title: Initiating adjunct low-dose hydroxyurea therapy for stroke prevention in children with SCA during the COVID-19 pandemic

text: There is a Blood Commentary on this article in this issue.


title: Special Anniversary Review: Twenty-five years of human immunodeficiency virus research: successes and challenges

text: During 25 years of research since HIV-1 was first identified in Paris, there have been great advances in our understanding of the virus and of the immune system. Practical advances include the early development of diagnostic tests of infection that made blood donation safe, and since 1996, combination anti-retroviral therapy that has great reduced incidence of AIDS in HIV-infected people who have access to the drugs. HIV prevention through behavioural change has been successful, and we do not yet have any safe and efficacious microbicides or vaccines.


title: A Veterinary Vaccine Development Process Map to assist in the development of new vaccines

text: Abstract The UK Government recognised the importance of vaccines in the control of new emerging disease threats and in 2015 established the UK Vaccine Network to focus on specific areas of need. One of these was the understanding of what is involved in the development of a new vaccine and what are the potential bottlenecks to a rapid response in the face of a pandemic such as COVID-19. A Working Group was established to initially produce a Vaccine Development Process Map for a Human Vaccine. However, in view of the importance of animal wellbeing and the significant impact of diseases with Zoonotic potential, a similar Map has been created outlining the Veterinary Vaccine Development Process. This paper describes the production of that Map and covers the process from the generation of a Target Product Profile (TPP) through Discovery and Feasibility, and on to Product Development and Registration.


Repurposing paclitaxel for the treatment of fibrosis: indication discovery for existing drugs


title: Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

text: Abstract The notion that an infectious respiratory pathogen can damage the central nervous system (CNS) and lead to neurological disease was tested using a human respiratory coronavirus, the OC43 strain of human coronavirus (HCoV-OC43). First, primary cell cultures were used to determine the susceptibility of each type of neural cells to virus infection. Neurons were the target cells, undergoing degeneration during infection, in part due to apoptosis. Second, neuropathogenicity was investigated in susceptible mice. Intracerebral inoculation of HCoV-OC43 into BALB/c mice led to an acute encephalitis with neuronal cell death by necrosis and apoptosis. Infectious virus was apparently cleared from surviving animals, whereas viral RNA persisted for several months. Some of the animals surviving to acute encephalitis presented an abnormal limb clasping reflex and a decrease in motor activity starting several months post-infection. These results suggest that viral persistence could be associated with an increased neuronal degeneration leading to neuropathology and motor deficits in susceptible individuals.


title: Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue‐experienced Chinese patients with chronic HBV infection

text: Summary. The study investigated the hepatitis B virus (HBV) genotypic resistance profile in 1803 nucleos(t)ide analogue (NA)‐experienced Chinese patients with chronic HBV infection. Serum HBV DNA was extracted, and the reverse transcriptase region was analysed by a high‐sensitive direct PCR sequencing and verified by clonal sequencing if necessary. Drug‐resistant mutations were detected in 560 of the 1803 patients, including 214 of 490 patients who received lamivudine (LAM), 35 of 428 patients who received adefovir (ADV), five of 18 patients who received telbivudine and 306 of 794 patients who received various sequential/combined NA therapies. ADV‐resistant mutations were detected in 36 of 381 patients who received LAM and then switched‐to ADV in contrast to one of 82 patients who received ADV add‐on LAM. Entecavir (ETV)‐resistant mutations were detected not only in LAM‐ and ETV‐treated patients but also in LAM‐treated ETV‐naïve patients. Double mutations rtM204I and rtL180M were detected more frequently in genotype C than in genotype B virus, and patients infected with this mutant had higher alanine transaminase levels than those infected with mutant containing the rtM204I substitution alone. Multidrug‐resistant HBV strains were identified in eight patients, including two novel strains with mutational patterns rtL180M + A181V + S202G + M204V + N236T and rtL180M + S202G + M204V + N236T. The results provide new information on HBV genotypic resistance profiles in a large cohort of Chinese patients with chronic HBV infection and may have important clinical implication for HBV drug resistance management in China.


title: Development of a highly effective low-cost vaporized hydrogen peroxide-based method for disinfection of personal protective equipment for their selective reuse during pandemics

text: BACKGROUND: Personal Protective Equipment (PPE) is required to safely work with biological agents of bacterial (i.e. Mycobacterium tuberculosis) or viral origin (Ebola and SARS). COVID-19 pandemic especially has created unforeseen public health challenges including a global shortage of PPE needed for the safety of health care workers (HCWs). Although sufficient stocks of PPE are currently available, their critical shortage may develop soon due to increase in demand and depletion of existing supply lines. To empower our HCWs and ensure their continued protection, proactive measures are urgently required to develop procedures to safely decontaminate the PPEs to allow their “selective reuse” during contingency situations. METHODS: Herein, we have successfully developed a decontamination method based on vaporized hydrogen peroxide (VHP). We have used a range of concentration of hydrogen peroxide to disinfect PPE (coveralls, face-shields, and N-95 masks). To ensure a proper disinfection, we have evaluated three biological indicators namely Escherichia coli, Mycobacterium smegmatis and spores of Bacillus stearothermophilus, considered as the gold standard for disinfection processes. We next evaluated the impact of repeated VHP treatment on physical features, permeability, and fabric integrity of coveralls and N-95 masks. Next, we performed Scanning Electron Microscopy (SEM) to evaluate microscopic changes in fiber thickness of N-95 masks, melt blown layer or coverall body suits. Considering the fact that any disinfection procedure should be able to meet local requirements, our study included various regionally procured N-95 masks and coveralls available at our institute All India Institute of Medical Sciences (AIIMS), New Delhi, India. Lastly, the practical utility of VHP method developed herein was ascertained by operationalizing a dedicated research facility disinfecting used PPE during COVID-19. RESULTS: Our prototype studies show that a single VHP cycle (7–8% Hydrogen peroxide) could disinfect PPE and PPE housing room of about 1200 cubic feet (length10 ft × breadth 10 ft × height 12 ft) in less than 10 min, as noted by a complete loss of B. stearothermophilus spore revival. The results are consistent and reproducible as tested in over 10 cycles in our settings. Further, repeated VHP treatment did not result in any physical tear, deformity or other appreciable change in the coverall and N-95 masks. Our permeation tests evaluating droplet penetration did not reveal any change in permeability post-VHP treatments. Also, SEM analysis indeed revealed no significant change in fiber thickness or damage to fibers of coveralls or melt blown layer of N-95 masks essential for filtration. There was no change in user comfort and experience following VHP treatment of PPE. Based on results of these studies, and parameters developed and optimized, an institutional research facility to disinfect COVID-19 PPE is successfully established and operationalized with more than 80% recovery rate for used PPE post-disinfection. CONCLUSIONS: Our study, therefore, successfully establishes the utility of VHP to effectively disinfect PPE for a possible reuse as per the requirements. VHP treatment did not damage coveralls, cause physical deformity and also did not alter fabric architecture of melt blown layer. We observed that disinfection process was successful consistently and therefore believe that the VHP-based decontamination model will have a universal applicability and utility. This process can be easily and economically scaled up and can be instrumental in easing global PPE shortages in any biosafety facility or in health care settings during pandemic situation such as COVID-19.


title: Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection

text: Abstract Background The clinical significance of viral load and co-infections in children with respiratory infections is not clear. Objective To evaluate the correlation of viral load as well as viral and bacterial co-infections with disease severity in hospitalized children with lower respiratory tract infections (LRTIs). Study design This is a prospective study conducted in children admitted for LRTIs for two seasons. To determine viral and bacterial load of respiratory pathogens we performed multiplex real-time polymerase chain reaction and semiquantitative bacterial cultures on nasopharyngeal aspirates (NPA). Results During the study period 244 (60%) children were hospitalized for LRTI with acute virus-induced wheezing and 160 (40%) for radiologic confirmed pneumonia. In the first NPA, viruses were identified in 315 (78%) of the 404 samples and bacteria in 198 (63.3%) of 311 samples. The viral load significantly decreased between the first and second NPA sample in most single and viral co-infections, except rhinovirus and human bocavirus infections. Viral load was inversely related to CRP in RSV infections, whereas a positive correlation was observed in adenovirus infections. Duration of hospitalization was significantly longer in RSV single infections compared to rhinovirus single infections whereas in the latter, leucocytosis and use of systemic steroids was more common. In RSV viral co-infections the presence of fever, leucocytosis, and the use of antibiotics was significantly more frequent. Positive cultures of Haemophilus influenzae dominated in RSV and rhinovirus single infections and Moraxella catarrhalis in RSV viral co-infections. Conclusions Specific viral single and co-infections as well as viral load contribute to disease severity in children with LRTIs.


