Evidence, Experience, Expertise, and the US Coronavirus Disease 2019 Public Health Response.

The U.S. Centers for Disease Control and Prevention (CDC), state, tribal, and local health departments assess available and promising interventions and individual and population health outcomes when crafting public health recommendations. This supplement provides a snapshot of some of the science, experience, and expertise supporting the COVID-19 response.

Epidemiology, Outcomes, and Trends of Patients With Sepsis and Opioid-Related Hospitalizations in U.S. Hospitals.

OBJECTIVES: Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN: Retrospective cohort study. SETTING: About 373 U.S. hospitals. PATIENTS: Adults hospitalized between January 2009 and September 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness.The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS: Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.

Bacterial Infections Associated With Substance Use Disorders, Large Cohort of United States Hospitals, 2012-2017.

BACKGROUND: Rises in the incidence of bacterial infections, such as infective endocarditis (IE), have been reported in conjunction with the opioid crisis. However, recent trends for IE and other serious infections among persons with substance use disorders (SUDs) are unknown. METHODS: Using the Premier Healthcare Database, we identified hospitalizations from 2012 through 2017 among adults with primary discharge diagnoses of bacterial infections and secondary SUD diagnoses, using International Classification of Diseases, Clinical Modification Ninth and Tenth Revision codes. We calculated annual rates of infections with SUD diagnoses and evaluated temporal trends. Blood and cardiac tissue specimens were identified from IE hospitalizations to describe the microbiology distribution and temporal trends among hospitalizations with and without SUDs. RESULTS: Among 72 481 weighted IE admissions recorded, SUD diagnoses increased from 19.9% in 2012 to 39.4% in 2017 (P < .0001). Hospitalizations with SUDs increased from 1.1 to 2.1 per 100 000 persons for IE, 1.4 to 2.4 per 100 000 persons for osteomyelitis, 0.5 to 0.9 per 100 000 persons for central nervous system abscesses, and 24.4 to 32.9 per 100 000 persons for skin and soft tissue infections. For adults aged 18-44 years, IE-SUD hospitalizations more than doubled, from 1.6 in 2012 to 3.6 in 2017 per 100 000 persons. Among all IE-SUD hospitalizations, 50.3% had a Staphylococcus aureus infection, compared with 19.4% of IE hospitalizations without SUDs. CONCLUSIONS: Rates of hospitalization for serious infections among persons with SUDs are increasing, driven primarily by younger age groups. The differences in the microbiology of IE hospitalizations suggest that SUDs are changing the epidemiology of these infections.

Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Electronic Clinical Data and Impact on Hospital Outcome Comparisons.

OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using electronic health record-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to ≥ 2.0 mg/dL, decrease in platelets to < 100 cells/µL, or lactate ≥ 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All estimates were reliability adjusted to account for random variation using hierarchical logistic regression modeling. The sensitivity of hospitals' claims data was low and variable: median 30% (range, 5-54%) for sepsis, 66% (range, 26-84%) for acute kidney injury, 39% (range, 16-60%) for thrombocytopenia, 36% (range, 29-44%) for hepatic injury, and 66% (range, 29-84%) for shock. Correlation between claims and clinical data was moderate for sepsis prevalence (Pearson coefficient, 0.64) and mortality (0.61). Among hospitals in the lowest sepsis mortality quartile by claims, 46% shifted to higher mortality quartiles using clinical data. Using implicit sepsis criteria based on infection and organ dysfunction codes also yielded major differences versus clinical data. CONCLUSIONS: Variation in the accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospitals' sepsis rates and outcomes. Using objective clinical data may facilitate more meaningful hospital comparisons.

Assessing Variability in Hospital-Level Mortality Among U.S. Medicare Beneficiaries With Hospitalizations for Severe Sepsis and Septic Shock.

