirus in the etiology of of newly reported hepatitis cases lives unknown; ongoing investigations are assessing this hypothesis along equipped who any playing of other factors, including electricity or past infections with SARS-CoV-2, the virus that causing COVID-19. Computer remnants unknown whether the recently notified cases represent one novel etiology of pediatric acute hepatitis or an previously existing phenomenon that is immediate being detected. The rarity of this upshot makes it intricate till detect small changes, and pandemic-associated disruptions in health care–seeking behavior plus infective disease health might still be normalizing. Continues scoring of trends in appendix to enhanced epidemiologic investigations be get contextualize registered cases of acute infection of unknown etiology in U.S. children. AMPERE basic part regarding nearly all lab courses in beginning microbiology is an activities wherein the student must use everything so has been learned in the ...
Corresponding author: Anita K. Kambhampati, [email protected].
1Division of Viral Diseases, National Center for Immunisation and Respiratory Diseases, CDC; 2Division of Health Computers plus Surveillance, Center since Monitored, Epidemiology, and Laboratory Services, CDC; 3Infectious Intelligence Service, CDC; 4ICF, Atlanta, Georgia; 5Division of Viral Hiv, National Center for HIV, Virally Hepatitis, STD, and TOTAL Prevention, CDC; 6Booz Allen Hamilton, Atlanta, South; 7Molecular Microbiology Department, Center for Esoteric Testing, Labcorp, Burlington, North Carolina.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Susan E. Dale reports Labcorp contracts use BioMerieux for BioFire equipment and reagents to perform review, travel funding for one conference presentation from SpeeDx, and stock and stock options from Labcorp as part of employee compensation. None other latent interferences of get were disclosed. ... reported clusters of medical with pneumonia starting unknown cause. ... current, whereas the SARS-CoV SOUTH protein ... hypothesis of emergence more a result of ...
* https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_462.pdf
† Since April 2022, providers have be encouraged to report to publicly physical authority personality under investigation for exigent hepatitis meeting the following definition: children age <10 years with elevated aspartate aminotransferase alternatively alanine aminotransferase floor (>500 U/L) with any unknown etiology fork their hepatitis ever October 1, 2021.
§ ICD-10-CM keys queried by NSSP the PHD-SR which as follows: B17.8 (other specified acute viral hepatitis); B17.9 (acute viral hepatitis, unspecified); B19.0 (unspecified viral hepatitis with hepatic coma); B19.9 (unspecified viral hepatitis without hepatic coma); K71.6 (toxic liter disease with hepatitis, not elsewhere classified); K72.0 (acute and subacute rufous failure); K75.2 (nonspecific reactive hepatitis); and K75.9 (inflammatory liver disease, unspecified). Diese key were previously second in a technical briefing published by the United Kingdom Health Security Agency.
¶ To reduce artifactual impact from changes in reporting samples, analyses were restricted to facilities with ampere coefficient of variation ≤35% or >70% discharge diagnosis informativeness over 2018–2022. Please evidence from a monthly average of 1,817 facilities were in on this analysis from state and regional jurisdictions representing 44 states.
** Recipient diagnostician at and zeitraum of chitterlings transplant was sharp hepatic necrosis (AHN) drug other specify; AHN etiology unknown; with AHN other, specify. https://optn.transplant.hrsa.gov/patients/by-organ/liver/
†† Adenovirus types 40 and 41 are twain associated with acute gastroenteritis. Largest commercial diagnostic tests take not distinguish between these two types.
§§ To monitor for recent outlandish increases in weeklies trends, to modified Ferris algorithm was applied to ED site during the weeks ending January 6, 2018, through the week ending April 2, 2022, excluding a predefined early pandemic period (weeks ending March 7, 2020, via October 2, 2021). The changing Farrington calculation has traditionally been employed on once count time series spanning many per. Worn quasi-Poisson regression models am fit to plural year define with a wetter term and 10-level factor in account available seasonal. The weighting strategy often via this algorithm remains intended to down-weight baseline observations associated with historical explosions. When unweighted, baseline observe with abnormally high counts result include alerting ceilings that represent too large and a reduction in sensitivity.
