ARTICLE | doi:10.20944/preprints202305.0888.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: airborne viruses; epidemic triggering; SARS-CoV2; infectious aerosol transport; long-distance atmospheric transport; epidemic risk assessment
Online: 12 May 2023 (05:11:38 CEST)
In the present work, we investigate the possibility that long-range airborne transport of infectious aerosols could initiate an epidemic outbreak at distances downwind beyond one hundred kilometers. For this, we have developed a simple atmospheric transport box-model which, for a hypothetical case of a COVID-19 outbreak, was compared to a more sophisticated 3-dimensional transport-dispersion model (HYSPLIT) calculation. Coupled with an extended Wells-Riley description of infection airborne spread, it shows that, the very low probability of outdoor transmission can be compensated by high numbers and densities, such as occurs in large cities, of infected and susceptible people in the source upwind and in the target downwind respectively. This may result in the creation of a few primary cases. It is worth pointing out that the probability of being infected remains very small at the individual level. Therefore, this process alone, which depends on population sizes, geography, seasonality and meteorology, can only “trigger” an epidemic which could then spread by the standard infection routes
BRIEF REPORT | doi:10.20944/preprints202003.0446.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID19; infectious diseases
Online: 31 March 2020 (05:08:29 CEST)
The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.
REVIEW | doi:10.20944/preprints202306.0076.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: myopathies; myositis; autoimmune; infectious
Online: 1 June 2023 (09:17:11 CEST)
Myopathies are characterized by a diverse clinical picture affecting the skeletal muscle which includes weakness, fatigue and pain. Acquired myopathies are given importance because treatment is readily available however, some inherited myopathies can be treated as well. These myopathies can be grouped by etiology into infectious myopathies, autoimmune myopathies, granulomatous myopathies, metabolic myopathies, skeletal muscle channelopathies and Duchenne muscular dystrophy. Infectious myopathies are caused by microbiological agents. Autoimmune myopathies result from immunologic disorders causing inflammatory changes in the muscle. Granulomatous myopathy is associated with non-caseating granulomatous inflammation. Metabolic myopathies are caused by abnormal metabolic processes in the myocytes. Drug-induced myopathies are acute or subacute onset of muscle weakness after intake of a certain medications even at therapeutic doses. Critical illness myopathy stem from sepsis syndrome with failure to wean from respirator. Rhabdomyolysis is an acute myopathy, which is an urgent complex condition that involves rapid dissolution of damaged skeletal muscle. Skeletal channel myopathies are due to dysfunctions in the ion channels of the muscle. Duchenne muscular dystrophy is a genetic condition characterized by mutations in the dystrophin gene, resulting in pathologic muscle wasting. Therapies abound in myopathies as these are targeted in Infectious, Granulomatous and Autoimmune Myositides. Included in treatable myopathies are certain metabolic myopathies, rhabdomyolysis, periodic paralysis, critical illness myopathy and drug-induced myopathies. Symptomatic therapies are applied in channelopathies of muscle and dystrophinopathies can be potentially treated nowadays. Complementary rehabilitation practices are part of the management regimen.
CASE REPORT | doi:10.20944/preprints202006.0118.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: paediatric; immunology; infectious disease; gastroenterology
Online: 9 June 2020 (05:11:12 CEST)
Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a newly described condition. It has a spectrum of presentations related to hyperinflammation and cytokine storm. We report the first case of PIMS-TS in a child on established anti-Tumor Necrosis Factor-alpha (anti-TNF-α) therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6-weeks of daily fever with mucocutaneous, gastrointestinal, renal and hematologic involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia (up to 691 µ/L; normal 15-80 µg/L), C-reactive protein (CRP) (>100mg/L for >10 days, normal 0-5 mg/L), erythrocyte sedimentation rate (ESR) consistently >100mm/hr (normal 0-15 mm/hr), raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase (LDH), anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin (PUO) were negative. The condition was refractory to treatment with intravenous immunoglobulin (IVIG) but improved within 24hrs of high dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow up. Polymerase chain reaction (PCR) and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock or organ failure. It is postulated that prior anti-TNF-α therapy attenuated the disease course. Infliximab therapy may interfere with serology testing and produce false negative results. This case supports the need for investigation into infliximab as primary therapy for PIMS-TS.
ARTICLE | doi:10.20944/preprints202304.0411.v2
Subject: Public Health And Healthcare, Primary Health Care Keywords: Probabilistic model; Patient safety; Infectious Mononucleosis
Online: 19 April 2023 (04:39:26 CEST)
Infectious mononucleosis (Mono) is mostly caused by the Epstein-Barr virus (EBV), and can spread through infected people sharing food and drinks with others. Once this virus gets into your system, it is there to stay. The virus can get activated when a person has low immunity and can cause major complications. Furthermore, if physicians miss the diagnosis of this disease, and prescribe penicillin-based antibiotics, it can cause severe rash and adverse reactions that compromise patient safety. This paper develops a simple Hidden Markov Model using which a Viterbi algorithm provides the maximum a posteriori probability estimate for the most likely hidden state path, given a sequence of symptoms arising as observations from a patient with hidden EBV positive or negative states. Apart from bringing awareness to help reduce missed diagnoses and subsequent adverse events, this work provides a tool for health care systems to better incorporate prompts during electronic medical record (EMR) interactions to help physicians catch potential missed diagnoses during a visit. This research demonstrates how statistical models can be used to assess likelihood of underlying conditions that require tests to be offered by physicians in order to make a definitive diagnosis. The model developed and applied herein for estimating likelihood of EBV infection from a series of observations has the potential to alter guidelines within healthcare systems to ensure that the safety of patients, particularly teens, is not compromised due to a lack of definitive diagnosis for Mono at point of care.
ARTICLE | doi:10.20944/preprints202212.0417.v1
Subject: Biology And Life Sciences, Virology Keywords: RNA sequencing; metagenomics; infectious diseases; diagnostics
Online: 22 December 2022 (04:25:19 CET)
Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol – the RAPIDprep assay – with the aim to provide cause agnostic laboratory diagnosis of infection within 24 hours of sample collection by sequencing ribosomal RNA-depleted total RNA. The method is based on the synthesis and amplification of double-stranded cDNA followed by short-read sequencing with minimal handling and clean-up steps to improve processing time. The approach was optimized and applied to a range of clinical respiratory samples to demonstrate diagnostic and quantitative performance. Our results showed robust depletion of both human and microbial rRNA, and library amplification across different sample types, qualities and extraction kits using a single protocol without input nucleic acid quantification or quality assessment. Furthermore, we demonstrate the genomic yield of both known and undiagnosed pathogens with complete genomes recovered in most cases to inform molecular epidemiological investigations and vaccine design. The RAPIDprep assay is a simple and effective tool, and representative of an important shift towards integration of modern genomic techniques to infectious disease investigations.
CONCEPT PAPER | doi:10.20944/preprints202012.0337.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Feline Infectious Peritonitis (FIP); coronavirus; dsRNA
Online: 14 December 2020 (13:27:55 CET)
Our perspective article covers major findings concerning Feline Infectious Peritonitis (FIP) - a fatal coronaviral disease of cats. In the context of FIP pathogenesis, we outline disease signalment and focus on the challenges and promises of FIP invoking coronavirus RNA detection. In particular, we outline critical aspects of coronavirus RNA replication and biogenesis. We infer the replicative intermediates of feline coronavirus may constitute an underappreciated factor triggering the progression of the maladaptive immune response underlying FIP pathogenesis.
REVIEW | doi:10.20944/preprints202002.0358.v3
Subject: Biology And Life Sciences, Virology Keywords: Infectious diseases; Coronavirus; SARS-CoV-2; COVID-19; Pneumonia; China
Online: 28 February 2020 (13:21:43 CET)
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.
REVIEW | doi:10.20944/preprints202305.1972.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: transfusion; blood; pathogen reduction; emerging infectious diseases
Online: 29 May 2023 (05:05:21 CEST)
Emerging infectious disease threats are becoming more frequent due to various social, political and geographical pressures including increased human-animal contact, global trade, transportation and changing climate conditions. As a result, the threat that emerging agents can be spread by blood contact or transfusion of blood products also becomes increasingly problematic. Blood transfusion is essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving components can become a vector for spreading diseases, particularly to vulnerable populations. New methods have been implemented on a global basis for prevention of transfusion transmission via plasma, platelet, and whole blood products. Implementing proactive pathogen reduction methods can significantly reduce the likelihood of disease transmission via blood transfusion, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety which is based on a photochemical method involving Riboflavin and UV light. We provide examples of how emerging threats such as Ebola, SARS-CoV-2, Hepatitis E, monkeypox and other agents have been evaluated in real time regarding effectiveness of this method for reducing the likelihood of disease transmission via transfusion. Keywords: transfusion; blood; pathogen reduction; emerging infectious diseases.
ARTICLE | doi:10.20944/preprints202107.0239.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Probiotics; Canine; Lactobacilli; Feed supplementation; Infectious diseases
Online: 12 July 2021 (10:13:26 CEST)
Antibiotics are commonly used to treat infectious diseases. However, massive and inappropriate antibiotics usage cause many problems including the emergence and spread of antibiotic-resistant bacteria. To avoid this issue, in modern countries the interest of using probiotics in feed supplementation to promote health and prevent or treat intestinal infectious diseases in companion animals like dogs has been increasing. We evaluate the probiotic potential of Lactobacilli isolated from healthy dogs faeces. The isolated Lactobacilli were first confirmed by 16SrRNA sequencing, then in vitro tests were conducted to assess survival potential of Lactobacilli under simulated gastrointestinal conditions and adhesion ability to gut epithelia, effects on epithelial barrier function, anti-inflammatory activities, effects on defensin peptides (beta-defensin 3) and inhibitory effects on common pathogens. Lactobacilli showed considerable potential to survive in simulated gastrointestinal environmental conditions, low pH, high bile salt concentrations along with good adhesion properties with MODE-K cells. Pathogenic bacterial growth and their adhesion to MODE-K cells was significantly inhibited by Lactobacilli. Real-time PCR analyses further demonstrated that L. acidophilus strain AR1 and AR3 inhibit Salmonella-induced proinflammatory cytokines (IL-6, IL-8, 1ꞵ) production and reinforce expression of tight junction protein (occludin). None of the strain induce mRNA expression of beta-defensin 3 in MODE-K cells. Based on in vitro results the L. acidophilus strain AR1 has potential to be supplemented in canine feed. However, further in vivo studies investigating health-promoting effects are awaited.
