This report updates CDC's recommendations for using yellow fever (YF) vaccine (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunizations Practices: MMWR 2002;51[No. RR-17]). Since the previous YF vaccine recommendations were published in 2002, new or additional information has become available on the epidemiology of YF, safety profile of the vaccine, and health regulations related to the vaccine. This report summarizes the current epidemiology of YF, describes immunogenicity and safety data for the YF vaccine, and provides recommendations for the use of YF vaccine among travelers and laboratory workers. YF is a vectorborne disease resulting from the transmission of yellow fever virus (YFV) to a human from the bite of an infected mosquito. It is endemic to sub-Saharan Africa and tropical South America and is estimated to cause 200,000 cases of clinical disease and 30,000 deaths annually. Infection in humans is capable of producing hemorrhagic fever and is fatal in 20%-50% of persons with severe disease. Because no treatment exists for YF disease, prevention is critical to lower disease risk and mortality. A traveler's risk for acquiring YFV is determined by multiple factors, including immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and local rate of virus transmission at the time of travel. All travelers to countries in which YF is endemic should be advised of the risks for contracting the disease and available methods to prevent it, including use of personal protective measures and receipt of vaccine. Administration of YF vaccine is recommended for persons aged >or=9 months who are traveling to or living in areas of South America and Africa in which a risk exists for YFV transmission. Because serious adverse events can occur following YF vaccine administration, health-care providers should vaccinate only persons who are at risk for exposure to YFV or who require proof of vaccination for country entry. To minimize the risk for serious adverse events, health-care providers should observe the contraindications, consider the precautions to vaccination before administering vaccine, and issue a medical waiver if indicated.

INTRODUCTION: The number of cancer cases in the United States continues to grow as the number of older adults increases. Accurate, reliable and detailed incidence data are needed to respond effectively to the growing human costs of cancer in an aging population. The purpose of this study was to examine the characteristics of incident cases and evaluate the impact of death-certificate-only (DCO) cases on cancer incidence rates in older adults. METHODS: Using data from 47 cancer registries and detailed population estimates from the Surveillance, Epidemiology and End Results (SEER) Program, we examined reporting sources, methods of diagnosis, tumor characteristics, and calculated age-specific incidence rates with and without DCO cases in adults aged 65 through ≥95 years, diagnosed 2011 through 2015, by sex and race/ethnicity. RESULTS: The percentage of cases (all cancers combined) reported from a hospital decreased from 90.6% (ages 65-69 years) to 69.1% (ages ≥95 years) while the percentage of DCO cases increased from 1.1% to 19.6%. Excluding DCO cases, positive diagnostic confirmation decreased as age increased from 96.8% (ages 65-69 years) to 69.2% (ages ≥95 years). Compared to incidence rates that included DCO cases, rates in adults aged ≥95 years that excluded DCO cases were 41.5% lower in Black men with prostate cancer and 29.2% lower in Hispanic women with lung cancer. DISCUSSION: Loss of reported tumor specificity with age is consistent with fewer hospital reports. However, the majority of cancers diagnosed in older patients, including those aged ≥95 years, were positively confirmed and were reported with known site, histology, and stage information. The high percentage of DCO cases among patients aged ≥85 years suggests the need to explore additional sources of follow-back to help possibly identify an earlier incidence report. Interstate data exchange following National Death Index linkages may help registries identify and remove erroneous DCO cases from their databases.

In 2016, Sanofi Pasteur (S-P) experienced a manufacturing disruption of yellow fever vaccine (YF-Vax), the only U.S.-licensed YF-Vax, depleting the U.S. supply by mid-2017. Sanofi Pasteur received approval to import Stamaril, S-P's French-manufactured YF-Vax, for use in 260 U.S. civilian clinics under an expanded access investigational new drug program (EAP). The CDC also broadened its YF-Vax indication in early 2018. Our objective was to assess usage at participating Global TravEpiNet (GTEN) clinics, a U.S. CDC-supported national consortium of clinical sites that administer vaccines, during this period of limited availability and changing recommendations. We analyzed 2012-2018 GTEN data for YF-Vax usage, unavailability, and reasons for refusal. We also performed a brief voluntary survey of GTEN sites to better understand their experience during the shortage. Yellow fever vaccine unavailability at certain GTEN clinics was intermittent and recurrent, starting months before total depletion. Unavailability at GTEN clinics peaked weeks before the total depletion. Compared with historic norms, YF-Vax usage following initial vaccine availability limitations did not change until vaccine recommendations were broadened. Refusal of recommended YF-Vax also decreased during this period. Queried sites participating in the EAP felt their supply of vaccine was adequate. Our analysis suggests that in response to depletion of a travel vaccine, an EAP can make an unlicensed product available, patients will participate in such a program, and the program can respond to expanding recommendations for vaccine usage.

