Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-26 (of 26 Records) |
Query Trace: Cardemil CV[original query] |
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Two rotavirus outbreaks caused by genotype G2P[4] at large retirement communities: cohort studies.
Cardemil CV , Cortese MM , Medina-Marino A , Jasuja S , Desai R , Leung J , Rodriguez-Hart C , Villarruel G , Howland J , Quaye O , Tam KI , Bowen MD , Parashar UD , Gerber SI . Ann Intern Med 2012 157 (9) 621-31 BACKGROUND: Outbreaks of rotavirus gastroenteritis in elderly adults are reported infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were reported in 2 Illinois retirement facilities. OBJECTIVE: To implement control measures, determine the extent and severity of illness, and assess risk factors for disease among residents and employees. DESIGN: Cohort studies using surveys and medical chart abstraction. SETTING: Two large retirement facilities in Cook County, Illinois. PATIENTS: Residents and employees at both facilities and community residents with rotavirus disease. MEASUREMENTS: Attack rates, hospitalization rates, and rotavirus genotype. RESULTS: At facility A, 84 of 324 residents (26%) were identified with clinical or laboratory-confirmed rotavirus gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The facility B outbreak lasted 9.3 weeks. Ill employees were identified at both locations. In each facility, attack rates seemed to differ by residential setting, with the lowest rates among those in more separated settings or with high baseline level of infection control measures. The causative genotype for both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme immunoassay or genotyping reverse transcription polymerase chain reaction for at least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the older adult community but only 15 of 40 (38%) pediatric samples. LIMITATION: Medical or cognitive impairment among residents limited the success of some interviews. CONCLUSION: Rotavirus outbreaks can occur among elderly adults in residential facilities and can result in considerable morbidity. Among older adults, G2P[4] may be of unique importance. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. PRIMARY FUNDING SOURCE: None. |
Risk of hospitalization and mortality following medically attended norovirus infection-Veterans Health Administration, 2010-2018
Cates J , Cardemil CV , Mirza SA , Lopman B , Hall AJ , Holodniy M , Lucero-Obusan C . Open Forum Infect Dis 2023 10 (11) ofad556 BACKGROUND: While prior studies have suggested a role for norovirus gastroenteritis in contributing to severe morbidity and mortality, the importance of norovirus as a causal pathogen for hospitalization and mortality remains poorly understood. We estimated the effect of laboratory-confirmed norovirus infection on hospitalization and mortality among a national cohort of veterans who sought care within the Veterans Affairs health care system. METHODS: We analyzed electronic health record data from a cohort study of adults who were tested for norovirus within the Veterans Affairs system between 1 January 2010 and 31 December 2018. Adjusted risk ratios (aRRs) for hospitalization and mortality were estimated using log-binomial regression models, adjusting for age, Clostridioides difficile, underlying medical conditions, and nursing home residence. RESULTS: In total, 23 196 veterans had 25 668 stool samples tested for norovirus; 2156 samples (8.4%) tested positive. Testing positive for norovirus infection, compared with testing negative, was associated with a slight increased risk of hospitalization (aRR, 1.13 [95% confidence interval, 1.06-1.21]) and a significant increased risk of mortality within 3 days after the norovirus test (2.14 [1.10-4.14]). The mortality aRR within 1 week and 1 month were reduced to 1.40 (95% confidence interval, .84-2.34) and 0.97 (.70-1.35), respectively. CONCLUSIONS: Older veterans with multiple comorbid conditions were at a slight increased risk of hospitalization and significant increased risk of mortality in the 3 days after a norovirus-positive test, compared with those testing negative. Clinicians should be aware of these risks and can use these data to inform clinical management for veterans with norovirus. |
Association of Secretor Status and Recent Norovirus Infection With Gut Microbiome Diversity Metrics in a Veterans Affairs Population.
Johnson JA , Read TD , Petit RA3rd , Marconi VC , Meagley KL , Rodriguez-Barradas MC , Beenhouwer DO , Brown ST , Holodniy M , Lucero-Obusan CA , Schirmer P , Ingersoll JM , Kraft CS , Neill FH , Atmar RL , Kambhampati AK , Cates JE , Mirza SA , Hall AJ , Cardemil CV , Lopman BA . Open Forum Infect Dis 2022 9 (5) ofac125 Norovirus infection causing acute gastroenteritis could lead to adverse effects on the gut microbiome. We assessed the association of microbiome diversity with norovirus infection and secretor status in patients from Veterans Affairs medical centers. Alpha diversity metrics were lower among patients with acute gastroenteritis but were similar for other comparisons. |
COVID-19-Related Hospitalization Rates and Severe Outcomes Among Veterans From 5 Veterans Affairs Medical Centers: Hospital-Based Surveillance Study.
