Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-16 (of 16 Records) |
Query Trace: Baker JM[original query] |
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Deaths associated with pediatric hepatitis of unknown etiology, United States, October 2021-June 2023
Almendares O , Baker JM , Sugerman DE , Parashar UD , Reagan-Steiner S , Kirking HL , Gastañaduy PA , Tate JE . Emerg Infect Dis 2024 30 (4) 644-53 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. |
Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022
Cates J , Baker JM , Almendares O , Balachandran N , McKeever ER , Kambhampati AK , Cubenas C , Vinjé J , Cannon JL , Chhabra P , Freeman B , Reagan-Steiner S , Bhatnagar J , Gastañaduy PA , Kirking HL , Sugerman D , Parashar UD , Tate JE . Lancet Child Adolesc Health 2023 7 (11) 773-785 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. |
Adeno-associated virus type 2 in US children with acute severe hepatitis.
Servellita V , Gonzalez AS , Lamson DM , Foresythe A , Huh HJ , Bazinet AL , Bergman NH , Bull RL , Garcia KY , Goodrich JS , Lovett SP , Parker K , Radune D , Hatada A , Pan CY , Rizzo K , Bertumen JB , Morales C , Oluniyi PE , Nguyen J , Tan J , Stryke D , Jaber R , Leslie MT , Lyons Z , Hedman HD , Parashar U , Sullivan M , Wroblewski K , Oberste MS , Tate JE , Baker JM , Sugerman D , Potts C , Lu X , Chhabra P , Pediatric Hepatitis of Unknown Etiology Working Group , Ingram LA , Shiau H , Britt W , Sanchez LHG , Ciric C , Rostad CA , Vinjé J , Kirking HL , Wadford DA , Raborn RT , St George K , Chiu CY . Nature 2023 As of August 2022, clusters of acute severe hepatitis of unknown etiology in children have been reported from 35 countries, including the United States(1,2). Previous studies have found human adenoviruses (HAdVs) in the blood from cases in Europe and the United States(3-7), although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment based sequencing, and agnostic metagenomic sequencing to analyze samples from 16 HAdV-positive cases from October 1, 2021 to May 22, 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus 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 etiology (P<0.001). In controls, HAdV-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 (EBV), human herpesvirus 6 (HHV-6), and/or enterovirus A71 (EV-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. |
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.
Baker JM , Shah MM , O'Hegarty M , Pomeroy M , Keiser P , Ren P , Weaver SC , Maknojia S , Machado RRG , Mitchell BM , McConnell A , Tate JE , Kirking HL . J Pediatric Infect Dis Soc 2022 11 (12) 550-556 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. |
A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.
GutierrezSanchez LH , Shiau H , Baker JM , Saaybi S , Buchfellner M , Britt W , Sanchez V , Potter JL , Ingram LA , Kelly D , Lu X , Ayers-Millsap S , Willeford WG , Rassaei N , Bhatnagar J , Bullock H , Reagan-Steiner S , Martin A , Rogers ME , Banc-Husu AM , Harpavat S , Leung DH , Moulton EA , Lamson DM , StGeorge K , Hall AJ , Parashar U , MacNeil A , Tate JE , Kirking HL . N Engl J Med 2022 387 (7) 620-630 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.). |
Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged <10 Years - United States, October 2021-June 2022.
Cates J , Baker JM , Almendares O , Kambhampati AK , Burke RM , Balachandran N , Burnett E , Potts CC , Reagan-Steiner S , Kirking HL , Sugerman D , Parashar UD , Tate JE . MMWR Morb Mortal Wkly Rep 2022 71 (26) 852-858 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.
Kambhampati AK , Burke RM , Dietz S , Sheppard M , Almendares O , Baker JM , Cates J , Stein Z , Johns D , Smith AR , Bull-Otterson L , Hofmeister MG , Cobb S , Dale SE , Soetebier KA , Potts CC , Adjemian J , Kite-Powell A , Hartnett KP , Kirking HL , Sugerman D , Parashar UD , Tate JE . MMWR Morb Mortal Wkly Rep 2022 71 (24) 797-802 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
Baker JM , Buchfellner M , Britt W , Sanchez V , Potter JL , Ingram LA , Shiau H , GutierrezSanchez LH , Saaybi S , Kelly D , Lu X , Vega EM , Ayers-Millsap S , Willeford WG , Rassaei N , Bullock H , Reagan-Steiner S , Martin A , Moulton EA , Lamson DM , StGeorge K , Parashar UD , Hall AJ , MacNeil A , Tate JE , Kirking HL . MMWR Morb Mortal Wkly Rep 2022 71 (18) 638-640 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.