Sanofi Pasteur, the manufacturer of the only yellow fever vaccine (YF-VAX) licensed in the United States, has announced that their stock of YF-VAX is totally depleted as of July 24, 2017. YF-VAX for civilian use will be unavailable for ordering from Sanofi Pasteur until mid-2018, when their new manufacturing facility is expected to be completed. However, YF-VAX might be available at some clinics for several months, until remaining supplies at those sites are exhausted. In anticipation of this temporary total depletion, in 2016, Sanofi Pasteur submitted an expanded access investigational new drug application to the Food and Drug Administration to allow for importation and use of Stamaril. The Food and Drug Administration accepted Sanofi Pasteur's application in October 2016.

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

BACKGROUND: Influenza and pneumonia combined are the leading causes of death due to infectious diseases in the United States. We describe factors associated with pneumonia among adults hospitalized with influenza. METHODS: Through the Emerging Infections Program, we identified adults ≥ 18 years, who were hospitalized with laboratory-confirmed influenza during October 2005 through April 2008, and had a chest radiograph (CXR) performed. Pneumonia was defined as the presence of a CXR infiltrate and either an ICD-9-CM code or discharge summary diagnosis of pneumonia. RESULTS: Among 4,765 adults hospitalized with influenza, 1392 (29 %) had pneumonia. In multivariable analysis, factors associated with pneumonia included: age ≥ 75 years, adjusted odds ratio (AOR) 1.27 (95 % confidence interval 1.10-1.46), white race AOR 1.24 (1.03-1.49), nursing home residence AOR 1.37 (1.14-1.66), chronic lung disease AOR 1.37 (1.18-1.59), immunosuppression AOR 1.45 (1.19-1.78), and asthma AOR 0.76 (0.62-0.92). Patients with pneumonia were significantly more likely to require intensive care unit (ICU) admission (27 % vs. 10 %), mechanical ventilation (18 % vs. 5 %), and to die (9 % vs. 2 %). CONCLUSIONS: Pneumonia was present in nearly one-third of adults hospitalized with influenza and was associated with ICU admission and death. Among patients hospitalized with influenza, older patients and those with certain underlying conditions are more likely to have pneumonia. Pneumonia is common among adults hospitalized with influenza and should be evaluated and treated promptly.

Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices.

IMPORTANCE: Travelers from around the globe will attend the 2014 Federation Internationale de Football Association (FIFA) World Cup and the 2016 Olympic and Paralympic Games in Brazil. Travelers to these mass gathering events may be exposed to a range of health risks, including a variety of infectious diseases. Most travelers who become ill will present to their primary care physicians, and thus it is important that clinicians are aware of the risks their patients encountered. OBJECTIVE: To highlight health and safety concerns for people traveling to these events in Brazil so that health care practitioners can better prepare travelers before they travel and more effectively diagnose and treat travelers after they return. EVIDENCE REVIEW: We reviewed both peer-reviewed and gray literature to identify health outcomes associated with travel to Brazil and mass gatherings. Thirteen specific infectious diseases are described in terms of signs, symptoms, and treatment. Relevant safety and security concerns are also discussed. FINDINGS: Travelers to Brazil for mass gathering events face unique health risks associated with their travel. CONCLUSIONS AND RELEVANCE: Travelers should consult a health care practitioner 4 to 6 weeks before travel to Brazil and seek up-to-date information regarding their specific itineraries. For the most up-to-date information, health care practitioners can visit the Centers for Disease Control and Prevention (CDC) Travelers' Health website (http://wwwnc.cdc.gov/travel) or review CDC's Yellow Book online (http://wwwnc.cdc.gov/travel/page/yellowbook-home-2014).