Cardemil CV , Dahl R , Prill MM , Cates J , Brown S , Perea A , Marconi V , Bell L , Rodriguez-Barradas M , Rivera-Dominguez G , Beenhouwer D , Poteshkina A , Holodniy M , Lucero-Obusan C , Balachandran N , Hall AJ , Kim L , Langley G . JMIR Public Health Surveill 2020 7 (1) e24502 BACKGROUND: COVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the US. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, is needed. OBJECTIVE: We aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among Veterans in a multi-site surveillance network. METHODS: We implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers (VAMCs: Atlanta, Bronx, Houston, Palo Alto, and Los Angeles), collectively serving >396,000 patients annually. From February 27- July 17 2020, we actively identified SARS-CoV-2 positive inpatient cases through screening of admitted patients and review of laboratory test results. We manually abstracted medical charts for demographics, underlying medical conditions, and clinical outcomes of COVID-19 hospitalized patients. We calculated hospitalization incidence and incidence rate ratios, and relative risk (RR) for invasive mechanical ventilation, intensive care unit (ICU) admission, and death after adjusting for age, race and ethnicity, and underlying medical conditions. RESULTS: We identified 621 laboratory-confirmed hospitalized COVID-19 cases. Median age was 70 years, 66% were aged ≥65 years, and 94% were male. Most COVID-19 diagnoses were among non-Hispanic Blacks (52%), followed by non-Hispanic Whites (25%) and Hispanic or Latinos (18%). Hospitalization rates were highest among Veterans aged ≥85 years, Hispanic or Latino, and non-Hispanic Black (430, 317 and 298 per 100,000, respectively); Veterans aged ≥85 years had a 14-fold increased rate of hospitalization compared with Veterans aged 18-29 years (95% CI: 5.7-34.6), while Hispanic or Latino and Black Veterans had a 4.6 and 4.2-fold increased rate of hospitalization compared with non-Hispanic White Veterans (95% CI: 3.6-5.9), respectively. Overall, 11.6% of patients required invasive mechanical ventilation, 26.6% were admitted to the intensive care unit (ICU), and 16.9% died in hospital. The adjusted RR for invasive mechanical ventilation and ICU admission did not differ by age group or race/ethnicity, but Veterans aged ≥65 had a 4.5-fold increased risk of death while hospitalized with COVID-19 compared with those aged <65 years (95% CI: 2.4-8.6). CONCLUSIONS: COVID-19 surveillance at 5 VAMCs across the US demonstrated higher hospitalization rates and severe outcomes in older Veterans, and higher hospitalization rates in Hispanic or Latino and non-Hispanic Black Veterans compared to non-Hispanic White Veterans. These data highlight the need for targeted prevention and timely treatment for Veterans, with special attention to increasing age, Hispanic or Latino and non-Hispanic Black Veterans. |
Hospital-based Surveillance for Pediatric Norovirus Gastroenteritis in Bangladesh, 2012-2016.
Satter SM , Abdullah Z , Cardemil CV , Flora MS , Gurley ES , Rahman M , Talha M , Islam MD , Hossain ME , Balachandran N , Lopman B , Rahman M , Vinjé J , Hall AJ , Parashar UD . Pediatr Infect Dis J 2020 40 (3) 215-219 BACKGROUND: Globally, noroviruses are recognized as an important cause of acute gastroenteritis (AGE), but data from low and middle-income countries are limited. AIMS: To examine the epidemiology and strain diversity of norovirus infections among children hospitalized for AGE in Bangladesh. METHODS: We implemented active surveillance of children <5 years of age hospitalized with AGE at 8 geographically dispersed tertiary care hospitals in Bangladesh from July 2012 to June 2016. We tested random samples of AGE cases stratified by site and age group for norovirus by real-time RT-PCR. Noro-positive specimens were genotyped. Coinfection with rotavirus was assessed based on prior EIA testing. RESULTS: We enrolled 5622 total AGE cases, of which 1008 were tested for norovirus. Total of 137 (14%) AGE cases tested positive for norovirus (range, 11%-17% by site). Most (94%) norovirus-associated hospitalizations were among children less than 2 years of age. Norovirus was detected year-round, with higher detection from March to June (20%-38%) and November to January (9%-18%). Genogroup II (GII) noroviruses were detected in 96% of cases, and the most frequent genotypes were GII.4 Sydney [P4 New Orleans] (33%), GII.3 [P16] (20%), and GII.4 Sydney [P16] (11%). The proportion of norovirus-positive specimens was significantly greater among rotavirus-negative AGE patients compared with rotavirus-positive AGE patients (27% vs. 5%, P < 0.001). As measured by the Vesikari severity score, a similar proportion of norovirus and rotavirus positive AGE patients were considered severe (68% vs. 70%, P = 0.86). CONCLUSIONS: Norovirus is an important cause of AGE hospitalization in Bangladeshi children with most infections caused by GII viruses. |
Risk for In-Hospital Complications Associated with COVID-19 and Influenza - Veterans Health Administration, United States, October 1, 2018-May 31, 2020.