title: Use of an innovative and non-invasive device for virologic sampling of cough aerosols in patients with community and hospital acquired pneumonia: a pilot study

text: Background: The aetiology of lower respiratory tract infections is challenging to investigate. Despite the wide array of diagnostic tools, invasive techniques, such as bronchoalveolar lavage (BAL), are often required to obtain adequate specimens. PneumoniaCheck(TM) is a new device that collects aerosol particles from cough, allowing microbiological analyses. Up to now it has been tested only for bacteria detection, but no study has investigated its usefulness for virus identification. Methods: In this pilot study we included 12 consecutive patients with pneumonia. After testing cough adequacy via a peak flow meter, a sampling with PneumoniaCheck(TM) was collected and a BAL was performed in each patient. Microbiological analyses for virus identification were performed on each sample and concordance between the two techniques was tested (sensitivity, specificity and positive/negative predictive values), taking BAL results as reference. Results: BAL was considered adequate in 10 patients. Among them, a viral pathogen was identified by PneumoniaCheck(TM) 6 times, each on different samples, whereas BAL allowed to detect the presence of a virus on 7 patients (14 positivities). Overall, the specificity for PneumoniaCheck(TM) to detect a virus was 100%, whereas the sensitivity was 66%. When considering only herpes viruses, PneumoniaCheck(TM) showed a lower sensitivity, detecting a virus in 1/4 of infected patients (25%). Conclusions: In this pilot study PneumoniaCheck(TM) showed a good correlation with BAL for non-herpes virologic identification in pneumonia patients, providing excellent specificity. Further studies on larger population are needed to confirm these results and define its place in the panorama of rapid diagnostic tests for lower respiratory tract infections.


Technology: Fluid lens flows into focus


title: Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA

text: Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA constructs encoding short-hairpin RNAs (shRNAs). Their use as therapeutic antiviral against HIV-1 is limited, because of the emergence of viral escape mutants. In order to solve this durability problem, we tested DNA constructs encoding virus-specific long-hairpin RNAs (lhRNAs) for their ability to inhibit HIV-1 production. Expression of lhRNAs in mammalian cells may result in the synthesis of many siRNAs targeting different viral sequences, thus providing more potent inhibition and reducing the chance of viral escape. The lhRNA constructs were compared with in vitro diced double-stranded RNA and a DNA construct encoding an effective nef-specific shRNA for their ability to inhibit HIV-1 production in cells. Our results show that DNA constructs encoding virus-specific lhRNAs are capable of inhibiting HIV-1 production in a sequence-specific manner, without inducing the class I interferon genes. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/sj.gt.3302786) contains supplementary material, which is available to authorized users.


title: Fifty-Five Years of International Epidemic-Assistance Investigations Conducted by CDC’s Disease Detectives

text: For more than 60 years, the Centers for Disease Control and Prevention (CDC) has used its scientific expertise to help people throughout the world live healthier, safer, longer lives through science-based health action. In 1951, CDC officially established the Epidemic Intelligence Service to help build public health capacity. During 1950–2005, CDC’s Epidemic Intelligence Service officers conducted 462 international epidemiologic field investigations in 131 foreign countries and 7 territories. Investigations have included responding to emerging infectious and noninfectious disease outbreaks, assisting in disaster response, and evaluating core components of public health programs worldwide. Approximately 81% of investigations were responses to infectious disease outbreaks, but the proportion of investigations related to chronic and other noninfectious conditions increased 7-fold (6%–45%). These investigations have contributed to detecting and characterizing new pathogens (e.g., severe acute respiratory syndrome–associated coronavirus) and conditions, provided insights regarding factors that cause or contribute to disease acquisition (e.g., Ebola hemorrhagic fever), led to development of new diagnostics and surveillance technologies, and provided information upon which global health policies and regulations can be based. CDC’s disease detectives will undoubtedly continue to play a critical role in global health and in responding to emerging global disease threats.


title: Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection

text: Abstract The deregulation of cellular long non-coding RNA (lncRNA) expression during a human adenovirus infection was studied by deep sequencing. Expression of lncRNAs increased substantially following the progression of the infection. Among 645 significantly expressed lncRNAs, the expression of 398 was changed more than 2-fold. More than 80% of them were up-regulated and 80% of them were detected during the late phase. Based on the genomic locations of the deregulated lncRNAs in relation to known mRNAs and miRNAs, they were predicted to be involved in growth, structure, apoptosis and wound healing in the early phase, cell proliferation in the intermediate phase and protein synthesis, modification and transport in the late phase. The most significant functions of cellular RNA-binding proteins, previously shown to interact with the deregulated lncRNAs identified here, are involved in RNA splicing, nuclear export and translation events. We hypothesize that adenoviruses exploit the lncRNA network to optimize their reproduction.


title: A Review of the Strategies and Studies on the Prevention and Control of the New Coronavirus in Workplaces

text: Workplaces are susceptible places for exposure to the new coronavirus (Covid-19) infection due to gathering of many people Hence, different instructions have been promoted by international organizations regarding high-risk employees and the necessity of implementing health policies to prevent exposure and infection in the workplace Here we reviewed the required strategies to prevent and control COVID-19 in the workplace In conclusion, considering the fast spreading and growing prevalence of the new corona virus disease in the world over, all managers, employers, and business owners should receive the necessary information and training on prevention and control strategies based on scientific guidelines and standards


The value of CT imaging for COVID-19 pneumonia: report of a false-negative nucleic acid test case.


title: A hidden cause of hypokalemic paralysis in a patient with prostate cancer

text: Hypokalemic paralysis is a medical emergency due to the risks of cardiac arrhythmia, respiratory failure, and rhabdomyolysis. Besides supplementing patients with KCl to hasten recovery, the astute physician must search for the underlying cause to avoid missing a treatable and curable disorder. We report on an elderly Korean man who presented with marked limb paralysis, myalgias, and mild hypertension. He had prostate cancer treated with orchiectomy and hormone therapy 2 years previously. The major biochemical abnormalities were hypokalemia (K(+): 1.7 mmol/l) associated with high renal K(+) wasting and metabolic alkalosis (HCO(3)(−): 42.6 mmol/l). Low plasma renin activity, low aldosterone concentration, and normal cortisol concentration pointed to a state of pseudohyperaldosteronism. While reviewing his drug history, the patient revealed he had been consuming eight packs (100 ml/pack) of a Korean herbal tonic daily to treat his prostate cancer for the past 2 months. A significant amount of glycyrrhizic acid (0.23 mg/ml), an active ingredient of licorice, was detected in the tonic. Discontinuation of the herbal tonic along with KCl supplementation achieved recovery in 2 weeks. As many complementary/alternative medicines for cancer contain licorice, this must be kept in mind as a cause of hypokalemia in cancer patients.


title: 2019 Novel Coronavirus: an Emerging Global Threat

text: The coronavirus (CoV) epidemic that began in China in December 2019 follows earlier epidemics of severe acute respiratory syndrome CoV in China and Middle East respiratory syndrome CoV in Saudi Arabia. The full genome of the 2019 novel coronavirus (2019-nCoV) has now been shared, and data have been gathered from several case series. As of February 11, 2020, there have been 45,182 laboratory-confirmed cases, the vast majority in China, with 1115 deaths, for an overall case-fatality rate of 2.5%. Cases have been confirmed in 27 countries. On average, each patient infects 2.2 other people. Symptomatic infection appears to predominantly affect adults, with a 5-day estimated incubation period between infection and symptom onset. The most common presenting symptoms are fever, cough, dyspnea, and myalgias and/or fatigue. All cases reported to date have shown radiographic evidence of pneumonia. 2019-nCoV is diagnosed by real-time reverse transcriptase polymerase chain reaction. Treatment is largely supportive, with regimens including antiviral therapy. Corticosteroids are not routinely recommended. Hand hygiene, prompt identification and isolation of suspect patients, and appropriate use of personal protective equipment are the most reliable methods to contain the epidemic.


title: THE RISE AND FALL OF TOBACCO AS A BOTANICAL MEDICINE

text: A forgotten and valuable chapter in the history of tobacco concerns its role as a botanical medicine. For three hundred years following its importation into Europe, tobacco came to be considered a universal remedy highly prescribed by physicians. In the early history of tobacco, the literature on its medicinal benefits was voluminous. Nonetheless, bitter opposition to its use for non-medicinal purposes began to arise. There was little doubt of its medicinal efficacy at first, but with time, as the concepts and practice of medicine changed, the tide of medical opinion turned against it. Medical support for the therapeutic use of tobacco reached its nadir during the mid-nineteenth century, when it was dropped from most medical pharmacoepiae. Medical opinion on the health hazards of recreational smoking required another 100 years to arrive at the contemporary opinion that cigarette smoking is the single most important preventable environmental factor contributing to illness, disability and death in the U. S.