BACKGROUND: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in U.S. Emerging Infections Program sites. METHODS: Cases were children 6-59 months of age hospitalized for laboratory-confirmed influenza infections during 2005-08. Age- and zip-code-matched controls were enrolled. Data on child, caregiver, and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization. RESULTS: We enrolled 290 (64%) of 454 eligible cases and 1,089 (49%) of 2,204 eligible controls. Risk for influenza hospitalization increased with maternal age <26 years (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-2.9); household income below the poverty threshold (OR 2.2, CI 1.4-3.6); smoking by >50% of household members (OR 2.9, CI 1.4-6.6); lack of household influenza vaccination (OR 1.8, CI 1.2-2.5); and presence of chronic illnesses, including hematologic/oncologic (OR 11.8, CI 4.5-31.0), pulmonary (OR 2.9, CI 1.9-4.4), and neurologic (OR 3.8, CI 1.6-9.2) conditions. Full influenza immunization decreased the risk among children aged 6-23 months (OR 0.5, CI 0.3-0.9) but not among those 24-59 months of age (OR 1.5, CI 0.8-3.0; p-value for difference = 0.01). CONCLUSIONS: Chronic illnesses, young maternal age, poverty, household smoking, and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness.

BACKGROUND: The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic. METHODS: Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA) genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model. RESULTS: Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases) were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases), C (n = 11 clusters, 27 cases), and Y (n = 9 clusters, 35 cases); 20 clusters (62.5%) were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States. CONCLUSIONS: Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of transmission in populations.

Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57, 95% confidence interval [95% CI] = 1.27-5.22) or going to Nigeria (OR = 3.01, 95% CI = 1.37-6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk-benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations.

BACKGROUND: Because pneumococcal pneumonia was prevalent during previous influenza pandemics, we evaluated invasive pneumococcal pneumonia (IPP) rates during the 2009 influenza A(H1N1) pandemic. METHODS: We identified laboratory-confirmed, influenza-associated hospitalizations and IPP cases (pneumococcus isolated from normally sterile sites with discharge diagnoses of pneumonia) using active, population-based surveillance in the U.S. We compared IPP rates during peak pandemic months (April 2009-March 2010) to mean IPP rates in non-pandemic years (April 2004-March 2009) and, using Poisson models, to 2006-8 influenza seasons. RESULTS: Higher IPP rates occurred during the peak pandemic month compared to non-pandemic periods in 5-24 (IPP rate per 10 million: 48 v. 9 (95% confidence interval (CI) 5-13), 25-49 (74 v. 53 (CI 41-65)), 50-64 (188 v. 114 (CI 85-143)), and ≥65 year-olds (229 v. 187 (CI 159-216)). In the models with seasonal influenza rates included, observed IPP rates during the pandemic peak were within the predicted 95% CIs, suggesting this increase was not greater than observed with seasonal influenza. CONCLUSIONS: The recent influenza pandemic likely resulted in an out-of-season IPP peak among persons ≥5 years. The IPP peak's magnitude was similar to that seen during seasonal influenza epidemics.

BACKGROUND: The Emerging Infections Programs (EIP) network has conducted population-based surveillance for hospitalizations due to laboratory-confirmed influenza among children since 2003, with the network expanding in 2005 to include adults. METHODS: From 15 April 2009 through 30 April 2010, the EIP conducted surveillance among 22.1 million people residing in 10 states. Incidence rates per 100,000 population were calculated using US Census Bureau data. Mean historic rates were calculated on the basis of previously published and unpublished EIP data. RESULTS: During the 2009 pandemic of influenza A virus subtype H1N1 infection, rates of hospitalizations due to laboratory-confirmed influenza were 202, 88, 49, 31, 27, 36, 28, and 27 episodes per 100,000 among persons aged <6 months, 6-23 months, 2-4 years, 5-17 years, 18-49 years, 50-64 years, 65-74 years, and ≥75 years, respectively. Comparative mean rates from previous influenza seasons during which EIP conducted surveillance were 153, 53, 20, 6, 4, 8, 20, and 56 episodes per 100,000 among persons aged <6 months, 6-23 months, 2-4 years, 5-17 years, 18-49 years, 50-64 years, 65-74 years, and ≥75 years, respectively. CONCLUSIONS: During the pandemic, rates of hospitalization due to laboratory-confirmed influenza among individuals aged 5-17 years and 18-49 years increased 5-fold and 6-fold, respectively, compared with mean rates from previous influenza seasons. Hospitalization rates for other pediatric and adult age groups increased, compared with mean rates from previous influenza seasons, whereas the rate among individuals aged ≥75 years decreased.