OBJECTIVES: To assess the variability in short-term sepsis mortality by hospital among Centers for Medicare and Medicaid Services beneficiaries in the United States during 2013-2014. DESIGN: A retrospective cohort design. SETTING: Hospitalizations from 3,068 acute care hospitals that participated in the Centers for Medicare and Medicaid Services inpatient prospective payment system in 2013 and 2014. PATIENTS: Medicare fee-for-service beneficiaries greater than or equal to 65 years old who had an inpatient hospitalization coded with present at admission severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Individual level mortality was assessed as death at or within 7 days of hospital discharge and aggregated to calculate hospital-level mortality rates. We used a logistic hierarchal linear model to calculate mortality risk-adjusted for patient characteristics. We quantified variability among hospitals using the median odds ratio and calculated risk-standardized mortality rates for each hospital. The overall crude mortality rate was 34.7%. We found significant variability in mortality by hospital (p < 0.001). The middle 50% of hospitals had similar risk-standardized mortality rates (32.7-36.9%), whereas the decile of hospitals with the highest risk-standardized mortality rates had a median mortality rate of 40.7%, compared with a median of 29.2% for hospitals in the decile with the lowest risk-standardized mortality rates. The median odds ratio (1.29) was lower than the adjusted odds ratios for several measures of patient comorbidities and severity of illness, including present at admission organ dysfunction, no identified source of infection, and age. CONCLUSIONS: In a large study of present at admission sepsis among Medicare beneficiaries, we showed that mortality was most strongly associated with underlying comorbidities and measures of illness on arrival. However, after adjusting for patient characteristics, mortality also modestly depended on where a patient with sepsis received care, suggesting that efforts to improve sepsis outcomes in lower performing hospitals could impact sepsis survival.

The Potential for Interventions in a Long-term Acute Care Hospital to Reduce Transmission of Carbapenem-Resistant Enterobacteriaceae in Affiliated Healthcare Facilities.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are high-priority bacterial pathogens targeted for efforts to decrease transmissions and infections in healthcare facilities. Some regions have experienced CRE outbreaks that were likely amplified by frequent transmission in long-term acute care hospitals (LTACHs). Planning and funding of intervention efforts focused on LTACHs is one proposed strategy to contain outbreaks; however, the potential regional benefits of such efforts are unclear. METHODS: We designed an agent-based simulation model of patients in a regional network of 10 healthcare facilities including 1 LTACH, 3 short-stay acute care hospitals (ACHs), and 6 nursing homes (NHs). The model was calibrated to achieve realistic patient flow and CRE transmission and detection rates. We then simulated the initiation of an entirely LTACH-focused intervention in a previously CRE-free region, including active surveillance for CRE carriers and enhanced isolation of identified carriers. RESULTS: When initiating the intervention at the first clinical CRE detection in the LTACH, cumulative CRE transmissions over 5 years across all 10 facilities were reduced by 79%-93% compared to no-intervention simulations. This result was robust to changing assumptions for transmission within non-LTACH facilities and flow of patients from the LTACH. Delaying the intervention until the 20th CRE detection resulted in substantial delays in achieving optimal regional prevalence, while still reducing transmissions by 60%-79% over 5 years. CONCLUSIONS: Focusing intervention efforts on LTACHs is potentially a highly efficient strategy for reducing CRE transmissions across an entire region, particularly when implemented as early as possible in an emerging outbreak.

Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014.

Importance: Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective: To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population: Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures: Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures: Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results: A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, -2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (-3.3%/y [95% CI, -5.6% to -1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (-1.3%/y [95% CI, -3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (-7.0%/y [95% CI, -8.8% to -5.2%], P < .001), as did death or discharge to hospice (-4.5%/y [95% CI, -6.1% to -2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance: In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.

Effects of vaccine program against pandemic influenza A(H1N1) virus, United States, 2009-2010.

In April 2009, the United States began a response to the emergence of a pandemic influenza virus strain: A(H1N1)pdm09. Vaccination began in October 2009. By using US surveillance data (April 12, 2009-April 10, 2010) and vaccine coverage estimates (October 3, 2009-April 18, 2010), we estimated that the A(H1N1)pdm09 virus vaccination program prevented 700,000-1,500,000 clinical cases, 4,000-10,000 hospitalizations, and 200-500 deaths. We found that the national health effects were greatly influenced by the timing of vaccine administration and the effectiveness of the vaccine. We estimated that recommendations for priority vaccination of targeted priority groups were not inferior to other vaccination prioritization strategies. These results emphasize the need for relevant surveillance data to facilitate a rapid evaluation of vaccine recommendations and effects.