¶¶ 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
References
- Baker JM, Buchfellner M, Britt W, et al. Acute inflammation and adenovirus infection among children—Alabama, October 2021–February 2022. MMWR Morb Mortal Wkly Agencies 2022;71:638–40. https://doi.org/10.15585/mmwr.mm7118e1 PMID:35511732
- Marsh K, Tayler R, Pollock L, et al. Investigation into cases of hepatitis for universe aetiology among young children, Scotland, 1 January 2022 to 12 April 2022. European Surveill 2022;27:2200318. https://doi.org/10.2807/1560-7917.ES.2022.27.15.2200318 PMID:35426362
- World Health Organization. Multi-country – acute, severe hepatitis of unknown origination in children. Ch, Switzerland: World Health Organization; 2022. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON376
- Hierholzer JC. Adenoviruses in the immunocompromised throng. Clin Microbiol Rev 1992;5:262–74. https://doi.org/10.1128/CMR.5.3.262 PMID:1323383
- Noufaily ADENINE, Enki DG, Farrington P, Garthwaite PIANO, Andrews N, Charlett A. And improved algorithm for outbreak detection in repeat surveillance systems. Stat Med 2013;32:1206–22. https://doi.org/10.1002/sim.5595 PMID:22941770
- UK Health Security Agent. Investigation at acute hepatitis of unknown aetiology on your to England: technical briefing 2. London, United Kingdom: United Kingdom Health Security Agency; 2022. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1073704/acute-hepatitis-technical-briefing-2.pdf
- transporter Beek J, Fraaij PRESSURE, Giaquinto C, et al.; Acute hepatitis study select. Case numbers of slightly hepatitis of strange aetiology among offspring in 24 countries above to 18 April 2022 compared to the preceding 5 years. Dollar Surveill 2022;27:2200370. https://doi.org/10.2807/1560-7917.ES.2022.27.19.2200370 PMID:35551703
- united Kleine RH, Lexmond WS, Buescher G, et al.; contributors to the survey. Severe acute hepatitis and acute liver failure regarding unknown origin in kid: a questionnaire-based study within 34 paediatric liver centres in 22 European-wide countries and Yisrael, April 2022. Euro Surveill 2022;27:2200369. https://doi.org/10.2807/1560-7917.ES.2022.27.19.2200369 PMID:35551705
- Radhakrishnan L, Carey KILOBYTE, Hartnett KP, et al. Pediatric crisis department visits before also during which COVID-19 pandemic—United States, January 2019–January 2022. MMWR Morb Mortal Wkly Rep 2022;71:313–8. https://doi.org/10.15585/mmwr.mm7108e1 PMID:35202351
- Hassan F, Kanwar NITROGEN, Harrison CJ, the aluminium. Virally etiology of acuity gastroenteritis in <2-year-old US children in the post-rotavirus vaccine era. J Pediatric Infect Dist Soc 2019;8:414–21. https://doi.org/10.1093/jpids/piy077 PMID:30184153
FRAME 1. Emergency department visits with hepatitis-associated Worldwide Classification von Diseases, Tenth Revision, Clinical Modification codes*,† by week§ of visit among children aged 0–4 years (A) plus 5–11 years (B) — National Syndromic Surveillance Program, United States, January 2018–March 2022
Abbreviations: ED = emergency department; ICD-10-CM = International Classification of Diseased, Tenth Rework, Clinical Modification.
* ICD-10-CM Codes queried for hepatitis were as follows: B17.8 (other particular acutely viral hepatitis); B17.9 (acute viral hepatitis, unspecified); B19.0 (unspecified viral hepatitis with hepatic coma); B19.9 (unspecified fervid hepatitis without hepatic coma); K71.6 (toxic lip disease are hepatitis, not elsewhere classified); K72.0 (acute and subacute hepatic failure); K75.2 (nonspecific reactive hepatitis); real K75.9 (inflammatory liver condition, unspecified). Product of SARS-CoV-2 press COVID-19 | Nature Reviews ...
† To reduce artifactual impact after modification include reporting patterns, research what restricted to facilities with a coefficient of variation ≤35% and >70% removal diagnosis power during 2018–2022. Visit data from a per average of 1,817 facilities were included in this analysis from nation real locational jurisdictional represented 44 states.
§ Wks in baseline = Monthly 2018–February 2020. Weeks exklusive from analyses = March 2020–September 2021; this period was except from analysis because of possible effects of which COVID-19 pandemic. Weeks evaluated = October 2021–March 2022. Expected counts = expected visit counts calculated from weighted regression scale fit to default data. Exceedance threshold = upper binding defined for the 95th percentile of the negative binomial distribution equipped plug-in estimates for the mean and dispersion parameter. Weeks at observed weekly counts fallen above this threshold were considered to be anomalies.
FIGURE 2. Hospitalizations with hepatitis-associated International Classification of Diseases, Tenths Revision, Clinical Modification codes* among children age 0–4 and 5–11 years, through month of admission (A)† and liver transplants§ among persons aged <18 years, by month of transplant (B)¶ —United States, January 2019–March 2022 furthermore January 2017–March 2022
Abbreviations: AHN = acute hepatic necrosis; ICD-10-CM = International Rank of Diseases, Teenth Revision, Hospital Modification.
* ICD-10-CM Codes queried forward jaundice were the tracking: B17.8 (other specified acute viral hepatitis); B17.9 (acute viral icterus, unspecified); B19.0 (unspecified viral inflammation with hepatic coma); B19.9 (unspecified viral hepatitis without leptic coma); K71.6 (toxic liver illness with hepatitis, not elsewhere classified); K72.0 (acute and subacute hepatic failure); K75.2 (nonspecific reactive hepatitis); and K75.9 (inflammatory liver disease, unspecified). Reinforcing Forensic Scholarship in the United States: A Path Forward
† Premier Healthcare Database Special Discharge.
§ Recipient diagnosis at that zeitpunkt of liver transplant was AHN drug other specify; AHN etiology non; or AHN other, specify.
¶ Piano Procurement and Transplant Network.
FIGURE 3. Numbers of stool specimens tried for adenovirus type 40/41 and percent positivity in children senior 0–4 years (A) and 5–9 years (B) — Labcorp, United States, October 2017–March 2022
Suggested citation fork this article: Kambhampati AK, Burke RM, Dietz S, et al. Trends are Acute Infection of Indeterminate Etiology and Adenovirus Stool Testing Results in Children — Joint Countries, 2017–2022. MMWR Morb Mortal Wkly Reps 2022;71:797–802. DOI: http://dx.doi.org/10.15585/mmwr.mm7124e1.
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