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A 13-year-old Idaho boy was treated in February 2019 for a hybrid influenza strain that contained genetic components of both seasonal influenza and 2009 influenza A(H1N1), according to a CDC report.
Kristoffer Skaalum Hansen, Bo Langhoff Hønge, Hans Beier Ommen, Charles Marinus Pedersen, Merete Storgaard
Simin Ma, Xiaoquan Lai, Zhe Chen, Shenghao Tu, Kai Qin
The World Health Organization (WHO) named the coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as 2019 novel coronavirus disease (COVID-19) and declared it as a pandemic. Similar to the influenza virus, SARS-CoV-2 is commonly transmitted through respiratory droplets and contact. The world’s population is generally susceptible to SARS-CoV-2 infection. Most COVID-19 patients show mild influenza-like symptoms, such as fever, cough, and fatigue. However, approximately 5% of patients rapidly progress to acute respiratory distress syndrome (ARDS), septic shock, and multiple organ failure and are admitted to intensive care units.
Anke Huss, Laura A.N. Derks, Dick J.J. Heederik, Inge M. Wouters
Legionella is a bacterial species able to cause influenza-like illness (Pontiac fever) or severe pneumonia (Legionnaires Disease, LD). We assessed Legionella presence and concentration in composting facilities in the Netherlands.
Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9.
Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013 to 2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) model to select and quantify the dominant factor of H7N9 infection.
All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80 to 0.93. Respectively, a long-term LPMs closure for 10–13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p > 0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR = 0.35). Shenzhen implemented partial closure for first 3 epidemics (p > 0.05) and all closure in the latest 2 epidemic waves (RRR = 0.64).
Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and rural remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure seems greater than that of meteorology on H7N9 transmission.
Skowronski D, Zou M, Clarke Q, et al.
AbstractInfluenza vaccine effectiveness against influenza and non-influenza respiratory viruses (NIRV) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN), spanning 2010-11 to 2016-17. Vaccine significantly reduced the risk of influenza illness by >40% with no effect on coronaviruses or other NIRV risk.
Clare L Whitehead, Susan P Walker
131 million women give birth annually. This population is particularly vulnerable to emerging infectious pathogens due to alterations in immune, respiratory, and cardiovascular physiology that occur during pregnancy. Recent outbreaks of severe acute respiratory syndrome, Middle East respiratory syndrome, influenza H1N1, Ebola virus disease, and Zika virus disease exposed high rates of maternal morbidity and mortality, fetal loss, and fetal harm. Early data regarding pregnancy outcomes in COVID-19 are reassuring: maternal outcomes are similar to non-pregnant adults, and vertical transmission and neonatal infection are rare.
Fukuyama S, Iwatsuki-Horimoto K, Kiso M, et al.
AbstractThe avian influenza A(H7N9) virus has caused high mortality in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In this study, we employed non-human primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as 20–26 years) caused more severe symptoms than infection of young animals (defined as 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, one aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.
Seyed Ahmad Hashemi,
Mohamad Reza Taghavi,
Mina Sadat Mohajeri Zadeh Heydari,
Hasan Namdar Ahmad Abad,
Hamed Ghasem Zadeh‐Moghadam,
Journal of Medical Virology, Accepted Article.
Le Maréchal M, , Mailles A, et al.
AbstractBackgroundNew diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause, and to describe to what extent the patient’s initial presentation may be predictive of encephalitis etiology, particularly Herpes simplex virus (HSV) and Varicella-zona virus (VZV).MethodsThe national cohort of infectious encephalitis in France (ENCEIF) is an ongoing prospective cohort study implemented in France in 2016. Patients presenting with a documented or suspected acute infectious encephalitis were included. Focusing on the variables describing the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of the patient and the etiologic pathogen.ResultsAs of 1st August 2018, data from 349 patients were analysed. The most frequent pathogens were HSV (25%), VZV (11%), Tick-borne encephalitis virus (6%), Listeria (5%), Influenza virus (3%), and encephalitis of unknown cause (EUC) (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or haemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis.ConclusionNo initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement of diagnostic tools. In this context, the recommendation for a universal, early probabilistic initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.