title: Specific detection of H5N1 avian influenza A virus in field specimens by a one-step RT-PCR assay

text: BACKGROUND: Continuous outbreaks of the highly pathogenic H5N1 avian influenza A in Asia has resulted in an urgent effort to improve current diagnostics to aid containment of the virus and lower the threat of a influenza pandemic. We report here the development of a PCR-based assay that is highly specific for the H5N1 avian influenza A virus. METHODS: A one-step reverse-transcription PCR assay was developed to detect the H5N1 avian influenza A virus. The specificity of the assay was shown by testing sub-types of influenza A virus and other viral and bacterial pathogens; and on field samples. RESULTS: Validation on 145 field specimens from Vietnam and Malaysia showed that the assay was specific without cross reactivity to a number of other infuenza strains as well as human respiratory related pathogens. Detection was 100% from allantoic fluid in H5N1 positive samples, suggesting it to be a reliable sampling source for accurate detection. CONCLUSION: The assay developed from this study indicates that the primers are specific for the H5N1 influenza virus. As shown by the field tested results, this assay would be highly useful as a diagnostic tool to help identify and control influenza epidemics.


title: Evaluation of the FilmArray(®) Respiratory Panel for Clinical Use in a Large Children's Hospital

text: BACKGROUND: Respiratory pathogens are a leading cause of hospital admission and traditional detection methods are time consuming and insensitive. Multiplex molecular detection methods have recently been investigated in hope of replacing these traditional techniques with rapid panel‐based testing. OBJECTIVES: This study evaluated the FilmArray(®) Respiratory Panel ([FARP], Idaho Technology Inc., Salt Lake City, UT) as a replacement for direct fluorescent antibody (DFA) testing in a pediatric hospital. METHODS: Eleven of the 21 FARP analytes (Adenovirus, Bordetella pertussis, human Metapneumovirus, Influenza A, Influenza A H1N1 2009, Influenza B, Parainfluenza [1, 2, & 3], Respiratory Syncytial Virus, and rhinovirus) were evaluated using nasopharyngeal specimens. Positive samples were pooled in groups of 5. Samples identified by reference methods as positive for respiratory pathogens were used for the majority of positive samples. DFA was the reference method for ten analytes; Luminex(TM) xTAG Respiratory Virus Panel (RVP) was the reference method for rhinovirus. Discrepant results were resolved by positive culture and fluorescent antibody stain and/or laboratory‐developed real‐time polymerase chain reaction (PCR) assays (LDT). RESULTS: The agreement for most analytes was in concordance with the established reference methods with the exception of Adenovirus. Additionally, the FARP detected several pathogens not previously detected by DFA, and most were confirmed by LDT. Several DFA‐positive analytes were confirmed as true‐negatives by the FARP and LDT. CONCLUSION: FARP overall performed better than DFA with the exception of Adenovirus, making the FARP an attractive alternative to laboratories looking to replace DFA with a rapid, user‐friendly, multiplex molecular assay. J. Clin. Lab. Anal. 27:148–154, 2013. © 2013 Wiley Periodicals, Inc.


title: Drivers of foot‐and‐mouth disease in cattle at wild/domestic interface: Insights from farmers, buffalo and lions

text: Humans live increasingly in the proximity of natural areas, leading to increased interactions between people, their livestock and wildlife. AIM: We explored the role of these interactions in the risk of disease transmission (foot‐and‐mouth disease [FMD]) between cattle and the African buffalo (the maintenance host) and how a top predator, the lion, may modulate these interactions. LOCATION: The interface of Hwange National Park (HNP) and surrounding communal lands, Zimbabwe. METHOD: We combined a longitudinal serological cattle survey for FMD, GPS‐collar data and cattle owners’ interviews during four seasons in 2010–2011. RESULTS: Overall FMD incidence in cattle was low, but showed a peak during the rainy season. The incidence dynamic was significantly explained by cattle incursion into the protected area (i.e., buffer zone of 3 km inside HNP) and not by contacts with buffalo or contacts among cattle. These results suggest that FMD virus either survives in the environment or is transmitted by other ungulate groups or species. The analysis of incursion frequency in the buffer suggests that (1) buffalo and cattle are avoiding each other up to 2 months after one species track and that (2) lions make frequent incursions in the buffer few days to few weeks after buffalo had used it, whereas buffalo did not use areas occupied by lions. Lions could thus reduce the spatio‐temporal overlap between cattle and buffalo in the interface, which could contribute to the low level of FMD incidence. MAIN CONCLUSIONS: During the rainy season, traditional herding practices push cattle away from growing crops near villages into the HNP but not during the dry season, suggesting that cattle owners may decide to rely on lower quality resources in the communal land in the dry season to avoid the risks of infection and/or predation in the HNP. This study highlights the complex dynamics that operates at human/livestock/wildlife interfaces.


title: Factors associated with uptake of influenza vaccine in people aged 50 to 64 years in Hong Kong: a case–control study

text: BACKGROUND: In Hong Kong, people aged 50–64 years were added as a recommended priority group (recommended group) for influenza vaccination by the Department of Health (DH) starting from 2011/12 onwards. The coverage rate of influenza vaccination for this age group was suboptimal at 8.5 % in 2012/13. This study investigates the factors associated with the uptake of influenza vaccination among adults in Hong Kong aged 50–64 years. METHODS: A case–control study was conducted in communities by street intercept interviews from 17 July to 15 August 2013. Cases were adults aged 50–64 years who had received the influenza vaccine in 2011/12 or 2012/13, while controls were the same as the cases, except they had not received the influenza vaccine in 2011/12 or 2012/13. Multiple logistic regression analysis was performed on the data to explore the associations between vaccination status and the variables. RESULTS: Six hundred and four respondents in total were interviewed and included in the analysis. There were 193 cases (vaccinated) and 411 controls (non-vaccinated), with a case-to-control ratio of 1:2.1. The following were strongly associated with vaccination compared to other factors: ‘eligible for free government vaccine’ (OR6.38, 95 % CI, 3.43-11.87, p < 0.001); ‘willing to receive flu vaccination for free’ (OR4.84, 95 % CI, 2.13-11.03, p < 0.001); ‘perceived having severe or moderate symptoms when contracting flu’ (OR2.90, 95 % CI, 1.21-6.97, p = 0.02), and ‘convenient to reach a vaccination location’ (OR2.87, 95 % CI, 1.06-7.74, p = 0.04). The majority of the cases (80.8 %) and controls (93.9 %) were not aware that they belonged to a recommended group for influenza vaccination and most (>80 %) were willing to be vaccinated if it was free. CONCLUSIONS: Factors related to free and convenient vaccination, the perception of the severity of symptoms when contracting influenza had a comparatively strong association with influenza vaccination uptake amongst 50–64 year olds, compared to other factors.


title: A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients

text: Abstract Background/Aims Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients. Methods Multicentre, prospective, open-label, randomized, phase III clinical trial. Eighty co-infected patients were randomized to receive ribavirin 800–1000 mg/day in combination with, group A: interferon alpha2a 3MIU thrice weekly; group B: IFNα2a 3MIU daily, plus amantadine 200 mg/day; treatment duration was 24–48 weeks according to HCV genotype. Results Forty-one patients were randomized in group A and 39 in group B. Intention-to-treat analysis showed a sustained virological response, defined as HCV-RNA negativization, 6 months after stopping treatment in 22% of patients from group A and 13% from group B (P>0.05). The lack of a 2-log drop in HCV-RNA levels after 12 weeks of treatment showed a 100% predictive value of lack of sustained response. Conclusions Amantadine addition and interferon intensification do not improve the low efficacy of combination of interferon alfa plus ribavirin in HIV/HCV co-infected patients. Patients with no early virologic response did not have any probability of sustained response.


