Burden of Norovirus in the United States, as Estimated Based on Administrative Data: Updates for Medically Attended Illness and Mortality, 2001-2015.

BACKGROUND: Up-to-date estimates of the burden of norovirus, a leading cause of acute gastroenteritis (AGE) in the United States, are needed to assess the potential value of norovirus vaccines in development. We aimed to estimate the rates, annual counts, and healthcare charges of norovirus-associated ambulatory clinic encounters, emergency department (ED) visits, hospitalizations, and deaths in the United States. METHODS: We analyzed administrative data on AGE outcomes from 1 July 2001 through 30 June 2015. Data were sourced from IBM MarketScan Commercial and Medicare Supplemental Databases (ambulatory clinic and ED visits), the Healthcare Utilization Project National Inpatient Sample (hospitalizations), and the National Center for Health Statistics multiple-cause-of-mortality data (deaths). Outcome data (ambulatory clinic and ED visits, hospitalizations, or deaths) were summarized by month, age group, and setting. Healthcare charges were estimated based on insurance claims. Monthly counts of cause-unspecified gastroenteritis-associated outcomes were modeled as functions of cause-specified outcomes, and model residuals were analyzed to estimate norovirus-associated outcomes. Healthcare charges were estimated by applying average charges per cause-unspecified gastroenteritis encounter to the estimated number of norovirus encounters. RESULTS: We estimate 900 deaths (95% confidence interval [CI], 650-1100), 109 000 hospitalizations (95% CI, 80 000-145 000), 465 000 ED visits (95% CI, 348 000-610 000), and 2.3 million ambulatory clinic encounters (95% CI, 1.7-2.9 million) annually due to norovirus, with an associated $430-$740 million in healthcare charges. CONCLUSIONS: Norovirus causes a substantial health burden in the United States each year, and an effective vaccine could have important public health impact.

Validation of Acute Gastroenteritis-related International Classification of Diseases, Clinical Modification Codes in Pediatric and Adult US Populations.

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.

Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

COVID-19 Among American Indian and Alaska Native Persons - 23 States, January 31-July 3, 2020.

Although non-Hispanic American Indian and Alaska Native (AI/AN) persons account for 0.7% of the U.S. population,* a recent analysis reported that 1.3% of coronavirus disease 2019 (COVID-19) cases reported to CDC with known race and ethnicity were among AI/AN persons (1). To assess the impact of COVID-19 among the AI/AN population, reports of laboratory-confirmed COVID-19 cases during January 22†-July 3, 2020 were analyzed. The analysis was limited to 23 states§ with >70% complete race/ethnicity information and five or more laboratory-confirmed COVID-19 cases among both AI/AN persons (alone or in combination with other races and ethnicities) and non-Hispanic white (white) persons. Among 424,899 COVID-19 cases reported by these states, 340,059 (80%) had complete race/ethnicity information; among these 340,059 cases, 9,072 (2.7%) occurred among AI/AN persons, and 138,960 (40.9%) among white persons. Among 340,059 cases with complete patient race/ethnicity data, the cumulative incidence among AI/AN persons in these 23 states was 594 per 100,000 AI/AN population (95% confidence interval [CI] = 203-1,740), compared with 169 per 100,000 white population (95% CI = 137-209) (rate ratio [RR] = 3.5; 95% CI = 1.2-10.1). AI/AN persons with COVID-19 were younger (median age = 40 years; interquartile range [IQR] = 26-56 years) than were white persons (median age = 51 years; IQR = 32-67 years). More complete case report data and timely, culturally responsive, and evidence-based public health efforts that leverage the strengths of AI/AN communities are needed to decrease COVID-19 transmission and improve patient outcomes.

Risk Factors Associated With Increased Mortality From Intussusception in African Infants.

