Showing papers by "Timothy M. Uyeki published in 2014"

Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

Abstract: Background The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. Methods Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase–polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. Results Among 139 persons with confirmed H7N9 virus infectio...

Clinical Care of Two Patients with Ebola Virus Disease in the United States

Abstract: Summary West Africa is currently experiencing the largest outbreak of Ebola virus disease (EVD) in history. Two patients with EVD were transferred from Liberia to our hospital in the United States for ongoing care. Malaria had also been diagnosed in one patient, who was treated for it early in the course of EVD. The two patients had substantial intravascular volume depletion and marked electrolyte abnormalities. We undertook aggressive supportive measures of hydration (typically, 3 to 5 liters of intravenous fluids per day early in the course of care) and electrolyte correction. As the patients’ condition improved clinically, there was a concomitant decline in the amount of virus detected in plasma.

Comparison of patients hospitalized with influenza A subtypes H7N9, H5N1, and 2009 pandemic H1N1.

Abstract: Background Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections Methods We compared individual-level data from patients hospitalized with infection by H7N9 (n=123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population Results The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P< 001) and a higher proportion was male (71%; P< 02) After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 968; 95% confidence interval, 524–179) H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P<005) H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P< 001), and the median time from onset to death was 18 days for H7N9 (P= 002) vs 11 days for H5N1 and 15 days for pH1N1 (P= 154) Conclusions The identification of known risk factors for severe seasonal infl uenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity

The substantial hospitalization burden of influenza in central China: surveillance for severe, acute respiratory infection, and influenza viruses, 2010–2012

Abstract: Background Published data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype. Methods Surveillance was conducted at four hospitals in Jingzhou, China from 2010 to 2012. We enrolled hospitalized patients who had temperature ≥37·3°C and at least one of: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. A nasopharyngeal swab was collected from each case-patient within 24 hours of admission for influenza testing by real-time reverse transcription PCR. Results Of 17 172 SARI patients enrolled, 90% were aged <15 years. The median duration of hospitalization was 5 days. Of 16 208 (94%) SARI cases tested, 2057 (13%) had confirmed influenza, including 1427 (69%) aged <5 years. Multiple peaks of influenza occurred during summer, winter, and spring months. Influenza was associated with an estimated 115 and 142 SARI hospitalizations per 100 000 during 2010–2011 and 2011–2012 [including A(H3N2): 55 and 44 SARI hospitalizations per 100 000; pandemic A(H1N1): 33 SARI hospitalizations per 100 000 during 2010–2011; influenza B: 26 and 98 hospitalizations per 100 000], with the highest rate among children aged 6–11 months (3603 and 3805 hospitalizations per 100 000 during 2010–2011 and 2011–2012, respectively). Conclusions In central China, influenza A and B caused a substantial number of hospitalizations during multiple periods each year. Our findings strongly suggest that young children should be the highest priority group for annual influenza vaccination in China.

Preventing and Controlling Influenza with Available Interventions

Abstract: With influenza activity surging, critical illness and deaths have been reported in young and middle-aged U.S. adults. The predominant virus has been the strain that caused the 2009 H1N1 pandemic. Despite challenges, there's much we can do to reduce the impact of influenza.

Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

Abstract: Background: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. Methods and Findings: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1-3) and 6 days (IQR 4-10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4-7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5-26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. Conclusions: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. Trial Registration: ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185.

Ebola virus disease and children: what pediatric health care professionals need to know.

Abstract: The largest outbreak of Ebola virus disease (EVD) in history is occurring in West Africa. On August 8, 2014, the World Health Organization (WHO) declared this outbreak to be a Public Health Emergency of International Concern.1 As of October 8, 2014, 8399 EVD cases (including 416 in health care personnel) with 4033 deaths were reported, although reported cases are likely a substantial underestimate of the outbreak magnitude.2 Most EVD cases have been reported in Guinea, Liberia, and Sierra Leone, with fewer cases in Nigeria and a single case in Senegal. Although the suspected index case for this outbreak is believed to be a 2-year-old child who died in Guinea in December 2013, limited information is available on the impact of this outbreak on children.3 Cases of EVD were also identified in the Democratic Republic of the Congo, but analyses of viruses suggest that the Democratic Republic of the Congo outbreak is not linked to the wider epidemic. As of October 15, 2014, 3 EVD cases, including 2 health care personnel, had been identified in the United States and 5 EVD cases, including 4 health care personnel, were identified in West Africa and medically evacuated to the United States for further care. This situation is rapidly evolving, and new information will be posted to the Centers for Disease Control and Prevention (CDC) (http://www.cdc.gov/vhf/ebola/index.html) and WHO (http://www.who.int/mediacentre/factsheets/fs103/en/) websites as it becomes available. Our report is intended to complement information on the CDC webpages, with a focus on what pediatric health care professionals need to know.

Influenza-associated intensive-care unit admissions and deaths - California, September 29, 2013-January 18, 2014.