Health psychology and the coronavirus (COVID‐19) global pandemic: A call for research


title: The consequences of the COVID‐19 pandemic

text: [Image: see text] Deputy Editor‐in‐Chief, Dr Patrick Chien, discusses the latest thinking in women's health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/july-editorial-2020


title: Determining the filtration efficiency of half-face medical protection mask (N99) against viral aerosol

text: Hospital-based outbreaks of severe acute respiratory syndrome (SARS) have once again highlighted the vulnerability of healthcare workers (HCWs). Use of personal respiratory protective equipment was the main method used by HCWs to avoid nosocomial transmission. This paper describes the technology used to evaluate the filtration efficiency of the half-face medical protection mask (N99), manufactured by Firmshield Biotechnology, against viral aerosol. Viral aerosol was generated and then sampled simultaneously with and without the test mask. This enables a percentage efficiency value to be calculated against test phage f2 aerosols (surrogates of viral pathogen aerosols). At the same time the mask filtration efficiency against NaCl particle aerosol was determined by use of TSI8130 equipment and face-fit factor was tested by use of TSI8020 equipment. The half-face medical protection mask (N99) evaluated by use of the viral aerosol had a filtration efficiency >99%. The mask filtration efficiency against NaCl particle aerosol was 99.634 ± 0.024% and it had a good face-fit factor. This half-face medical protection mask (N99) can protect the wearer from viral aerosol disease transmission. The test method can be used to assess filtration efficacy against viral aerosol of masks used for respiratory protection.


title: An analysis of changes in emergency department visits after a state declaration during the time of COVID-19

text: Abstract Objective In the initial period of the COVID-19 pandemic there has been a substantial decrease in the number of patients seeking care in the ED. An initial step in estimating the impact of these changes is to characterize the patients, visits, and diagnoses for whom care is being delayed or deferred. Methods We conducted an observational study, examining demographics, visit characteristics, and diagnoses for all ED patient visits to an urban Level-1 trauma center before and after a state emergency declaration and comparing them to a similar period in 2019. We estimated percent change based on the ratios of before and after periods with respect to 2019 and the decline per week using Poisson regression. Finally, we evaluated whether each factor modified the change in overall ED visits. Results After the state declaration, there was a 49.3% decline in ED visits overall, 35.2% (95%CI: -38.4 to -31.9) as compared to 2019. Disproportionate declines were seen in visits by pediatric and older patients, women, and Medicare recipients as well as for presentations of syncope, cerebrovascular accidents, urolithiasis, abdominal and back pain. Significant proportional increases were seen in ED visits for upper respiratory infections, shortness of breath, and chest pain. Conclusions There have been significant changes in patterns of care-seeking during the COVID-19 pandemic. Declines in ED visits, especially for certain demographic groups and disease processes, should prompt efforts to understand these phenomena, encourage appropriate care-seeking, and monitor for the morbidity and mortality that may result from delayed or deferred care.


title: Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: BACKGROUND AND PURPOSE—: Hyperacute assessment and management of patients with stroke, termed code stroke, is a time-sensitive and high-stakes clinical scenario. In the context of the current coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus, the ability to deliver timely and efficacious care must be balanced with the risk of infectious exposure to the clinical team. Furthermore, rapid and effective stroke care remains paramount to achieve maximal functional recovery for those needing admission and to triage care appropriately for those who may be presenting with neurological symptoms but have an alternative diagnosis. METHODS—: Available resources, COVID-19-specific infection prevention and control recommendations, and expert consensus were used to identify clinical screening criteria for patients and provide the required nuanced considerations for the healthcare team, thereby modifying the conventional code stroke processes to achieve a protected designation. RESULTS—: A protected code stroke algorithm was developed. Features specific to prenotification and clinical status of the patient were used to define precode screening. These include primary infectious symptoms, clinical, and examination features. A focused framework was then developed with regard to a protected code stroke. We outline the specifics of personal protective equipment use and considerations thereof including aspects of crisis resource management impacting team role designation and human performance factors during a protected code stroke. CONCLUSIONS—: We introduce the concept of a protected code stroke during a pandemic, as in the case of COVID-19, and provide a framework for key considerations including screening, personal protective equipment, and crisis resource management. These considerations and suggested algorithms can be utilized and adapted for local practice.


title: Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection

text: Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage.


title: Middle East respiratory syndrome clinical practice guideline for hemodialysis facilities

text: The Korean Society of Nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of Middle East respiratory syndrome (MERS) in 2015. The Korean Society of Nephrology MERS Task Force Team took an immediate action and drafted ‘the clinical recommendation for hemodialysis facilities’ to follow when the first and the only confirmed case was reported in the hemodialysis unit. Owing to the dedicated support from medical doctors, dialysis nurses, and related medical companies, we could prevent further transmission of MERS infection successfully in hemodialysis units. This special report describes the experience of infection control during MERS outbreak in 2015 and summarizes the contents of ‘the clinical practice guideline for hemodialysis facilities dealing with MERS patients’ built upon our previous experience.


title: Antiretroviral HIV drugs in COVID‐19 research: promises and risks. An opinion piece

text: The unprecedented global scale of COVID‐19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarise the evidence for antiretrovirals to treat COVID‐19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.


title: VADR: validation and annotation of virus sequence submissions to GenBank

text: GenBank contains over 3 million viral sequences. The National Center for Biotechnology Information (NCBI) previously made available a tool for validating and annotating influenza virus sequences that is used to check submissions to GenBank. Before this project, there was no analogous tool in use for non-influenza viral sequence submissions. We developed a system called VADR (Viral Annotation DefineR) that validates and annotates viral sequences in GenBank submissions. The annotation system is based on the analysis of the input nucleotide sequence using models built from curated RefSeqs. Hidden Markov models are used to classify sequences by determining the RefSeq they are most similar to, and feature annotation from the RefSeq is mapped based on a nucleotide alignment of the full sequence to a covariance model. Predicted proteins encoded by the sequence are validated with nucleotide-to-protein alignments using BLAST. The system identifies 43 types of “alerts” that (unlike the previous BLAST-based system) provide deterministic and rigorous feedback to researchers who submit sequences with unexpected characteristics. VADR has been integrated into GenBank’s submission processing pipeline allowing for viral submissions passing all tests to be accepted and annotated automatically, without the need for any human (GenBank indexer) intervention. Unlike the previous submission-checking system, VADR is freely available (https://github.com/nawrockie/vadr) for local installation and use. VADR has been used for Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019. Other viruses with high numbers of submissions will be added incrementally. VADR improves the speed with which non-flu virus submissions to GenBank can be checked and improves the content and quality of the GenBank annotations. The availability and portability of the software allow researchers to run the GenBank checks prior to submitting their viral sequences, and thereby gain confidence that their submissions will be accepted immediately without the need to correspond with GenBank staff. Reciprocally, the adoption of VADR frees GenBank staff to spend more time on services other than checking routine viral sequence submissions.


title: Mechanisms of autoimmunity and AIDS: prospects for therapeutic intervention

text: Summary The network theory of autoimmunity is presented with recent experimental data relevant to the understanding of the pathogenesis of AIDS. Schematically, effector T cells specific for self-antigens exist normally, but their activity is modulated and prevented by networks of regulatory T cells. As a result of mimicry between molecular components of microorganisms and self-antigens, autoimmune disease can be triggered by specific foreign pathogens which alter the state of activity of the network from suppression to activation. Conversely, by a procedure known as T-cell vaccination, autologous effector T cells re-injected after in vitro stimulation and attenuation may alter the state of the network from an activation to a suppression. Numerous observations are reviewed that support the concept of autoimmune activity in the destruction of non-infected T4 cells. Such activity is presumed to be triggered by an antigen of viral origin, the most likely, but not the only one, being the envelope protein gp120. Based on this hypothesis, a T-cell vaccination procedure against effector T cells responsible for autoimmunopathic activity in HIV-seropositive patients is proposed, similar to the one known from experimental study of autoimmunity and presently being tested in human autoimmune diseases. Its purpose would be to prevent T-cell loss and the onset of immunodeficiency disease in HIV-seropositive patients. Apart from its potential therapeutic value, this procedure will have use as a therapeutic test from which insight will be gained about the immunopathogenesis of AIDS.


title: Effects of ribavirin on the replication and genetic stability of porcine reproductive and respiratory syndrome virus

text: BACKGROUND: Although modified live virus (MLV) vaccines are commonly used for porcine reproductive and respiratory syndrome virus (PRRSV) control, there have been safety concerns due to the quick reversion of MLV to virulence during replication in pigs. Previous studies have demonstrated that mutant viruses emerged from lethal mutagenesis driven by antiviral mutagens and that those viruses had higher genetic stability compared to their parental strains because they acquired resistance to random mutation. Thus, this strategy was explored to stabilize the PRRSV genome in the current study. RESULTS: Four antiviral mutagens (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated for their antiviral effects against VR2332, a prototype of type 2 PRRSV. Among the mutagens, ribavirin and 5-fluorouracil had significant antiviral effects against VR2332. Consequently, VR2332 was serially passaged in MARC-145 cells in the presence of ribavirin at several concentrations to facilitate the emergence of ribavirin-resistant mutants. Two ribavirin-resistant mutants, RVRp13 and RVRp22, emerged from serial passages in the presence of 0.1 and 0.2 mM ribavirin, respectively. The genetic stability of these resistant mutants was evaluated in MARC-145 cells and compared with VR2332. As expected, the ribavirin-resistant mutants exhibited higher genetic stability compared to their parental virus. CONCLUSIONS: In summary, ribavirin and 5-fluorouracil effectively suppressed PRRSV replication in MARC-145 cells. However, ribavirin-resistant mutants emerged when treated with low concentrations (≤0.2 mM) of ribavirin, and those mutants were genetically more stable during serial passages in cell culture.