OBJECTIVES: Morbidity and mortality from intussusception, the leading cause of bowel obstruction in infants, is higher in Africa than in other regions of the world, but the reasons have not been well examined. We sought to identify risk and protective factors associated with death or intestinal resection following intussusception. METHODS: Infants with intussusception from 7 sub-Saharan African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) were enrolled through active, hospital-based surveillance from February 2012 to December 2016. We examined demographic, clinical, and socioeconomic factors associated with death or intestinal resection following intussusception, using multivariable logistic regression. RESULTS: A total of 1017 infants <1 year of age with intussusception were enrolled. Overall, 13% of children (133/1017) died during the hospitalization, and 48% (467/966) required intestinal resection. In multivariable analyses, female sex [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-3.3], longer duration of symptoms before presentation (OR 1.1; 95% CI 1.0-1.2), and undergoing intestinal resection (OR 3.4; 95% CI 1.9-6.1) were associated with death after intussusception. Diagnosis by ultrasound or enema (OR 0.4; 95% CI 0.3-0.7), and employment of a household member (OR 0.7; 95% CI 0.4-1.0) were protective against intestinal resection. CONCLUSIONS: Delays in hospital presentation and female sex were significantly associated with death, whereas higher socioeconomic status and availability of radiologic diagnosis reduced likelihood of undergoing resection. Efforts should be intensified to improve the awareness, diagnosis, and management of intussusception in sub-Saharan African countries to reduce morbidity and mortality from intussusception in these resource-limited settings.

The role of funded partnerships in working towards decreasing COVID-19 vaccination disparities, United States, March 2021-December 2022.

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

Typhoid Fever in the Eastern Mediterranean Region: A Systematic Review, 1990-2021.

The occurrence and antimicrobial resistance (AMR) of typhoid fever in the WHO Eastern Mediterranean Region (EMR) are poorly characterized. Robust surveillance data are needed to inform strategies for typhoid control and prevention in the region. We conducted a systematic review of typhoid fever occurrence, complications, and AMR patterns in EMR countries. We identified 70 studies published from 1990 to 2021, including a total of 44,541 cases with blood culture confirmed typhoid fever in 12 EMR countries, with 48 (69%) studies and 42,008 cases from Pakistan. Among 56 studies with AMR data, fluroquinolone (68% of 13,013 tested isolates), and multidrug resistance (40% of 15,765 tested isolates) were common. Forty (57%) of the 56 studies were from Pakistan, and all reports of extensively drug resistant Salmonella Typhi (48% of 9,578 tested isolates) were from studies in Pakistan. Our findings support the need for continued efforts to strengthen surveillance and laboratory capacity for blood-culture detection of typhoid fever in the region, including data from an ongoing collaboration among CDC, the American University of Beirut, and the WHO EMR office.

Deaths in Children and Adolescents Associated With COVID-19 and MIS-C in the United States.

OBJECTIVES: To describe the demographics, clinical characteristics, and hospital course among persons <21 years of age with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated death. METHODS: We conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons <21 years of age during February 12 to July 31, 2020. All states and territories were invited to participate. We abstracted demographic and clinical data, including laboratory and treatment details, from medical records. RESULTS: We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5-19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition. CONCLUSIONS: SARS-CoV-2-associated deaths among persons <21 years of age occurred predominantly among Black (non-Hispanic) and Hispanic persons, male patients, and older adolescents. The most commonly reported underlying conditions were obesity, asthma, and developmental disorders. Decedents with coronavirus disease 2019 were more likely than those with MIS-C to have underlying medical conditions.

Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes.

BACKGROUND: Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other. PROCEDURE: We performed ELANE genotyping on all individuals and paternal sperm in an SCN kindred with eight SCN progeny of a sperm donor and six different mothers. RESULTS: One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype. The mutant allele was detected in the donor's spermatozoa, representing 18% of the ELANE gene pool, but not in DNA from his lymphocytes, neutrophils, or buccal mucosa, indicating gonadal mosaicism. CONCLUSIONS: The coexistence of CN and SCN phenotypes in this kindred with a shared paternal haplotype strongly suggests both a role for modifying genes in determination of congenital neutropenia disease phenotypes, and the classification of CN and SCN within a spectrum of phenotypes expressing varying degrees of the same disease process.

Cost of pediatric hospitalizations in Burkina Faso: A cross-sectional study of children aged <5 years enrolled through an acute gastroenteritis surveillance program.