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: deforestation; emerging infectious diseases; zoonosis; planetary health
Online: 26 June 2020 (12:47:05 CEST)
The COVID-19 pandemic and increased rates of documented Emerging Infectious Diseases (EIDs) in human populations over the last century have drawn attention on understanding pathogens spill over to humans and their zoonotic origin. In this paper we argue that we need to change the thinking about the fundamental cause of zoonoses. Our premise is that deforestation is the primary cause of EIDs events and that, to prevent future pandemics, it needs to be addressed without further delays. Therefore, we review recent trends of proximate and underlying determinants of deforestation, forest degradation and related biodiversity losses while seeking to clarify their links to the determinants of EIDs events. Acknowledging the magnitude of the challenge, we propose responses to stop global deforestation from a trans-disciplinary, intersectoral perspective led by indigenous people. While we envisage that stopping deforestation is the most important approach with long term direct and indirect effects on human, animal and plants health, providing climate changes mitigation and preventing otherwise difficult to predict EID events, we argue that such an initiative may usefully be complemented by reducing contacts between humans and wildlife animals and regulating rather than banning markets where wild animals are sold alive.Finally, we discuss transformative changes to improve planetary-wide forests preservation, soil, plants, animal, and human protection, together with a further understanding of EIDs transmission dynamics, public health veterinary and human disease surveillance, for improved global collective preparedness and action for the management of zoonotic EIDs.
BRIEF REPORT | doi:10.20944/preprints202004.0513.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: COVID-19; social distancing; infectious diseases; pandemic
Online: 29 April 2020 (14:16:47 CEST)
In late February 2020, Coronavirus disease-2019 (COVID-19) has aggressively spread around many bordering provinces of the three most productive regions of northern Italy (Lombardy, Veneto and Emilia Romagna). The first outbreak exploded in the municipality of Codogno (Lombardy). The province of Ferrara (Emilia Romagna) has been indicated as an anomaly due to the lower number of confirmed cases (1·065 cases per 1000 population). We argue that the spread of the virus throughout Emilia Romagna has a possible explanation in the geographical location of most of its provinces along the Via Emilia, an ancient Roman road that runs throughout the region, which we consider as a proxy for citizens’ movement, number of contacts, and social interactions. In order to test this hypothesis, we used a non-linear multiple regression analysis on aggregate province data to investigate the association between the rates of confirmed cases and the distance from the Via Emilia. The results indicate that the infection rate decreases proportionally to the distance from Via Emilia (-14% every 10 km, p<0·001). Further studies are needed, but Ferrara’s “peculiarity” might have a geographical/behavioral explanation, due to its isolation from the regional main connection routes, which are still revolving around a road built by the ancient Romans 2,000 years ago.
COMMUNICATION | doi:10.20944/preprints202004.0414.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; infectious disease; transmission; response; Africa
Online: 23 April 2020 (11:41:54 CEST)
Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.
BRIEF REPORT | doi:10.20944/preprints202305.0719.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Epstein-Barr virus; acute infectious diseases; salivary shedding
Online: 10 May 2023 (09:07:35 CEST)
Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. As the occurrence of EBV in saliva during acute infectious diseases has not been systematically researched so far, this pilot cross-sectional study aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. A total of 40 patients with acute infectious diseases was enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. The most common acute infectious disease was COVID-19 pneumonia, followed by haemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. The presented preliminary data does not indicate acute infectious conditions as a marked “contributor” in increasing salivary EBV shedding.
REVIEW | doi:10.20944/preprints202212.0381.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Epidemiology; melioidosis; infectious disease; mortality; risk factors; transmission
Online: 21 December 2022 (03:42:32 CET)
Melioidosis, or Whitmore's disease, is an infectious disease initiated by a bacteria known as Burkholderia pseudomallei. This bacteria is commonly found in contaminated soil and water. In Malaysia, the mortality from melioidosis infection was reported to be higher than in other infectious diseases. The research on melioidosis is still limited in Malaysia but slightly increasing. The article's objective was to seek all the melioidosis research related to mortality in Malaysia. The information from the selected papers was then abstracted into two sections; Section 1: Review of literature and Section 2: Findings on mortality from melioidosis in Malaysia. In Section 1, the information on transmission and clinical features of melioidosis, demographic, severity of melioidosis, a clinical signs of melioidosis, diagnosis of melioidosis, management of melioidosis, the economic burden of melioidosis, and incidence of mortality from melioidosis were discussed in this paper. Meanwhile, in Section 2, the findings on mortality of melioidosis in Malaysia were discussed according to eight published articles. It is important to manage patients with melioidosis with appropriate treatment and management to reduce severe complications, high fatality rate, and relapse. More published research on melioidosis will provide input to the clinicians on a more detailed understanding of how to improve the diagnosis of melioidosis and the prognosis factors of this disease.
ARTICLE | doi:10.20944/preprints202207.0046.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: infectious keratitis; corneal infection; antibiotic susceptibility; antimicrobial resistance
Online: 4 July 2022 (09:41:43 CEST)
Infectious keratitis (IK) represents a major cause of corneal blindness. This study aims to investigate the demographics, risk factors, microbiological characteristics and antibiotic susceptibility patterns of IK in Taiwan over the past 15 years. A retrospective population-based study was conducted using the Chang Gung Research Database. Patients with IK were identified by diagnostic codes for corneal ulcer from 2004 to 2019. Of 7807 included subjects, 45.2% of patients had positive corneal cultures. The proportion of contact lens-related IK declined, while that of IK related to systemic diseases grew. The percentage of isolated gram-positive bacteria surpassed that of gram-negative bacteria in the 15-year period. The prevalence of Pseudomonas aeruginosa showed a decreasing trend (p = 0.004), whereas coagulase-negative Staphylococcus (CNS) and Propionibacterium species were increasingly detected (p < 0.001). Overall, the trend of antibiotic susceptibility of both gram-positive and gram-negative bacteria did not change throughout the study period. The susceptibility to the test antibiotics maintained over 90% in gram-negative isolates during 15 years. Vancomycin preserved 100% susceptibility to all gram-positive isolates. Since most tested antibiotics exhibited stable susceptibility over decades, this study reinforced that fluoroquinolones and fortified vancomycin continue to be good empiric therapies for treating bacterial keratitis in Taiwan.
ARTICLE | doi:10.20944/preprints202103.0025.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Influenza; epidemiology; spatiotemporal; seasonality; global; transmission; infectious disease
Online: 1 March 2021 (14:05:52 CET)
Influenza epidemics in temperate regions display dynamics that are characterized by pronounced seasonal peaks during the winter. The general lack of influenza cases during the off-season may result from the virus physically disappearing at the end of the season, in which case it must be imported annually. Alternatively, it may result from persistent asymptomatic carriers or unnoticed local transmission chains that develop into local epidemics as conditions become conducive. Here I attempt to understand these differing explanations by analyzing the global distribution of the four major subtypes that comprise influenza over a period of 18 years based on FluNet data, the surveillance network and database compiled by the WHO, and the NCBI influenza data resource, a repository of relevant genetic information. Examining the annual proportion of each subtype, I find considerable variations in subtype annual proportions between the regions. Moreover, I find that seasonal influenza subtypes can remain confined to specific temperate regions, without showing measurable global presence. These results indicate that although largely undetected during the off-season, influenza is likely to persist locally, and imply a ‘local-global’ model where annual influenza epidemics are a mixture of local strains undergoing reactivation together with an influx of global variants.
REVIEW | doi:10.20944/preprints202009.0545.v1
Subject: Medicine And Pharmacology, Surgery Keywords: Meta-analysis; Procalcitonin; pancreatic surgery; pancreaticoduodenectomy; Infectious complications
Online: 23 September 2020 (08:07:40 CEST)
Aim of study:Aim of this meta-analysis is to evaluate post-operative procalcitonin as a marker to predict post- operative infectious complications after pancreatic surgeries.Material and Methods:Systemic literature search was performed using MEDLINE, EMBASE and to identify studies evaluating the diagnostic accuracy of Procalcitonin (PCT) as a predictor for detecting infectious complications on postoperative days (POD) 3 and 5 following pancreatic surgery. A meta-analysis was performed using random effect model and pooled predictive parameters for POD 3 and 5 were derived. Geometric means were calculated for PCT cut offs. Results:6 studies included day 3 PCT analysis, 2 studies included both day 3 and day 5 analysis. Total data of 471 patients were derived. 161 patients developed infectious complications. Pooled sensitivity, specificity, pooled area under curve, diagnostic odds ratio (DOR), positive and negative like hood ratio of day 3 PCT were 74%,79%,0.8453, 11.03,3.17 and 0.31 respectively. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative like hood ratio of day 5 PCT were 83%,70%,12.91,2.91 and 0.25 respectively. Geometric means for PCT cut off for day 3 and 5 were 0.80 and 0.43. Conclusion:Postoperative procalcitonin particularly day 3 procalcitonin levels predict post-operative infectious complications following pancreatic surgeries.
ARTICLE | doi:10.20944/preprints202005.0216.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: children; infectious disease; lower respiratory tract infections; gastrointestinal
Online: 12 May 2020 (12:59:25 CEST)
The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.