title: Emerging viral zoonoses: Frameworks for spatial and spatiotemporal risk assessment and resource planning

text: Abstract Spatial epidemiological tools are increasingly being applied to emerging viral zoonoses (EVZ), partly because of improving analytical methods and technologies for data capture and management, and partly because the demand is growing for more objective ways of allocating limited resources in the face of the emerging threat posed by these diseases. This review documents applications of geographical information systems (GIS), remote sensing (RS) and spatially-explicit statistical and mathematical models to epidemiological studies of EVZ. Landscape epidemiology uses statistical associations between environmental variables and diseases to study and predict their spatial distributions. Phylogeography augments epidemiological knowledge by studying the evolution of viral genetics through space and time. Cluster detection and early warning systems assist surveillance and can permit timely interventions. Advanced statistical models can accommodate spatial dependence present in epidemiological datasets and can permit assessment of uncertainties in disease data and predictions. Mathematical models are particularly useful for testing and comparing alternative control strategies, whereas spatial decision-support systems integrate a variety of spatial epidemiological tools to facilitate widespread dissemination and interpretation of disease data. Improved spatial data collection systems and greater practical application of spatial epidemiological tools should be applied in real-world scenarios.


title: Aspects of the Health Inspection Authority in the People’s Republic of China

text: BACKGROUND: In China, there was a pressing need to establish a governmental agency to oversee the organizations that provide public health and medical services. The Chinese Health Inspection Authority (HIA), a relatively independent organization functioning at each administrative level (provincial, municipal, and county), was mandated to conduct 11 health inspection functions to maintain efficient public health and medical services. These functions include issuing health permit, conducting health supervision and inspection, health testing and evaluation, case investigation, complaint handling, managing public health crisis, monitoring and safeguarding public health at major public events, enforcing supervision and inspection compliance, public health education, information management, and team training and management. Since the reform of the health inspection system by the Ministry of Health in 2000, the HIA underwent a series of changes and transitions. This study aimed to describe and assess the five factors that were considered to be important for meeting service delivery objectives of the HIA in the People’s Republic of China. METHODS: A total of 604 HIAs, sampled across three geographical regions of China at three administrative levels, participated in a cross-sectional survey conducted in 2013. Descriptive statistics were used to analyze the status of mandated operations, manpower, revenue and expenditures, and institutional infrastructure. Differences in these characteristics across the geographical regions and administrative levels were compared. RESULTS: On average, the HIAs had not fully implemented the 11 mandated functions at any administrative levels. Governmental financial allocations were the main sources of revenue. Three primary personnel employment models coexisted and most employed the quasi-civil service employment model. The institutional infrastructure did not meet governmental mandated standards with respect to building area or the number and types of equipment available to conduct key functions. CONCLUSIONS: In 2012, the majority of the HIAs in China at the provincial, municipal, and county levels did not meet the mandated requirements, although positive indications toward meeting these requirements were observed. It is necessary for the government to pay more attention to institutional resources (buildings, equipment, and the level of the staff’s educational attainment) and ensure that the HIAs can meet their service delivery objectives.


docid: tmpidjrp

title: Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

text: Diverse pathogens are detected in Alzheimer’s disease (AD) brains. A bioinformatics survey showed that AD genome-wide association study (GWAS) genes (localized in bone marrow, immune locations and microglia) relate to multiple host/pathogen interactomes (Candida albicans, Cryptococcus neoformans, Bornavirus, Borrelia burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza, Chlamydia pneumoniae, Porphyrymonas gingivalis, Helicobacter pylori, Toxoplasma gondii, Trypanosoma cruzi). These interactomes also relate to the AD hippocampal transcriptome and to plaque or tangle proteins. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi, or protozoa in immunocompetent cells. AD genes are enriched in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance, as supported by the old age of AD patients, implying resistance to earlier infections. APOE4 is concentrated in regions of high parasitic burden and protects against childhood tropical infections and hepatitis C. Immune/inflammatory gain of function applies to APOE4, CR1, and TREM2 variants. AD genes are also expressed in the blood-brain barrier (BBB), which is disrupted by AD risk factors (age, alcohol, aluminum, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption, smoking) and by pathogens, directly or via olfactory routes to basal-forebrain BBB control centers. The BBB benefits from statins, NSAIDs, estrogen, melatonin, memantine, and the Mediterranean diet. Polymicrobial involvement is supported by upregulation of bacterial, viral, and fungal sensors/defenders in the AD brain, blood, or cerebrospinal fluid. AD serum amyloid-β autoantibodies may attenuate its antimicrobial effects favoring microbial survival and cerebral invasion leading to activation of neurodestructive immune/inflammatory processes, which may also be augmented by age-related immunosenescence. AD may thus respond to antibiotic, antifungal, or antiviral therapy.


title: Kawasaki disease: What is the epidemiology telling us about the etiology?

text: Summary Kawasaki disease (KD) is an important and common inflammatory vasculitis of early childhood with a striking predilection for the coronary arteries. It is the predominant cause of paediatric acquired heart disease in developed countries. Despite 40 years of research, the aetiology of KD remains unknown and consequently there is no diagnostic test and treatment is non-specific and sub-optimal. The consensus is that KD is due to one or more widely distributed infectious agent(s), which evoke an abnormal immunological response in genetically susceptible individuals. The epidemiology of KD has been extensively investigated in many populations and provides much of the supporting evidence for the consensus regarding etiology. These epidemiological data are reviewed here, in the context of the etiopathogenesis. It is suggested that these data provide additional clues regarding the cause of KD and may account for some of the continuing controversies in the field.


title: Efficacy of neural vision therapy to enhance contrast sensitivity function and visual acuity in low myopia

text: Purpose To evaluate the efficacy and safety of neural vision enhancement technology (NVC, NeuroVision, Inc.) to improve visual acuity and contrast sensitivity function in eyes with low myopia. Setting Singapore Eye Research Institute, Singapore, Singapore. Methods This noncomparative interventional case series comprised 20 Asian adults between 19 and 53 years of age with low myopia (cycloplegic spherical equivalence [SE] from −0.5 diopter [D] to −1.5 D in the worst eye; astigmatism not exceeding 0.5 D in either eye; uncorrected visual acuity [UCVA] ≤0.7 logMAR) who had NVC treatment. The main outcome measures were distance UCVA, uncorrected contrast sensitivity, refraction, accommodative amplitude, and safety. Results All eyes had improvement in UCVA and contrast sensitivity. After treatment, the mean distance UCVA improved by a mean of 2.1 lines on the Early Treatment Diabetic Retinopathy Study logMAR chart. The mean contrast sensitivity improved over a range of spatial frequencies on sine-wave contrast sensitivity chart testing (1.5 to 18 cycles per degree). Follow-up data up to 12 months posttreatment showed that the gains were retained. Treatment did not alter refraction (mean spherical equivalent) or accommodative amplitudes. No adverse effects were reported. Conclusion Preliminary evidence suggests NVC treatment is safe and improves UCVA and uncorrected contrast sensitivity in adult patients with low myopia.


title: Coronavirus Disease 2019 in Children Cared for at Texas Children’s Hospital: Initial Clinical Characteristics and Outcomes

text: We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.


