Showing papers by "Timothy M. Uyeki published in 2015"
TL;DR: A patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence is described.
Abstract: Among the survivors of Ebola virus disease (EVD), complications that include uveitis can develop during convalescence, although the incidence and pathogenesis of EVD-associated uveitis are unknown We describe a patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14 weeks after the onset of EVD and 9 weeks after the clearance of viremia
365 citations
TL;DR: While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date.
Abstract: Background. The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management.
Methods. We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma.
Results. While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date.
Conclusions. It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
168 citations
TL;DR: The clinical course and management of the index case patient and 2 nurses who developed EVD after caring for him and the first 2 patients with EBOV infection acquired in the United States are described.
Abstract: Ebola virus (EBOV) infections have caused extraordinary morbidity and mortality among persons in Guinea, Sierra Leone, and Liberia since late 2013 (1–6). More than 850 cases of Ebola virus disease (EVD) have been reported among health care personnel in western Africa (5). On 30 September 2014, the first case of EVD identified in the United States was confirmed in a Liberian man who traveled from Liberia to Dallas, Texas, on 20 September and became ill 4 days later. He was admitted to an intensive care unit (ICU) isolation room on 29 September and died on 8 October. Subsequently, 2 nurses who had cared for this patient in the ICU became ill and were diagnosed with EVD. In this article, we review the clinical and laboratory data for these 3 patients and describe the clinical course and management of the index patient and the first 2 patients with EBOV infection acquired in the United States.
104 citations
TL;DR: NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness; superinfections and corticosteroids increase mortality; Antiviral and non-antiviral management strategies should be considered.
Abstract: We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008–2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory-failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ⩽2 days and 65.5% ⩽5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19–0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52–3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23–0.84) death risks. Best survival was shown when treatment started within ⩽2 days (adjusted HR 0.20, 95% CI 0.12–0.32), but there was benefit with treatment within 3–5 days (adjusted HR 0.35, 95% CI 0.21–0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27–0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14–2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered.
80 citations
TL;DR: A patient with EVD who received brincidofovir and convalescent plasma is presented and the relative contributions of supportive care, investigational therapies, and patient's immune-response on survival could not be determined.
Abstract: From 2014 to May 2015, >26 000 Ebola virus disease (EVD) cases were reported from West Africa. We present a patient with EVD who received brincidofovir and convalescent plasma. The relative contributions of supportive care, investigational therapies, and patient's immune-response on survival could not be determined. Randomized trials are needed.
77 citations
TL;DR: In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood.
Abstract: Importance Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick. Objective To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus. Design and Setting Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014. Interventions The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa. Results The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected. Conclusions and Relevance It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.
77 citations
TL;DR: Co-circulation of H5N1 in poultry and humans during seasonal influenza epidemic periods signals the need for enhanced surveillance and biosafety measures.
Abstract: Co-circulation of influenza A(H5N1) and seasonal influenza viruses among humans and animals could lead to co-infections, reassortment, and emergence of novel viruses with pandemic potential. We assessed the timing of subtype H5N1 outbreaks among poultry, human H5N1 cases, and human seasonal influenza in 8 countries that reported 97% of all human H5N1 cases and 90% of all poultry H5N1 outbreaks. In these countries, most outbreaks among poultry (7,001/11,331, 62%) and half of human cases (313/625, 50%) occurred during January–March. Human H5N1 cases occurred in 167 (45%) of 372 months during which outbreaks among poultry occurred, compared with 59 (10%) of 574 months that had no outbreaks among poultry. Human H5N1 cases also occurred in 59 (22%) of 267 months during seasonal influenza periods. To reduce risk for co-infection, surveillance and control of H5N1 should be enhanced during January–March, when H5N1 outbreaks typically occur and overlap with seasonal influenza virus circulation.
50 citations
TL;DR: Follow-up data for Ebola survivors who were treated in the United States are presented and new findings are presented on the health sequelae of Ebola virus disease.
Abstract: Limited data are available on the health sequelae of Ebola virus disease. In this report, follow-up data for Ebola survivors who were treated in the United States are presented.
45 citations
TL;DR: At markets where swine and persons are in close contact, swine-origin IAVs are prevalent and potentially provide conditions for novel IAV emergence, and genetic sequence similarities of 99%-100% among Iavs of 1 market customer and swine indicated interspecies transmission.
Abstract: Background. Live animal markets have been implicated in transmission of influenza A viruses (IAVs) from animals to people. We sought to characterize IAVs at 2 live animal markets in Minnesota to assess potential routes of occupational exposure and risk for interspecies transmission.