REVIEW | doi:10.20944/preprints202305.1725.v1
Subject: Medicine And Pharmacology, Hematology Keywords: Molecular biology; infectious diseases; clinical diagnostic; early detection; prognosis
Online: 25 May 2023 (03:34:18 CEST)
Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.
ARTICLE | doi:10.20944/preprints202305.0587.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: air travel; infectious disease; sentinel surveillance; wastewater surveillance; aircraft
Online: 9 May 2023 (07:49:15 CEST)
Modern commercial air travel connects disparate human populations with the global airline industry transporting up to 4.5 billion passengers annually in the years leading up to the COVID-19 pandemic. While such connections are convenient for commerce and tourism, air travel networks can also be efficient distributors of infectious diseases such as influenza, SARS-CoV-1, hemorrhagic fevers, and more recently SARS-CoV-2 and monkeypox. During the COVID-19 pandemic, public health agencies used multi-layered control strategies including pre-departure testing and vaccination requirements, masking, post-arrival testing, and quarantine to manage the risk of COVID-19 transmission associated with air travel. Simultaneously, the surveillance of aircraft wastewater emerged as a promising new data source to screen for SARS-CoV-2 infections, including newly emergent lineages, among international air travelers. Herein, we review the potential of aircraft wastewater for public health surveillance. The known contributing population and flight itinerary combined with the highly concentrated waste stream and convenient sampling during routine lavatory servicing make aircraft wastewater a strategic opportunity for unintrusive surveillance of the global fluxes of human pathogens. We estimate for the cases of fecal- or urine-shed pathogens, sampling from 3,500 and 1,250 flights per week, respectively, would be required to survey 10% of all global long-haul flight passengers. In the case of the United States, achieving 10% coverage of all international arrivals would require sampling from 925 and 322 flights per week, respectively. Aircraft wastewater surveillance could also be integrated with network and infectious disease models to better inform traditional public health control measures during emerging epidemics. Given the tremendous potential for public good and the massive economic costs of epidemics, governments should consider international collaboration to create a global aircraft wastewater surveillance system.
ARTICLE | doi:10.20944/preprints202304.0106.v1
Subject: Biology And Life Sciences, Virology Keywords: Feline Infectious Peritonitis; Rottlerin; Drug Delivery System; Liposome; Antivirals
Online: 7 April 2023 (03:40:34 CEST)
Rottlerin(R) is a natural extract from Mallotus philippensis with antiviral properties. Feline Infectious Peritonitis (FIP) is a fatal disease characterized by systemic granulomatous inflammation and high mortality, with no established prevention or cure. We investigated antiviral effect of liposome loaded R, Rottlerin-liposome(RL) against Feline infectious peritonitis virus (FIPV), the causative agent. We demonstrated that R and RL inhibited FIPV replication in dose dependently with a PKCδ related manner, not only in the early endocytosis step but also in the late step of replication. RL resolved the low solubility issue of rottlerin and improved its inhibition efficacy at the cellular level. Based on these findings, we suggest that RL has a value for further research as a potential antiviral agent against FIPV.
ARTICLE | doi:10.20944/preprints202210.0217.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Brain Organoids; Artificial Intelligence; Machine Learning; infectious diseases; Nipah
Online: 17 October 2022 (02:03:36 CEST)
The evolving global SARS-CoV-2 pandemic emphasizes how unprepared we are for the emergence of the next lethal viral pathogen. A list of potential candidates was created by the World Health Organization which named Nipah virus infection as the highly lethal prototypic member of that list. Building on our earlier viral pandemic preparedness research into SARS-CoV-2 we have created computer simulations of Nipah virus infection complicated by encephalitis, the most common cause of Nipah-associated mortality. In the current experiments, we first created updated simulations of wild-type whole-brain organoids (aiWBO). Upon validation, the aiWBO were infected with the simulated Nipah virus genome. The Nipah encephalitis simulations (aiWBO-NiV) were then used to find optimal single, double, and triple protein combinations for candidates as potential targets for vaccine development. Our data suggest that the use of multi-viral proteins/epitopes chimera is the most promising approach to Nipah vaccine development and that employing artificial intelligence to guide the identification of promising vaccine candidates is an efficient and cost-effective strategy for future viral pandemic preparedness.
ARTICLE | doi:10.20944/preprints202209.0440.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: infectious diseases; chikungunya; antiviral; flavonoids; fisetin; toll-like receptors
Online: 28 September 2022 (12:15:36 CEST)
In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin's ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.
ARTICLE | doi:10.20944/preprints202208.0057.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: infectious bronchitis; viral evolution; whole genome sequencing; DMV; QX.
Online: 2 August 2022 (09:27:23 CEST)
Infectious bronchitis virus (IBV) is a highly variable RNA virus that affects chickens worldwide. Due to its inherited tendency to suffer point mutations and recombination events during viral replication, emergent IBV strains have been linked to nephropathogenic and reproductive disease that are more severe than the typical respiratory disease, leading, in some cases, to mortality, severe production losses, and/or unsuccessful vaccination. QX and DMV/1639 strains are examples of the above-mentioned IBV evolutionary pathway and clinical outcome. In this study, our purpose was to systematically compare whole genomes of QX and DMV strains looking at each IBV gene individually. Phylogenetic analyses and amino acid site searches were performed in datasets obtained from GenBank accounting for all IBV genes and using our own relevant sequences as a basis. The QX dataset studied is more genetically diverse than the DMV dataset, partially due to the greater epidemiological diversity within the five QX strains used as a basis compared to the four DMV strains from our study. Historically, QX strains have emerged and spread earlier than DMV strains in Europe and Asia. Consequently, there are more QX sequences deposited in GenBank than DMV strains, assisting in the identification of a larger pool of QX strains. It is likely that a similar evolutionary pattern will be observed among DMV strains as they develop and spread in North America.
ARTICLE | doi:10.20944/preprints202004.0492.v2
Subject: Social Sciences, Psychology Keywords: COVID-19; pandemic; misconception; mathematical modeling; infectious disease; Nigeria
Online: 20 January 2021 (14:11:38 CET)
In March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2, to be a pandemic. Since the declaration, Nigeria economy has been greatly impacted thus resulting in a recession. This paper considers a couple of misconceptions among Nigerian people in the COVID-19 pandemic era thereby causing the spread of the novel virus and hence making the situation difficult for the government to handle. In particular, we discuss the first and second waves of the pandemic as it affects the Nigerian people. The impact of the pandemic on animals and the role of mathematical epidemiologists in combatting the spread is discussed herein. We give some recommendations that could be adopted by the government and the good people of Nigeria to reduce the further spread of the virus.
REVIEW | doi:10.20944/preprints202006.0301.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Nanotechnology; Nanomaterials; Antiviral; Sanitizers; Nanomedicine; Infectious Diseases; COVID-19
Online: 24 June 2020 (14:21:10 CEST)
The current emerging COVID-19 pandemic has caused a global impact on every major aspect of our societies. It is known that SARS-Cov-2 can endure harsh environmental conditions for up to 72 h, which may contribute to its rapid spread. Therefore, effective containment strategies, such as sanitizing, are critical. Nanotechnology can represent an alternative to reduce the COVID-19 spread, particularly in critical areas, such as healthcare facilities and public places. Nanotechnology-based products are effective at inhibiting different pathogens, including viruses, regardless of their drug-resistant profile, biological structure, or physiology. Although there are several approved nanotechnology-based antiviral products, this work aims to highlight the use of nanomaterials as sanitizers for the prevention of the spread of mainly SARS-Cov-2. It has been widely demonstrated that nanomaterials are an alternative for sanitizing surfaces to inactivate the virus. Also, antimicrobial nanomaterials can reduce the risk of secondary microbial infections on COVID-19 patients, as they inhibit the bacteria and fungi that can contaminate healthcare-related facilities. Finally, cost-effective, easy-to-synthesize antiviral nanomaterials could reduce the burden of the COVID-19 on challenging environments and in developing countries.
ARTICLE | doi:10.20944/preprints201805.0165.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: infectious bronchitis virus; protection; co-expressing; subunit vaccine; challenge
Online: 10 May 2018 (12:02:08 CEST)
Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which causes considerable economic losses to the poultry industry worldwide. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing S1 and N proteins, mono-expressing S1 or N proteins alone of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, boosting with the same dose 14 days later, and following challenge with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels as well as the percentages of CD4+ and CD8+ T lymphocytes were detected within 28 days post-vaccination (dpv). The morbidity, mortality, and re-isolation of virus from the tracheas and kidneys of challenged birds were evaluated at 5 days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocyte in rHBM-S1-N group were higher than those of rHBM-S1 and rHBM-N groups, especially the cellular immunity response. At 5 dpc, the mortality, morbidity and virus re-isolation rate of rHBM-S1-N were slightly higher than those of H120 group, but were lower than those of rHBM-S1 group and rHBM-N group. The present study demonstrated that the protection of recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing S1 or N protein alone. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.
ARTICLE | doi:10.20944/preprints202303.0492.v1
Subject: Medicine And Pharmacology, Tropical Medicine Keywords: Malaria parasitaemia; Risk factors; Malaria Diagnosis; infectious mode in children
Online: 28 March 2023 (14:58:24 CEST)
Background: Malaria remains a serious public health concern worldwide, particularly in tropical and subtropical regions, and the leading causes of mortality and morbidity in children especially among those aged under five in developing countries. Malaria can be fatal if not promptly and accurately diagnosed, especially in children.This study was carried out to determine the level of malaria infection and its associated risk factors among febrile children.Methods: Blood samples were collected and analyzed from two- hundred (200) systematically selected febrile children aged 1-10 years old. assay of samples collected were carried out using standard methods.data were collected using a pretested structured questionnaire. Results: Results obtained from study subjects shows that, of the eighty-seven (87) infected subjects, 34 (39.1%) were aged 1-5 years, while 52 (59.8%) were within the range of 6 years and above.severity of infection showed 48 (55.2%) with scanty parasitic infection while 25 (28.7%) showed moderate infection, and 13 (14.9%) showed heavy infection.The association of age and level of parasitemia showed that 34 (58.8% ) subjects below 5 years, recorded scanty malaria compared to 14.7% with severe malaria within the age range.Considering gender, of the 33 infected female subjects, 45.5% had scanty malaria, 36.4% showed moderate malaria, while 18.2% had severe malaria, compared to the males subjects.Conclusion: This study reveals the prevalence of malaria infection with some level of severity among children at our study location.The need for prompt diagnosis and improved access to all malaria interventions becomes relevant,with a special focus on the high risk group.