Sakamoto H, Ishikane M, Ueda P.
This study uses data from the National Institutes of Infectious Diseases Japan to compare weekly influenza activity in the 2019/2020 vs the 2014-2019 seasons given mitigation strategies taken in 2020 to limit the spread of COVID-19.
Hartley DM, Perencevich EN.
For decades, leading scientists and influential professional societies have warned of the dangers of emerging infections and the specter of a global pandemic. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent spread has lived up to and surpassed many of the warnings and has caused an evolving global public health and economic crisis. Significantly, no pharmaceutical agents are known to be safe and effective at preventing or treating coronavirus disease 2019 (COVID-19), the resulting illness. This leaves the medical and public health community with only nonpharmaceutical interventions (NPIs) to rely on for reducing the burden of COVID-19. These measures aim to reduce disease transmission both locally and globally and include bans on public gatherings, compulsory stay-at-home policies, mandating closures of schools and nonessential businesses, face mask ordinances, quarantine and cordon sanitaire (ie, a defined quarantine area from which those inside are not allowed to leave), among others. The effectiveness of NPIs has been studied theoretically, especially within the context of pandemic influenza, and also through analysis of historical observational data. A common finding of these studies is that implementing NPIs, especially when done rapidly after initial detection of a new contagious pathogen, can reduce transmission.
Spellberg B, Haddix M, Lee R, et al.
This study characterizes the prevalence of reverse-transcriptase polymerase chain reaction results positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients presenting with influenzalike illness who underwent nasopharyngeal swab testing for influenza and respiratory syncytial virus over 4 days in March 2020.
The aim of the study was to identify the pathogens, in addition to bordetella pertussis (B. pertussis), which cause pertussis-like syndrome in children and to compare clinical presentation between those with B. pertussis and pertussis-like syndrome.
A cross-sectional analysis was conducted from March 2016 to September 2018. In total, 281 children with suspected pertussis infections were enrolled in this study. Multi-pathogen detection was performed.
In total, 281 children were enrolled including 139 males and 142 females. Among them, 149 (53.0%) were B. pertussis positive, and 72 (15.6%) children tested positive for other pathogens. Mycoplasma pneumoniae (MP, 27 cases) was the most common causative pathogen in pertussis-like syndrome, followed by human rhinovirus (HRV, 23 cases), Streptococcus pneumoniae (SP, 13 cases), Haemophilus influenzae (HI, 12 cases) and parainfluenza virus 3 (Pinf-3, 9 cases). Children in the B. pertussis group had a higher rate of vaccination and longer hospital stay (P
Martínez-Baz I, Navascués A, Portillo M, et al.
AbstractBackgroundPeople with diabetes are at high risk of severe influenza complications. Influenza vaccination effect among diabetic patients remains inconclusive. We estimated the average effect of the influenza vaccination status in the current and prior seasons in preventing laboratory-confirmed influenza hospitalization in diabetic patients.MethodsPatients attended in hospitals and primary healthcare centres with influenza-like illness were tested for influenza from the 2013–2014 to 2018–2019 seasons in Navarre, Spain. A test-negative case-control design in diabetic inpatients compared the influenza vaccination status in the current and 5 prior seasons between laboratory-confirmed influenza cases and negative controls. Vaccination status of influenza-confirmed cases was compared between diabetic inpatients and outpatients. Influenza vaccination effect was compared between diabetic patients and ≥60 years old or chronic non-diabetic patients.ResultsOf 1670 diabetic inpatients tested, 569 (34%) were confirmed for influenza and 1101 were test-negative controls. The average effect in preventing influenza hospitalization was 46% (95% CI, 28–59%) for current-season vaccination and 44% (95% CI, 20–61%) for vaccination in prior seasons only in comparison to unvaccinated patients in the current and prior seasons. Among diabetic patients with confirmed influenza, current-season vaccination reduced the probability of hospitalization (adjusted odds ratio: .35; 95% CI, .15–.79). In diabetic patients, vaccination effect against influenza hospitalizations was not inferior to that in older or chronic non-diabetic patients.ConclusionsOn average, influenza vaccination of diabetic population reduced by around half the risk of influenza hospitalization. Vaccination in prior seasons maintained a notable protective effect. These results reinforce the recommendation of influenza vaccination for diabetic patients.