Methods. We implemented surveillance for IAVs among employees, swine, and environment (air and surfaces) during a 12-week period (October 2012–January 2013) at 2 markets epidemiologically associated with persons with swine-origin IAV (variant) infections. Real-time reverse transcription polymerase chain reaction (rRT-PCR), viral culture, and whole-genome sequencing were performed on respiratory and environmental specimens, and serology on sera from employees at beginning and end of surveillance.
Results. Nasal swabs from 11 of 17 (65%) employees tested positive for IAVs by rRT-PCR; 7 employees tested positive on multiple occasions and 1 employee reported influenza-like illness. Eleven of 15 (73%) employees had baseline hemagglutination inhibition antibody titers ≥40 to swine-origin IAVs, but only 1 demonstrated a 4-fold titer increase to both swine-origin and pandemic A/Mexico/4108/2009 IAVs. IAVs were isolated from swine (72/84), air (30/45), and pen railings (5/21). Whole-genome sequencing of 122 IAVs isolated from swine and environmental specimens revealed multiple strains and subtype codetections. Multiple gene segment exchanges among and within subtypes were observed, resulting in new genetic constellations and reassortant viruses. Genetic sequence similarities of 99%–100% among IAVs of 1 market customer and swine indicated interspecies transmission.
Conclusions. At markets where swine and persons are in close contact, swine-origin IAVs are prevalent and potentially provide conditions for novel IAV emergence.
39 citations
TL;DR: Evidence of infection was low despite frequent exposure to infected poultry and low use of personal protective equipment.
Abstract: The risk for influenza A(H5N1) virus infection is unclear among poultry workers in countries where the virus is endemic. To assess H5N1 seroprevalence and seroconversion among workers at live bird markets (LBMs) in Bangladesh, we followed a cohort of workers from 12 LBMs with existing avian influenza surveillance. Serum samples from workers were tested for H5N1 antibodies at the end of the study or when LBM samples first had H5N1 virus–positive test results. Of 404 workers, 9 (2%) were seropositive at baseline. Of 284 workers who completed the study and were seronegative at baseline, 6 (2%) seroconverted (7 cases/100 poultry worker–years). Workers who frequently fed poultry, cleaned feces from pens, cleaned food/water containers, and did not wash hands after touching sick poultry had a 7.6 times higher risk for infection compared with workers who infrequently performed these behaviors. Despite frequent exposure to H5N1 virus, LBM workers showed evidence of only sporadic infection.
38 citations
TL;DR: During November 2014–April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt, and 99% reported poultry exposure.
Abstract: During November 2014-April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt. Among infected persons, 99% reported poultry exposure: 19% to ill poultry and 35% to dead poultry. Only 1 person reported wearing personal protective equipment while working with poultry.
TL;DR: Estimates of influenza vaccination in children with NNDDs are comparable to published reports of vaccination in healthy children, which continue to be suboptimal.
TL;DR: Reducing EVD diarrheal losses with loperamide might allow for correction of negative fluid balance, reduce hypovolemic shock, limit electrolyte losses, and consequently improve survival, and the reduction in environmental contamination may lower the risk of nosocomial transmission to healthcare personnel and other patients under evaluation.
Abstract: The number of cases of Ebola virus disease (EVD) in West Africa has surpassed 19 000 [1]. Efforts to identify, isolate, and provide medical care to patients with EVD are ongoing, and efforts to improve clinical care must focus on improved management of massive gastrointestinal fluid loss. Gastrointestinal fluid losses, largely through diarrhea, are a hallmark manifestation of EVD that contribute to hypovolemic shock, severe electrolyte abnormalities, and high mortality [2, 3]. In contrast to cholera toxin–mediated diarrheal losses, in which oral rehydration solution alone dramatically reduces mortality [4], oral rehydration for patients with EVD is often insufficient to accomplish resuscitation or repletion of ongoing fluid losses. However, EVD is a systemic viral illness with profound and debilitating manifestations, including high fever, asthenia, myalgia, and delirium, that limit self-directed oral rehydration. New strategies are needed to limit mortality related to cholera-like gastrointestinal fluid losses in EVD.
Massive gastrointestinal fluid and electrolyte losses may be successfully managed in resource-rich settings through careful estimation of volume losses, close laboratory monitoring of electrolytes and organ function, and replacement of fluid losses through balanced intravenous infusions over the course of illness [3]. This same level of intensive monitoring and care cannot be achieved in most EVD treatment units in West Africa, where high case loads, staffing shortages, and limited time in personal protective equipment because of the risk of heat exposure prohibit extended patient care interactions. In this setting, administration of antidiarrheal agents to limit gastrointestinal fluid and electrolyte losses may provide “a solution that prevents the problem at its source”. However, use of antidiarrheal agents for the management of EVD-mediated diarrhea is infrequently reported, and no safety and efficacy data to guide use in EVD exist.