REVIEW | doi:10.20944/preprints202208.0486.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Influenza A virus; SARS-COV-2; matrix metalloproteinases; infectious diseases
Online: 29 August 2022 (10:43:53 CEST)
Matrix metalloproteinases are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are involved in the inflammatory response by regulating the activities of TNF-alpha and IL-1beta, which are pro-inflammatory cytokines, in addition to extracellular matrix components. Since the regulation of inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases, many studies have been conducted on the role of MMPs in pathogenesis. In addition, various studies have demonstrated that MMPs are involved in the pathogenesis of infectious diseases by regulating the expression and activity of MMPs by infection with pathogens. In this review, we discuss the role of MMPs in infectious diseases and the role of MMPs in inflammatory responses and present their potential as therapeutic targets in infectious diseases.
ARTICLE | doi:10.20944/preprints202105.0438.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Deep learning, infectious keratitis, cropped corneal image, slit-lamp images
Online: 19 May 2021 (10:09:06 CEST)
In this study, we aimed to develop a deep learning model for identifying bacterial keratitis (BK) and fungal keratitis (FK) by using slit-lamp images. We retrospectively collected slit-lamp images of patients with culture-proven microbial keratitis between January 1, 2010, and December 31, 2019, from two medical centers in Taiwan. We constructed a deep learning algorithm, consisting of a segmentation model for cropping cornea images and a classification model that applies convolutional neural networks to differentiate between FK and BK. The model performance was evaluated and presented as the area under the curve (AUC) of the receiver operating characteristic curves. A gradient-weighted class activation mapping technique was used to plot the heatmap of the model. By using 1330 images from 580 patients, the deep learning algorithm achieved an average diagnostic accuracy of 80.00%. The diagnostic accuracy for BK ranged from 79.59% to 95.91% and that for FK ranged from 26.31% to 63.15%. DenseNet169 showed the best model performance, with an AUC of 0.78 for both BK and FK. The heat maps revealed that the model was able to identify the corneal infiltrations. The model showed better diagnostic accuracy than the previously reported diagnostic performance of both general ophthalmologists and corneal specialists.
ARTICLE | doi:10.20944/preprints202007.0186.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: infectious diseases; epidemics; dynamical modeling; COVID-19; first-order systems
Online: 9 July 2020 (12:08:34 CEST)
The semi-logarithmic plot of the cumulative number of cases of epidemics resembles the response of a first-order systems for a step load. This similarity was utilized to develop a first order model that can be used for extracting information about the dynamics of infectious disease epidemics. The developed model was validated using COVID-19 data of China. It was also heuristically fitted to other 13 countries. Obtained results indicated that the model can reliably forecasts the number of infected person, epidemic growth speed towards steady-state condition (process time constant, T), and time to reach steady-state condition (4T). The developed model will help public health authorities in developing more effective control strategies of epidemics.
REVIEW | doi:10.20944/preprints202004.0510.v1
Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID19; RNA replication; protein structure; infectious disease
Online: 29 April 2020 (12:52:18 CEST)
COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.
REVIEW | doi:10.20944/preprints202004.0061.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Forests; Emerging infectious diseases; Disease transmission; Human pathogen; Environmental impacts
Online: 6 April 2020 (14:06:44 CEST)
Deforestation and associated changing landscapes are major components of environmental changes, with important implications for ecosystem functioning and biodiversity conservation. Tropical forests are hot spots of biodiversity and provide multiple goods and ecosystem services which benefit people in many ways Forest also play an important role in health-related legends, myths, and fairy tales from all over the world, and are important sources of new potential emerging microbial threats to human. Although plausibly numerous abundant microbial forms with a forest origin may exist, our systematic literature review shows that forest-derived infection studies are relatively unexplored, and both taxonomically and geographically biased. Since biodiversity has been associated with emergence of novel infectious diseases at macro-scale, we describe the main biogeographical patterns in the emerging infection-biodiversity-forest loss nexus. Then, we illustrate four fine-scale case studies to decipher the underlying processes of increased infection risk in changing forest clearing landscapes. Finally, we identify scientific challenges and regional management measures required to mitigate these important new emerging threats.
ARTICLE | doi:10.20944/preprints201809.0609.v1
Subject: Engineering, Control And Systems Engineering Keywords: resilience engineering; disaster management; assessment model; capacity diagnosis; infectious disease
Online: 30 September 2018 (11:17:41 CEST)
Safety management assessment systems for national level units’ in South Korea focus on responding capacity to cope with impending accident occurrence and danger occurrence. Since the four stage systems for prevention-preparation-response-recovery, which are core elements of national disaster management, assess the capacities by item such as those of individuals, disaster management departments, institutions, and management networks, there is no assessment function for the organic operation states of the entire systems. Therefore, for efficient disaster management, systematic evaluation indices that will enable active pre-checks in departments in organizations should be developed in place of the existing simply checking methods. In this study, an assessment model that will enable active disaster management centered on practice was developed using resilience engineering techniques. This model consists of disaster management items from the viewpoint of proactive responses instead of prevention. A total of 56 items that constitute four capacities; which are prediction (13 items), monitoring (14 items), proactive response (15 items), and safety learning (14 items) capacities were adopted in this model through Delphi analysis. Institutional capacities for infectious disease disaster management were evaluated based on this model and the resultant scores were prediction 4.41, monitoring 4.63, proactive response 4.69, safety learning 4.56 out of the full score of 5.0 points with an overall average of 4.51. This is an excellent capacity management score comparable to the score 4.57 of diagnosis of similar capacities by the WHO\_JEE (The Joint External Evaluation) in 2017. In fact, in 2015, when infectious disease capacity management was poor, in case of MERS (Middle East Respiratory Syndrome) infectious disease spread in South Korea, 36 patients died and 6,729 patients were isolated. However, through capacity reinforcement, in the case of MERS occurrence in South Korea in September 2018, a management capacity that prevented spread was shown as one confirmed case was completely cured in 10 days and 21 contacts were isolated and tested negative. Therefore, this capacity management assessment model is judged to be usable in enhancing disaster response and management capacities.
ARTICLE | doi:10.20944/preprints201609.0098.v1
Subject: Computer Science And Mathematics, Probability And Statistics Keywords: ecological niche model; environment; overdispersion; negative binomial; leishmaniasis; infectious disease
Online: 27 September 2016 (10:17:31 CEST)
Leishmaniasis is the third most common vector-borne disease and a very important protozoan infection. Cutaneous leishmaniasis is one of the most common types of leishmaniasis infectious diseases with up to 2 million occurrences of new cases each year worldwide. A dynamic transmission multivariate time series model was applied to the data to account for overdispersion and evaluate the effects of three environmental layers as well as seasonality in the data. Furthermore, ecological niche modeling was used to investigate the geographical suitable conditions for cutaneous leishmaniasis using temperature, precipitation and altitude as environmental layers, together with the leishmaniasis presence data. A retrospective analysis of the cutaneous leishmaniasis spatial data in Afghanistan between 2003 and 2009 indicates a steady increase from 2003 to 2007, a small decrease in 2008, then another increase in 2009. An upward trend and regularly repeating patterns of highs and lows was observed related to the months of the year which suggests seasonality effect in the data. Two peaks were observed in the disease occurrence-- January to March and September to December -- which coincide with the cold period. Ecological niche modelling indicates that precipitation has the greatest contribution to the potential distribution of leishmaniasis.
REVIEW | doi:10.20944/preprints202305.0307.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Microorganisms; Severe combined immunodeficiency; Infectious diseases; Management; Antibi-otics; Antifungals; HST
Online: 5 May 2023 (05:41:05 CEST)
Severe combined immunodeficiency (SCID) is a primary inherited immunodeficiency that could be fatal, usually due to opportunistic infections caused by bacteria, viruses, fungi, and protozoa if left untreated. Opportunistic infections are the most common presentation of SCID these include viral, fungal, or intracellular bacteria, and infection should prompt immunological investigation. This review aimed to provide a comprehensive approach to the microrganisms associated with severe combined immunodeficiency (SCID) and its management. The authors described SCID as a syndrome and summarized the different microorganisms that affect children and how they are managed.
ARTICLE | doi:10.20944/preprints202106.0477.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Infective endocarditis; Kidney Transplantation; Survival analysis; graft failure; transplant infectious diseases
Online: 18 June 2021 (11:17:15 CEST)
Purpose: Kidney Transplant Recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation and outcome. While infective endocarditis (IE) is among such complications in KTRs, literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. Methods: We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria), in adult KTRs from January 2007 to December 2018 were included, as well as two controls per case, and followed until December 31 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan-Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Results: Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated only age was significantly associated with the occurrence of IE in our study (63.8 years for cases vs. 55.6 years for controls, P=0.03) Patient and death-censored graft survival were greatly diminished five years after IE compared to controls being 50.3% vs. 80.6% (p<0.003) and 29.7% vs. 87.5% (p<0.002), respectively. Conclusion: IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant.