Baker JM , Nakayama JY , O'Hegarty M , McGowan A , Teran RA , Bart SM , Mosack K , Roberts N , Campos B , Paegle A , McGee J , Herrera R , English K , Barrios C , Davis A , Roloff C , Sosa LE , Brockmeyer J , Page L , Bauer A , Weiner JJ , Khubbar M , Bhattacharyya S , Kirking HL , Tate JE . MMWR Morb Mortal Wkly Rep 2022 71 (9) 341-346 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. |
Risk Factors Associated With SARS-CoV-2 Seropositivity Among US Health Care Personnel.
Jacob JT , Baker JM , Fridkin SK , Lopman BA , Steinberg JP , Christenson RH , King B , Leekha S , O'Hara LM , Rock P , Schrank GM , Hayden MK , Hota B , Lin MY , Stein BD , Caturegli P , Milstone AM , Rock C , Voskertchian A , Reddy SC , Harris AD . JAMA Netw Open 2021 4 (3) e211283 IMPORTANCE: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. OBJECTIVE: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. EXPOSURES: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. MAIN OUTCOME AND MEASURES: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. RESULTS: Among 2 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP. |
Longer-term direct and indirect effects of infant rotavirus vaccination across all ages in the United States in 2000-2013: Analysis of a large hospital discharge data set
Baker JM , Tate JE , Steiner CA , Haber MJ , Parashar UD , Lopman BA . Clin Infect Dis 2019 68 (6) 976-983 BACKGROUND: Rotavirus disease rates dramatically declined among children <5 years of age since the rotavirus vaccine was introduced in 2006; population-level impacts remain to be fully elucidated. METHODS: Data from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras. RESULTS: Following vaccine introduction, a decrease in rotavirus hospitalizations occurred with a shift toward biennial patterns across all ages. The 0-4-year age group experienced the largest decrease in rotavirus hospitalizations (rate ratio, 0.14; 95% confidence interval, .09-.23). The 5-19-year and 20-59-year age groups experienced significant declines in rotavirus hospitalization rates overall; the even postvaccine calendar years were characterized by progressively lower rates, and the odd postvaccine years were associated with reductions in rates that diminished over time. Those aged >/=60 years experienced the smallest change in rotavirus hospitalization rates overall, with significant reductions in even postvaccine years compared with prevaccine years (rate ratio, 0.51; 95% confidence interval, .39-.66). CONCLUSIONS: Indirect impacts of infant rotavirus vaccination are apparent in the emergence of biennial patterns in rotavirus hospitalizations that extend to all age groups ineligible for vaccination. These observations are consistent with the notion that young children are of primary importance in disease transmission and that the initial postvaccine period of dramatic population-wide impacts will be followed by more complex incidence patterns across the age range in the long term. |
Post-vaccination serum anti-rotavirus immunoglobulin A as a correlate of protection against rotavirus gastroenteritis across settings
Baker JM , Tate JE , Leon J , Haber MJ , Pitzer VE , Lopman BA . J Infect Dis 2020 222 (2) 309-318 BACKGROUND: A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of post-vaccine serum anti-rotavirus immunoglobulin A (IgA) that serves as an individual-level immune correlate of protection against rotavirus gastroenteritis. METHODS: Individual-level data on 5,074 infants enrolled in nine GlaxoSmithKline Rotarix Phase II/III clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis. RESULTS: Seroconversion (IgA >/=20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis up to 1 year of age. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR=0.04, 95% confidence interval (CI)=0.01-0.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (0.46, 0.25-0.86). As the IgA threshold increased, the risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings. DISCUSSION: Post-vaccination anti-rotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis up to 1 year of age. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance. |
Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries
Baker JM , Tate JE , Leon J , Haber MJ , Lopman BA . PLoS Med 2019 16 (12) e1003005 BACKGROUND: Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course. Our study aimed to identify a range of individual-level characteristics, including concomitant receipt of OPV, that affect rotavirus vaccine immunogenicity in high- and low-child-mortality settings, controlling for individual- and country-level factors. Our central hypothesis was that OPV administered concomitantly with rotavirus vaccine reduced rotavirus vaccine immunogenicity. METHODS AND FINDINGS: Pooled, individual-level data from GlaxoSmithKline's Phase II and III clinical trials of the monovalent rotavirus vaccine (RV1), Rotarix, were analyzed, including 7,280 vaccinated infants (5-17 weeks of age at first vaccine dose) from 22 trials and 33 countries/territories (5 countries/territories with high, 13 with moderately low, and 15 with very low child mortality). Two standard markers for immune response were examined including antirotavirus immunoglobulin A (IgA) seroconversion (defined as the appearance of serum antirotavirus IgA antibodies in subjects initially seronegative) and serum antirotavirus IgA titer, both collected approximately 4-12 weeks after administration of the last rotavirus vaccine dose. Mixed-effect logistic regression and mixed-effect linear regression of log-transformed data were used to identify individual- and country-level predictors of