title: Prediction of High Incidence of Dengue in the Philippines

text: BACKGROUND: Accurate prediction of dengue incidence levels weeks in advance of an outbreak may reduce the morbidity and mortality associated with this neglected disease. Therefore, models were developed to predict high and low dengue incidence in order to provide timely forewarnings in the Philippines. METHODS: Model inputs were chosen based on studies indicating variables that may impact dengue incidence. The method first uses Fuzzy Association Rule Mining techniques to extract association rules from these historical epidemiological, environmental, and socio-economic data, as well as climate data indicating future weather patterns. Selection criteria were used to choose a subset of these rules for a classifier, thereby generating a Prediction Model. The models predicted high or low incidence of dengue in a Philippines province four weeks in advance. The threshold between high and low was determined relative to historical incidence data. PRINCIPAL FINDINGS: Model accuracy is described by Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, and Specificity computed on test data not previously used to develop the model. Selecting a model using the F(0.5) measure, which gives PPV more importance than Sensitivity, gave these results: PPV = 0.780, NPV = 0.938, Sensitivity = 0.547, Specificity = 0.978. Using the F(3) measure, which gives Sensitivity more importance than PPV, the selected model had PPV = 0.778, NPV = 0.948, Sensitivity = 0.627, Specificity = 0.974. The decision as to which model has greater utility depends on how the predictions will be used in a particular situation. CONCLUSIONS: This method builds prediction models for future dengue incidence in the Philippines and is capable of being modified for use in different situations; for diseases other than dengue; and for regions beyond the Philippines. The Philippines dengue prediction models predicted high or low incidence of dengue four weeks in advance of an outbreak with high accuracy, as measured by PPV, NPV, Sensitivity, and Specificity.


title: Simultaneous Detection of CDC Category “A” DNA and RNA Bioterrorism Agents by Use of Multiplex PCR & RT-PCR Enzyme Hybridization Assays

text: Assays to simultaneously detect multiple potential agents of bioterrorism are limited. Two multiplex PCR and RT-PCR enzyme hybridization assays (mPCR-EHA, mRT-PCR-EHA) were developed to simultaneously detect many of the CDC category “A” bioterrorism agents. The “Bio T” DNA assay was developed to detect: Variola major (VM), Bacillus anthracis (BA), Yersinia pestis (YP), Francisella tularensis (FT) and Varicella zoster virus (VZV). The “Bio T” RNA assay (mRT-PCR-EHA) was developed to detect: Ebola virus (Ebola), Lassa fever virus (Lassa), Rift Valley fever (RVF), Hantavirus Sin Nombre species (HSN) and dengue virus (serotypes 1–4). Sensitivity and specificity of the 2 assays were tested by using genomic DNA, recombinant plasmid positive controls, RNA transcripts controls, surrogate (spiked) clinical samples and common respiratory pathogens. The analytical sensitivity (limit of detection (LOD)) of the DNA asssay for genomic DNA was 1×10(0)∼1×10(2) copies/mL for BA, FT and YP. The LOD for VZV whole organism was 1×10(−2) TCID(50)/mL. The LOD for recombinant controls ranged from 1×10(2)∼1×10(3)copies/mL for BA, FT, YP and VM. The RNA assay demonstrated LOD for RNA transcript controls of 1×10(4)∼1×10(6) copies/mL without extraction and 1×10(5)∼1×10(6) copies/mL with extraction for Ebola, RVF, Lassa and HSN. The LOD for dengue whole organisms was ∼1×10(−4) dilution for dengue 1 and 2, 1×10(4) LD(50)/mL and 1×10(2) LD(50)/mL for dengue 3 and 4. The LOD without extraction for recombinant plasmid DNA controls was ∼1×10(3) copies/mL (1.5 input copies/reaction) for Ebola, RVF, Lassa and HSN. No cross-reactivity of primers and probes used in both assays was detected with common respiratory pathogens or between targeted analytes. Clinical sensitivity was estimated using 264 surrogate clinical samples tested with the BioT DNA assay and 549 samples tested with the BioT RNA assay. The clinical specificity is 99.6% and 99.8% for BioT DNA assay and BioT RNA assay, respectively. The surrogate sensitivities of these two assays were 100% (95%CI 83–100) for FT, BA (pX02), YP, VM, VZV, dengue 2,3,4 and 95% (95%CI 75–100) for BA (pX01) and dengue 1 using spiked clinical specimens. The specificity of both BioT multiplex assays on spiked specimens was 100% (95% CI 99–100). Compared to other available assays (culture, serology, PCR, etc.) both the BioT DNA mPCR-EHA and BioT RNA mRT-PCR-EHA are rapid, sensitive and specific assays for detecting many category “A” Bioterrorism agents using a standard thermocycler.


title: The Hemagglutinin-Esterase Fusion Glycoprotein Is a Primary Determinant of the Exceptional Thermal and Acid Stability of Influenza D Virus

text: Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID(50)]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min. Furthermore, the data showed that IDV was extremely resistant to inactivation by low pH. After being treated at pH 3.0 for 30 min, IDV lost only approximately 20% of its original infectiousness, while all other types of influenza viruses were completely inactivated. Finally, replacement of the hemagglutinin (HA) and neuraminidase (NA) proteins of a temperature- and acid-sensitive IAV with the hemagglutinin-esterase fusion (HEF) protein of a stable IDV through a reverse genetic system largely rendered the recombinant IAVs resistant to high-temperature and low-pH treatments. Together, these results indicated that the HEF glycoprotein is a primary determinant of the exceptional temperature and acid tolerance of IDV. Further investigation into the viral entry and fusion mechanism mediated by the intrinsically stable HEF protein of IDV may offer novel insights into how the fusion machinery of influenza viruses evolve to achieve acid and thermal stability, which as a result promotes the potential to transmit across mammal species. IMPORTANCE Influenza D virus (IDV) utilizes cattle as a primary reservoir. Increased outbreaks in pigs and serological evidence of human infection have raised a concern about the potential of IDV adapting to humans. Here, we directly compared IDV’s stability to that of other influenza types (A, B, and C) following prolonged incubation at high temperatures or in a low-pH environment. We found that IDV is the most stable of the four types of influenza viruses. Importantly, we demonstrated that the hemagglutinin-esterase fusion (HEF) protein, which drives the fusion between viral and host cell membranes, is the primary determinant for the high thermal and acid stability of IDV. Considering that there is a link between the acid stability of the hemagglutinin protein of influenza A virus and its cross-species transmission, further investigation of the mechanism of HEF-directed viral tolerance may offer novel insights into tissue tropism and cross-species transmission of influenza viruses.


title: Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017

text: OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. DESIGN: Outbreak investigation. SETTING: Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit. METHODS: Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases. RESULTS: In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive. CONCLUSIONS: We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.


title: An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro

text: There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We here report on an aglycon analogue of the antibiotic teicoplanin (code name LCTA-949) that inhibits DENV-induced cytopathic effect (CPE) in a dose-dependent manner. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In conclusion, LCTA-949 exerts in vitro activity against several flaviviruses and does so (as shown for DENV) by interfering with an early step in the viral replication cycle.


title: Atypical presentations of coronavirus disease 2019 in a patient with acute obstructive suppurative cholangitis

text: Abstract During the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak in Wuhan, China, we experienced a case of SARS-CoV-2 infection with atypical presentations in a patient with acute obstructive suppurative cholangitis (AOSC), who was initially admitted with jaundice and fever. The patient had no other typical symptoms of COVID-19 such as cough, dyspnea, nausea, vomiting, abdominal pain and diarrhea except for fever, but her epidemiological history was clear. COVID-19 was finally confirmed by repeated viral nucleic acid testing, but her repetitive lungs CT imaging findings had been atypical. After endoscopic-related operations and antiviral treatment, the patient was subsequently recovered and discharged. This particular case is being reported to provide a reference and guidance for the diagnosis and management of COVID-19 in AOSC.


title: Public health event communication under the International Health Regulations (2005) in the Western Pacific Region, September 2006-January 2017

text: • The International Health Regulations, or IHR (2005), establishes timely communication between the World Health Organization (WHO) and Member States to manage acute public health events and protect health security. Experiences of the WHO IHR contact point for the Western Pacific Region demonstrated the communication mechanism has achieved its functions in the Region. • Investment in IHR communication as part of the Asia Pacific Strategy for Emerging Diseases and Public Health Emergencies (APSED III) during peaceful times between public health emergencies builds capacity, confidence and trust in information sharing during emergencies. • IHR communication is integral to the national, regional and global epidemic intelligence and risk assessments system. • Regular simulation exercises (for example, IHR Exercise Crystal) play an important role in testing and strengthening IHR communication. • IHR communication continues to be vital for Member States and WHO country offices to advise on health security.


title: Stimulation of rotavirus IgA, IgG and neutralising antibodies in baboon milk by parenteral vaccination

text: Abstract A rhesus rotavirus vaccine adjuvanted with ISCOMs was injected intramuscularly to 5 pregnant baboons, with repeated doses 1–2 and 14 weeks after delivery. Maternal blood and milk samples and blood samples from their babies were collected at 2-weekly intervals until 26 weeks after parturition. Samples were assayed for rotavirus antibodies by ELISAs and neutralisation tests. Vaccination produced statistically significant increases in maternal serum IgG and neutralising antibodies, and in milk IgA, IgG, and neutralising antibodies. Control baboon mothers sampled from 12 weeks after delivery had lower serum and milk antibody titres, but responded to vaccination at 16 weeks by producing a similar antibody profile in serum and milk to those previously vaccinated. Because of the endemic nature of human rotaviral infections, similar maternal vaccinations have potential as a means of increasing milk antibodies to a level at which they may be protective to infants.