OBJECTIVES: We assessed telephone surveys as a novel surveillance method, comparing data obtained by telephone with existing national influenza surveillance systems, and evaluated the utility of telephone surveys. METHODS: We used the 2007 Behavioral Risk Factor Surveillance System (BRFSS) and the 2007 National Immunization Survey-Adult (NIS-Adult) to estimate the incidence of influenza-like illness (ILI), medically attended ILI, provider-diagnosed influenza, influenza testing, and treatment of influenza with antiviral medications during the 2006-2007 influenza season. RESULTS: With the January-May BRFSS, among persons aged 18 years and older, the cumulative incidence of seasonal ILI and provider-diagnosed influenza was 37.9 and 5.7 adults per 100 persons, respectively. Monthly medically attended ILI and provider-diagnosed influenza among adults were temporally associated with influenza activity, as documented by national surveillance. With the NIS-Adult survey data, estimated provider-diagnosed influenza, influenza testing, and antiviral treatment were 2.8%, 1.4%, and 0.6%, respectively. CONCLUSIONS: Our telephone interview-based estimates of influenza morbidity were consistent with those from national influenza surveillance systems. Telephone surveys may provide an alternative method by which population-based influenza morbidity information can be gathered. (Am J Public Health. Published online ahead of print December 13, 2012: e1-e9. doi:10.2105/AJPH.2012.300799).

OBJECTIVES: Introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine has resulted in a dramatic reduction of Hib disease in the U.S. and an increase in the relative importance of infections caused by nontypeable strains. The current project describes the characteristics and clinical outcomes of pediatric and adult patients with invasive H. influenzae (HI) and, through multivariable analysis, identifies risk factors for in-hospital mortality. METHODS: HI cases were identified during 1999-2008 through active surveillance as part of Active Bacterial Core surveillance (ABCs). Multivariable analysis was performed with logistic regression to identify factors predictive of in-hospital death. RESULTS: 4839 cases of HI were identified from 1999-2008. Children accounted for 17.1% of cases and adults 82.9%. Underlying conditions were present in 20.7% of children and 74.8% of adults. In-hospital mortality was highest in cases ≥65 years (21.9%) and <3 months (16.2%). The risk of in-hospital death in children <1 year was higher among those who were prematurely-born (<28 weeks, OR 7.1, 95% CI 3.2-15.6; 28-36 weeks OR 2.1, 95% CI 0.9-4.8) and, among children aged 1-17 years, higher in those with healthcare-associated onset and dialysis (OR 5.66, 95% CI 1.84-17.39; OR 18.11, 95% CI 2.77-118.65). In adults, age ≥40 was associated with death in nontypeable, but not encapsulated, infections. Infections with nontypeable strains increased the risk of death in cases ≥65 years (OR 1.81, 95% CI 1.31-2.52). Healthcare-associated HI, bacteremia without identifiable focus, bacteremic pneumonia, associated cirrhosis, cerebrovascular accident, dialysis, heart failure, and non-hematologic malignancy also increased the risk of death in adults. CONCLUSION: Prematurity in infants, advanced age and certain chronic diseases in adults were associated with an increased risk of in-hospital death. Nontypeable HI was associated with higher mortality in the elderly.

BACKGROUND: Providers must counsel travelers to yellow fever (YF)-endemic areas, although risk estimates of disease and vaccine serious adverse events (SAEs) may be imprecise. The impact of risk information and patients' requests for participation in vaccine decisions on providers' recommendations is unknown. METHODS: Vaccine providers were surveyed regarding decisions for 4 patient scenarios before and after being presented information about risk of YF disease vs vaccine SAEs. Participants' theoretical attitudes were compared with actual responses to scenarios in which patients wanted to share vaccine decisions. Analyses were done by using chi(2) tests with significance level of .05. RESULTS: Forty-six percent of respondents made appropriate initial YF vaccine administration decisions for a pregnant woman, 73% for an immunosuppressed man, and 49% for an 8-month-old infant. After receiving scenario-specific information, 20%, 54%, and 23% of respondents respectively who initially responded incorrectly changed to a more appropriate decision. Thirty-one percent of participants made consistently appropriate decisions. Among participants who made ≥1 incorrect decision, 35.7% made no decision changes after receiving information. In the scenario in which either a decision to withhold or to administer vaccine was acceptable, 19% of respondents refused a patient's request for vaccine. CONCLUSIONS: Targeted information is necessary but insufficient to change the process of vaccine administration decision making. Providers need additional education to enable them to apply evidence, overcome cognitive decision-making errors, and involve patients in vaccine decisions.