Kou S, Yang S, Chang C, et al.
AbstractThis report presents a novel approach to estimate the number of COVID-19 cases, including undocumented infections, in the US, by combining CDC’s influenza-like illness surveillance data with aggregated prescription data. We estimated that the cumulative number of COVID-19 cases in the US by April 4 was above 2.5 million.
Deng X, Yang J, Wang W, et al.
AbstractObjectiveTo assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals.MethodsWe collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation.ResultsWe analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year; 95%CI: 1.11-1.16), and being male (OR 1.83; 95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered.ConclusionsOur CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.
Colin R Simpson, Benjamin D Thomas, Kirsty Challen, Daniela De Angelis, Ellen Fragaszy, Steve Goodacre, Andrew Hayward, Wei Shen Lim, G James Rubin, Malcolm G Semple, Marian Knight, NIHR hibernated pandemic studies collaborative group
In response to delays in research for 2009 influenza A/H1N1, in 2012 the National Institute for Health Research (NIHR), a UK funder, funded a portfolio of nine projects.1 These projects were put on standby in a maintenance-only state awaiting activation in the event of new influenza pandemic. The portfolio covered key pathways of health care, including surveillance, primary prevention, triage, and clinical management. In 2018, a request was made by NIHR to adapt these projects to include new and emerging infectious diseases.
L. Tsai et al.
Elena Cuadrado-Payán, Enrique Montagud-Marrahi, Manuel Torres-Elorza, Marta Bodro, Miquel Blasco, Esteban Poch, Alex Soriano, Gaston J Piñeiro
Since December, 2019, coronavirus disease 2019 (COVID-19) has been an international public health emergency.1–3 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimics the influenza virus regarding clinical presentation, transmission mechanism, and seasonal coincidence.3 Thus, co-infection by both viruses is feasible. To the best of our knowledge, only one case of co-infection is known, although the diagnosis was sequential.4 Here, we present four cases of SARS-CoV-2 and influenza co-infection, diagnosed simultaneously.
Tong W, Yung C, Chiew L, et al.
AbstractWe reviewed the impact of a universal face masking policy on respiratory viral infections(RVIs) among admitted very-low-birthweight infants in our neonatal department. There was a significant decrease in RVI incidence, specifically in our step-down level 2 unit, with respiratory syncytial virus and parainfluenza virus being the most common viruses isolated.
X. Wu et al.
R. dos Santos Bezerra et al.
R. Soo et al.
S. Kuo et al.
With respect to serums and vaccines in influenza, there are certain simple facts and considerations that physicians will do well to keep in mind at this time. The main point to keep always in sight is that unfortunately we as yet have no specific serum or other specific means for the cure of influenza, and no specific vaccine or vaccines for its prevention. Such is the fact, all claims and propagandist statements in the newspapers and elsewhere to the contrary notwithstanding. This being the case, efforts at treatment and prevention by serums and vaccines, now hurriedly undertaken, are simply experiments in a new field, and the true value of the results cannot be predicted by any one. Indeed, the exact results can be determined if at all only after a time, in most cases probably not until the epidemic is past and all the returns fully canvassed. Consequently the physician must keep his head level and not allow himself to be led into making more promises than the facts warrant. This warning applies especially to health officers in their public relations.
Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon.
A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis.
A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19–50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5–19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (
Arinjay Banerjee, Karen L. Mossman, Matthew S. Miller
MHC class II (MHCII) has recently been identified as a cellular receptor for bat influenza viruses. Here, we discuss the possible implications of viral exploitation of this critical host defense molecule and highlight the need for more intense study of bat–influenza virus interactions.