title: Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance

text: Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use.


title: Methylprednisolone added to tocilizumab reduces mortality in SARS‐CoV‐2 pneumonia: An observational study

text: Although there are few randomized controlled trials (RCTs) evaluating the efficacy of drugs to treat COVID‐19, different molecules have been used empirically and with great interest in those intended to control the excessive inflammatory response produced by SARS‐CoV‐2. By blocking the IL‐6 receptor, tocilizumab has a role in controlling the inflammatory response. Clinical improvement of respiratory parameters and hospital stay have been described in small series in a series of patients without a control group [1]. There are currently numerous ongoing clinical trials aimed to clarifying the role of this molecule in COVID‐19. The guidelines for the treatment of SARS‐CoV‐2 pneumonia from the Spanish Ministry of Health contemplate the use of tocilizumab as a therapeutic tool for those patients with severe respiratory failure or rapid respiratory deterioration with criteria for admission to the intensive care unit (ICU).


title: Venous Thromboembolism Complicated with COVID-19: What Do We Know So Far?

text: Coronavirus disease (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for the ongoing 2019–2020 pandemic. Venous thromboembolism (VTE), a frequent cardiovascular and/or respiratory complication among hospitalized patients, is one of the known sequelae of the illness. Hospitalized COVID-19 patients are often elderly, immobile, and show signs of coagulopathy. Therefore, it is reasonable to assume a high incidence of VTE among these patients. Presently, the incidence of VTE is estimated at around 25% of patients hospitalized in the intensive care unit for COVID-19 even under anticoagulant treatment at prophylactic doses. In this review, we discuss present knowledge of the topic, the unique challenges of diagnosis and treatment of VTE, as well as some of the potential mechanisms of increased risk for VTE during the illness. Understanding the true impact of VTE on patients with COVID-19 will potentially improve our ability to reach a timely diagnosis and initiate proper treatment, mitigating the risk for this susceptible population during a complicated disease.


title: ACEI/ARB Use and Risk of Infection or Severity or Mortality of COVID-19: A Systematic Review and Meta-analysis

text: We have sparse knowledge of the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and the progression of this disease. We systematically assessed these relationships. Unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted, with an end date of May 9, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Fourteen articles involving more than 19000 COVID-19 cases were included. Our results showed that ACEI/ARB exposure is not associated with a higher risk of COVID-19 infection (OR = 0.99; 95% CI, 0.95-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure is not associated with a higher risk of severity (OR = 0.98; 95%CI 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95%CI 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared those with non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95% CI 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm previous concern regarding a harmful role of ACEI/ARB in COVID-19 patients. The present study support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic or COVID-19 patients.


docid: purplsjn

title: Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells

text: Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4(+) T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells. In order to investigate the intracellular localization of Hepatitis C virus core protein, we have used a lentiviral system to transduce Jurkat T cells and subsequently localize the protein using immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis C virus core protein mostly localizes in the nucleus and specifically in the nucleolus. In addition, we performed pull-down assays combined with Mass Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus core in Jurkat T cells. We found proteins such as NOLC1, PP1γ, ILF3, and C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4(+) T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. Thus, in the current work, we show the ultrastructural localization of Hepatitis C virus core and the first profile of HCV core associated proteins in T cells, and we discuss the functions and interconnections of these proteins in molecular networks where relevant biological modifications have been described upon the expression of Hepatitis C virus core protein. Thereby, the current work constitutes a necessary step toward understanding the mechanisms underlying HCV core mediated alterations that had been described in relevant biological processes in CD4(+) T cells.


Continue ACE inhibitors/ ARB’S till further evidence in Coronavirus disease 2019 (COVID-19)


title: Severe acute respiratory syndrome (SARS)

text: Several cases of life threatening respiratory disease with no identifiable cause were reported from Guangdong Province, China; these were soon followed by reports from many other countries. The disease was named as severe acute respiratory syndrome (SARS). A novel coronavirus, isolated from the respiratory secretions of patients, has been implicated in the causation of SARS. The modes of transmission include droplet spread, close contact, and Fomites; shedding of virus from respiratory tract is the primary mode of transmission. SARS clinically presents with high-grade fever, chills and rigors, myalgia, headache, cough with or without sputum production, dyspnea, and dizziness. Chest radiographs reveal unilateral or bilateral, predominantly peripheral, areas of consolidation progressing with in a short time of bilateral patchy consolidation. Preliminary reports suggest a milder illness in young children. The case definition of probable SARS cases, laboratory investigations and precautions for prevention of spread are discussed.


title: Characteristics of Adult Outpatients and Inpatients with COVID-19 — 11 Academic Medical Centers, United States, March–May 2020

text: Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).


docid: bxuzbogj

title: Innovation in observation: a vision for early outbreak detection

text: The emergence of new infections and resurgence of old ones—health threats stemming from environmental contamination or purposeful acts of bioterrorism—call for a worldwide effort in improving early outbreak detection, with the goal of ameliorating current and future risks. In some cases, the problem of outbreak detection is logistically straightforward and mathematically easy: a single case of a disease of great concern can constitute an outbreak. However, for the vast majority of maladies, a simple analytical solution does not exist. Furthermore, each step in developing reliable, sensitive, effective surveillance systems demonstrates enormous complexities in the transmission, manifestation, detection, and control of emerging health threats. In this communication, we explore potential future innovations in early outbreak detection systems that can overcome the pitfalls of current surveillance. We believe that modern advances in assembling data, techniques for collating and processing information, and technology that enables integrated analysis will facilitate a new paradigm in outbreak definition and detection. We anticipate that moving forward in this direction will provide the highly desired sensitivity and specificity in early detection required to meet the emerging challenges of global disease surveillance.


title: Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil

text: INTRODUCTION: Human rhinovirus (RV) is a common cause of acute respiratory infection (ARI) in children. We aimed to characterise the clinical and demographic features associated with different RV species detected in children attending hospital with ARI, from low-income families in North-east Brazil. METHODS: Nasopharyngeal aspirates were collected from 630 children <5years with ARI. Clinical diagnosis and disease severity were also recorded. Samples were analysed by multiplex PCR for 18 viral and atypical bacterial pathogens; RV positive samples underwent partial sequencing to determine species and type. RESULTS: RV was the fourth commonest pathogen accounting for 18.7% of pathogens detected. RV was commonly detected in children with bronchiolitis, pneumonia and asthma/episodic viral wheeze (EVW). Species and type were assigned in 112 cases (73% RV-A; 27% RV-C; 0% RV-B). Generally, there were no differences in clinical or demographic characteristics between those infected with RV-A and RV-C. However, in children with asthma/EVW, RV-C was detected relatively more frequently than RV-A (23% vs 5%; p=0.04). CONCLUSIONS: Our findings highlight RV as a potentially important pathogen in this setting. Generally, clinical and demographic features were similar in children in whom RV A and C species were detected. However, RV-C was more frequently found in children with asthma/EVW than RV-A.


title: Influenza A

text: The influenza viruses, which contain single-stranded RNA, are classified into 3 types, A, B, and C …


title: “Vital in today's time”: Evaluation of a disaster table-top exercise for pharmacists and pharmacy staff

text: BACKGROUND: While the importance of pharmacists’ involvement in disaster management is becoming increasingly recognised in the literature, there remains little research on methods for preparing pharmacists and pharmacy staff for disasters. Objective(s): To investigate the use of a table-top disaster exercise to improve disaster awareness and preparedness for pharmacists and pharmacy staff attending The Society of Hospital Pharmacists of Australia (SHPA) Medicine Management conference 2019. METHODS: A table-top disaster exercise was developed by the research team and presented as a workshop at the SHPA's annual conference in 2019. The workshop presented attendees with the hypothetical ‘Cyclone Oma’ that was tracking across the fictional state of ‘New Cardiff’. Each workshop table was assigned a different hospital and was required to respond to Cyclone Oma as the scenario evolved. Workshop attendees were invited to complete a pre- and post-survey assessing their perceptions of disaster management and preparedness for pharmacists and pharmacy staff. RESULTS: The pre- and post-workshop survey was completed by 41 out of the 47 attendees. Participants’ assessments of their understanding of disaster management activities increased after attending the workshop (p < 0.001). Most participants felt the workshop improved their understanding of their role in a disaster (87.8%, 36/41) and allowed them to identify their strengths and weaknesses in disaster management (90.2%, 37/41). The workshop was well received with 92.7% (38/41) of participants stating they would like further continuing professional development opportunities in disaster management. CONCLUSIONS: This is the first disaster table-top exercise in Australia targeted specifically at the pharmacy workforce to be conducted and evaluated. The exercise improved understanding of disaster management and was well received by the participants. This research calls for further education and training opportunities in disaster management targeted at the pharmacy workforce.