The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19-35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001-2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001-2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ≥1 dose increased from 38% to 97%. Case-control VE for ≥1 dose was estimated as 75% against all-serotype IPD (annual range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the screening method, the overall VE was 86% for ≥1 dose (annual range: -240-70%) against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs.

BACKGROUND: Case-control studies evaluating post-licensure effectiveness of conjugate vaccines can be laborious and costly. We applied an indirect cohort method to evaluate the effectiveness of seven-valent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) and compared the results to the effectiveness measured using a standard case-control study conducted during the same time period. METHODS: IPD cases among children 2-59 months old were identified through the Active Bacterial Core surveillance system during 2001-2009. We used logistic regression to calculate the odds ratio of vaccination (versus no vaccination) among cases (PCV7-type IPD cases) and non-cases (non-PCV7-type IPD cases), controlling for the presence of underlying conditions. Vaccine effectiveness (VE) was calculated as one minus the adjusted odds ratio. RESULTS: Among 4225 IPD cases reported during 2001-2009, 2680 (63%) had serotype information and vaccine history. Effectiveness of ≥1 dose of PCV7 against PCV7-types was 88% (95% confidence interval (CI) 78-94%) among children with comorbid conditions and 97% (95% CI 92-98%) among healthy children. Among healthy children, VE was higher in 2001-2003 (97%, 95% CI 95-98%) compared to 2004-2009 (81%, 95% CI 64-90%). The annual estimates of VE in 2004-2009 showed great variability and wide confidence intervals due to the small number of PCV7-type cases. CONCLUSIONS: An indirect cohort design using IPD surveillance data confirms the findings of the case-control study and, therefore, appears suitable for estimating PCV7effectiveness. This method would be most useful shortly after vaccine introduction, and less useful in a setting of very high vaccine coverage and fewer vaccine-type cases.

Viscerotropic disease (VTD) is defined as acute multiple organ system dysfunction that occurs following vaccination. The severity of VTD ranges from relatively mild multisystem disease to severe multiple organ system failure and death. The term VTD was first used shortly after the initial published reports in 2001 of febrile multiple organ system failure following yellow fever (YF) vaccination [1–7]. To date, VTD has been reported only in association with YF vaccine and has been thus referred to as YF vaccine-associated viscerotropic disease (YEL-AVD). | YF vaccine is manufactured from the live attenuated 17D virus substrain. It is considered relatively safe and effective in preventing YF disease, which results from YF virus transmission through the bite of an infected mosquito [8]. YF virus circulates in sub-Saharan Africa and tropical South America, where it causes endemic and intermittently epidemic disease. Most YF disease in these areas is attributable to jungle (sylvatic) or savanna (intermediate) transmission cycles, which occur predominantly in sparsely populated forested areas and rural villages, respectively [8]. To protect vulnerable populations, endemic countries target YF vaccination efforts towards their residents, who reside in both rural and urban settings with varying resources.

Influenza antiviral treatment is recommended for all persons hospitalized with influenza virus infection. During the 2010-2011 influenza season, antiviral treatment of children and adults hospitalized with laboratory-confirmed influenza declined significantly compared to treatment during the 2009 pandemic (children: 56% versus 77%, p <0.01; adults 77% versus 82%, p<0.01).