Adams, S. E., Lugovtsev, V. Y., Kan, A., Bovin, N. V., Donnelly, R. P., Ilyushina, N. A.
Each year, 5-20% of the population of the United States becomes infected with influenza A virus. Combination therapy with two or more antiviral agents has been considered as a potential treatment option for influenza virus infection. However, the clinical results derived from combination treatment with two or more antiviral drugs have been variable. We examined the effectiveness of co-treatment with two distinct classes of anti-influenza drugs, i.e., neuraminidase (NA) inhibitor, laninamivir, and interferon (IFN)-1, against the emergence of drug-resistant virus variants in vitro. We serially passaged pandemic A/California/04/09 (A(H1N1)pdm09) influenza virus in a human lung epithelial cell line (Calu-3) in the presence or absence of increasing concentrations of laninamivir or laninamivir plus IFN-1. Surprisingly, laninamivir used in combination with IFN-1 promoted the emergence of the E119G NA mutation five passages earlier than laninamivir alone (passage 2 vs passage 7, respectively). Acquisition of this mutation resulted in significantly reduced sensitivity to NA inhibitors, laninamivir (~284-fold) and zanamivir (~1024-fold), and decreased NA enzyme catalytic activity (~5-fold) compared to the parental virus. Moreover, the E119G NA mutation emerged together with concomitant hemagglutinin (HA) mutations (T197A and D222G), which were selected more rapidly by combination treatment with laninamivir plus IFN-1 (passage 2 and 3, respectively) than by laninamivir alone (passage 10). Our results show that treatment with laninamivir alone or in combination with IFN-1 can lead to the emergence of drug-resistant influenza virus variants. Addition of IFN-1 in combination with laninamivir may promote acquisition of drug resistance more rapidly than treatment with laninamivir alone.
Lim, J. J., Nilsson, A. C., Silverman, M., Assy, N., Kulkarni, P., McBride, J. M., Deng, R., Li, C., Yang, X., Nguyen, A., Horn, P., Maia, M., Castro, A., Peck, M. C., Galanter, J., Chu, T., Newton, E. M., Tavel, J. A.
Background. For patients hospitalized with severe influenza A, morbidity and mortality remain high. MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, has demonstrated pharmacological activity in animal studies and in a human influenza A challenge study. We evaluated the safety and efficacy of MHAA4549A plus oseltamivir against influenza A infection in hospitalized patients.Methods. The CRANE trial was a phase 2b, randomized, double-blind, placebo-controlled study of single intravenous (IV) doses of placebo, 3600-mg, or 8400-mg MHAA4549A together with oral oseltamivir (+OTV), in patients hospitalized with severe influenza A. Patients, enrolled across 68 clinical sites in 18 countries, were randomized 1:1:1. The primary outcome was the median time to normalization of respiratory function defined as the time to removal of supplemental oxygen support to maintain a stable SpO2 ≥ 95%. Safety, pharmacokinetics, and effects on influenza viral load were also assessed.Results. 166 patients were randomized and analyzed during a preplanned interim analysis. Compared to placebo+OTV, MHAA4549A+OTV did not significantly reduce the time to normalization of respiratory function (placebo+OTV: 4.28 days; 3600-mg MHAA4549A+OTV: 2.78 days; 8400-mg MHAA4549A+OTV: 2.65 days), nor did it improve other secondary clinical outcomes. Adverse event frequency was balanced across cohorts. MHAA4549A+OTV did not further reduce viral load versus placebo+OTV.Conclusions. In hospitalized patients with influenza A, MHAA4549A did not improve clinical outcomes over OTV alone. Variability in patient removal from oxygen supplementation limited the utility of the primary endpoint. Validated endpoints are needed to assess novel treatments for severe influenza A.
Bartsch S, Mitgang E, Geller G, et al.
