Showing papers by "Timothy M. Uyeki published in 2010"
TL;DR: A review of virologic, epidemiologic, and clinical data on 2009 H1N1 virus infections and summarizes key issues for clinicians worldwide can be found in this paper, where a novel influenza A virus of swine origin caused human infection and acute respiratory illness in Mexico.
Abstract: Copyright © 2010 Massachusetts Medical Society. During the spring of 2009, a novel influenza A (H1N1) virus of swine origin caused human infection and acute respiratory illness in Mexico.1,2 After initially spreading among persons in the United States and Canada,3,4 the virus spread globally, resulting in the first influenza pandemic since 1968 with circulation outside the usual influenza season in the Northern Hemisphere (see the Supplementary Appendix, available with the full text of this article at NEJM.org). As of March 2010, almost all countries had reported cases, and more than 17,700 deaths among laboratory-confirmed cases had been reported to the World Health Organization (WHO).5 The number of laboratory-confirmed cases significantly underestimates the pandemic’s impact. In the United States, an estimated 59 million illnesses, 265,000 hospitalizations, and 12,000 deaths had been caused by the 2009 H1N1 virus as of mid-February 2010.6 This article reviews virologic, epidemiologic, and clinical data on 2009 H1N1 virus infections and summarizes key issues for clinicians worldwide.
1,013 citations
TL;DR: In this article, the most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined, including type I and type II pneumocytes, were the primary infected cells.
Abstract: In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection.
373 citations
TL;DR: The results suggest that “silent spreaders” (ie, individuals who are infectious while asymptomatic or presymptome) may be less important in the spread of influenza epidemics than previously thought.
Abstract: Background Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no comparable quantitative data to our knowledge on naturally acquired infections. Methods In a community-based study in Hong Kong in 2008, we followed up initially healthy individuals to quantify trends in viral shedding on the basis of cultures and reverse-transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. Results Trends in symptom scores more closely matched changes in molecular viral loads measured with RT-PCR for influenza A than for influenza B. For influenza A virus infections, the replicating viral loads determined with cultures decreased to undetectable levels earlier after illness onset than did molecular viral loads. Most viral shedding occurred during the first 2-3 days after illness onset, and we estimated that 1%-8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding at RT-PCR were asymptomatic, and viral shedding was low in these cases. Conclusions Our results suggest that "silent spreaders" (ie, individuals who are infectious while asymptomatic or presymptomatic) may be less important in the spread of influenza epidemics than previously thought.
285 citations
TL;DR: The findings highlight the potential for severe illness and adverse neonatal outcomes among pregnant 2009 H1N1 influenza-infected women and suggest the benefit of early oseltamivir treatment.
274 citations
TL;DR: Oseltamivir treatment is effective in reducing the duration of symptoms, but evidence of household reduction in transmission of influenza virus was inconclusive.
Abstract: Background
Large clinical trials have demonstrated the therapeutic efficacy of oseltamivir against influenza. Here we assessed its indirect effectiveness in reducing household secondary transmission in an incident cohort of influenza index cases and their household members.
107 citations
TL;DR: 2009 H1N1-associated acute encephalitis and encephalopathy appear to be variable in severity, including a subset of patients with a malignant clinical course complicated by high morbidity and mortality.
Abstract: Influenza virus infection of the respiratory tract is associated with a range of neurologic complications. The emergence of 2009 pandemic influenza A (H1N1) virus has been linked to neurological complications, including encephalopathy and encephalitis. Case report and literature review. We reviewed case management of a 20-year old Hispanic male who developed febrile upper respiratory tract signs and symptoms followed by a confusional state. He had rapid neurologic decline and his clinical course was complicated by refractory seizures and malignant brain edema. He was managed with oseltamavir and peramavir, corticosteroids, intravenous gamma globulin treatment, anticonvulsants, intracranial pressure management with external ventricular drain placement, hyperosmolar therapy, sedation, and mechanical ventilation. Reverse transcriptase polymerase chain reaction analysis of nasal secretions confirmed 2009 H1N1 virus infection; cerebrospinal fluid (CSF) was negative for 2009 H1N1 viral RNA. Follow-up imaging demonstrated improvement in brain edema but restricted diffusion in the basal ganglia. We provide a review of the clinical spectrum of neurologic complications of seasonal influenza and 2009 H1N1, and current approaches towards managing these complications. 2009 H1N1-associated acute encephalitis and encephalopathy appear to be variable in severity, including a subset of patients with a malignant clinical course complicated by high morbidity and mortality. Since the H1N1 influenza virus has not been detected in the CSF or brain tissue in patients with this diagnosis, the emerging view is that the host immune response plays a key role in pathogenesis.