Abstract: The California Department of Public Health (CDPH) conducts surveillance on severe influenza illness among California residents aged <65 years. Severe cases are defined as those resulting in admission to an intensive care unit (ICU) or death; reporting of ICU cases is voluntary, and reporting of fatal cases is mandatory. This report describes the epidemiologic, laboratory, and clinical characteristics of ICU and fatal influenza cases with symptom onset on or after September 29, 2013, and reported by January 18, 2014 of the 2013-14 influenza season. At the time of this report, local health jurisdictions (LHJs) in California had reported 94 deaths and 311 ICU admissions of patients with a positive influenza test result. The 405 reports of severe cases (i.e., fatal and ICU cases combined) were more than in any season since the 2009 pandemic caused by the influenza A (H1N1)pdm09 (pH1N1) virus. The pH1N1 virus is the predominant circulating influenza virus this season. Of 405 ICU and fatal influenza cases, 266 (66%) occurred among patients aged 41-64 years; 39 (10%) severe influenza illnesses occurred among children aged <18 years. Only six (21%) of 28 patients with fatal illness whose vaccination status was known had received 2013-14 seasonal influenza vaccine ≥2 weeks before symptom onset. Of 80 patients who died for whom sufficient information was available, 74 (93%) had underlying medical conditions known to increase the risk for severe influenza, as defined by the Advisory Committee on Immunization Practices (ACIP). Of 47 hospitalized patients with fatal illness and known symptom onset and antiviral therapy dates, only eight (17%) received neuraminidase inhibitors within 48 hours of symptom onset. This report supports previous recommendations that vaccination is important to prevent influenza virus infections that can result in ICU admission or death, particularly in high-risk populations, and that empiric antiviral treatment should be promptly initiated when influenza virus infection is suspected in hospitalized patients, despite negative results from rapid diagnostic tests.

Demographic and clinical predictors of mortality from highly pathogenic avian influenza A (H5N1) virus infection: CART analysis of international cases.

Abstract: Background: Human infections with highly pathogenic avian influenza (HPAI) A (H5N1) viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions. Methods: We included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar), including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality. Findings: We identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6–29 years) and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.76– 0.86). Interpretation: A model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection. Citation: Patel RB, Mathur MB, Gould M, Uyeki TM, Bhattacharya J, et al. (2014) Demographic and Clinical Predictors of Mortality from Highly Pathogenic Avian

Seasonal Patterns in Human A (H5N1) Virus Infection: Analysis of Global Cases

Abstract: Background Human cases of highly pathogenic avian influenza (HPAI) A (H5N1) have high mortality. Despite abundant data on seasonal patterns in influenza epidemics, it is unknown whether similar patterns exist for human HPAI H5N1 cases worldwide. Such knowledge could help decrease avian-to-human transmission through increased prevention and control activities during peak periods. Methods We performed a systematic search of published human HPAI H5N1 cases to date, collecting month, year, country, season, hemisphere, and climate data. We used negative binomial regression to predict changes in case incidence as a function of season. To investigate hemisphere as a potential moderator, we used AIC and the likelihood-ratio test to compare the season-only model to nested models including a main effect or interaction with hemisphere. Finally, we visually assessed replication of seasonal patterns across climate groups based on the Koppen-Geiger climate classification. Findings We identified 617 human cases (611 with complete seasonal data) occurring in 15 countries in Southeast Asia, Africa, and the Middle East. Case occurrence was much higher in winter (n = 285, p = 0.03) than summer (n = 64), and the winter peak occurred across diverse climate groups. There was no significant interaction between hemisphere and season. Interpretation Across diverse climates, HPAI H5N1 virus infection in humans increases significantly in winter. This is consistent with increased poultry outbreaks and HPAI H5N1 virus transmission during cold and dry conditions. Prioritizing prevention and control activities among poultry and focusing public health messaging to reduce poultry exposures during winter months may help to reduce zoonotic transmission of HPAI H5N1 virus in resource-limited settings.

Critically Ill Patients With Influenza A(H1N1)pdm09 Virus Infection in 2014

Abstract: Since 2009, H1N1pdm09 virus has continued to circulate and cause critical illness worldwide, but it has not predominated in the United States until this season, with a corresponding resurgence of influenza-related hospitalizations, critical illness, severe ARDS, and deaths. This year more than 60% of laboratory-confirmed influenzaassociated hospitalizations and deaths reported in adults younger than 65 years to date have been attributed to H1N1. 3,4 No significant antigenic changes in circulating H1N1pdm09 virus strains compared with vaccine strains have been detected since 2009. The relative effect on young and middle-aged adults might be partially due to their low influenza vaccine coverage and crossreactive immunity to H1N1pdm09 virus that elderly individuals have acquired from past exposure to antigenically related viruses. Based on lessons learned from the 2009 H1N1 pandemic, we offer suggestions for the care and management of H1N1pdm09 patients at risk for critical illness during this influenza season.

Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents

Abstract: Background Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. Objectives We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. Methods We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Results Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. Conclusions We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways.

Modes of Transmission of Influenza B Virus in Households

Abstract: Introduction While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei “aerosols” in transmission is controversial.

Influenza virus infection mimicking an acute abdomen in a female adolescent.

Abstract: We report an adolescent with respiratory symptoms admitted for clinical signs of an acute abdomen. The only diagnostic finding was influenza A viral RNA detected in an upper respiratory tract specimen. Influenza should be considered in the differential diagnosis of children with respiratory illness and abdominal pain during influenza season.

Caught napping in the time of tropical diseases

Abstract: Airline deregulation in 1978 and optimization of routes have been a boon to foreign travel, including to and from Canada, which has one of the fastest growing populations of the G8 countries. Millions of overseas tourists visit Canada each year. More than 20% (almost 7 million) of Canada’s population is foreign born, with at least 50% of new immigrants arriving from tropical locales. Recent immigrants may travel to and from their countries of origin.