INTRODUCTION: Diarrheal illness is a leading cause of hospitalizations among children <5 years. We estimated the costs of inpatient care for rotavirus and all-cause acute gastroenteritis (AGE) in two Burkina Faso hospitals. METHODS: We conducted a cross-sectional study among children <5 years from December 2017 to June 2018 in one urban and one rural pediatric hospital. Costs were ascertained through caregiver interview and chart abstraction. Direct medical, non-medical, and indirect costs per child incurred are reported. Costs were stratified by rotavirus results. RESULTS: 211 children <5 years were included. AGE hospitalizations cost 161USD (IQR 117-239); 180USD (IQR 121-242) at the urban and 154USD (IQR 116-235) at the rural site. Direct medical costs were higher in the urban compared to the rural site (140USD (IQR 102-182) vs. 90USD (IQR 71-108), respectively). Direct non-medical costs were higher at the rural versus urban site (15USD (IQR 10, 15) vs. 11USD (IQR 5-20), respectively). Indirect costs were higher at the rural versus urban site (35USD (IQR 8-91) vs. 0USD (IQR 0-26), respectively). Rotavirus hospitalizations incurred less direct medical costs as compared to non-rotavirus hospitalizations at the rural site (79USD (IQR 64-103) vs. 95USD (IQR 80-118)). No other differences by rotavirus testing status were observed. The total median cost of a hospitalization incurred by households was 24USD (IQR 12-49) compared to 75USD for government (IQR 59-97). Direct medical costs for households were higher in the urban site (median 49USD (IQR 31-81) versus rural (median 14USD (IQR 8-25)). Households in the lowest wealth quintiles at the urban site expended 149% of their monthly income on the child's hospitalization, compared to 96% at the rural site. CONCLUSIONS: AGE hospitalization costs differed between the urban and rural hospitals and were most burdensome to the lowest income households. Rotavirus positivity was not associated with greater household costs.

Timeliness of rotavirus vaccination at sentinel sites in four early-adopter African countries.

BACKGROUND: The majority of countries with the highest rotavirus-associated death rates are in sub-Saharan Africa. In 2009, the World Health Organization (WHO) recommended routine vaccination against rotavirus worldwide, with unique age recommendations to administer the first dose before 15 weeks of age and last dose by 32 weeks of age. These age restrictions were relaxed in January 2013, but they may still lead to lower rotavirus vaccine coverage. METHODS: Children age-eligible to have received rotavirus vaccine that were enrolled in Ghana, Zimbabwe, Rwanda or Burkina Faso's active rotavirus surveillance platforms from 2013 to 2017 and had a stool specimen that tested rotavirus-negative were included in the analysis. Proportion vaccinated and timeliness of rotavirus vaccine versus DTPw-HepB-Hib (pentavalent) first dose and last dose were compared at weeks 15 and 32, respectively, using Chi-square analyses. Odds ratios were calculated using logistic regression. RESULTS: Among children who received rotavirus vaccine dose 1, 96-99% received this dose by 15 weeks of age and among children who received the last dose, 98-99% received it by 32 weeks of age. In all four countries, there was no significant difference in the proportion of children who received first dose rotavirus versus pentavalent vaccine by week 15, or last dose rotavirus versus concordant pentavalent vaccine by week 32. Delayed administration of first dose pentavalent vaccine was significantly associated with missing first dose of rotavirus vaccine in 3 of the 4 countries studied, although delays in administration were rare (1-4%). CONCLUSIONS: Rotavirus vaccination was timely among sentinel sites in these four early rotavirus vaccine-introducing countries in Africa. Late presentation for vaccination may have resulted in some children with access to care missing first dose of rotavirus vaccine; however, vaccination delays were infrequent and therefore the potential impact of the age restrictions on overall proportion vaccinated was minimal.

A decade of experience with rotavirus vaccination in the United States - vaccine uptake, effectiveness, and impact.

INTRODUCTION: Prior to 2006, nearly every U.S. child was infected with rotavirus by 5 years of age, and rotavirus was the leading cause of severe childhood gastroenteritis. In February 2006 and June 2008, the Advisory Committee on Immunization Practices recommended a live attenuated pentavalent rotavirus vaccine (RV5) and a monovalent rotavirus vaccine (RV1), respectively, for routine vaccination of infants in the United States. AREAS COVERED: We reviewed U.S. data on coverage, vaccine effectiveness (VE), and vaccine impact from 2006 to 2017. National rotavirus vaccine coverage estimates increased since vaccine introduction but plateaued at 71-75% in 2013-2015, a level 15-20% lower than that of other routine childhood vaccines. Pooled VE of full series RV5 and RV1 against rotavirus-associated hospitalizations and emergency department visits were 84% (95% CI: 80-87%) and 83% (95% CI: 72-89%), respectively. Vaccine introduction resulted in a median decline in rotavirus-associated hospitalizations and emergency department visits of 80% and 57%, respectively, along with indirect protection of unvaccinated age groups and a decrease in health-care costs. A biennial pattern in rotavirus detection emerged post-vaccine implementation. EXPERT COMMENTARY: The increasing use of rotavirus vaccines has substantially diminished the burden and changed the epidemiology of rotavirus disease in U.S. children; efforts to increase rotavirus vaccine coverage should continue.