BACKGROUND: Many assumed high morbidity and mortality would accompany the emergence of MRSA USA300 infections as a cause of healthcare-associated infections (HAIs). We evaluated patients with invasive MRSA infections to assess differences in outcomes between infections caused by USA100 and USA300. METHODS: Population-based data for invasive MRSA infections were used to identify two cohorts: (1) non-dialysis patients with central line-associated bloodstream infections (CLABSI); and (2) patients with community-onset pneumonia (PNEUMO) during 2005-2007 from 6 US metropolitan areas. Medical records of patients with confirmed MRSA USA100 or USA300 were reviewed. Logistic regression and, when appropriate, survival analysis was performed to evaluate mortality, early and late complications, and length of stay. RESULTS: A total of 236 and 100 patients were included in the CLABSI and PNEUMO cohorts, respectively. USA300 was the only independent predictor of early complications for PNEUMO patients (OR=2.6, P=.02). Independent predictors of CLABSI late complications included intensive care unit (ICU) admission before MRSA culture (aOR=2.1, P=.01) and Charlson comorbidity index (aOR=2.6; P=.003), but not strain type. PNEUMO patients were significantly more likely to die if they were older (P=.02), black (P<.001) or infected with USA100 strain (P=.02); while those with CLABSI were more likely to die if they were older (P<.001), had comorbidities (P<.001) or had an ICU admission before MRSA culture (P=.001). CONCLUSIONS: USA300 was associated with early complications in PNEUMO patients. However, it was not associated with mortality for either PNEUMO or CLABSI patients. Concerns regarding higher mortality from HAIs caused by USA300 may not be warranted.

Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3x the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, approximately 17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics.

BACKGROUND AND OBJECTIVES: We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. METHODS: We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. RESULTS: Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. CONCLUSIONS: A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) caused approximately 44,000 US invasive pneumococcal disease (IPD) cases in 2008. Antibiotic nonsusceptibility complicates IPD treatment. Using penicillin susceptibility breakpoints adopted in 2008, we evaluated antibiotic-nonsusceptible IPD trends in light of the introductions of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 and a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010. METHODS: IPD cases were defined by isolation of pneumococcus from a normally sterile site in individuals residing in Active Bacterial Core surveillance (ABCs) areas during 1998-2008. Pneumococci were serotyped and tested for antibiotic susceptibility using broth microdilution. RESULTS: During 1998-2008, ABCs identified 43,198 IPD cases. Penicillin-nonsusceptible strains caused 6%-14% of IPD cases, depending on age. Between 1998-1999 and 2008, penicillin-nonsusceptible IPD rates declined 64% for children aged <5 years (12.1-4.4 cases per 100,000), and 45% for adults aged ≥65 (4.8-2.6 cases per 100,000). Rates of IPD nonsusceptible to multiple antibiotics mirrored these trends. During 2007-2008, serotypes in PCV13 but not PCV7 caused 78%-97% of penicillin-nonsusceptible IPD, depending on age. CONCLUSIONS: Antibiotic-nonsusceptible IPD rates remain below pre-PCV7 rates for children <5 and adults ≥65 years old. PCV13 vaccines hold promise for further nonsusceptibility reductions.

BACKGROUND: Statins may have anti-inflammatory and immunomodulatory effects that could reduce the risk of mortality from influenza virus infections. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program conducts active surveillance for persons hospitalized with laboratory-confirmed influenza in 59 counties in 10 states. We analyzed data for hospitalized adults during the 2007-2008 influenza season to evaluate the association between receiving statins and influenza-related death. RESULTS: We identified 3043 patients hospitalized with laboratory-confirmed influenza, of whom 1013 (33.3%) received statins and 151 (5.0%) died within 30 days of their influenza test. Patients who received statins were more likely to be older, male, and white; to suffer from cardiovascular, metabolic, renal, and chronic lung disease; and to have been vaccinated against influenza that season. In a multivariable logistic regression model, administration of statins prior to or during hospitalization was associated with a protective odds of death (adjusted odds ratio, 0.59 [95% confidence interval, .38-.92]) when adjusting for age; race; cardiovascular, lung, and renal disease; influenza vaccination; and antiviral administration. CONCLUSIONS: Statin use may be associated with reduced mortality in patients hospitalized with influenza.

BACKGROUND: With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. METHODS: Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008. RESULTS: During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100,000 population; 15.3% of cases were fatal. Incidence was higher among adults aged ≥65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged ≥18 years. CONCLUSIONS: Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States.