title: The year 2020, a milestone in breaking the vicious cycle of poverty and illness in China

text: Marking the end of the five-year programme initiated by the Chinese Government to lift more than 70 million people out of poverty, the year 2020 is a milestone. Poverty alleviation has moved strongly forward in China and the major health indicators are now better than the average of all middle- and high-income countries. However, the dual burden of infectious and chronic diseases remains a challenge with respect to achieving the health target in the United Nations 2030 Agenda for sustainable development goals (SDGs). In 2015, about 44% of the poor population in China were impoverished by illness but already in 2018, multi-sectoral actions delivered by the Health-related Poverty Alleviation programme had reduced the number almost by half. In the past three years 15 million poor people (98% of the poor population) with infectious and chronic diseases had been treated and taken care of thanks to financial support through multiple health insurance schemes and other governmental subsidies. This article discusses the lessons learnt with regard to health-related poverty alleviation in China with special reference to those still remaining impoverished by illness. Consolidation of the achievements reached and provision of basic needs to those still disadvantaged and in poor health will require a major improvement of accessibility to, and affordability of, health services. The next step towards enhanced productivity and better living conditions will involve upgrading of the capacity of health professionals in the poor regions, promotion of coherent efforts in health-related poverty alleviation and rural revitalization measures. As an additional measure, data monitoring and research on health poverty alleviation should be strengthened as they are essential to generate the evidence and knowledge needed to support the move in the direction envisioned by the SDGs, and the new Healthy China 2030 programme.


title: Review article: gastrointestinal features in COVID‐19 and the possibility of faecal transmission

text: BACKGROUND: There is little published evidence on the gastrointestinal features of COVID‐19. AIMS: To report on the gastrointestinal manifestations and pathological findings of patients with COVID‐19, and to discuss the possibility of faecal transmission. METHODS: We have reviewed gastrointestinal features of, and faecal test results in, COVID‐19 from case reports and retrospective clinical studies relating to the digestive system published since the outbreak. RESULTS: With an incidence of 3% (1/41)‐79% (159/201), gastrointestinal symptoms of COVID‐19 included anorexia 39.9% (55/138)‐50.2% (101/201), diarrhoea 2% (2/99)‐49.5% (146/295), vomiting 3.6% (5/138)‐66.7% (4/6), nausea 1% (1/99)‐29.4% (59/201), abdominal pain 2.2% (3/138)‐6.0% (12/201) and gastrointestinal bleeding 4% (2/52)‐13.7% (10/73). Diarrhoea was the most common gastrointestinal symptom in children and adults, with a mean duration of 4.1 ± 2.5 days, and was observed before and after diagnosis. Vomiting was more prominent in children. About 3.6% (5/138)‐15.9% (32/201) of adult and 6.5% (2/31)‐66.7% (4/6) of children patients presented vomiting. Adult and children patients can present with digestive symptoms in the absence of respiratory symptoms. The incidence of digestive manifestations was higher in the later than in the early stage of the epidemic, but no differences in digestive symptoms among different regions were found. Among the group of patients with a higher proportion of severe cases, the proportion of gastrointestinal symptoms in severe patients was higher than that in nonsevere patients (anorexia 66.7% vs 30.4%; abdominal pain 8.3% vs 0%); while in the group of patients with a lower severe rate, the proportion with gastrointestinal symptoms was similar in severe and nonsevere cases (nausea and vomiting 6.9% vs 4.6%; diarrhoea 5.8% vs 3.5%). Angiotensin converting enzyme 2 and virus nucleocapsid protein were detected in gastrointestinal epithelial cells, and infectious virus particles were isolated from faeces. Faecal PCR testing was as accurate as respiratory specimen PCR detection. In 36% (5/14)‐53% (39/73) faecal PCR became positive, 2‐5 days later than sputum PCR positive. Faecal excretion persisted after sputum excretion in 23% (17/73)‐82% (54/66) patients for 1‐11 days. CONCLUSIONS: Gastrointestinal symptoms are common in patients with COVID‐19, and had an increased prevalence in the later stage of the recent epidemic in China. SARS‐CoV‐2 enters gastrointestinal epithelial cells, and the faeces of COVID‐19 patients are potentially infectious.


title: Structure-based modeling of SARS-CoV-2 peptide/HLA-A02 antigens

text: As a first step toward the development of diagnostic and therapeutic tools to fight the Coronavirus disease (COVID-19), we aim to characterize CD8+ T cell epitopes in the SARS-CoV-2 peptidome that can trigger adaptive immune responses. Here, we use RosettaMHC, a comparative modeling approach which leverages existing high-resolution X-ray structures from peptide/MHC complexes available in the Protein Data Bank, to derive physically realistic 3D models for high-affinity SARS-CoV-2 epitopes. We outline an application of our method to model 439 9mer and 279 10mer predicted epitopes displayed by the common allele HLA-A*02:01, and we make our models publicly available through an online database (https://rosettamhc.chemistry.ucsc.edu). As more detailed studies on antigen-specific T cell repertoires become available, RosettaMHC models of antigens from different strains and HLA alleles can be used as a basis to understand the link between peptide/HLA complex structure and surface chemistry with immunogenicity, in the context of SARS-CoV-2 infection.


Emerging diseases threaten conservation.


docid: avkequza

title: Molecular constraints to interspecies transmission of viral pathogens

text: The successful replication of a viral pathogen in a host is a complex process involving many interactions. These interactions develop from the coevolution of pathogen and host and often lead to a species specificity of the virus that can make interspecies transmissions difficult. Nevertheless, viruses do sporadically cross species barriers into other host populations, including humans. In zoonotic infections, many of these interspecies transfer events are dead end, where transmission is confined only to the animal-to-human route but sometimes viruses adapt to enable spread from human to human. A pathogen must overcome many hurdles to replicate successfully in a foreign host. The viral pathogen must enter the host cell, replicate with the assistance of host factors, evade inhibitory host products, exit the first cell and move on to the next, and possibly leave the initial host and transmit to another. Each of these stages may require adaptive changes in the pathogen. Although the factors that influence each stage of the replication and transmission of most agents have not been resolved, the genomics of both hosts and pathogens are now at hand and we have begun to understand some of the molecular changes that enable some viruses to adapt to a new host.


title: Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia

text: BACKGROUND: The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. METHODS: As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. RESULTS: HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0–2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6–26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5–38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6–2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9–82]) was strongly associated with CAP. CONCLUSIONS: Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing.


title: Rapid response in the COVID-19 pandemic: a Delphi study from the European Pediatric Dialysis Working Group

text: BACKGROUND: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic. METHODS: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics. RESULTS: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines. CONCLUSIONS: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists’ response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00467-020-04584-6) contains supplementary material, which is available to authorized users.


title: COVID‐19 and herpes zoster co‐infection presenting with trigeminal neuropathy

text: BACKGROUND: Varicella‐zoster virus (VZV) is a human neurotropic virus that remains in a latent state within ganglionic neurons throughout the entire neuroaxis after the primary infection. Whenever herpes zoster leads to trigeminal involvement, the ophthalmic division is the most implicated. COVID‐19 emerged as a viral cause of severe acute respiratory syndrome that spread all over the world in the last months. Co‐infection with COVID and other viruses has been registered, but sparsely and embracing the respiratory ones. METHODS: report a case of a co‐infection of COVID‐19 with VZV, and review the literature. RESULTS: 39‐year‐old immunocompetent man with oligosymptomatic infection by COVID‐19 evolved to left facial herpes zoster affecting the three divisions of trigeminal nerve. The co‐infection was remotely registered with other respiratory virus, being influenza the most mentioned. However, the present case is associated to the emergence of a latent virus infection, which might be related to the viral inflammatory response, especially ascending from the nasal cavity, where trigeminal branches are also placed. CONCLUSIONS: The emergence of the latent infection by VZV under a rare presentation might illustrate the impact at least locally of COVID‐19, once retrograde reactivation of VZV was possibly induced in a young immunocompetent patient.


title: Editorial: increasing IBD prevalence and its complications in the context of the COVID‐19 pandemic

text: LINKED CONTENT This article is linked to King et al papers. To view these articles, visit https://doi.org/10.1111/apt.15701 and https://doi.org/10.1111/apt.15769.