Impact of a media campaign for disaster mental health counseling in post-September 11 New York.

OBJECTIVE: After the September 11, 2001, terrorist attacks on the World Trade Center, the New York State Office of Mental Health (NYOMH) initiated a three-phase multifaceted, multilingual media campaign that advertised the availability of counseling services. This study evaluated the association between patterns of spending within this campaign and the volume of calls received and referred to a counseling program. METHODS: Spending on television, radio, print, and other advertising was examined, as was the corresponding volume of calls to the NetLife hotline seeking referrals to counseling services. RESULTS: From September 2001 to December 2002, $9.38 million was spent on Project Liberty media campaigns. Call volumes increased during months when total monthly expenditures peaked. Initially, flyers, billboards, and other material items accounted for most monthly expenses. Over time, spending for television and radio advertisements increased, whereas other advertising declined. Temporal patterns show that in periods after an increase in media spending, call volumes increased independently of other sentinel events such as the one-year anniversary of the attacks. CONCLUSIONS: Sustained advertising through multiple media outlets appeared to be effective in encouraging individuals to seek mental health services.

Treating hepatitis C in American Indians/Alaskan Natives: A survey of Project ECHO(®) (Extension for Community Healthcare Outcomes) utilization by Indian Health Service providers.

BACKGROUND: American Indians/Alaskan Natives have a high mortality associated with hepatitis C virus, yet treatment rates are low. The ECHO (Extension for Community Healthcare Outcomes) model(™), a videoconferencing technology for primary care providers, is underutilized at Indian Health Service facilities. PURPOSE: To ascertain Indian Health Service providers' benefit of and barriers to utilizing hepatitis C virus TeleECHO clinics. METHODS: We electronically sent an Active Participant Survey to Indian Health Service providers utilizing hepatitis C virus TeleECHO clinic and a Non-Participant Survey to other Indian Health Service providers interested in this clinic. RESULTS: In total, 100% of Active Participant Survey respondents perceive moderate to major benefit of hepatitis C virus TeleECHO clinic in managing hepatitis C virus, and 67% of Non-Participant Survey respondents reported lack of administrative time as the major barrier to utilizing this resource. CONCLUSION: Indian Health Service providers participating in hepatitis C virus TeleECHO clinic perceive this resource as highly beneficial, but widespread utilization may be impractical without allocating time for participation.

Fatal Granulomatous Amebic Encephalitis Due to Balamuthia mandrillaris in New Mexico: A Case Report.

Balamuthia mandrillaris is a free-living amoeba that can cause granulomatous amebic encephalitis (GAE). We report a case in an individual with a history of alcohol abuse, cocaine use, and ditch water exposure. This is the first reported case of GAE due to B mandrillaris in New Mexico.

Cladribine plus rituximab is an effective therapy for newly diagnosed mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma that is incurable with standard chemotherapy. There is no consensus on the best initial therapy, especially for elderly patients, who are not candidates for aggressive treatment approaches. Current National Comprehensive Cancer Network (NCCN) treatment guidelines include rituximab (R) plus cladribine for the initial treatment of MCL. However, few data are available to substantiate this recommendation. Therefore, to further define the role of R-cladribine for the initial treatment of MCL, we performed a retrospective chart review of 31 patients with MCL (median age, 67) treated with R-cladribine. The majority of responding patients also received R maintenance. The overall response rate was 87%, with 61% of patients achieving a complete remission (CR/CRu). The estimated median follow-up was 32.5 months, median PFS was 37.5 months, and median OS was 85.2 months. One of 19 (5.3%) subjects in CR/CRu relapsed (median follow-up of 23 months). CR/CRu was associated with improved survival (p < 0.0001), while a high mantle cell international prognostic index (MIPI) was associated with worse survival (p = 0.05). There was one toxic death (neutropenic pseudomonal sepsis) related to treatment. R-cladribine is an effective therapy for previously untreated MCL, and these results validate the use of R-cladribine for the initial treatment of MCL.