Epidemiology of Sepsis in US Children and Young Adults.

Background: Most multicenter studies of US pediatric sepsis epidemiology use administrative data or focus on pediatric intensive care units. We conducted a detailed medical record review to describe sepsis epidemiology in children and young adults. Methods: In a convenience sample of hospitals in 10 states, patients aged 30 days-21 years, discharged during 1 October 2014-30 September 2015, with explicit diagnosis codes for severe sepsis or septic shock, were included. Medical records were reviewed for patients with documentation of sepsis, septic shock, or similar terms. We analyzed overall and age group-specific patient characteristics. Results: Of 736 patients in 26 hospitals, 442 (60.1%) had underlying conditions. Most patients (613 [83.3%]) had community-onset sepsis, although most community-onset sepsis was healthcare associated (344 [56.1%]). Two hundred forty-one patients (32.7%) had outpatient visits 1-7 days before sepsis hospitalization, of whom 125 (51.9%) received antimicrobials ≤30 days before sepsis hospitalization. Age group-related differences included common underlying conditions (<5 years: prematurity vs 5-12 years: chronic pulmonary disease vs 13-21 years: chronic immunocompromise); medical device presence ≤30 days before sepsis hospitalization (1-4 years: 46.9% vs 30 days-11 months: 23.3%); percentage with hospital-onset sepsis (<5 years: 19.6% vs ≥5 years: 12.0%); and percentage with sepsis-associated pathogens (30 days-11 months: 65.6% vs 13-21 years: 49.3%). Conclusions: Our data suggest potential opportunities to raise sepsis awareness among outpatient providers to facilitate prevention, early recognition, and intervention in some patients. Consideration of age-specific differences may be important as approaches are developed to improve sepsis prevention, risk prediction, recognition, and management.

Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009.

BACKGROUND: During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009. METHODS: Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. RESULTS: Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early. CONCLUSIONS: During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.

Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP).

This report updates previous recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of antiviral agents for the prevention and treatment of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2008;57[No. RR-7]).This report contains information on treatment and chemoprophylaxis of influenza virus infection and provides a summary of the effectiveness and safety of antiviral treatment medications. Highlights include recommendations for use of 1) early antiviral treatment of suspected or confirmed influenza among persons with severe influenza (e.g., those who have severe, complicated, or progressive illness or who require hospitalization); 2) early antiviral treatment of suspected or confirmed influenza among persons at higher risk for influenza complications; and 3) either oseltamivir or zanamivir for persons with influenza caused by 2009 H1N1 virus, influenza A (H3N2) virus, or influenza B virus or when the influenza virus type or influenza A virus subtype is unknown; 4) antiviral medications among children aged <1 year; 5) local influenza testing and influenza surveillance data, when available, to help guide treatment decisions; and 6) consideration of antiviral treatment for outpatients with confirmed or suspected influenza who do not have known risk factors for severe illness, if treatment can be initiated within 48 hours of illness onset. Additional information is available from CDC's influenza website at http://www.cdc.gov/flu, including any updates or supplements to these recommendations that might be required during the 2010-11 influenza season. Health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information. Recommendations related to the use of vaccines for the prevention of influenza during the 2010-11 influenza season have been published previously (CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices [ACIP], 2010. MMWR 2010;59[No. RR-8]).

Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010.