Cates J , Lucero-Obusan C , Dahl RM , Schirmer P , Garg S , Oda G , Hall AJ , Langley G , Havers FP , Holodniy M , Cardemil CV . MMWR Morb Mortal Wkly Rep 2020 69 (42) 1528-1534 Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, although increasing evidence indicates that infection with SARS-CoV-2, the virus that causes COVID-19, can affect multiple organ systems (1). Data that examine all in-hospital complications of COVID-19 and that compare these complications with those associated with other viral respiratory pathogens, such as influenza, are lacking. To assess complications of COVID-19 and influenza, electronic health records (EHRs) from 3,948 hospitalized patients with COVID-19 (March 1-May 31, 2020) and 5,453 hospitalized patients with influenza (October 1, 2018-February 1, 2020) from the national Veterans Health Administration (VHA), the largest integrated health care system in the United States,* were analyzed. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, complications in patients with laboratory-confirmed COVID-19 were compared with those in patients with influenza. Risk ratios were calculated and adjusted for age, sex, race/ethnicity, and underlying medical conditions; proportions of complications were stratified among patients with COVID-19 by race/ethnicity. Patients with COVID-19 had almost 19 times the risk for acute respiratory distress syndrome (ARDS) than did patients with influenza, (adjusted risk ratio [aRR] = 18.60; 95% confidence interval [CI] = 12.40-28.00), and more than twice the risk for myocarditis (2.56; 1.17-5.59), deep vein thrombosis (2.81; 2.04-3.87), pulmonary embolism (2.10; 1.53-2.89), intracranial hemorrhage (2.85; 1.35-6.03), acute hepatitis/liver failure (3.13; 1.92-5.10), bacteremia (2.46; 1.91-3.18), and pressure ulcers (2.65; 2.14-3.27). The risks for exacerbations of asthma (0.27; 0.16-0.44) and chronic obstructive pulmonary disease (COPD) (0.37; 0.32-0.42) were lower among patients with COVID-19 than among those with influenza. The percentage of COVID-19 patients who died while hospitalized (21.0%) was more than five times that of influenza patients (3.8%), and the duration of hospitalization was almost three times longer for COVID-19 patients. Among patients with COVID-19, the risk for respiratory, neurologic, and renal complications, and sepsis was higher among non-Hispanic Black or African American (Black) patients, patients of other races, and Hispanic or Latino (Hispanic) patients compared with those in non-Hispanic White (White) patients, even after adjusting for age and underlying medical conditions. These findings highlight the higher risk for most complications associated with COVID-19 compared with influenza and might aid clinicians and researchers in recognizing, monitoring, and managing the spectrum of COVID-19 manifestations. The higher risk for certain complications among racial and ethnic minority patients provides further evidence that certain racial and ethnic minority groups are disproportionally affected by COVID-19 and that this disparity is not solely accounted for by age and underlying medical conditions. |
CrAssphage as a novel tool to detect human fecal contamination on environmental surfaces and hands
Park GW , Ng TFF , Freeland AL , Marconi VC , Boom JA , Staat MA , Montmayeur AM , Browne H , Narayanan J , Payne DC , Cardemil CV , Treffiletti A , Vinjé J . Emerg Infect Dis 2020 26 (8) 1731-1739 CrAssphage is a recently discovered human gut-associated bacteriophage. To validate the potential use of crAssphage for detecting human fecal contamination on environmental surfaces and hands, we tested stool samples (n = 60), hand samples (n = 30), and environmental swab samples (n = 201) from 17 norovirus outbreaks for crAssphage by real-time PCR. In addition, we tested stool samples from healthy persons (n = 173), respiratory samples (n = 113), and animal fecal specimens (n = 68) and further sequenced positive samples. Overall, we detected crAssphage in 71.4% of outbreak stool samples, 48%-68.5% of stool samples from healthy persons, 56.2% of environmental swabs, and 60% of hand rinse samples, but not in human respiratory samples or animal fecal samples. CrAssphage sequences could be grouped into 2 major genetic clusters. Our data suggest that crAssphage could be used to detect human fecal contamination on environmental surfaces and hands. |
Incidence, etiology, and severity of acute gastroenteritis among prospectively enrolled patients in 4 Veterans Affairs hospitals and outpatient centers, 2016-18.
Cardemil CV , Balachandran N , Kambhampati A , Grytdal S , Dahl RM , Rodriguez-Barradas MC , Vargas B , Beenhouwer DO , Evangelista KV , Marconi VC , Meagley KL , Brown ST , Perea A , Lucero-Obusan C , Holodniy M , Browne H , Gautam R , Bowen MD , Vinje J , Parashar UD , Hall AJ . Clin Infect Dis 2020 73 (9) e2729-e2738 BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well-characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Bronx, Houston and Los Angeles), collectively serving >320,000 patients annually. METHODS: From July 1, 2016-June 30, 2018, we actively identified AGE inpatient cases and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatient cases through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens via multiplex gastrointestinal PCR panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatient cases, 394 controls, and 506 outpatient cases. Clostridioides difficile and norovirus were most frequently detected among inpatients (cases vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; p<0.01 for both) and outpatients (norovirus: 10.7%; C. difficile: 10.5%). Incidence per 100,000 population was highest among outpatients (AGE: 2715; C. difficile: 285; norovirus: 291) and inpatients >/=65 years old (AGE: 459; C. difficile: 91; norovirus: 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/EIEC cases. Overall, 12% of AGE inpatient cases had ICU stays and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US Veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round. |
Primary care physician knowledge, attitudes, and diagnostic testing practices for norovirus and acute gastroenteritis
Cardemil CV , O'Leary ST , Beaty BL , Ivey K , Lindley MC , Kempe A , Crane LA , Hurley LP , Brtnikova M , Hall AJ . PLoS One 2020 15 (1) e0227890 BACKGROUND: Norovirus is a leading cause of acute gastroenteritis (AGE) across the age spectrum; candidate vaccines are in clinical trials. While norovirus diagnostic testing is increasingly available, stool testing may not be performed routinely, which can hamper surveillance and burden of disease estimates. Additionally, lack of knowledge of the burden of disease may inhibit provider vaccine recommendations, which could affect coverage rates and ultimately the impact of the vaccine. Our objectives were to understand physicians' stool testing practices in outpatients with AGE, and physician knowledge of norovirus, in order to improve surveillance and prepare for vaccine introduction. METHODS: Internet and mail survey on AGE, norovirus, and future norovirus vaccines conducted January to March 2018 among national networks of primary care pediatricians, family practice and general internal medicine physicians. RESULTS: The response rate was 59% (820/1383). During peak AGE season, physicians estimated they ordered stool tests for a median of 15% (interquartile range: 5-33%) of