Showing papers by "Timothy M. Uyeki published in 2013"

Aerosol transmission is an important mode of influenza A virus spread.

Abstract: Influenza A viruses are believed to spread between humans through contact, large respiratory droplets and small particle droplet nuclei (aerosols), but the relative importance of each of these modes of transmission is unclear. Volunteer studies suggest that infections via aerosol transmission may have a higher risk of febrile illness. Here we apply a mathematical model to data from randomized controlled trials of hand hygiene and surgical face masks in Hong Kong and Bangkok households. In these particular environments, inferences on the relative importance of modes of transmission are facilitated by information on the timing of secondary infections and apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We find that aerosol transmission accounts for approximately half of all transmission events. This implies that measures to reduce transmission by contact or large droplets may not be sufficient to control influenza A virus transmission in households.

Preliminary Report: Epidemiology of the Avian Influenza A (H7N9) Outbreak in China

Abstract: Qun Li, M.D., Lei Zhou, M.D., Minghao Zhou, Ph.D., Zhiping Chen, M.D., Furong Li, M.D., Huanyu Wu, M.D., Nijuan Xiang, M.D., Enfu Chen, M.P.H., Fenyang Tang, M.D., Dayan Wang, M.D., Ling Meng, M.D., Zhiheng Hong, M.D., Wenxiao Tu, M.D., Yang Cao, M.D., Leilei Li, Ph.D., Fan Ding, M.D., Bo Liu, M.D., Mei Wang, M.D., Rongheng Xie, M.D., Rongbao Gao, M.D., Xiaodan Li, M.D., Tian Bai, M.D., Shumei Zou, M.D., Jun He, M.D., Jiayu Hu, M.D., Yangting Xu, M.D., Chengliang Chai, M.D., Shiwen Wang, M.D., Yongjun Gao, M.D., Lianmei Jin, M.D., Yanping Zhang, M.D., Huiming Luo, M.D., Hongjie Yu, M.D., M.P.H., Lidong Gao, M.D., Xinghuo Pang, M.D., Guohua Liu, M.D., Yuelong Shu, Ph.D., Weizhong Yang, M.D., Timothy M. Uyeki, M.D., M.P.H., M.P.P., Yu Wang, M.D., Fan Wu, M.D., and Zijian Feng, M.D., M.P.H.

Global Concerns Regarding Novel Influenza A (H7N9) Virus Infections

Abstract: Because the novel influenza A (H7N9) virus discovered in three critically ill patients in China has not previously been detected in humans or animals, there are many urgent questions and global public health concerns to be addressed.

Outbreak of Variant Influenza A(H3N2) Virus in the United States

Abstract: Background Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. Methods We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. Results From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%-100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. Conclusions In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings.

Highly pathogenic avian influenza A(H7N3) virus in poultry workers, Mexico, 2012.

Abstract: We identified 2 poultry workers with conjunctivitis caused by highly pathogenic avian influenza A(H7N3) viruses in Jalisco, Mexico. Genomic and antigenic analyses of 1 isolate indicated relatedness to poultry and wild bird subtype H7N3 viruses from North America. This isolate had a multibasic cleavage site that might have been derived from recombination with host rRNA.

Neuraminidase Inhibitors for Critically Ill Children With Influenza

Abstract: OBJECTIVE: Timely treatment with neuraminidase inhibitor (NAI) drugs appears to improve survival in adults hospitalized with influenza. We analyzed California surveillance data to determine whether NAI treatment improves survival in critically ill children with influenza. METHODS: We analyzed data abstracted from medical records to characterize the outcomes of patients aged 0 to 17 years hospitalized in ICUs with laboratory-confirmed influenza from April 3, 2009, through September 30, 2012. RESULTS: Seven hundred eighty-four influenza cases aged P P = .04). Cases with NAI treatment initiated earlier in illness were less likely to die. CONCLUSIONS: Prompt treatment with NAIs may improve survival of children critically ill with influenza. Recent decreased frequency of NAI treatment of influenza may be placing untreated critically ill children at an increased risk of death.

The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies

Abstract: BACKGROUND Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. METHODS Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified. RESULTS In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3(rd) versus 1(st) tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3(rd) versus 1(st) tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only. CONCLUSIONS In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome.