REVIEW | doi:10.20944/preprints202102.0432.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; SARS-CoV-2; Infectious disease; Pandemics; Epidemics; Biomedical Research
Online: 19 February 2021 (10:03:47 CET)
It is known for decades that viruses from the Coronoviridae family can adapt to human-to-human transmission. In 2020, SARS-CoV-2 caused a global pandemic of unprecedented scale imposing the loss of millions of human lives and being at the heart of a global economic crisis. Thus, we overviewed key research advances generated from the identification of the etiological agent to a better understanding of its origin, evolution and factors underlying global spread. Furthermore, we analyze the scientific productivity using the PubMed database. We found that the total number of publications increased more than 8% in 2020 when compared with 2019 or the average publications per year in the previous quinquennial. Remarkably, 86,638 publications related with COVID-19 and SARS-CoV-2 were published in 2020. Furthermore, there was also an increase in 2020 of publications in other major infectious diseases, such as AIDS, tuberculosis, or malaria. This success is likely the result from the vigorous, international, collaborative, and multidisciplinary response by the research community. During 2020 it was demonstrated, that with adequate support, it is possible to boost the rate of scientific progress in infectious diseases. Sustained investment in science will be key to address existing and future pandemics as the human population increases.
REVIEW | doi:10.20944/preprints202008.0065.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: SARS-CoV-2; SARS-CoV; influenza; pneumonia; respiratory tract infectious diseases
Online: 3 August 2020 (08:44:56 CEST)
The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.
ARTICLE | doi:10.20944/preprints202006.0289.v1
Subject: Computer Science And Mathematics, Computational Mathematics Keywords: reproduction number; infectious disease epidemiology; COVID-19; epidemic modelling; mobility index
Online: 24 June 2020 (09:03:44 CEST)
Real-time estimation of the parameters characterising infectious disease transmission is important for optimization quarantine interventions during outbreaks. One of the most significant parameters is the effective reproduction number - number of secondary cases produced by a single infection. The current study presents an approach for estimating the effective reproduction number and its application to COVID-19 outbreak. The method is based on fitting SIR epidemic model to observation data in a sliding time window and allows to show real-time dynamics of reproduction number at any phase of epidemic for countries globally. Online data on COVID-19 daily cases of infections, recoveries, deaths are used.Finally, time-dependent reproduction number is explored in connection with dynamics of peoples mobility. The method allows to assess the disease transmission potential and understand the effect of interventions on epidemics spread. It also can be easily adapted to future outbreaks of different pathogens. The tool is available online as Python code from the Github repository.
Subject: Computer Science And Mathematics, Applied Mathematics Keywords: nonlinear mathematical model; modeling infectious diseases; logistic equation; integrability; exact solution
Online: 13 May 2020 (15:33:57 CEST)
A mathematical model is proposed for quantitative description of the outbreak of novel coronavirus COVID-19 Although the model is relatively simple, the comparison with the public data shows that an exact solution solution of the model (with the correctly-specified parameters) leads to the results, which are in good agreement with the measured data in China and Austria. Prediction of the total number of the COVID-19 cases is discussed and examples are presented using the measured data in Austria, France and Poland.
REVIEW | doi:10.20944/preprints202004.0080.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: cancer-related viruses; CRISPR-Cas diagnostic tools; DETECTR; infectious disease; SHERLOCKv2
Online: 7 April 2020 (09:43:22 CEST)
Sensitive and precise nucleic acid detection is critical for clinical diagnostics and biotechnological advancements. Diagnostic in infectious disease field is very unique from diagnosing any other disease, that is time is of the essence; in outbreaks people die even with each passing hour in some cases, if the correct diagnosis wasn't make; for example Zika in particularly is a very challenging virus to diagnose, because it's in very few numbers of copies in the infected person, so it need high sensitive diagnostic approach to spot it, In particular, the advanced tools SHERLOCKv2 and DETECTR, give almost an immediate detection of attomolar amounts of pathogenic nucleic acids with specificity similar to that of PCR but with slight technical settings and that will guide the correct intervention for the patient. SHERLOCKv2 and DETECTR technologies are game changers for our ability to identify infectious disease and rapid detection of tumor DNA or cancer-related viruses with ultra-sensitive tests that don’t require a lot of complicated processing to go through. In this paper, we will review cutting-edge infectious disease diagnosis by CRISPR-Cas systems.
ARTICLE | doi:10.20944/preprints201912.0097.v1
Subject: Computer Science And Mathematics, Information Systems Keywords: IoT (Internet of Things); bot; botnet; propagation; nodes; sensor; infectious; mitigation
Online: 7 December 2019 (17:03:34 CET)
Nodes in wireless sensor networks (WSN) are characterized particularly by their limited power and memory capabilities. Limited memory is an important parameter as it defines the size of the operating system and the processing code. As established previously, energy and memory efficiency is the most important evaluation factors of WSNs as they are directly related to data loss and network lifetime. However, based on our simulation results, memory efficiency determines the selection or abandon of nodes by the botmaster for the propagation of bots in an IoT infrastructure. Consequently, the node’s memory efficiency determined the spread of bots in the network and provides defense actors with an insight of the botmaster behavior for mitigation of the attack. Conventional botnet propagation and mitigation models did not consider the impact of node’s memory efficiency in the IoT platform. To address this gap, we build IoT-SIEF, a novel propagation model with forensic capability that will analyze command and control propagation behavior based on the perspective of the node’s memory efficiency. IoT-SIEF model used to explore the dynamics of propagation using numerical simulation with more than 50% outperform other models in mitigating the number of secondary bots. Consequently, it can serve as a basis for assisting the planning, design, and defense of such networks from the investigator's point of view.
ARTICLE | doi:10.20944/preprints202305.2260.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: neutrophil-to-lymphocyte rati; feline infectious peritonitis; white blood cells; biomarker; FIP
Online: 31 May 2023 (14:21:33 CEST)
Abstract: Systemic inflammatory response syndrome (SIRS) is a clinical diagnosis based on abnormalities in patients' vital signs and white blood cell count. Neutrophil-lymphocyte ratio (NLR) is used as an easily accessible parameter to assess the patient's inflammatory status and stress. There are some studies showing that NLR affected by the inflammatory response is a criterion to support the diagnosis of SIRS. In this study, it was aimed to compare the interrelation between SIRS (+) and SIRS (-) groups in patients with high positive feline coronavirus (FCoV) in the light of NLR. Based on the anamneses, physical examination findings, laboratory findings, enzyme immunoassay antibody test kit titer were included in the sick groups. These patients were further categorized based on the presence of SIRS symptoms, vital signs and laboratory findings. The NLR as diagnostic marker demonstrated to differ between high antibody titer FCoV positive and healthy cats. However the diagnostic significance of NLR remains questionable between the high antibody titer FCoV positive cats with SIRS (+) and SIRS (-). As a result of our study NLR can be used as a blood parameter like albumin/globulin ratio and elevated total bilirubin in cats with high FCoV antibody titer and high probability of developing FIP.
ARTICLE | doi:10.20944/preprints202203.0123.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Depression; psychoimmune resilience; tricyclic antidepressants; serotonin; modulation of inflammatory response; infectious diseases
Online: 8 March 2022 (11:04:46 CET)
Brucellosis infection induces fever, chills, sweats, headache, myalgia, arthralgia, anorexia, fa-tigue, and mood disorders. In mice, it causes a rise in IL-6, TNF-, and IFN-; and reduces sero-tonin and dopamine levels in hippocampus. There is loss in muscle strength and equilibrium and increased anxiety and hopelessness. Imipramine (ImiP) is a tricyclic antidepressant that increases the capacity of macrophages to destroy intracellular microorganisms in vivo. The effect of ImiP was evaluated in Balb/c mice infected with Brucella abortus 2308. Serum levels were determined in IFN-, IL-6, TNF-, IL-12, MCP-1, and IL-10 by FACS; the bacterial count in the spleen, by CFU; the serotonin concentration in the hippocampus, by HPLC; and strength, equilibrium, and mood by behavioral tests. Our results showed that infected vs. control mice had a significant rise in lev-els of IFN-, IL-6, TNF-, and IL-12 with a low IFN-/IL-6 ratio, elevated bacterial-counts, alter-ations in serotonin concentration at hippocampus, and decreased muscular strength, equilibrium, and mood. Infected mice treated with ImiP vs. infected mice showed: 1) improved mood; 2) in-creased hippocampal serotonin availability, splenic dendritic cells, and macrophage phagocytic activity; and 3) upturn inflammation and reduced CFU ability. Our results support that ImiP fa-vors positive outcomes in subjects handling Brucella infections likely by improving psychoim-mune resilience.
ARTICLE | doi:10.20944/preprints202107.0020.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: IBV; infectious bronchitis; variants; whole-genome sequencing, enteric tropism; runting-stunting syndrome
Online: 1 July 2021 (11:25:48 CEST)
Abstract: Infectious bronchitis virus (IBV) induces respiratory and urogenital disease in chickens. Although IBV replicates in the gastrointestinal tract, enteric lesions are uncommon. We have reported a case of runting-stunting syndrome in commercial broilers from which an IBV variant was isolated from the intestines. The isolate, CalEnt, demonstrated an enteric tissue tropism in chicken embryos and SPF chickens experimentally. Here, we determined the full genome of CalEnt and compared it to other IBV strains, in addition to comparing the pathobiology of CalEnt and M41 in commercial broilers. Despite the high whole-genome identity to other IBV strains, CalEnt is rather unique in nucleotide composition. The S gene phylogenetic analyses showed great similarity between CalEnt and Cal 99. Clinically, vent staining was slightly more frequent in CalEnt-infected birds than those challenged with M41. Furthermore, IBV IHC detection was more evident and the viral shedding in feces was overall higher with the CalEnt challenge compared with M41. Despite underlying intestinal lesions caused by coccidiosis and salmonellosis vaccination, microscopic lesions in CalEnt-infected chickens were more severe than in M41-infected chickens or controls, supporting the enteric tropism of CalEnt. Further studies in SPF chickens are needed to determine the pathogenesis of the virus, its molecular mechanisms for the enteric tropism, and its influence in intestinal health.