AbstractBackgroundThe protection that an influenza vaccine offers can vary significantly from person-to-person due to differences in immune systems, body types, and other factors. The question then is what is the value of efforts to reduce this variability such as making vaccines more personalized and tailored to individuals.MethodsWe developed a compartment model of the United States to simulate different influenza seasons and the impact of reducing the variability in responses to the influenza vaccine across the population.ResultsGoing from a vaccine that varied in efficacy (0-30%) to one that had a uniform 30% efficacy for everyone averted 16.0-31.2 million cases, $1.9-$3.6 billion in direct medical costs, and $16.1-$42.7 billion in productivity losses. Going from 0-50% in efficacy to just 50% for everyone averted 27.7-38.6 million cases, $3.3-$4.6 billion in direct costs and $28.8-$57.4 billion in productivity losses. Going from 0-70% to 70% averted 33.6-54.1 million cases, $4.0-$6.5 billion in direct costs and $44.8-$64.7 billion in productivity losses.ConclusionsThis study quantifies for policy makers, funders, and vaccine developers and manufacturers the potential impact of efforts to reduce variability in the protection that influenza vaccines offer (e.g., developing vaccines that are more personalized to different individual factors).
Hatachi T, Michihata N, Inata Y, et al.
AbstractBackgroundAcute encephalitis/encephalopathy (AE) associated with viral and other pathogens leads to neurological sequelae and mortality. Knowing the prognostic factors is therefore important for immediate interventions. We examined early-phase unfavorable prognostic factors among children with AE using a nationwide database.MethodsWe performed a retrospective cohort study using the Diagnosis Procedure Combination database, which includes approximately half of acute-care inpatients across Japan. We enrolled children aged ≤18 years who were hospitalized for AE and discharged from April 2010 to March 2018. The composite unfavorable outcome included the following at discharge: in-hospital death, tracheostomy, enteral tube feeding, and physical rehabilitation. Unfavorable prognostic factors were assessed using a multivariable Poisson regression model including patient characteristics, associated pathogens, and interventions within 2 days of admission adjusting for within-hospital clustering.ResultsThis study included 9,386 children with AE (median age of 3 years). A total of 241 (2.6%) in-hospital deaths occurred, and 2,027 (21.6%) patients had the composite unfavorable outcome. Significant unfavorable prognostic factors were age of 12 to 18 years, congenital anomalies, epilepsy, and Japan Coma Scale score of 100 to 300 at admission (i.e., worse levels of consciousness). In contrast, herpes simplex virus infection and influenza virus infection were associated with favorable outcomes.ConclusionsWe identified early-phase (within 2 days of admission) unfavorable prognostic factors among children with AE. These findings will help identify patients who may benefit from early aggressive therapeutic interventions.
Turner J, Lei T, Schmitz A, et al.
AbstractBackgroundCellular immune responses are not well-characterized during the initial days of acute symptomatic influenza infection.MethodsWe developed a prospective cohort of human subjects with confirmed influenza illness of varying severity who presented within a week of symptom onset. We characterized lymphocyte and monocyte populations as well as antigen-specific CD8+ T cell and B-cell responses from peripheral blood mononuclear cells using flow cytometry and ELISPOT assays.ResultsWe recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three subjects required mechanical ventilation. Influenza-specific CD8+ T cell responses expanded prior to the appearance of plasmablast B cells. However, the influenza-specific CD8+ T cell response was lower in infected subjects than responses seen in uninfected control subjects. Circulating populations of inflammatory monocytes were increased in most subjects compared to healthy controls. Inflammatory monocytes were significantly reduced in the three subjects requiring mechanical ventilation. Inflammatory monocytes were also reduced in a separate validation cohort of mechanically ventilated patients.ConclusionsAntigen-specific CD8+ T cells respond early during acute influenza infection at magnitudes that are lower than responses seen in uninfected individuals. Circulating inflammatory monocytes increase during acute illness and low absolute numbers are associated with very severe disease.
Journal of Medical Virology, EarlyView.
Ying Luo, Xu Yuan, Ying Xue, Liyan Mao, Qun Lin, Guoxing Tang, Huijuan Song, Weiyong Liu, Hongyan Hou, Feng Wang, Ziyong Sun
Lamers, M. M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T. I., Ravelli, R. B. G., Paul van Schayck, J., Mykytyn, A. Z., Duimel, H. Q., van Donselaar, E., Riesebosch, S., Kuijpers, H. J. H., Schippers, D., van de Wetering, W. J., de Graaf, M., Koopmans, M., Cuppen, E., Peters, P. J., Haagmans, B. L., Clevers, H.