Impact of the Fall 2009 Influenza A(H1N1)pdm09 Pandemic on US Hospitals

Abstract: Background:Understanding how hospitals functioned during the 2009 influenza A(H1N1)pdm09 pandemic may improve future public health emergency response, but information about its impact on US hospitals remains largely unknown.Research Design:We matched hospital and emergency department (ED) discharge

Surveillance of Influenza in Indonesia, 2003–2007

Abstract: Background Longitudinal data are limited about the circulating strains of influenza viruses and their public health impact in Indonesia. We conducted influenza surveillance among outpatients and hospitalized patients with influenza-like illness (ILI) across the Indonesian archipelago from 2003 through 2007. Methodology Demographic, clinical data, and respiratory specimens were collected for 4236 ILI patients tested for influenza virus infection by RT-PCR and viral culture. Principal Findings Influenza A and B viruses co-circulated year-round with seasonal peaks in influenza A virus activity during the rainy season (December–January). During 2003–2007, influenza viruses were identified in 20·1% (4236/21 030) of ILI patients, including 20·1% (4015/20 012) of outpatients, and 21·7% (221/1018) of inpatients. One H5N1 case was identified retrospectively in an outpatient with ILI. Antigenic drift in circulating influenza A and B virus strains was detected during the surveillance period in Indonesia. In a few instances, antigenically drifted viruses similar to the World Health Organization (WHO) vaccine strains were detected earlier than the date of their designation by WHO. Conclusions Influenza A and B virus infections are an important cause of influenza-like illness among outpatients and hospitalized patients in Indonesia. While year-round circulation of influenza viruses occurs, prevention and control strategies should be focused upon the seasonal peak during rainy season months. Ongoing virologic surveillance and influenza disease burden studies in Indonesia are important priorities to better understand the public health impact of influenza in South-East Asia and the implications of influenza viral evolution and global spread.

Antiviral susceptibility of highly pathogenic avian influenza A(H5N1) viruses isolated from poultry, Vietnam, 2009-2011.

Abstract: We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009–2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 2.3.2.1 viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness.

Seroprevalence of Antibodies against Highly Pathogenic Avian Influenza A (H5N1) Virus among Poultry Workers in Bangladesh, 2009

Abstract: We conducted a cross-sectional study in 2009 to determine the seroprevalence and risk factors for highly pathogenic avian influenza A (H5N1) [HPAI H5N1] virus antibodies among poultry workers at farms and live bird markets with confirmed/suspected poultry outbreaks during 2009 in Bangladesh. We tested sera by microneutralization assay using A/Bangladesh/207095/2008 (H5N1; clade 2.2.2) virus with confirmation by horse red blood cell hemagglutination inhibition and H5-specific Western blot assays. We enrolled 212 workers from 87 farms and 210 workers from three live bird markets. One hundred and two farm workers (48%) culled poultry. One hundred and ninety-three farm workers (91%) and 178 market workers (85%) reported direct contact with poultry that died during a laboratory confirmed HPAI H5N1 poultry farm outbreak or market poultry die-offs from suspected HPAI H5N1. Despite exposure to sick poultry, no farm or market poultry workers were seropositive for HPAI H5N1 virus antibodies (95% confidence interval 0–1%).

Seroepidemiologic investigation of an outbreak of pandemic influenza A H1N1 2009 aboard a US Navy Vessel—San Diego, 2009

Abstract: Background During summer 2009, a US Navy ship experienced an influenza-like illness outbreak with 126 laboratory-confirmed cases of pandemic influenza A (H1N1) 2009 virus among the approximately 2000-person crew. Methods During September 24–October 9, 2009, a retrospective seroepidemiologic investigation was conducted to characterize the outbreak. We administered questionnaires, reviewed medical records, and collected post-outbreak sera from systematically sampled crewmembers. We used real-time reverse transcription-PCR or microneutralization assays to detect evidence of H1N1 virus infection. Results Retrospective serologic data demonstrated that the overall H1N1 virus infection attack rate was 32%. Weighted H1N1 virus attack rates were higher among marines (37%), junior-ranking personnel (34%), and persons aged 19–24 years (36%). In multivariable analysis, a higher risk of illness was found for women versus men (odds ratio [OR] = 2·2; 95% confidence interval [CI]: 1·1–4·4), marines versus navy personnel (OR = 1·7; 95% CI, 1·0–2·9), and those aged 19–24 versus ≥35 years (OR = 3·9; 95% CI, 1·2–12·8). Fifty-three percent of infected persons did not recall respiratory illness symptoms. Among infected persons, only 35% met criteria for acute respiratory illness and 11% for influenza-like illness. Conclusions Approximately half of H1N1 infections were asymptomatic, and thus, the attack rate was higher than estimated by clinical illness alone. Enhanced infection control measures including pre-embarkation illness screening, improved self-reporting of illness, isolation of ill and quarantine of exposed contacts, and prompt antiviral chemoprophylaxis and treatment might be useful in controlling shipboard influenza outbreaks.