ARTICLE | doi:10.20944/preprints202008.0204.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-Cov-2; epidemic surveillance; emerging infectious disease; epidemic threshold
Online: 23 September 2020 (11:10:15 CEST)
Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2,000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26th 2020 and the sanitary alert on March 3rd. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.
HYPOTHESIS | doi:10.20944/preprints202007.0015.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronavirus; Substance P/Neurokinin-1 Receptor; respiratory illness; Infectious disease; trigeminal ganglion
Online: 3 July 2020 (05:54:18 CEST)
Novel severe acute respiratory syndrome coronavirus 2 infection (SARS-Cov-2) is an acute respiratory and infectious disease. This perspective aims to provide the basic understanding of the inflammation caused by SARS-Cov-2 and relation to trigeminal ganglion (TG). Virus enters through the mucous membranes of orofacial region and reach the TG where it resides and take control of its peptides including Substance P (SP).SP is the main neuropeptide, neuromodulator and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and consequently, it affects the immune cells, blood vessels to release the mediators for inflammation. Cytokine storming is initiated and cause respiratory distress, bronchoconstriction and death in complicated cases. Neurokinin-1 Receptor (NK-1R) antagonist and glucocorticoids may be used to alleviate the symptoms and treat this infection. SP is the main culprit seem to be involved in the triggering of inflammatory pathways in SARS-Cov-2 infection. It has direct association with cardiorespiratory rhythm, sleep-wake cycle, nociception, ventilator responses and regulates many important physiological and pathological roles. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation.
ARTICLE | doi:10.20944/preprints202004.0374.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; coronavirus; infectious disease; infection management; PCR test; mortality; kinetic analysis
Online: 3 June 2020 (05:10:05 CEST)
Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.
Subject: Social Sciences, Law Keywords: Infectious Diseases; Non-Communicable Diseases; Public Health Act; Laws and Regulations; Malawi
Online: 2 April 2020 (12:04:52 CEST)
Laws and regulations make powerful contribution in addressing multitudes of public health concerns. We examined the Public Health Act (PHA) in Malawi to understand its relevance to the ever-growing and changing threats posed by infectious and non-infectious diseases. The current Public Health Act of Malawi came into effect in 1948 to protect and preserve public health. The Act has undergone several amendments, the last one being in 1975. It draws much of its inspiration and standards from the 19th century British laws on insanitary housing, poor ventilation, and drainage. Such laws are silent on emerging major public health concerns including non-communicable diseases (NCDs) such as cardiovascular diseases and diabetes as well as road traffic injuries. This makes the Act outdated and ill equipped to address the 21st century public health concerns. Although supplementary legislation such as the HIV/AIDS Act and Mental Treatment Act have recently been enacted, they are yet to be consolidated into the Public Health Act. Consequently, existing policies and strategic plans that are meant to address gaps in public health and ensure coordinated effort lack support of laws and regulations. The Act also places great emphasis on mandatory vaccinations, quarantine and isolation against smallpox, a disease that has long been eradicated. Furthermore, although the Public Health Act outlines powers, duties and penalties, it fails to reinforce acceptable behaviour due to the insignificant penalties for noncompliance. There is a need for immediate and prompt revision and restructuring of the Public Health Act based on scientific evidence. Such laws require adequate consultation and interaction with key experts and stakeholders from a wide range of disciplines.
ARTICLE | doi:10.20944/preprints201809.0534.v1
Subject: Social Sciences, Geography, Planning And Development Keywords: syndemic; El Niño; infectious disease; diarrhea; malaria; respiratory; cholera; spatial cluster; GIS
Online: 27 September 2018 (06:04:08 CEST)
El Niño is a quasi-periodic pattern of climate variability and extremes often associated with hazards and disease. While El Niño links to individual diseases have been examined, less is known about the cluster of multi-disease risk referred to as an ecosyndemic, which emerges during extreme events. The objective of this study was to explore a mapping approach to represent the spatial distribution of ecosyndemics in Piura, Peru at the district-level during the first few months of 1998. Using geographic information systems and multivariate analysis, two methodologies were employed to map disease overlap of 7 climate-sensitive diseases and construct an ecosyndemic index, which was then mapped and applied to another El Niño period as proof of concept. The main findings showed that many districts across Piura faced multi-disease risk over several weeks in the austral summer of 1998. The distribution of ecosyndemics were spatially clustered in western Piura among 11 districts. Furthermore, the ecosydemic index in 1998 when compared to 1983 showed a strong positive correlation, demonstrating the utility of the index. The study supports PAHO efforts to develop multi-disease based and interprogrammatic approaches to control and prevention, particularly for climate and poverty-related infections in Latin America and the Caribbean.
REVIEW | doi:10.20944/preprints202305.1908.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; Mechanism of Action; Clinical and Epidemiological Features; Global Pandemic Infectious Disease
Online: 26 May 2023 (09:59:10 CEST)
The coronavirus disease 2019 (COVID-19) is a novel global pandemic infectious disease with higher potential for outbreaks than the other epidemic disease such as severe acute respiratory syndrome (SARS), influenza A (H1N1), and the Middle East respiratory syndrome (MERS), which identified in China on December 31, 2019. This disease is caused by a new generation of betacoronavirus termed as the 2019 novel coronavirus (2019-nCoV) or SARS-CoV-2. Although, the first report of this disease was in recent months, now, the COVID-19 is known as a global pandemics. Hence, the aim of this article is the quick review of the recent studies on the novel coronavirus disease 2019 including researches on the epidemiological parameters, mechanism of action, diagnosis, and treatment of the novel coronavirus disease, as well as clinical features of patients infected with COVID-19. Moreover, the novel COVID-19 has comprised of SARS, H1N1, and MERS.
ARTICLE | doi:10.20944/preprints202110.0104.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Candida; Corneal infection; Corneal ulcer; Contact lens; Fungal infection; Fusarium; Infectious keratitis; Keratoplasty
Online: 6 October 2021 (10:45:42 CEST)
Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen’s Medical Centre, Nottingham, and Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. A total of 117 patients (n=117 eyes) with FK were included in this study. The mean age was 59.0±19.6 years (range, 4-92 years) and 51.3% patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9±16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67±1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3mm), and poor presenting CDVA (<1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of <1.0 logMAR) and poor corneal healing (>60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p<0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcome, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need.
Subject: Public Health And Healthcare, Health Policy And Services Keywords: COVID-19; with- COVID-19 age; infectious disease; local healthcare projects; healthcare systems
Online: 16 September 2021 (14:59:34 CEST)
Objectives: This study aimed to analyze the awareness of local residents regarding healthcare projects and to suggest some ideas for the revision of local ones. Methods: To delve into the opinions of local residents, the author of this study created a questionnaire composed of eight questions on the general characteristics of the respondents, eight questions on satisfaction with health centers, 16 questions on the awareness of healthcare projects, and 22 questions on local healthcare. The survey was conducted for 409 residents who visited public centers in Gimcheon from 15 March to 14 April 2021. Results: Data analysis revealed the following: The proportion of local residents who use health centers was 39.1%, and those users visit health centers, on average, 3.92 times a year. Among healthcare projects, the project known by the highest proportion of people was vaccinations (84.5%), which was also the project that was most used (38.1%). Among healthcare projects needed in the with-COVID-19 age, respondents awarded the highest score to vaccinations (4.15 points on a five-point Likert scale) and the second highest score to infectious disease management (4.12). Conclusions: For healthcare projects, central and local governments should focus on activating vaccinations, solving the problem of medical accessibility through untact remote treatment and establishing national infectious disease-specializing hospitals and local infectious disease management based on such national hospitals.
ARTICLE | doi:10.20944/preprints202104.0101.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Mouse-Human Chimeric Antibody; Immunotherapy; Infectious diseases; Histoplasmosis; Paracoccidioidomycosis; Histoplasma capsulatum; Paracoccidioides lutzii
Online: 5 April 2021 (11:33:24 CEST)
Heat shock proteins (Hsps) are highly conserved molecules that are constitutively expressed and upregulated in response to physiological stress conditions. These immunogenic chaperones can have essential functions in fungi, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively, which are systemic mycoses with significant rates of morbidity and mortality. Current treatment consists of long-term antifungal agents, and there is an urgent need for new therapeutic approaches with higher efficacy, lower toxicity, better biodistribution and improved selectivity. We engineered an immunoglobulin G1 (IgG1) isotype chimeric mouse-human monoclonal antibody, titled ch-MAb 4E12, from the parental IgG2a MAb 4E12, a monoclonal antibody to H. capsulatum Hsp60 that is protective in experimental histoplasmosis and paracoccidioidomycosis models elicited by H. capsulatum var. capsulatum and Paracoccidioides lutzii, respectively. The ch-MAb 4E12 increased phagolysosomal fusion and enhanced the yeasts uptake by PMA differentiated human THP1 macrophage cells in vitro. At low concentrations, the chimeric antibody significantly reduced the pulmonary and splenic fungal burden compared to an irrelevant antibody or no treatment. These results are the first to show that a chimeric mouse-human antibody can modify infection caused by dimorphic fungi.
REVIEW | doi:10.20944/preprints202101.0184.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Alzheimer’s Disease; antibacterial; anti-biofilm; antifungal; antiviral; bacteria; infectious burden; parasites; pathogens; viruses
Online: 11 January 2021 (11:28:10 CET)
Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD remains poorly understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.
ARTICLE | doi:10.20944/preprints201810.0293.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: MRSA, MSSA, Staphylococcus aureus, mortality, gender, Methicillin-resistant Staphylococcus aureus, infectious disease, prevention
Online: 15 October 2018 (09:35:59 CEST)
Average of 41,900 patients are diagnosed annually with staphylococcus bacterial infection in California, 24,089 patients have Methicillin-resistant Staphylococcus Aureus (MRSA) and 17,810 patients have Methicillin-Sensitive Staphylococcus (MSSA). This paper demonstrates that there is a difference in mortality rate due to staphylococcus infection between males and females (P-value<0.05, CI 95%). Male patient diagnosed with S. aureus has 1.3 chance of mortality incidence than female patient. In addition, MRSA infection rate is 1.4 times MSSA infection (P-value<0.05, CI 95%), but the gap of infection is decreasing; however, mortality of both infections combined are more than threefold greater compared to three decades ago.