seroconversion (dichotomous) and antibody titer (continuous), respectively. Infants in high-child-mortality settings had lower odds of seroconverting compared with infants in low-child-mortality settings (odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.43-0.53, p < 0.001). Similarly, among those who seroconverted, infants in high-child-mortality settings had lower IgA titers compared with infants in low-child-mortality settings (mean difference [beta] = 0.83, 95% CI 0.77-0.90, p < 0.001). Infants who received OPV concomitantly with both their first and their second doses of rotavirus vaccine had 0.63 times the odds of seroconverting (OR = 0.63, 95% CI 0.47-0.84, p = 0.002) compared with infants who received OPV but not concomitantly with either dose. In contrast, among infants who seroconverted, OPV concomitantly administered with both the first and second rotavirus vaccine doses was found to be positively associated with antirotavirus IgA titer (beta = 1.28, 95% CI 1.07-1.53, p = 0.009). Our findings may have some limitations in terms of generalizability to routine use of rotavirus vaccine because the analysis was limited to healthy infants receiving RV1 in clinical trial settings. CONCLUSIONS: Our findings suggest that OPV given concomitantly with RV1 was a substantial contributor to reduced antirotavirus IgA seroconversion, and this interference was apparent after the second vaccine dose of RV1, as with the original clinical trials that our reanalysis is based on. However, our findings do suggest that the forthcoming withdrawal of OPV from the infant immunization schedule globally has the potential to improve RV1 performance. |
Chronic immune barrier dysregulation among women with a history of violence victimization
Swaims-Kohlmeier A , Haddad LB , Li ZT , Brookmeyer KA , Baker JM , Widom CS , Lamousin JC , Chi KH , Chen CY , Kersh EN , Johnson JA , Herbst-Kralovetz MM , Hogben M , Ofotokun I , Kohlmeier JE . JCI Insight 2019 4 (10) We explored the association between violence victimization and increased risk for acquiring sexually transmitted infections (STIs) in women by measuring cellular immune barrier properties from the female reproductive tract. STI-negative participants reporting repeated prior victimization occurrences through the lifetime trauma and victimization history (LTVH) instrument were more likely to exhibit alterations in barrier homeostasis and the composition of critical immune mediators irrespective of demographic parameters or presence of bacterial vaginosis. By combining cellular data with mixed-effect linear modeling, we uncovered differences in local T cells, MHCII+ antigen-presenting cells, and epithelial cells indicative of altered trafficking behavior, increased immunosuppressive function, and decreased barrier integrity at sites of STI exposure that correlate most strongly with LTVH score. These data evidence a biological link between a history of violence victimization and risk of STI acquisition through immune dysregulation in the female reproductive tract. |
Effects of the rotavirus vaccine program across age groups in the United States: analysis of national claims data, 2001-2016
Baker JM , Dahl RM , Cubilo J , Parashar UD , Lopman BA . BMC Infect Dis 2019 19 (1) 186 BACKGROUND: The direct effectiveness of infant rotavirus vaccination implemented in 2006 in the United States has been evaluated extensively, however, understanding of population-level vaccine effectiveness (VE) is still incomplete. METHODS: We analyzed time series data on rotavirus gastroenteritis (RVGE) and all-cause acute gastroenteritis (AGE) hospitalization rates in the United States from the MarketScan(R) Research Databases for July 2001-June 2016. Individuals were grouped into ages 0-4, 5-9, 10-14, 15-24, 25-44, and 45-64 years. Negative binomial regression models were fitted to monthly RVGE and AGE data to estimate the direct, indirect, overall, and total VE. RESULTS: A total of 9211 RVGE and 726,528 AGE hospitalizations were analyzed. Children 0-4 years of age had the largest declines in RVGE hospitalizations with direct VE of 87% (95% CI: 83, 90%). Substantial indirect effects were observed across age groups and generally declined in each older group. Overall VE against RVGE hospitalizations for all ages combined was 69% (95% CI: 62, 76%). Total VE was highest among young children; a vaccinated child in the post-vaccine era has a 95% reduced risk of RVGE hospitalization compared to a child in the pre-vaccine era. We observed higher direct VE in odd post-vaccine years and an opposite pattern for indirect VE. CONCLUSIONS: Vaccine benefits extended to unvaccinated individuals in all age groups, suggesting infants are important drivers of disease transmission across the population. Imperfect disease classification and changing disease incidence may lead to bias in observed direct VE. TRIAL REGISTRATION: Not applicable. |
Temporal relationship between healthcare-associated and nonhealthcare-associated norovirus outbreaks and Google trends data in the United States
Osuka H , Hall AJ , Wikswo ME , Baker JM , Lopman BA . Infect Control Hosp Epidemiol 2018 39 (3) 1-4 Healthcare-associated norovirus outbreaks increase later but have a more pronounced seasonality than nonhealthcare norovirus outbreaks. Healthcare-associated norovirus outbreaks had higher correlation with Google Trends activity than nonhealthcare outbreaks (R2=0.68 vs 0.39). Google Trends data may have the potential to supplement existing norovirus surveillance due to its real-time availability. Infect Control Hosp Epidemiol 2018;1-4. |
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