their outpatients with AGE. Stool tests were reported as more often available for ova and parasites, Clostridioides difficile, and bacterial culture (>95% for all specialties) than for norovirus (6-33% across specialties); even when available, norovirus-specific tests were infrequently ordered. Most providers were unaware that norovirus is a leading cause of AGE across all age groups (Pediatricians 80%, Family Practice 86%, General Internal Medicine 89%) or that alcohol-based hand sanitizers are ineffective against norovirus (Pediatricians 51%, Family Practice 66%, General Internal Medicine 62%). Concerns cited as major barriers to implementing a future norovirus vaccine included if the vaccine is not covered by insurance (General Internal Medicine 64%, Pediatricians 67%, Family Practice 74%) and lack of adequate reimbursement for vaccination (Pediatricians 43%, General Internal Medicine 46%, Family Practice 50%). Factors that providers believed were 'not at all a barrier' or 'minor barrier' to new vaccine introduction included the belief that "my patients won't need this vaccine" (General Internal Medicine 78%, Family Practice 86%, Pediatricians 90%) and "my patients already get too many vaccines" (Family Practice 89%, General Internal Medicine 92%, Pediatricians 95%). CONCLUSIONS: Primary care physicians had few concerns regarding future norovirus vaccine introduction, but have knowledge gaps on norovirus prevalence and hand hygiene for prevention. Also, physicians infrequently order stool tests for outpatients with AGE, which limits surveillance estimates that rely on physician-ordered stool diagnostics. Closing physician knowledge gaps on norovirus burden and transmission can help support norovirus vaccine introduction. |
Validation of acute gastroenteritis-related International Classification of Diseases, Clinical Modification Codes in pediatric and adult US populations
Pindyck T , Hall AJ , Tate JE , Cardemil CV , Kambhampati AK , Wikswo ME , Payne DC , Grytdal S , Boom JA , Englund JA , Klein EJ , Halasa N , Selvarangan R , Staat MA , Weinberg GA , Beenhouwer DO , Brown ST , Holodniy M , Lucero-Obusan C , Marconi VC , Rodriguez-Barradas MC , Parashar U . Clin Infect Dis 2019 70 (11) 2423-2427 International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes. |
Active Surveillance for Norovirus in a US Veterans Affairs Patient Population, Houston, Texas, 2015-2016.
Kambhampati AK , Vargas B , Mushtaq M , Browne H , Grytdal S , Atmar RL , Vinje J , Parashar UD , Lopman B , Hall AJ , Rodriguez-Barradas MC , Cardemil CV . Open Forum Infect Dis 2019 6 (4) ofz115 Background: Norovirus is a leading cause of acute gastroenteritis (AGE); however, few data exist on endemic norovirus disease burden among adults. Candidate norovirus vaccines are currently in development for all ages, and robust estimates of norovirus incidence among adults are needed to provide baseline data. Methods: We conducted active surveillance for AGE among inpatients at a Veterans Affairs (VA) hospital in Houston, Texas. Patients with AGE (>/=3 loose stools, >/=2 vomiting episodes, or >/=1 episode of both loose stool and vomiting, within 24 hours) within 10 days of enrollment and non-AGE control patients were enrolled. Demographic data and clinical characteristics were collected. Stool samples were tested using the FilmArray gastrointestinal panel; virus-positives were confirmed by real-time reverse transcription polymerase chain reaction and genotyped by sequencing. Results: From November 2, 2015 through November 30, 2016, 147 case patients and 19 control patients were enrolled and provided a stool specimen. Among case patients, 139 (95%) were male and 70 (48%) were aged >/=65 years. Norovirus was the leading viral pathogen detected (in 16 of 20 virus-positive case patients) and accounted for 11% of all AGE cases. No viral pathogens were detected among control patients. Incidence of norovirus-associated hospitalization was 20.3 cases/100 000 person-years and was similar among those aged <65 and >/=65 years. Conclusions: This active surveillance platform employed screening and enrollment of hospitalized VA patients meeting a standardized AGE case definition, as well as non-AGE control patients. Data from this study highlight the burden of norovirus in a VA inpatient population and will be useful in policy considerations of a norovirus vaccine. |
Trends in incidence of norovirus-associated acute gastroenteritis in four Veterans Affairs Medical Center populations in the United States, 2011-2015
Grytdal S , Browne H , Collins N , Vargas B , Rodriguez-Barradas MC , Rimland D , Beenhouwer DO , Brown ST , Bidwell Goetz M , Lucero-Obusan C , Holodniy M , Kambhampati A , Parashar U , Vinje J , Lopman B , Hall AJ , Cardemil CV . Clin Infect Dis 2019 70 (1) 40-48 BACKGROUND: Norovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Bronx, Houston, and Los Angeles) and examined trends over 4 surveillance years. METHODS: From November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served. RESULTS: Of 1,603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100,000, and 45/100,000 respectively) compared to May-October (3.0%, 131/100,000 and 13/100,000, respectively). An alternate-year pattern was also detected, with highest peak prevalence, outpatient, and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14-25%, 349-613/100,000, and 43-46/100,000). CONCLUSION: This multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and inter-annual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population. |
Cost of public health response and outbreak control with a third dose of measles-mumps-rubella vaccine during a university mumps outbreak - Iowa, 2015-2016
Marin M , Kitzmann TL , James L , Quinlisk P , Aldous WK , Zhang J , Cardemil CV , Galeazzi C , Patel M , Ortega-Sanchez IR . Open Forum Infect Dis 2018 5 (10) ofy199 Background: The United States is experiencing mumps outbreaks in settings with high 2-dose measles-mumps-rubella (MMR) vaccine coverage, mainly universities. The economic impact of mumps outbreaks on public health systems is largely unknown. During a 2015-2016 mumps outbreak at the University of Iowa, we estimated the cost of public health response that included a third dose of MMR vaccine. Methods: Data on activities performed, personnel hours spent, MMR vaccine doses administered, miles traveled, hourly earnings, and unitary costs were collected using a customized data tool. These data were then used to calculate associated costs. Results: Approximately 6300 hours of personnel time were required from state and local public health institutions and the university, including for vaccination and laboratory work. Among activities demanding time were case/contact investigation (36%), response planning/coordination (20%), and specimen testing and report preparation (13% each). A total of 4736 MMR doses were administered and 1920 miles traveled. The total cost was >$649 000, roughly equally distributed between standard outbreak control activities and third-dose MMR vaccination (55% and 45%, respectively). Conclusions: Public health response to the mumps outbreak at the University of Iowa required important amounts of personnel time and other resources. Associated costs were sizable enough to affect other public health activities. |
Progress on Norovirus vaccine research: Public health considerations and future directions.
