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\"Before the trials, WICKED found Thomas, the perfect boy, to help them build the Maze and find the cure for the Flare, a disease that plagues the world. But the truth of what is really going on is a secret and Thomas must uncover it before time runs out\"-- Provided by publisher.
Book
Acute flaccid myelitis: cause, diagnosis, and management
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host–virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.
Journal Article
Viral pneumonia
About 200 million cases of viral community-acquired pneumonia occur every year—100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.
Journal Article
The Hidden Geometry of Complex, Network-Driven Contagion Phenomena
The global spread of epidemics, rumors, opinions, and innovations are complex, network-driven dynamic processes. The combined multiscale nature and intrinsic heterogeneity of the underlying networks make it difficult to develop an intuitive understanding of these processes, to distinguish relevant from peripheral factors, to predict their time course, and to locate their origin. However, we show that complex spatiotemporal patterns can be reduced to surprisingly simple, homogeneous wave propagation patterns, if conventional geographic distance is replaced by a probabilistically motivated effective distance. In the context of global, air-traffic-mediated epidemics, we show that effective distance reliably predicts disease arrival times. Even if epidemiological parameters are unknown, the method can still deliver relative arrival times. The approach can also identify the spatial origin of spreading processes and successfully be applied to data of the worldwide 2009 H1N1 influenza pandemic and 2003 SARS epidemic.
Journal Article
Pan-viral serology implicates enteroviruses in acute flaccid myelitis
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1–6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.
Journal Article
Prone Positioning in Severe Acute Respiratory Distress Syndrome
Placing patients who require mechanical ventilation in the prone rather than the supine position improves oxygenation. In this trial, the investigators found a benefit with respect to all-cause mortality with this change in body position in patients with severe ARDS.
Prone positioning has been used for many years to improve oxygenation in patients who require mechanical ventilatory support for management of the acute respiratory distress syndrome (ARDS). Randomized, controlled trials have confirmed that oxygenation is significantly better when patients are in the prone position than when they are in the supine position.
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Furthermore, several lines of evidence have shown that prone positioning could prevent ventilator-induced lung injury.
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In several previous trials, these physiological benefits did not translate into better patient outcomes, since no significant improvement was observed in patient survival with prone positioning.
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However, meta-analyses
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Journal Article
Hand, foot, and mouth disease in China, 2008–12: an epidemiological study
Hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout east and southeast Asia. To better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in China on the basis of enhanced surveillance.
We extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese Center for Disease Control and Prevention between Jan 1, 2008, and Dec 31, 2012. We then compiled climatic, geographical, and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus serotype.
The surveillance registry included 7 200 092 probable cases of hand, foot, and mouth disease (annual incidence, 1·2 per 1000 person-years from 2010–12), of which 267 942 (3·7%) were laboratory confirmed and 2457 (0·03%) were fatal. Incidence and mortality were highest in children aged 12–23 months (38·2 cases per 1000 person-years and 1·5 deaths per 100 000 person-years in 2012). Median duration from onset to diagnosis was 1·5 days (IQR 0·5–2·5) and median duration from onset to death was 3·5 days (2·5–4·5). The absolute number of patients with cardiopulmonary or neurological complications was 82 486 (case-severity rate 1·1%), and 2457 of 82486 patients with severe disease died (fatality rate 3·0%); 1617 of 1737 laboratory confirmed deaths (93%) were associated with enterovirus 71. Every year in June, hand, foot, and mouth disease peaked in north China, whereas southern China had semiannual outbreaks in May and September–October. Geographical differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8–23% and 3–19%, respectively).
This is the largest population-based study up to now of the epidemiology of hand, foot, and mouth disease. Future mitigation policies should take into account the heterogeneities of disease burden identified. Additional epidemiological and serological studies are warranted to elucidate the dynamics and immunity patterns of local hand, foot, and mouth disease and to optimise interventions.
China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases, WHO, The Li Ka Shing Oxford Global Health Programme and Wellcome Trust, Harvard Center for Communicable Disease Dynamics, and Health and Medical Research Fund, Government of Hong Kong Special Administrative Region.
Journal Article
Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults
Improving the efficacy of influenza vaccination in older adults is a challenge. In this randomized clinical trial, a high-dose influenza vaccine was shown to be more effective than a standard-dose vaccine in the prevention of laboratory-confirmed influenza.
Between 1990 and 1999, seasonal influenza caused an average of 36,000 deaths and 226,000 hospitalizations per year in the United States.
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Adults 65 years of age or older are particularly vulnerable to complications associated with influenza and account for most seasonal influenza–related hospitalizations and deaths.
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Although vaccination currently represents the most effective intervention against influenza and associated complications,
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antibody response and protection elicited by the vaccine are lower among persons 65 years of age or older than among younger adults.
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Strategies to improve antibody responses to influenza vaccine in the older population, such as increasing the . . .
Journal Article
Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study
A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock.
We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus.
50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies.
MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection.
European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.
Journal Article
Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China
The first cases of human infection with the avian influenza A(H7N9) virus were identified in China in early 2013. This report describes findings for 139 persons with confirmed H7N9 virus infection through December 1, 2013.
The first identified cases of human infection with a novel influenza A(H7N9) virus occurred in eastern China during February and March 2013 and were characterized by rapidly progressive pneumonia, respiratory failure, the acute respiratory distress syndrome (ARDS), and fatal outcomes.
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We analyzed available data from field investigations to characterize the descriptive epidemiology of laboratory-confirmed cases of avian influenza A(H7N9) virus infection in humans that were reported to the Chinese Center for Disease Control and Prevention (China CDC) as of December 1, 2013. In this report, we summarize the epidemiologic findings of case investigations and follow-up monitoring of close contacts of . . .
Journal Article