Clinical experience with intravenous zanamivir under an emergency investigational new drug program in the United States.

Abstract: TO THE EDITOR—We read the article by Fraaij et al [1] and would like to summarize the available information on intravenous zanamivir from the Food and Drug Administration (FDA)'s Emergency Investigational New Drug (EIND) application process [2]. No intravenous an-tiviral agents for treatment of severe influenza are currently approved in the United States. Since the emergence of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09), intravenous zanamivir has been authorized through an EIND application to the FDA as an investigational treatment for patients with serious and life-threatening influenza. As part of the EIND process, treating physicians are encouraged to submit data to the FDA, but reporting of requested data is voluntary. We reviewed the FDA's EIND database on influenza patients who received intravenous zanamivir from April 2009 through April 2011. For the 200 patients identified, we performed a descriptive analysis of reported patient information on age, sex, pregnancy status, baseline comorbidities, virologic test results , antiviral resistance data, other antiviral treatments, clinical complications, supportive care modalities used, intravenous zanamivir treatment duration, adverse events (AEs), and outcomes (Table 1). At the time of intravenous zanamivir request, many patients were critically ill with underlying comorbidities and required intensive care unit admission for severe complications of influenza A virus infection (predominantly due to A[H1N1]pdm09), including respiratory failure and renal failure. Most patients

Antivirals for influenza: a summary of a systematic review and meta-analysis of observational studies.

Abstract: Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has provided some indication of benefit, the analysis is limited by the quality of the available evidence from randomized controlled trials. To supplement the existing information, the authors conducted a systematic review of observational studies of antiviral treatment for influenza. This report summarises the findings of that review. Similar to the randomised trials, the confidence in the estimates of the effects for decision-making is low to very low primarily due to the risk of selection and publication bias in the observational studies. From these observational studies, the summary estimates suggest that oseltamivir may reduce mortality, hospitalisation and duration of symptoms compared with no treatment. Inhaled zanamivir may also reduce symptom duration and hospitalisations, but patients may experience more complications compared with no treatment. Earlier treatment with antivirals is generally associated with better outcomes than later treatment. Further high-quality evidence is needed to inform treatment guidelines because of the overall low to very low quality of evidence.

Effects of Influenza on Pregnant Women and Infants

Abstract: Influenza vaccination during pregnancy has been shown to decrease the risk of influenza and its complications among pregnant women and their infants up to 6 months old. To adequately assess the benefits and potential risks that are associated with the use of influenza vaccine during pregnancy, it is necessary to examine the influenza-associated complications that occur among pregnant women and their children. Pregnant women have been shown to be at increased risk for morbidity and death with influenza illness during seasonal epidemics and pandemics. Newborn infants born to mothers with influenza during pregnancy, especially mothers with severe illness, are at increased risk of adverse outcomes, such as preterm birth and low birthweight. Infants <6 months old who experience influenza virus infection have the highest rates of hospitalization and death of all children. Here we review the risks for influenza-associated complications among pregnant women and infants <6 months old.

Seroprevalence of antibodies to highly pathogenic avian influenza A (H5N1) virus among close contacts exposed to H5N1 cases, China, 2005-2008.

Abstract: To assess the extent of highly pathogenic avian influenza (HPAI) A (H5N1) virus transmission, we conducted sero-epidemiologic studies among close contacts exposed to H5N1 cases in mainland China during 2005–2008. Blood specimens were collected from 87 household members and 332 social contacts of 23 H5N1 index cases for HPAI H5N1 serological testing by modified horse red-blood-cell hemagglutinin inhibition and microneutralization assays. All participants were interviewed with a standardized questionnaire to collect information about the use of personal protective equipment, illness symptoms, exposure to an H5N1 case during the infectious period, and poultry exposures. Two (2.3%) household contacts tested positive for HPAI H5N1 virus antibody, and all social contacts tested negative. Both seropositive cases had prolonged, unprotected, close contact with a different H5N1 index case, including days of bed-care or sleeping together during the index case’s infectious period, and did not develop any illness. None of the 419 close contacts used appropriate personal protective equipment including 17% who reported providing bedside care or having physical contact with an H5N1 case for at least 12 hours. Our findings suggest that HPAI H5N1 viruses that circulated among poultry in mainland China from 2005–2008 were not easily transmitted to close contacts of H5N1 cases.