The virus severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission via the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology
Michael D. Nowak,
Emilia Mia Sordillo,
Melissa R. Gitman,
Alberto E Paniz Mondolfi
Nils Littorin, Elisabeth Rünow, Jonas Ahl, Fredrik Resman, Kristian Riesbeck
To study effects of the introduction of pneumococcal conjugate vaccines (PCV) on the interspecies dynamics of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in pre-school children with respiratory tract infection.
As set forth elsewhere in this issue, widespread outbreaks of acute respiratory infection have occurred at irregular intervals for many centuries. The general clinical manifestations and the complications have been always practically the same. Owing to conditions that are far from being adequately understood, such infection now and again spreads over the world with great rapidity and in a manner that was altogether mysterious and disconcerting until we learned that it never spreads faster than human travel. It seems as if in the course of evolutionary processes there suddenly is liberated a form of infectious agent against which large numbers of people offer little or no resistance and which is transmitted readily from person to person under the most diverse hygienic and geographic circumstances. That the peculiarly subtile nature of these outbreaks was recognized long before the bacteriologic era is indicated by the introduction of the name influenza, which means, literally, influence. The question as to the real nature of this “influence,” it must be acknowledged, is not settled definitely. The discovery by Pfeiffer in 1890, at the time of the last pandemic, of the influenza bacillus (B. influenzae) in the sputum and respiratory tract of influenza patients seemed, it is true, to have settled the matter. At any rate, Pfeiffer’s claim that he had discovered the cause of influenza secured fairly general acceptance except possibly in France.
Ningfang Lian, Hansheng Xie, Su Lin, Jiefeng Huang, Jianming Zhao, Qichang Lin
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19.
Smith E, Fry A, Hicks L, et al.
AbstractBackgroundImproving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States (U.S.). We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI.MethodsWe enrolled outpatients aged ≥6 months with ARI from 50-60 U.S. clinics during five winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision-making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases to test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza.ResultsAmong 37,487 ARI outpatients, 9,659 (26%) were influenza-positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top three prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95%CI 32-39). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95%CI 3.6%-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons.ConclusionVaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.
Uzma Bashir Aamir,
Muhammad Rashid Mahmood,
Jaya Prasad Tripathy,
Syed Sohail Zahoor Zaidi,
Benjamin Jean Gaborit, Jean-François Bergmann, Cristina Mussini, Jose Ramon Arribas, Georg Behrens, Sharon Walmsley, Anton Pozniak, François Raffi
Severe coronavirus disease 2019 (COVID-19) is not just a serious respiratory viral disease, as influenza is, but rather a systemic multiorgan viral invasion. It is frequently complicated by overwhelming immunological reactions, with overactivation of T cells, leading to acute respiratory distress syndrome and multiorgan failure, secondary to immunopathological processes. The viral load of severe acute respiratory syndrome coronavirus 2 is not correlated with worsening symptoms, but it is the host inflammatory response that is a major cause of lung damage and subsequent mortality.
Chien-Chang Lee, Ye Liu, Kuan-Ting Lu, Chen Wei, Ke-Ying Su, Wan-Ting Hsu, Shy-Chyr Chen
This study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention.
Zhao, L., Yan, Y., Dai, Q., Li, X., Xu, K., Zou, G., Yang, K., Li, W., Guo, X., Yang, J., Li, Y., Xia, Q., Cao, R., Zhong, W.
Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug-resistance to specific anti-influenza drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug nitazoxanide with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza potentials with 10-fold improvement, compared with nitazoxanide, and were effective against a variety of influenza subtypes including oseltamivir-resistant strains. Notably, the combination using of compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effect against oseltamivir-resistant strain. Mode of action analysis demonstrated that compounds 4a/4d acted at the late phase of viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of up-regulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, our study pointed the optimization direction of nitazoxanide as anti-influenza drug, and discovered two novel-structured candidates 4a/4d with relatively broad-spectrum antiviral potential.