Mattison CP , Cardemil CV , Hall AJ . Expert Rev Vaccines 2018 17 (9) 773-784 INTRODUCTION: Noroviruses are the leading cause of foodborne illness worldwide, account for approximately one-fifth of acute gastroenteritis cases globally and cause a substantial economic burden. Candidate norovirus vaccines are in development, but there is currently no licensed vaccine. Areas covered: Noroviruses cause approximately 684 million cases and 212,000 deaths per year across all age groups, though burden estimates vary by study and region. Challenges to vaccine research include substantial and rapidly evolving genetic diversity, short-term and homotypic immunity to infection, and the absence of a single, well-established correlate of protection. Nonetheless, several norovirus vaccine candidates are currently in development, utilizing virus-like particles (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine (Phase I) are in clinical trials. Expert Commentary: A norovirus vaccine should target high risk populations, including the young and the elderly and protect against the most common circulating norovirus strains. A norovirus vaccine would be a powerful tool in the prevention and control of norovirus while lessening the burden of AGE worldwide. However, more robust burden and cost estimates are needed to justify investments in and guide norovirus vaccine development. |
Frequency and cost of vaccinations administered outside minimum and maximum recommended ages-2014 data from 6 sentinel sites of Immunization Information Systems
Rodgers L , Shaw L , Strikas R , Hibbs B , Wolicki J , Cardemil CV , Weinbaum C . J Pediatr 2017 193 164-171 OBJECTIVE: To quantify vaccinations administered outside minimum and maximum recommended ages and to determine attendant costs of revaccination by analyzing immunization information system (IIS) records. STUDY DESIGN: We analyzed deidentified records of doses administered during 2014 to persons aged <18 years within 6 IIS sentinel sites (10% of the US population). We quantified doses administered outside of recommended ages according to the Advisory Committee on Immunization Practices childhood immunization schedule and prescribing information in package inserts, and calculated revaccination costs. To minimize misreporting bias, we analyzed publicly funded doses for which reported lot numbers and vaccine types were consistent. RESULTS: Among 3 394 047 doses with maximum age recommendations, 9755 (0.3%) were given after the maximum age. One type of maximum age violation required revaccination: 1344 (0.7%) of 194 934 doses of the 0.25-mL prefilled syringe formulation of quadrivalent inactivated influenza vaccine (Fluzone Quadrivalent, Sanofi Pasteur, Swiftwater, PA) were administered at age >/=36 months (revaccination cost, $111 964). We identified a total of 7 529 165 childhood, adolescent, and lifespan doses with minimum age recommendations, 9542 of which (0.1%) were administered before the minimum age. The most common among these violations were quadrivalent injectable influenza vaccines (3835, or 0.7% of 526 110 doses administered before age 36 months) and Kinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium; DTaP-IPV) (2509, or 1.2% of 208 218 doses administered before age 48 months). The cost of revaccination for minimum age violations (where recommended) was $179 179. CONCLUSION: Administration of vaccines outside recommended minimum and maximum ages is rare, reflecting a general adherence to recommendations. Error rates were higher for several vaccines, some requiring revaccination. Vaccine schedule complexity and confusion among similar products might contribute to errors. Minimization of errors reduces wastage, excess cost, and inconvenience for parents and patients. |
Pathogen-specific burden of outpatient diarrhea in infants in Nepal: A multisite prospective case-control study
Cardemil CV , Sherchand JB , Shrestha L , Sharma A , Gary HE , Estivariz CF , Diez-Valcarce M , Ward ML , Bowen MD , Vinje J , Parashar U , Chu SY . J Pediatric Infect Dis Soc 2017 6 (3) e75-e85 Background: Nonsevere diarrheal disease in Nepal represents a large burden of illness. Identification of the specific disease-causing pathogens will help target the appropriate control measures. Methods: Infants aged 6 weeks to 12 months were recruited from 5 health facilities in eastern, central, and western Nepal between August 2012 and August 2013. The diarrhea arm included infants with mild or moderate diarrhea treatable in an outpatient setting; the nondiarrhea arm included healthy infants who presented for immunization visits or had a mild nondiarrheal illness. Stool samples were tested for 15 pathogens with a multiplex polymerase chain reaction (PCR) assay and real-time reverse-transcription (RT)-PCR assays for rotavirus and norovirus. Rotavirus- and norovirus-positive specimens were genotyped. We calculated attributable fractions (AFs) to estimate the pathogen-specific burden of diarrhea and adjusted for facility, age, stunting, wasting, and presence of other pathogens. Results: We tested 307 diarrheal and 358 nondiarrheal specimens. Pathogens were detected more commonly in diarrheal specimens (164 of 307 [53.4%]) than in nondiarrheal specimens (113 of 358 [31.6%]) (P < .001). Rotavirus (AF, 23.9% [95% confidence interval (CI), 14.9%-32.8%]), Salmonella (AF, 12.4% [95% CI, 6.6%-17.8%]), and Campylobacter (AF, 5.6% [95% CI, 1.3%-9.8%]) contributed most to the burden of disease. In these diarrheal specimens, the most common genotypes for rotavirus were G12P[6] (27 of 82 [32.9%]) and G1P[8] (16 of 82 [19.5%]) and for norovirus were GII.4 Sydney (9 of 26 [34.6%]) and GII.7 (5 of 26 [19.2%]). Conclusions: The results of this study indicate that the introduction of a rotavirus vaccine in Nepal will likely decrease outpatient diarrheal disease burden in infants younger than 1 year, but interventions to detect and target other pathogens, such as Salmonella and Campylobacter spp, should also be considered. |