COMMUNICATION | doi:10.20944/preprints201804.0045.v1
Subject: Medicine And Pharmacology, Other Keywords: evidence; poverty; health, financing; allocation; integrated; participation partnership; responsibility; infectious diseases; pandemics; Africa
Online: 4 April 2018 (05:33:16 CEST)
Quality evidence-based decisions and strategies are critical and valuable tools in strengthening health systems policies, strategic priorities action plans and comprehensive care delivery management. Our finding showed that there is scarcity of local/national and internal effective evidence-based and management strategies for informed decision making based on the disease or health epidemics nature, extend, ecological and geo-location of pandemics and epidemics crises burden and impacts. Evidence-based programs or projects are crucial in evolving pandemics and/or (Ebola, meningitis, Cholera and influenza) epidemics persistent morbidity and mortality/ case fatality reduction or prevention; as well as on poverty and inequity alleviation within the vulnerable population and citizenry over time. This paper assesses implications of evidence-based on health systems surveillance and monitoring systems, preparedness and emergency response gaps and needs in improving care delivery uptake and usefulness, coverage and effectiveness in Africa. Furthermore, the article advocates for quality, access to and uptake of knowledge-based policy-decision making and practice improvements in building efficient and standardized surveillance, preparedness and response approaches. Also, in enriching data sharing and inclusiveness through understanding the links between poverty, poor health and inequited related emerging infectious diseases epidemics in Africa. Leveraging on cumulative lessons learnt experiences and innovations in integrating participatory knowledge-based policies and approaches is paramount in fostering vulnerable population awareness and engagement, skills empowerment collaborative productivity and sustainable healthy solutions and measures. Strengthening new partnerships, alliances, and networks requires collaborative and quality evidence policy decisions, appropriate and reliable monitoring and evaluation systems approaches and strategies in improving local preparedness and emergency response capabilities against future emerging infectious diseases epidemics and fast-tracking poverty alleviation knowledge-based livelihoods and health solutions for impact. Furthermore, integrated, participative partnerships and collaborative responsibilities, cost effective and reliable evidence health financing and budget allocation, and targeted capacity development aiming at reducing and averting the burden of poverty related emerging threats and epidemics preparedness and response programs in African countries.
REVIEW | doi:10.20944/preprints202305.1048.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Canine; BOAS; brachycephaly; congenital; skin folds; allergy; infectious diseases; immunologic disorders; otitis externa, ethical
Online: 15 May 2023 (12:59:38 CEST)
Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but also comprise up to 30% of canine patients seen by veterinary dermatologists, with English Bulldogs and Pugs particularly overrepresented. Some skin diseases are associated with the abnormal anatomic conformation of brachycephalic dogs, while for others there is a underlying genetic basis or a general predisposition. Anatomic alterations associated with brachycephaly, leading to fold formation of the skin and stenosis of the ear canal, together with primary immunodeficiencies described in some breeds, favor the development of pyoderma, Malassezia dermatitis and otitis externa/media. Frequently neglected but often lifelong dermatological problems of brachycephalic dogs are an important consideration when discussing genetic and medical conditions affecting the welfare of those dogs. Here we review the current state of knowledge concerning dermatological problems of brachycephalic dogs, and combine it with clinical experience in the management of these challenging disorders.
ARTICLE | doi:10.20944/preprints202303.0270.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: genome sequence; infectious bursal disease virus; Nigeria; phylogenetic analysis; poultry; segments A and B
Online: 15 March 2023 (07:49:33 CET)
Infectious bursal disease (IBD) is a viral poultry disease known worldwide for impacting the economy and food security. The disease is endemic in Nigeria, with reported outbreaks in vaccinated poultry flocks. To gain insight into the dynamics of infectious bursal disease virus (IBDV) evolution in Nigeria, near-complete genomes of four IBDVs were evaluated. Amino acid sequences in the hypervariable region of the VP2 revealed conserved markers (222A, 242I, 256I, 294I and 299S), associated with very virulent (vv) IBDV, including the serine-rich heptapeptide motif (SWSASGS). Based on the newly proposed classification for segments A and B, the IBDVs clustered in the A3B5 group (where A3 are IBDVs with vvIBDV-like segment A and B5 are from non-vvIBDV-like segment B) forming a monophyletic subcluster. Unique amino acid mutations with yet-to-be-determined biological functions have been observed in both segments. Amino acid sequences of the Nigerian IBDVs showed that they are reassortant viruses. Circulation of reassortant IBDVs may be responsible for the vaccination failures observed in the Nigerian poultry population. Close monitoring of changes in the IBDV genome is recommended to nip deleterious changes in the bud, through the identification and introduction of the most appropriate vaccine candidates and advocacy/extension programs for properly implementing disease control.
REVIEW | doi:10.20944/preprints202107.0261.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: self-replicating RNA viruses; vaccines; infectious diseases; cancer; immune response; tumor regression; protection; approval
Online: 12 July 2021 (12:38:49 CEST)
Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.
REVIEW | doi:10.20944/preprints202009.0103.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: climate change; vector-borne disease; artificial intelligence; explainable AI; geospatial modeling; infectious disease; arbovirus
Online: 4 September 2020 (12:21:32 CEST)
As recent history has shown, changing climate not only threatens to increase the spread of known disease, but also the emergence of new and dangerous phenotypes. This occurred most recently with West Nile virus: a virus previously known for mild febrile illness rapidly emerged to become a major cause of mortality and long-term disability throughout the world. As we move forward, into increasingly uncertain times, public health research must begin to incorporate a broader understanding of the determinants of disease emergence – what, how, why, and when. The increasing mainstream availability of high-quality open data and high-powered analytical methods presents promising new opportunities. Up to now, quantitative models of disease outbreak risk have been largely based on just a few key drivers, namely climate and large-scale climatic effects. Such limited assessments, however, often overlook key interacting processes and downstream determinants more likely to drive local manifestation of disease. Such pivotal determinants may include local host abundance, human behavioral variability, and population susceptibility dynamics. The results of such analyses can therefore be misleading in cases where necessary downstream requirements are not fulfilled. It is therefore important to develop models that include climate and higher-level climatic effects alongside the downstream non-climatic factors that ultimately determine individual disease manifestation. Today, few models attempt to comprehensively address such dynamics: up until very recently, the technology simply hasn’t been available. Herein, we present an updated overview of current perspectives on the varying drivers and levels of interactions that drive disease spread. We review the predominant analytical paradigms, discuss their strengths and weaknesses, and highlight promising new analytical solutions. Our focus is on the prediction of arboviruses, particularly West Nile virus, as these diseases represent the pinnacle of epidemiological complexity – solution to which would serve as an effective “gatekeeper”. We present the current state-of-the-art with respect to known drivers of arbovirus outbreak risk and severity, differentially highlighting the impact of climate and non-climatic drivers. The reality of multiple classes of drivers interacting at different geospatial and temporal scales requires advanced new methodologies. We therefore close out by presenting and discussing some promising new applications of AI. Given the reality of accelerating disease risks due to climate change, public health and other related fields must begin the process of updating their research programs to incorporate these much needed, new capabilities.
ARTICLE | doi:10.20944/preprints202006.0039.v2
Subject: Computer Science And Mathematics, Analysis Keywords: Epidemiology; infectious disease; compartmental model; mathematical modelling and optimisation; COVID-19; SARS-CoV-2
Online: 12 June 2020 (12:14:28 CEST)
A compartmental epidemiological model with seven groups is introduced herein, to account for the dissemination of diseases similar to the Coronavirus disease 2019 (COVID-19). In its simplified version, the model contains ten parameters, four of which relate to characteristics of the virus, whereas another four are transition probabilities between the groups; the last two parameters enable the empirical modelling of the effective transmissibility, associated in this study with the cumulative number of fatalities due to the disease within each country. The application of the model to the fatality data (the main input herein) of five countries (to be specific, of those which had suffered most fatalities by April 30, 2020) enabled the extraction of an estimate for the basic reproduction number $R_0$ for the COVID-19 disease: $R_0=4.91(33)$.
REVIEW | doi:10.20944/preprints202009.0058.v1
Subject: Biology And Life Sciences, Virology Keywords: Emerging infectious diseases; coronaviruses; COVID-19; SARS-CoV; SARS-CoV-2; MERS-CoV; zoonotic diseases
Online: 3 September 2020 (04:54:38 CEST)
The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.
REVIEW | doi:10.20944/preprints202007.0389.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Lassa Fever; Virus; Infectious Disease; Hazard; West Africa; Health Care; Epidemiology; Epidemic; Measures; Burden; Management
Online: 17 July 2020 (15:19:59 CEST)
In recent years, Lassa fever has been announced as an infectious disease in the world, a few imported cases have been accounted for in various pieces of the world and there are developing worries of the possibilities of Lassa fever Virus as an organic weapon. Regardless of its assaulting impact, no substantial arrangement has been created to reduce the hazard of the ailment, about a large portion of 10 years after identifying it. A Review based on the documents from the literature search on PubMed, Scopus, Goggle Scholar and Science direct. Out of these, the final 16 articles that met the criteria were selected. Relevant information on epidemiology, the burden of management and control were obtained. Timely and effective containment of the Lassa fever disease in Lassa village four decades ago could have minimized the devastating effect and threats posed by this illness in the West African sub-region and indeed the entire globe. That was a hard lesson calling for much more proactive measures towards the eradication of the illness at primary, secondary, and tertiary levels of health care. Hence, the paper is aimed at appraising the threats associated with Lassa fever disease; its demands on curtailing the menace of the epidemic, and recommendations on important focal points.