BACKGROUND: The 2009 influenza pandemic led to guidelines emphasizing antiviral treatment for all persons hospitalized with influenza, including pregnant women. We compared antiviral use among adults hospitalized with influenza before and during the pandemic. METHODS: The Emerging Infections Program conducts active population-based surveillance for persons hospitalized with community-acquired, laboratory-confirmed influenza in 10 states. We analyzed data collected via medical record review of patients aged ≥18 years admitted during prepandemic (1 October 2005 through 14 April 2009) and pandemic (15 April 2009 through 31 December 2009) time frames. RESULTS: Of 5943 adults hospitalized with influenza in prepandemic seasons, 3235 (54%) received antiviral treatment, compared with 4055 (82%) of 4966 during the pandemic. Forty-one (22%) of 187 pregnant women received antiviral treatment in prepandemic seasons, compared with 369 (86%) of 430 during the pandemic. Pregnancy was a negative predictor of antiviral treatment before the pandemic (adjusted odds ratio [aOR], 0.24; 95% confidence interval [CI], .16-.35) but was independently associated with treatment during the pandemic (aOR, 1.97; 95% CI, 1.32-2.96). Antiviral treatment among adults hospitalized >2 days after illness onset increased from 43% before the pandemic to 79% during the pandemic (P < .001). CONCLUSIONS: Antiviral treatment of hospitalized adults increased during the pandemic, especially among pregnant women. This suggests that many clinicians followed published guidance to treat hospitalized adults with antiviral agents. However, compliance with antiviral recommendations could be improved.

The changing epidemiology of yellow fever and continued reports of rare but serious adverse events associated with yellow fever vaccine have drawn attention to the need to revisit criteria for the designation of areas with risk for yellow fever virus activity, and to revise the vaccine recommendations for international travel. WHO convened a working group of international experts to review factors important for the transmission of yellow fever virus and country-specific yellow fever information, to establish criteria for additions to or removal from the list of countries with risk for yellow fever virus transmission, to update yellow fever risk maps, and to revise the recommendations for vaccination for international travel. This report details the recommendations made by the working group about criteria for the designation of risk and specific changes to the classification of areas with risk for transmission of yellow fever virus.

OBJECTIVE: To describe the characteristics and clinical courses of asthmatic children hospitalized with seasonal or 2009 pandemic H1N1 influenza and compare complications by influenza type. METHODS: During the 2003-2009 influenza seasons and the 2009 pandemic, we conducted surveillance of 5.3 million children aged 17 years or younger for hospitalization with laboratory-confirmed influenza and identified those with asthma (defined as those aged 2-17 years with a history of asthma in their medical record or a discharge code for acute asthma exacerbation or status asthmaticus). We collected data from medical records on medical history and clinical course; data on asthma severity and control were not routinely collected. RESULTS: During the 2003-2009 influenza seasons, 701 (32%) of 2165 children hospitalized with influenza had asthma; during the 2009 pandemic, 733 (44%) of 1660 children had asthma. The median age of the asthmatic children was 7 years, and 73% had no additional medical conditions. Compared with asthmatic children with seasonal influenza, a higher proportion with 2009 pandemic H1N1 influenza required intensive care (16% vs 22%; P = .01) and were diagnosed with pneumonia (40% vs 46%; P = .04), whereas equal proportions had respiratory failure (5% vs 5%; P = .8) and died (1% vs 1%; P = .4). More asthmatic children with influenza A (seasonal or pandemic) had diagnoses of asthma exacerbations compared with those with influenza B (51% vs 29%; P < .01). CONCLUSIONS: The majority of asthmatic children hospitalized with influenza have no additional medical conditions. Complications such as pneumonia and need for intensive care occur in a substantial proportion, highlighting the importance of influenza prevention through vaccination among asthmatic children.

We sought to describe characteristics of hospitalized reproductive-aged (15-44 years) women with seasonal (2005/2006 through 2008/2009) and 2009 pandemic influenza A (H1N1) virus infection. We used population-based data from the Emerging Infections Program in 10 US states, and compared characteristics of pregnant (n = 150) and nonpregnant (n = 489) seasonal, and pregnant (n = 489) and nonpregnant (n = 1088) pandemic influenza cases using chi(2) and Fisher's exact tests. Pregnant women represented 23.5% and 31.0% of all reproductive-aged women hospitalized for seasonal and pandemic influenza, respectively. Significantly more nonpregnant than pregnant women with seasonal (71.2% vs 36.0%) and pandemic (69.7% vs 31.9%) influenza had an underlying medical condition other than pregnancy. Antiviral treatment was significantly more common with pandemic than seasonal influenza for both pregnant (86.5% vs 24.0%) and nonpregnant (82.0% vs 55.2%) women. Pregnant women comprised a significant proportion of influenza-hospitalized reproductive-aged women, underscoring the importance of influenza vaccination during pregnancy.