103 citations
TL;DR: The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.
Abstract: Influenza is a major cause of morbidity and hospitalization among children. While less often reported in adults, gastrointestinal symptoms have been associated with influenza in children, including abdominal pain, nausea, vomiting, and diarrhea. From September 2005 and April 2008, pediatric patients in Indonesia presenting with concurrent diarrhea and influenza-like illness were enrolled in a study to determine the frequency of influenza virus infection in young patients presenting with symptoms less commonly associated with an upper respiratory tract infection (URTI). Stool specimens and upper respiratory swabs were assayed for the presence of influenza virus. Seasonal influenza A or influenza B viral RNA was detected in 85 (11.6%) upper respiratory specimens and 21 (2.9%) of stool specimens. Viable influenza B virus was isolated from the stool specimen of one case. During the time of this study, human infections with highly pathogenic avian influenza A (H5N1) virus were common in the survey area. However, among 733 enrolled subjects, none had evidence of H5N1 virus infection. The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.
77 citations
TL;DR: The early internationalcritical care research response to the influenza A 2009 (H1N1) pandemic is described, including specifics of observational study case report form, registry, and clinical trial design, cooperation of international critical care research organizations, and the early results of these collaborations.
Abstract: As a critical care community, we have an obligation to provide not only clinical care but also the research that guides initial and subsequent clinical responses during a pandemic. There are many challenges to conducting such research. The first is speed of response. However, given the near inevitability of certain events, for example, viral respiratory illness such as the 2009 pandemic, geographically circumscribed natural disasters, or acts of terror, many study and trial designs should be preplanned and modified quickly when specific events occur. Template case report forms should be available for modification and web entry; centralized research ethics boards and funders should have the opportunity to preview and advise on such research beforehand; and national and international research groups should be prepared to work together on common studies and trials for common challenges. We describe the early international critical care research response to the influenza A 2009 (H1N1) pandemic, including specifics of observational study case report form, registry, and clinical trial design, cooperation of international critical care research organizations, and the early results of these collaborations.
37 citations
TL;DR: 2 pediatric cases of neurologic illness associated with 2009 H1N1, both with favorable outcomes are described in this issue of Neurology ®.
Abstract: Each year, respiratory complications of seasonal influenza result in substantial morbidity and mortality. However, evidence continues to accrue suggesting that influenza illness is associated with severe neurologic complications, including the 2009 pandemic influenza A (H1N1) virus infection. In this issue of Neurology ®, Webster et al.1 describe 2 pediatric cases of neurologic illness associated with 2009 H1N1, both with favorable outcomes.
Rare cases of influenza-associated neurologic complications have been reported for decades. “Acute encephalopathy” was reported in association with the devastating 1918 “Spanish” influenza A (H1N1) pandemic.2 Recognition of the association of salicylate ingestion in children with influenza and development of Reye syndrome has led to preventive efforts and a dramatic decrease in this complication.3
More recently, a wide range of other neurologic illnesses associated with influenza have been described, including posterior reversible encephalopathy, myelitis, stroke, acute necrotizing encephalitis, and seizures.4–6 However, sorting out a causal role of influenza virus in many of these conditions through careful clinicopathologic investigations combined with epidemiologic studies has been challenging. Much attention has focused on influenza-associated …
30 citations
TL;DR: The triaging system that used an ILI-score complimented clinicians' judgment of who needed oseltamivir and inpatient care and helped hospital staff manage a surge in demand for services.
Abstract: Background
Pandemic influenza A (H1N1) virus emerged during 2009. To help clinicians triage adults with acute respiratory illness, a scoring system for influenza-like illness (ILI) was implemented at Hospital Civil de Guadalajara, Mexico.
24 citations
TL;DR: The emergence of 2009 pandemic influenza A (H1N1) virus prompted early questions about how the virus was spreading and how easily it was transmitted, along with uncertainty about disease severity, clinical complications and risk factors for severe disease, and the effectiveness of antiviral treatment and control measures.
Abstract: The emergence of 2009 pandemic influenza A (H1N1) virus prompted early questions about how the virus was spreading and how easily it was transmitted, along with uncertainty about disease severity, clinical complications and risk factors for severe disease, and the effectiveness of antiviral treatment and control measures. Without a vaccine against the 2009 H1N1 virus, early control measures included both pharmaceutical interventions (the use of antiviral agents) and nonpharmaceutical interventions (e.g., school closures, isolation, and quarantine), depending on the specific outbreak setting, available resources, and goals. The use of these interventions varied according to country and the evolution of the . . .