This report updates the 2009 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8] and CDC. Use of influenza A (H1N1) 2009 monovalent vaccine---recommendations of the Advisory Committee on Immunization Practices [ACIP], 2009. MMWR 2009;58:[No. RR-10]). The 2010 influenza recommendations include new and updated information. Highlights of the 2010 recommendations include 1) a recommendation that annual vaccination be administered to all persons aged >or=6 months for the 2010-11 influenza season; 2) a recommendation that children aged 6 months--8 years whose vaccination status is unknown or who have never received seasonal influenza vaccine before (or who received seasonal vaccine for the first time in 2009-10 but received only 1 dose in their first year of vaccination) as well as children who did not receive at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine regardless of previous influenza vaccine history should receive 2 doses of a 2010-11 seasonal influenza vaccine (minimum interval: 4 weeks) during the 2010--11 season; 3) a recommendation that vaccines containing the 2010-11 trivalent vaccine virus strains A/California/7/2009 (H1N1)-like (the same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; 4) information about Fluzone High-Dose, a newly approved vaccine for persons aged >or=65 years; and 5) information about other standard-dose newly approved influenza vaccines and previously approved vaccines with expanded age indications. Vaccination efforts should begin as soon as the 2010-11 seasonal influenza vaccine is available and continue through the influenza season. These recommendations also include a summary of safety data for U.S.-licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2010-11 influenza season also will be available at this website. Recommendations for influenza diagnosis and antiviral use will be published before the start of the 2010-11 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

This report updates the 2008 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2008;57[No. RR-7]). Information on vaccination issues related to the recently identified novel influenza A H1N1 virus will be published later in 2009. The 2009 seasonal influenza recommendations include new and updated information. Highlights of the 2009 recommendations include 1) a recommendation that annual vaccination be administered to all children aged 6 months-18 years for the 2009-10 influenza season; 2) a recommendation that vaccines containing the 2009-10 trivalent vaccine virus strains A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; and 3) a notice that recommendations for influenza diagnosis and antiviral use will be published before the start of the 2009-10 influenza season. Vaccination efforts should begin as soon as vaccine is available and continue through the influenza season. Approximately 83% of the United States population is specifically recommended for annual vaccination against seasonal influenza; however, <40% of the U.S. population received the 2008-09 influenza vaccine. These recommendations also include a summary of safety data for U.S. licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2009-10 influenza season also can be found at this website. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

Seasonal influenza vaccines.

Influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated influenza vaccines have been available since the 1940s and are administered via intramuscular injection. Inactivated vaccines can be given to anyone six months of age or older. Live attenuated, cold-adapted influenza vaccines (LAIV) were developed in the 1960s but were not licensed in the United States until 2003, and are administered via nasal spray. Both vaccines are trivalent preparations grown in eggs and do not contain adjuvants. LAIV is licensed for use in the United States for healthy nonpregnant persons 2-49 years of age.Influenza vaccination induces antibodies primarily against the major surface glycoproteins hemagglutinin (HA) and neuraminidase (NA); antibodies directed against the HA are most important for protection against illness. The immune response peaks at 2-4 weeks after one dose in primed individuals. In previously unvaccinated children <9 years of age, two doses of influenza vaccine are recommended, as some children in this age group have limited or no prior infections from circulating types and subtypes of seasonal influenza. These children require both an initial priming dose and a subsequent booster dose of vaccine to mount a protective antibody response.The most common adverse events associated with inactivated vaccines are sore arm and redness at the injection site; systemic symptoms such as fever or malaise are less commonly reported. Guillian-Barré Syndrome (GBS) was identified among approximately 1 per 100,000 recipients of the 1976 swine influenza vaccine. The risk of influenza vaccine-associated GBS from seasonal influenza vaccine is thought to be at most approximately 1-2 cases per 1 million vaccinees, based on a few studies that have found an association; other studies have found no association.The most common adverse events associated with LAIV are nasal congestion, headache, myalgias or fever. Studies of the safety of LAIV among young children suggest an increased risk of wheezing in some young children, and the vaccine is not recommended for children younger than 2 years old, ages 2-4 old with a history of recurrent wheezing or reactive airways disease, or older persons who have any medical condition that confers an increased risk of influenza-related complications.The effectiveness of influenza vaccines is related predominantly to the age and immune competence of the vaccinee and the antigenic relatedness of vaccine strains to circulating strains. Vaccine effectiveness in preventing laboratory-confirmed influenza illness when the vaccine strains are well matched to circulating strains is 70-90% in randomized, placebo-controlled trials conducted among children and young healthy adults, but is lower among elderly or immunocompromised persons. In years with a suboptimal match, vaccine benefit is likely to be lower, although the vaccine can still provide substantial benefit, especially against more severe outcomes. Live, attenuated influenza vaccines have been most extensively studied among children, and have been shown to be more effective than inactivated vaccines in several randomized controlled trials among young children.Influenza vaccination is recommended in the United States for all children six months or older, all adults 50 years or older, all persons with chronic medical conditions, and pregnant women, and contacts of these persons, including healthcare workers. The global disease burden of influenza is substantial, and the World Health Organization has indicated that member states should evaluate the cost-effectiveness of introducing influenza vaccination into national immunization programs. More research is needed to develop more effective seasonal influenza vaccines that provide long-lasting immunity and broad protection against strains that differ antigenically from vaccine viruses.

Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose.

BACKGROUND: The duration of protection in children and adults (including health care workers) resulting from the hepatitis B vaccine primary series is unknown. METHODS: To determine the protection afforded by hepatitis B vaccine, Alaska Native persons who had received plasma-derived hepatitis B vaccine when they were >6 months of age were tested for antibody to hepatitis B surface antigen (anti-HBs) 22 years later. Those with levels <10 mIU/mL received 1 dose of recombinant hepatitis B vaccine and were evaluated on the basis of anti-HBs measurements at 10-14 days, 30-60 days, and 1 year. RESULTS: Of 493 participants, 60% (298) had an anti-HBs level >or=10 mIU/mL. A booster dose was administered to 164 persons, and 77% responded with an anti-HBs level >or=10 mIU/mL at 10-14 days, reaching 81% by 60 days. Response to a booster dose was positively correlated with younger age, peak anti-HBs response after primary vaccination, and the presence of detectable anti-HBs before boosting. Considering persons with an anti-HBs level >or=10 mIU/mL at 22 years and those who responded to the booster dose, protection was demonstrated in 87% of the participants. No new acute or chronic hepatitis B virus infections were identified. CONCLUSIONS: The protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 22 years. Booster doses are not needed.

Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008.

This report updates the 2007 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine and antiviral agents (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2007;56[No. RR-6]). The 2008 recommendations include new and updated information. Principal updates and changes include 1) a new recommendation that annual vaccination be administered to all children aged 5--18 years, beginning in the 2008--09 influenza season, if feasible, but no later than the 2009--10 influenza season; 2) a recommendation that annual vaccination of all children aged 6 months through 4 years (59 months) continue to be a primary focus of vaccination efforts because these children are at higher risk for influenza complications compared with older children; 3) a new recommendation that either trivalent inactivated influenza vaccine or live, attenuated influenza vaccine (LAIV) be used when vaccinating healthy persons aged 2 through 49 years (the previous recommendation was to administer LAIV to person aged 5--49 years); 4) a recommendation that vaccines containing the 2008--09 trivalent vaccine virus strains A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Florida/4/2006-like antigens be used; and, 5) new information on antiviral resistance among influenza viruses in the United States. Persons for whom vaccination is recommended are listed in boxes 1 and 2. These recommendations also include a summary of safety data for U.S. licensed influenza vaccines. This report and other information are available at CDC's influenza website (http://www.cdc.gov/flu), including any updates or supplements to these recommendations that might be required during the 2008--09 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

A primer on strategies for prevention and control of seasonal and pandemic influenza.

The United States has made considerable progress in pandemic preparedness. Limited attention, however, has been given to the challenges faced by populations that will be at increased risk of the consequences of the pandemic, including challenges caused by societal, economic, and health-related factors. This supplement to the American Journal of Public Health focuses on the challenges faced by at-risk and vulnerable populations in preparing for and responding to an influenza pandemic. Here, we provide background information for subsequent articles throughout the supplement. We summarize (1) seasonal influenza epidemiology, transmission, clinical illness, diagnosis, vaccines, and antiviral medications; (2) H5N1 avian influenza; and (3) pandemic influenza vaccines, antiviral medications, and nonpharmaceutical interventions.