Norovirus infection in older adults: Epidemiology, risk factors, and opportunities for prevention and control
Cardemil CV , Parashar UD , Hall AJ . Infect Dis Clin North Am 2017 31 (4) 839-870 Norovirus is the leading cause of acute gastroenteritis. In older adults, it is responsible for an estimated 3.7 million illnesses; 320,000 outpatient visits; 69,000 emergency department visits; 39,000 hospitalizations; and 960 deaths annually in the United States. Older adults are particularly at risk for severe outcomes, including prolonged symptoms and death. Long-term care facilities and hospitals are the most common settings for norovirus outbreaks in developed countries. Diagnostic platforms are expanding. Several norovirus vaccines in clinical trials have the potential to reap benefits. This review summarizes current knowledge on norovirus infection in older adults. |
Effectiveness of a third dose of MMR vaccine for mumps outbreak control
Cardemil CV , Dahl RM , James L , Wannemuehler K , Gary HE , Shah M , Marin M , Riley J , Feikin DR , Patel M , Quinlisk P . N Engl J Med 2017 377 (10) 947-956 BACKGROUND: The effect of a third dose of the measles-mumps-rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. METHODS: Of 20,496 university students who were enrolled during the 2015-2016 academic year, mumps was diagnosed in 259 students. We used Fisher's exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time-dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. RESULTS: Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. CONCLUSIONS: Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.). |
Uptake of rotavirus vaccine among US infants at Immunization Information System Sentinel Sites
Pringle K , Cardemil CV , Pabst LJ , Parashar UD , Cortese MM . Vaccine 2016 34 (50) 6396-6401 OBJECTIVE: Coverage with rotavirus vaccine among US children has been lower compared to that with other routine childhood vaccines. Our objectives were to examine rotavirus vaccine (RV) uptake over time compared to other routine vaccinations, ages at administration, and quantitate potential missed opportunities for RV receipt. METHODS: We analyzed data from 6 Immunization Information System (IIS) Sentinel Sites, which represent approximately 10% of the United States (US) pediatric population. Among infants aged 5 months, we compared uptake of 1 dose of RV, to that of Diphtheria, Tetanus, and acellular Pertussis (DTaP) and pneumococcal conjugate vaccine (PCV), for each quarter during 2006-2013. We used data from infants in the 2012 birth cohort to examine RV receipt in more detail. RESULTS: Among infants aged 5months, the average site coverage with 1 dose of RV reached 78% in 2010 and subsequently stayed steady at 79-81% through 2013. The average difference between 1 dose DTaP coverage and RV coverage remained between about 6 and 8 percentage points during mid-2012 through 2013. Infants born in 2012 received RV doses closely in line with the timing recommended by the ACIP. Approximately one-third of the difference in coverage between 1 dose of DTaP and 1 dose of RV among infants could be due to the maximum age restriction of the first RV dose. The other two-thirds of the difference appears to have been a result of potential missed opportunities for starting the RV series--these infants received another routine immunization when age eligible to receive RV dose 1, but did not receive RV. CONCLUSION: Uptake with RV during infancy remains below that of other routine vaccines. Understanding the barriers to administration of RV among age-eligible infants could help improve vaccine coverage. |
Use of immunization information systems in primary care
Kempe A , Hurley LP , Cardemil CV , Allison MA , Crane LA , Brtnikova M , Beaty BL , Pabst LJ , Lindley MC . Am J Prev Med 2016 52 (2) 173-182 INTRODUCTION: Immunization information systems (IISs) are highly effective for increasing vaccination rates but information about how primary care physicians use them is limited. METHODS: Pediatricians, family physicians (FPs), and general internists (GIMs) were surveyed by e-mail and mail from January 2015 to April 2015 from all states with an existing IIS. Providers were recruited to be representative of national provider organization memberships. Multivariable log binomial regression examined factors associated with IIS use (October 2015-April 2016). RESULTS: Response rates among pediatricians, FPs, and GIMs, respectively, were 75% (325/435), 68% (310/459), and 63% (272/431). A proportion of pediatricians (5%), FPs (14%), and GIMs (48%) did not know there was a state/local IIS; 81%, 72%, and 27% reported using an IIS (p<0.0001). Among those who used IISs, 64% of pediatricians, 61% of FPs, and 22% of GIMs thought the IIS could tell them a patient's immunization needs; 22%, 29%, and 51% did not know. The most frequently reported major barriers to use included the IIS not updating the electronic medical record (29%, 28%, 35%) and lack of ability to submit data electronically (22%, 27%, 31%). Factors associated with lower IIS use included FP (adjusted risk ratio=0.85; 95% CI=0.75, 0.97) or GIM (adjusted risk ratio=0.33; 95% CI=0.25, 0.42) versus pediatric specialty and older versus younger provider age (adjusted risk ratio=0.96; 95 CI%=0.94, 0.98). CONCLUSIONS: There are substantial gaps in knowledge of IIS capabilities, especially among GIMs; barriers to interoperability between IISs and electronic medical records affect all specialties. Closing these gaps may increase use of proven IIS functions including decision support and reminder/recall. |