Although the mechanism of EVD-mediated diarrhea has not yet been characterized, the large volume of watery stool suggests a secretory process. Tolerance of enteral feeding when gastrointestinal symptoms are adequately controlled suggests that the small intestine structure and function remain intact. Autopsy studies of patients with EVD who died show mild inflammation of small intestinal lamina propria, suggesting the possibility of an inflammatory component to a secretory form of diarrhea, as well [5]. Clinically significant gastrointestinal bleeding observed in a small subset of patients with EVD, estimated to be <5% [2], raises the possibility that gastrointestinal inflammation may contribute to disease pathogenesis.
Loperamide is a potent antidiarrheal agent with antiperistaltic and antisecretory effects [6]. Reducing EVD diarrheal losses with loperamide might allow for correction of negative fluid balance, reduce hypovolemic shock, limit electrolyte losses, and consequently improve survival. Recently, one author (D. S. C.) and colleagues reported that oral antiemetics and antidiarrheal therapy improved symptoms and reduced gastrointestinal fluid loss and environmental contamination in patients with EVD [2]. The reduction in environmental contamination may also lower the risk of nosocomial transmission to healthcare personnel and other patients under evaluation.
There are limited data on the use of loperamide for EVD-mediated diarrhea [2]. Reluctance to use loperamide for EVD-mediated diarrhea may be based on the perception that it is of no benefit for the secretory diarrhea observed in cholera or concern about the risk of toxic megacolon when used to treat some bacterial inflammatory causes of diarrhea, such as Clostridium difficile infection [7]. Animal and human studies of shigellosis in the 1960s and subsequent case reports of adverse events raised concern that antimotility drug use in patients with infectious diarrhea might contribute to a worse outcome [8]. However, multiple randomized, placebo-controlled, double-blinded trials of loperamide in combination with antibiotic therapy for management of infectious diarrhea in adults have demonstrated its safety and efficacy [9]. A meta-analysis of 13 clinical trials of loperamide use in children aged ≤12 years with infectious diarrhea and predominantly mild dehydration demonstrated a decrease in the duration and frequency of diarrhea [10]. Serious adverse events associated with loperamide use, including death, ileus, or lethargy, were reported only in children <3 years of age.
The Food and Drug Administration does not recommend loperamide use in children <24 months of age, and use is contraindicated in patients with dysentery (ie, stool with mucus or blood), but it may be used in combination with antibiotic treatment [11]. Loperamide should not be given to patients with suspected or documented ileus or intestinal paresis. Use of loperamide in patients with EVD to control gastrointestinal fluid losses and reduce environmental contamination appears rational, based on existing clinical observations and the available published data. However, controlled clinical trials of loperamide treatment of diarrhea in patients with EVD, in combination with oral rehydration solution, to assess safety and efficacy in adults and children, including its possible impact upon improving survival, are urgently needed. Until strategies to improve management of gastrointestinal fluid and electrolyte losses are refined and widely implemented in the management of EVD in West Africa, the presently observed high case-fatality will persist.
TL;DR: Hospitals and clinicians must prepare to provide care for patients with Ebola virus disease before such patients present for care, with particular attention to rigorous infection control to limit secondary cases.
Abstract: Objectives:To provide clinicians with practical considerations for care of children with Ebola virus disease in resource-rich settings.Data Sources:Review of the published medical literature, World Health Organization and government documents, and expert opinion.Data Synthesis:There are limited data
TL;DR: Findings are presented describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru.
Abstract: We present findings describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru. In 2010, the prevalence of infections by human coronaviruses 229E, OC43, NL63, or HKU1 was 6.4% in participants with influenza-like illness who tested negative for influenza viruses. Ten of 11 human coronavirus infections were identified in the fall-winter season. Human coronaviruses are present in different regions of Peru and are relatively frequently associated with influenza-like illness in Peru.
TL;DR: Enhanced understanding of EVD case definitions, clinical presentation, treatment procedures, and infection control strategies will improve the ability of health care workers to provide safe care for patients with EVD.
TL;DR: Findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season, as seasonal influenza was an important contributor to acute respiratory disease in East Jakarta.
Abstract: Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription-polymerase chain reaction. During October 2011-September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December-May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season.