Koshimichi, H., Retout, S., Cosson, V., Duval, V., De Buck, S., Tsuda, Y., Ishibashi, T., Wajima, T.
Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.
Bacterial meningitis remains a major threat for the population of the meningitis belt. Between 2004 and 2009, in the countries of this belt, more than 200,000 people were infected with a 10% mortality rate. However, for almost 20 years, important meningitis epidemics are also reported outside this belt. Research is still very poorly developed in this part of the word like in the Democratic Republic of Congo (DRC), which experiences recurrent epidemics. This article describes for the first time the spatio-temporal patterns of meningitis cases and epidemics in DRC, in order to provide new insights for surveillance and control measures.
Based on weekly suspected cases of meningitis (2000–2012), we used time-series analyses to explore the spatio-temporal dynamics of the disease. We also used both geographic information systems and geostatistics to identify spatial clusters of cases. Both using conventional statistics and the Cleveland’s algorithm for decomposition into general trend, seasonal and residuals, we searched for the existence of seasonality.
We observed a low rate of biological confirmation of cases (11%) using soluble antigens search, culture and PCR. The main strains found are Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis (A and C) serogroups. We identified 8 distinct spatial clusters, located in the northeastern and southeastern part of DRC, and in the capital city province, Kinshasa. A low seasonal trend was observed with higher incidence and attack rate of meningitis during the dry season, with a high heterogeneity in seasonal patterns occurring across the different districts and regions of DRC.
Despite challenges related to completeness of data reporting, meningitis dynamics shows weak seasonality in DRC. This tends to suggest that climatic, environmental factors might be less preponderant in shaping seasonal patterns in central Africa. The characterization of 8 distinct clusters of meningitis could be used for a better sentinel meningitis surveillance and optimization of vaccine strategy in DRC. Improving biological monitoring of suspected cases should be a priority for future eco-epidemiological studies to better understand the emergence and spread of meningitis pathogens, and the potential ecological, environmental drivers of this disease.
Robin Bruyndonckx, Samuel Coenen, Chris Butler, Theo Verheij, Paul Little, Niel Hens, Philippe Beutels, Margareta Ieven, Herman Goossens, the GRACE project group
Viral respiratory tract infections (RTIs) are a major public health problem due to their ease of transmission, substantial morbidity and wide occurrence. Their higher incidence and severity during winter months increases the burden of RTIs. Associated pathogens confined to winter months, with often overlapping epidemics, are respiratory syncytial virus (RSV) and influenza virus (influenza)(Eccles, 2002; Griffin et al., 2002; Mourtzoukou and Falagas, 2007). Although RTIs in patients presenting to primary care are usually self-limiting, infections in individuals at the extremes of the age spectrum are typically more severe, with prolonged symptoms and an increased risk of complications (Thompson et al., 2003; Falsey et al., 2005; Amand et al., 2018; Belongia et al., 2018a).
Northern European Conference on Travel Medicine (NECTM) 2020
Mødet udskudt på grund af COVID-19
3.06.2020 - 5.06.2020
ASM Microbe 2020
Aflyst på grund af COVID-19
18.06.2020 - 22.06.2020
Ph.d. forsvar ved Kristina Langholz Kristensen
International AIDS Conference (AIDS) 2020
6.07.2020 - 10.07.2020
International Liver Congress (ILC) 2020
27.08.2020 - 29.08.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Unusual dermatomycoses caused by Nannizzia nana : the geophilic origin of human infections
1.06.2020Latest Results for Infection
Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies
28.05.2020Clinical Infectious Diseases Advance Access
Ratio, rate, or risk?
28.05.2020The Lancet Infectious Diseases
Ethics and governance for digital disease surveillance
27.05.2020Science Express TOC RSS Feed
Reducing transmission of SARS-CoV-2
27.05.2020Science Express TOC RSS Feed
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