Measles immunity among pregnant women aged 15-44 years in Namibia, 2008 & 2010
Cardemil CV , Jonas A , Beukes A , Anderson R , Rota PA , Bankamp B , Jr HE , Sawadogo S , Patel SV , Zeko S , Muroua C , Gaeb E , Wannemuehler K , Gerber S , Goodson JL . Int J Infect Dis 2016 49 189-95 BACKGROUND: Namibia experienced a large measles outbreak starting in 2009, with 38% of reported cases in adults, including women of reproductive age. We assessed population immunity among pregnant women, to determine if immunization activities were needed in adults to achieve measles elimination in Namibia. METHODS: We tested 1,708 and 2,040 specimens for measles immunoglobulin G antibody from Namibian pregnant women aged 15-44 years sampled from the 2008 and 2010 National HIV Sentinel Survey, respectively. We determined the proportion of women seropositive overall and by 5-year age strata, and analyzed factors associated with seropositivity by logistic regression, including age, facility type, gravidity, HIV status, and urban/rural status. We tested for any difference in seropositivity between 2008 and 2010. RESULTS: In both analysis years, measles seropositivity was lower in 15-19 year olds (77%) and 20-24 year olds (85-87%) and higher in 25-44 year olds (90%-94%) (p<0.001, 2008; p<0.001, 2010). Overall measles seropositivity did not differ between 2008 (87%) and 2010 (87%) (p=0.7). HIV status did not affect seropositivity. CONCLUSIONS: Late in a large measles outbreak, 13% of pregnant women in Namibia, and almost one in four 15-19 year old pregnant women, remained measles-susceptible. In Namibia, immunization campaigns with measles-containing vaccine should be considered for adults. |
Rubella immunity among pregnant women aged 15-44 years, Namibia, 2010
Jonas A , Cardemil CV , Beukes A , Anderson R , Rota PA , Bankamp B , Gary HE Jr , Sawadogo S , Patel SV , Zeko S , Muroua C , Gaeb E , Wannemuehler K , Gerber S , Goodson JL . Int J Infect Dis 2016 49 196-201 BACKGROUND: The level of rubella susceptibility among women of reproductive age in Namibia is unknown. Documenting the risk of rubella will help estimate the potential burden of disease in Namibian women and the risk of congenital rubella syndrome (CRS) in offspring, and will guide strategies for rubella vaccine introduction. METHODS: We tested 2,044 specimens from pregnant Namibian women aged 15-44 years sampled from the 2010 National HIV Sentinel Survey for rubella immunoglobulin G antibody. We determined the proportion of women seropositive for rubella by 5-year age strata and analyzed factors associated with seropositivity, including age, gravidity, HIV status, facility type, and urban/rural status, by logistic regression. RESULTS: Overall rubella seroprevalence (95% Confidence Interval [CI]) was 85% (95%CI 83%-86%). Seroprevalence varied by age group (83%-90%) and health district (71%-100%). In the multivariable model, women from urban residences had higher odds of seropositivity as compared to women from rural residences (OR 1.40; 95%CI 1.09-1.81). CONCLUSIONS: In the absence of a routine rubella immunization program, the high level of rubella seropositivity suggests rubella virus transmission in Namibia, yet 15% of pregnant Namibian women remain susceptible to rubella. Introduction of rubella vaccine will help reduce the risk of rubella in pregnant women and CRS in infants. |
The effect of diarrheal disease on bivalent oral polio vaccine (bOPV) immune response in infants in Nepal
Cardemil CV , Estivariz C , Shrestha L , Sherchand JB , Sharma A , Gary HE Jr , Oberste MS , Weldon WC 3rd , Bowen MD , Vinje J , Schluter WW , Anand A , Mach O , Chu SY . Vaccine 2016 34 (22) 2519-26 BACKGROUND: A globally-coordinated phase out of all type 2 containing oral polio vaccine (OPV) is planned for April 2016 during which bivalent 1+3 OPV (bOPV) will replace trivalent OPV (tOPV) in routine immunization schedules and campaigns. Diarrhea impairs the immune response to tOPV, but the effect of diarrhea on bOPV is unknown. METHODS: Infants aged 6 weeks to 11 months, who had received <3 doses of OPV and had mild-moderate diarrhea or no diarrhea, were recruited at five health facilities in Nepal. Neutralizing antibody titers to poliovirus types 1 and 3 were measured before and 28 days after bOPV administration. The effect of diarrhea and other factors on seroconversion or boosting in antibody titers to poliovirus was assessed by multivariable analysis. RESULTS: Infants with diarrhea, versus those without diarrhea, had reduced response for poliovirus types 1 (56% [87/156] vs 66% [109/164]) and 3 (34% [70/209] vs 52% [122/236]). After adjusting for other factors, infants with diarrhea had significantly reduced response for type 3 (odds ratio [OR]=0.44, 95% CI 0.29-0.68), as did infants with >5 loose stools per day (OR=0.36, 95% CI 0.21-0.62). CONCLUSIONS: Diarrhea reduced the immune response to bOPV. Provision of additional doses of polio vaccine is necessary to maintain high population immunity in areas with high prevalence of diarrheal disease. CLINICAL TRIAL REGISTRY: This study is registered at clinicaltrials.gov as NCT01559636. |
Factors associated with provider reporting of child and adolescent vaccination history to immunization information systems: results from the National Immunization Survey, 2006-2012