TL;DR: Huai et al. as mentioned in this paper investigated the first known outbreak of pandemic 2009 influenza A (H1N1) at a primary school in China and found that the attack rate was 4% (50/1314), and children from all grades were affected.
Abstract: Please cite this paper as: Huai et al. (2010) A primary school outbreak of pandemic 2009 influenza A (H1N1) in China. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2010.00150.x.
Background We investigated the first known outbreak of pandemic 2009 influenza A (H1N1) at a primary school in China.
Objectives To describe epidemiologic findings, identify risk factors associated with 2009 H1N1 illness, and inform national policy including school outbreak control and surveillance strategies.
Methods We conducted retrospective case finding by reviewing the school’s absentee log and retrieving medical records. Enhanced surveillance was implemented by requiring physicians to report any influenza-like illness (ILI) cases to public health authorities. A case–control study was conducted to detect potential risk factors for 2009 H1N1 illness. A questionnaire was administered to 50 confirmed cases and 197 age-, gender-, and location-matched controls randomly selected from student and population registries.
Results The attack rate was 4% (50/1314), and children from all grades were affected. When compared with controls, confirmed cases were more likely to have been exposed to persons with respiratory illness either in the home or classroom within 7 days of symptom onset (OR, 4·5, 95% CI: 1·9–10·7). No cases reported travel or contact with persons who had traveled outside of the country.
Conclusions Findings in this outbreak investigation, including risk of illness associated with contacting persons with respiratory illness, are consistent with those reported by others for seasonal influenza and 2009 H1N1 outbreaks in school. The outbreak confirmed that community-level transmission of 2009 H1N1 virus was occurring in China and helped lead to changes in the national pandemic policy from containment to mitigation.
TL;DR: A sustained influenza intervention bundle was associated with clinical and economic benefits to a Thai hospital and exceeded the intervention costs of US $6,471 per unit for postintervention outbreak investigations.
Abstract: OBJECTIVE. To evaluate the feasibility and effectiveness of an influenza control bundle to minimize healthcare-associated seasonal influenza transmission among healthcare workers (HCWs) in an intensive care unit (ICU) equipped with central air conditioning. METHODS. A quasi-experimental study was conducted in a 500-bed tertiary care center in Thailand from July 1, 2005, through June 30, 2009. The medical ICU (MICU) implemented an influenza control bundle including healthcare worker (HCW) education, influenza screening of adult community-acquired pneumonia patients, antiviral treatment of patients and ill HCWs who tested positive for influenza, promotion of influenza vaccination among HCWs, and reinforcement of standard infection control policies. The surgical ICU (SICU) and coronary care unit (CCU) received no intervention. RESULTS. The numbers of influenza infections among HCWs during the pre- and postintervention periods were 18 cases in 5,294 HCW-days and 0 cases in 5,336 HCW-days in the MICU (3.4 vs 0 cases per 1,000 HCW-days; P<.001), 19 cases in 4,318 HCW-days and 20 cases in 4,348 HCW-days in the SICU (4.4 vs 4.6 cases per 1,000 HCW-days; P = .80), and 18 cases in 5,000 HCW-days and 18 cases in 5,143 HCW-days in the CCU (3.6 vs 3.5 cases per 1,000 HCW-days; P = .92), respectively. Outbreak-related influenza occurred in 7 MICU HCWs, 6 SICU HCWs, and 4 CCU HCWs before intervention and 0 MICU HCWs, 9 SICU HCWs, and 8 CCU HCWs after intervention. Before and after intervention, 25 (71%) and 35 (100%) of 35 MICU HCWs were vaccinated, respectively (P<.001); HCW vaccination coverage did not change significantly in the SICU (21 [70%] of 30 vs 24 [80%] of 30; P = .89) and CCU (19 [68%] of 28 vs 21 [75%] of 28; P = .83). The estimated costs of US $6,471 per unit for postintervention outbreak investigations exceeded the intervention costs of US $4,969. CONCLUSION. A sustained influenza intervention bundle was associated with clinical and economic benefits to a Thai hospital.
TL;DR: A mild winter influenza season, difficulty obtaining recommended agents, and lack of access to subtype diagnosis and surveillance data may have contributed to reduced antiviral use during 2008-09.
TL;DR: A 29-year-old man was transferred to this hospital because of fever, a nonproductive cough, and myalgias developed, and he was hypoxemic.
Abstract: A 29-year-old man was transferred to this hospital because of fever and respiratory distress. Nine days earlier, fever, a nonproductive cough, and myalgias developed. On admission to this hospital, he was hypoxemic. Computed tomography of the chest revealed diffuse infiltrates. Respiratory failure, renal failure, and hypotension developed. On the sixth hospital day, a diagnostic test result was received.