A National Approach to Pediatric Sepsis Surveillance.

Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of age-dependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment.

An outbreak of hepatitis A associated with green onions.

BACKGROUND: In November 2003, a large hepatitis A outbreak was identified among patrons of a single Pennsylvania restaurant. We investigated the cause of the outbreak and factors that contributed to its unprecedented size. METHODS: Demographic and clinical outcome data were collected from patients with laboratory confirmation of hepatitis A, and restaurant workers were tested for hepatitis A. A case-control study was conducted among patrons who dined at the restaurant between October 3 and October 6, 2003. Sequence analysis was performed on a 315-nucleotide region of viral RNA extracted from serum specimens. RESULTS: Of 601 patients identified, 3 died; at least 124 were hospitalized. Of 425 patients who recalled a single dining date at the restaurant, 356 (84 percent) had dined there between October 3 and October 6. Among 240 patients in the case-control study, 218 had eaten mild salsa (91 percent), as compared with 45 of 130 controls (35 percent) (odds ratio, 19.6; 95 percent confidence interval, 11.0 to 34.9) for whom data were available. A total of 98 percent of patients and 58 percent of controls reported having eaten a menu item containing green onions (odds ratio, 33.3; 95 percent confidence interval, 12.8 to 86.2). All restaurant workers were tested, but none were identified who could have been the source of the outbreak. Sequences of hepatitis A virus from all 170 patients who were tested were identical. Mild salsa, which contained green onions grown in Mexico, was prepared in large batches at the restaurant and provided to all patrons. CONCLUSIONS: Green onions that were apparently contaminated before arrival at the restaurant caused this unusually large foodborne outbreak of hepatitis A. The inclusion of contaminated green onions in large batches that were served to all customers contributed to the size of the outbreak.

Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007.

This report updates the 2006 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine and antiviral agents (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55[No. RR-10]). The groups of persons for whom vaccination is recommended and the antiviral medications recommended for chemoprophylaxis or treatment (oseltamivir or zanamivir) have not changed. Estimated vaccination coverage remains <50% among certain groups for whom routine annual vaccination is recommended, including young children and adults with risk factors for influenza complications, health-care personnel (HCP), and pregnant women. Strategies to improve vaccination coverage, including use of reminder/recall systems and standing orders programs, should be implemented or expanded. The 2007 recommendations include new and updated information. Principal updates and changes include 1) reemphasizing the importance of administering 2 doses of vaccine to all children aged 6 months--8 years if they have not been vaccinated previously at any time with either live, attenuated influenza vaccine (doses separated by > or =6 weeks) or trivalent inactivated influenza vaccine (doses separated by > or =4 weeks), with single annual doses in subsequent years; 2) recommending that children aged 6 months--8 years who received only 1 dose in their first year of vaccination receive 2 doses the following year, with single annual doses in subsequent years; 3) highlighting a previous recommendation that all persons, including school-aged children, who want to reduce the risk of becoming ill with influenza or of transmitting influenza to others should be vaccinated; 4) emphasizing that immunization providers should offer influenza vaccine and schedule immunization clinics throughout the influenza season; 5) recommending that health-care facilities consider the level of vaccination coverage among HCP to be one measure of a patient safety quality program and implement policies to encourage HCP vaccination (e.g., obtaining signed statements from HCP who decline influenza vaccination); and 6) using the 2007--2008 trivalent vaccine virus strains A/Solomon Islands/3/2006 (H1N1)-like (new for this season), A/Wisconsin/67/2005 (H3N2)-like, and B/Malaysia/2506/2004-like antigens. This report and other information are available at CDC's influenza website (http://www.cdc.gov/flu). Updates or supplements to these recommendations (e.g., expanded age or risk group indications for currently licensed vaccines) might be required. Immunization providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.