Cardemil CV , Cullen KA , Harris L , Greby SM , Santibanez TA . J Public Health Manag Pract 2015 22 (3) 245-54 CONTEXT: Use of Immunization information systems (IISs) by providers can improve vaccination rates by identifying missed opportunities. However, provider reporting of children's vaccination histories to IISs remains suboptimal. OBJECTIVE: To assess factors associated with provider reporting to an IIS. DESIGN: Analysis of 2006-2012 National Immunization Survey (NIS) and NIS-Teen data. NIS and NIS-Teen are ongoing random-digit-dial telephone surveys of households with children and adolescents, respectively, followed by a mail survey to providers to obtain the patient's vaccination history. SETTING AND PARTICIPANTS: A total of 115 285 children aged 19 to 35 months and 83 612 adolescents aged 13 to 17 years and their immunization providers in the United States. MAIN OUTCOME MEASURES: The percentage of children and adolescents with 1 or more providers reporting to or obtaining vaccination information from their local IISs. Multivariable logistic regression was used to examine patient and provider factors associated with provider reporting to IISs and adjusted prevalence of children and adolescents with 1 or more providers reporting to IISs. RESULTS: In 2012, 79.4% of children and 77.4% of adolescents had 1 or more providers report any of their vaccination data to an IIS, and 41.9% of children and 51.5% of adolescents had providers who obtained any of their vaccination histories from an IIS. During 2006-2012, children and adolescents were more likely to have any of their vaccination data reported to an IIS if they received care from all public versus all private providers (children: 84.4% vs 69.6%, P < .0001; adolescents: 84.6% vs 66.4%, P < .0001), had 1 or more providers who ordered vaccines from a state or local health department (children: 76.7% vs 59.5%, P < .0001; adolescents: 77.0% vs 55.6%, P < .0001), or had 1 or more providers obtain vaccination information from the IIS (children: 86.1% vs 71.2%, P < .0001; adolescents: 83.7% vs 64.6%, P < .0001). CONCLUSIONS: Health department staff should target providers less likely to use IIS services, including private providers, and providers not ordering vaccines from health departments to ensure they use IIS services. |
Poliovirus immunity among pregnant females aged 15-44 years, Namibia, 2010
Cardemil CV , Jonas A , Gerber S , Weldon WC 3rd , Oberste MS , Beukes A , Sawadogo S , Patel SV , Zeko S , Muroua C , Gaeb E , Wannemuehler K , Goodson JL . J Infect Dis 2014 210 Suppl 1 S136-42 BACKGROUND: Poliovirus (PV) antibody seroprevalence studies assess population immunity, verify an immunization program's performance and vaccine efficacy, and guide polio eradication strategy. Namibia experienced a polio outbreak among adults in 2006, yet population seroimmunity was unknown. METHODS: We tested 2061 specimens from Namibian pregnant females aged 15-44 years for neutralizing antibody to PV types 1-3 (PV1-3); all females were sampled during the 2010 National HIV Sentinel Survey. We determined the proportion of females seropositive for PV antibody by 5-year age strata, and analyzed factors associated with seropositivity, including age, gravidity, human immunodeficiency virus (HIV) infection status, residence, and antiretroviral treatment, by log-binomial regression. RESULTS: The seroprevalence was 94.6% for PV1, 97.0% for PV2, and 85.1% for PV3. HIV-positive females had significantly lower seroprevalence than HIV-negative females for PV1 (91.8% vs 95.3%; P < .01) and PV3 (80.0% vs 86.1%; P < .01) but not for PV2 (96.4% vs 97.1%; P = .3). The prevalence ratio of seropositivity for HIV-positive females versus HIV-negative females was 0.95 (95% confidence interval [CI], .92-.98) for PV1, 0.99 (95% CI, .97-1.01) for PV2, and 0.92 (95% CI, .87-.96) for PV3. CONCLUSIONS: Despite relatively high PV seroprevalence, Namibia might remain at risk for a PV outbreak, particularly in lower-seroprevalence populations, such as HIV-positive females. Namibia should continue to maintain high routine polio vaccination coverage. |
Surveillance during an era of rapidly changing poliovirus epidemiology in India: the role of one vs. two stool specimens in poliovirus detection, 2000-2010
Cardemil CV , Rathee M , Gary H , Wannemuehler K , Anand A , Mach O , Bahl S , Wassilak S , Chu SY , Khera A , Jafari HS , Pallansch MA . Epidemiol Infect 2013 142 (1) 1-9 SUMMARY: Since 2004, efforts to improve poliovirus detection have significantly increased the volume of specimen testing from acute flaccid paralysis (AFP) patients in India. One option to decrease collection and testing burden would be collecting only a single stool specimen instead of two. We investigated stool specimen sensitivity for poliovirus detection in India to estimate the contribution of the second specimen. We reviewed poliovirus isolation data for 303984 children aged <15 years with AFP during 2000-2010. Using maximum-likelihood estimation, we determined specimen sensitivity of each stool specimen, combined sensitivity of both specimens, and sensitivity added by the second specimen. Of 5184 AFP patients with poliovirus isolates, 382 (7.4%) were identified only by the second specimen. Sensitivity was 91.4% for the first specimen and 84.5% for the second specimen; the second specimen added 7.3% sensitivity, giving a combined sensitivity of 98.7%. Combined sensitivity declined, and added sensitivity increased, as the time from paralysis onset to stool collection increased (P = 0.032). The sensitivity added by the second specimen is important to detect the last chains of poliovirus transmission and to achieve certification of polio eradication. For sensitive surveillance, two stool specimens should continue to be collected from each AFP patient in India. |
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