ARTICLE | doi:10.20944/preprints201907.0328.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Dengue virus (DENV); geographical information systems (GIS); public health; travelers; arboviruses; infectious diseases epidemiology; Honduras
Online: 29 July 2019 (04:36:31 CEST)
Background: After serious epidemics of chikungunya (CHIKV) and Zika (ZIKV) in the Americas, dengue (DENV) have reemerged in most countries. We analyzed the incidence, incidence rates, and evolution of DENV cases in Honduras from 2015-2018 and the ongoing 2019 epidemic. Methods: Using epidemiological weeks (EW) surveillance data on the DENV in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departmental, and municipal levels. Results: From 1 January 2016 to 21 July 2019, a total of 109,557 cases of DENV were reported, 28,603 in 2019, for an incidence rate of 312.32 cases/100,000 pop this year; 0.13% laboratory-confirmed. The highest peak was reached on the EW 28°, 2019 (5,299 cases; 57.89 cases/100,000 pop). The department with the highest number of cases and incidence rate was Cortes (8,404 cases, 479.68 cases/100,000 pop in 2019). Discussion: The pattern and evolution of DENV epidemic in 2019 in Honduras has been similar to that which occurred for in 2015. As previously reported, this epidemic involved the north and central areas of the country predominantly, reaching municipality incidences there >1,000 cases/100,000 pop (1%). Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of risk for travelers who visit specific areas in a destination country.
ARTICLE | doi:10.20944/preprints201907.0308.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: orthohantavirus; bunyavirus; VHF; viruses; haemorrhagic fever; epidemiology; infectious diseases; Barbados; Caribbean; virology; incidence; vectors; Americas
Online: 28 July 2019 (11:43:17 CEST)
Analysis of the demographic, temporal and seasonal distribution of hantavirus infections in Barbados was conducted using national surveillance data for 861 laboratory confirmed cases during 2008-2016. The crude incidence rate of hantavirus infections varied from 5.05 to 100.16 per 100,000 persons per year. One major hantavirus epidemic occurred in Barbados during 2010. Hantavirus cases occurred throughout the year with low level transmission during the dry season (December to June) with increased transmission during rainy season (July to November) and a seasonal peak in August. Hantavirus incidence rates were significantly higher in females than males every year during the study period. More than 50% of hantavirus cases were 30 years of age or less. The highest incidence rate (63.36 cases per 100,000 population) was observed among patients 0–4 years of age. This represents the first epidemiological data for hantavirus disease among an entire population in the English-speaking Caribbean.
ARTICLE | doi:10.20944/preprints201811.0621.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Zika virus (ZIKV); geographical information systems (GIS); public health; travelers; arboviruses; infectious diseases epidemiology; Honduras
Online: 1 February 2019 (09:44:12 CET)
Background: Zika virus (ZIKV) infection has significantly affected Latin America in 2015–2017. Most studies have been reported from Brazil and Colombia, and only a few from Central America. For these reasons we analyzed the incidence, incidence rates and evolution of cases in Honduras from 2016–2017. Methods: Using epidemiological weeks (EW) surveillance data on the ZIKV epidemics in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departmental and municipal levels. Results: From 1 January 2016 to 31 December 2017, a total of 32,607 cases of ZIKV were reported (98.5% in 2016 for an incidence rate of 36.85 cases/100,000 pop; 1% confirmed by RT-PCR). The highest peak was reached on the EW 6°, 2016 (2,559 cases; 29.34 cases/100,000 pop). The department with the highest number of cases and incidence rate was Cortés (13,128 cases, 791.08 cases/100,000 pop in 2016). Discussion: The pattern and evolution of ZIKV infection in Honduras has been similar to that which occurred for chikungunya in 2015. As previously reported, infection with chikungunya involved predominantly the central and capital area of the country, reaching incidences there >750 cases/100,000 pop. Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of risk for travelers who visit specific areas in a destination country.
ARTICLE | doi:10.20944/preprints202211.0315.v1
Subject: Biology And Life Sciences, Virology Keywords: Tick-borne encephalitis virus; Yellow fever virus; vaccine strain; chimeric virus; infectious subgenomic amplicons; candidate vaccines
Online: 16 November 2022 (16:35:12 CET)
Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of Flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.
REVIEW | doi:10.20944/preprints202207.0315.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: protocol; review; zoonosis; zoonotic diseases; infectious diseases; burden of diseases; DALY; zDALY; monetary burden; animal losses
Online: 21 July 2022 (08:12:41 CEST)
Background: When we talk about zoonoses, it is undeniable that we have a human and animal population that has been isolated in studies over time. Besides human and animal health, zoonoses also impact the economy and society. Therefore, the integration of the analysis in this area is essential to optimize resources in public health decisions. We have new challenges in public health that we need to overcome in a more comprehensive method such as One Health. For better measures in public health, the dual burden of zoonoses seems a logical way to determine the integral impact of such diseases in society and thus take better measures to prevent and reduce the impact of these diseases. Methods: We follow the guidelines for “Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). We search human and animal zoonoses on Embase, Ovid Medline, Scopus, Web of Science, and Google Scholar, from an unrestricted period until November 2021. For the search, we consider the Disability Adjusted Life Years (DALYs) for the human zoonotic burden and the animal zoonotic burden in monetary terms. A librarian collaborates to optimize the search string for the databases, and two reviewers screen eligible articles (first by title, then by abstracts, and finally, by full-text assessment.) For the analysis, we aim to convert the burden of zoonoses of all selected studies into the zoonotic Disability Adjusted Life Years (zDALYs) – including the human and animal components. Discussion: The study results will provide information on published studies that have accounted for the dual burden of zoonoses (both human and animal health aspects.) In addition, the synthesis of the available literature will address the knowledge gap in this area in order to know to what extent it is possible to convert the burden of human zoonoses to the animal burden of zoonoses and integrate them into a more comprehensive approach (dual burden of zoonoses.)
ARTICLE | doi:10.20944/preprints202105.0129.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: infectious disease; organizational justice; stress; loneliness; compassion fatigue; meditation; prayer; insomnia; mental health; perspective study; emergency
Online: 7 May 2021 (09:12:57 CEST)
The Covid-19 pandemic has severely tested the mental health of frontline health care workers. A repeated cross-sectional study can provide information on how their mental health evolved during the various phases of the pandemic. The intensivists of a COVID-19 hub hospital in Rome were investigated with a baseline survey during the first wave of the pandemic in April 2020 and were contacted again in December 2020, during the second wave. 152 of the 205 eligible workers responded to an online questionnaire designed to measure procedural justice, occupational stress (effort/reward imbalance), sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and turnover intention. Workers reported a further increase in workload and compassion fatigue, which had already risen during the first wave, and a marked reduction in the time devoted to meditation and mental activities. A low level of confidence in the adequacy of safety procedures and the need to work in isolation, together with an increased workload and lack of time for meditation were the most significant predictors of occupational stress in a stepwise linear regression model. Occupational stress was, in turn, a significant predictor of insomnia, anxiety, low job satisfaction, burnout, and intention to leave the hospital. The number of workers manifesting symptoms of depression increased significantly to exceed 60%. Action to prevent occupational risks and enhance individual resilience cannot be postponed.
CASE REPORT | doi:10.20944/preprints202011.0286.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Clinical Neurology; Neuroinvasive Disease; Encephalitis; Meningitis; MRI Brain Scans; West-Nile Virus; Infectious Diseases; Diagnostic Tools
Online: 9 November 2020 (17:36:58 CET)
A case report of the diagnosis of Long Term Sequelae of West Nile Neuroinvasive Disease in a patient with 9 years history. Empirical data of symptoms and test reports has been presented and based on the available data likely pathogenesis of the disease has been discussed. The empirical data has been compared to the published literature to reach a highly confident diagnosis.
ARTICLE | doi:10.20944/preprints202008.0104.v1
Subject: Social Sciences, Behavior Sciences Keywords: coronavirus disease 2019 (COVID-19); pandemic; infectious disease; psychological (mental) consequences; mental distress; outbreak; epidemiological study
Online: 4 August 2020 (16:16:23 CEST)
Background: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and life-threatening highly infectious disease. The people of Bangladesh are at high risk of COVID-19 and have already experienced various socio-economic, health and psychological (mental) consequences. Particularly, mental health problems are dominantly reported in the literature and should be controlled. The main objective of this epidemiological study is to assess the mental distress and identify its determinants using online-based survey. Such information is urgently needed to develop feasible strategies for Bangladesh. Methods: An online survey was conducted for this study from May 01 to May 05, 2020. A total of 240 respondents provided self-reported online responses. Respondent’s mental distress was measured by the General Health Questionnaire 12 (GHQ-12) and by the self-rated mental health (SRMH) question. Various kinds of statistical analyses ranging from simple to multivariable logistic recession were performed using SPSS 23.0. Results: About 31.3% and 48.3% of respondents were mentally distressed by GHQ-12 and SRMH question, respectively. Logistic regression analysis revealed that mental distress was significantly higher among those respondents, whose usual activity was affected by the coronavirus (OR = 6.40, 95% CI: 1.87 - 21.90, p<0.001) and whose financial stress was increased due to lockdown (OR = 2.12, 95% CI: 1.01 – 4.46, p<0.05) on GHQ-12. Female sex (OR = 1.97, 95% CI: 1.03 – 3.75, p<0.05) and respondents with poor mental health before the outbreak (OR = 3.38, 95% CI: 1.18 – 9.72, p<0.05) were also significantly affected by mental distress on SRMH. Conclusions: At least thirty percent of the respondents were found to be mentally distressed. Some of the study findings, particularly significant determinants, should be considered while developing strategies to reduce the burden of mental distress among study respondents or similar group in Bangladesh.
ARTICLE | doi:10.20944/preprints202006.0153.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; geographical information systems (GIS); coronavirus; epidemiology of infectious diseases; public health.
Online: 12 June 2020 (12:36:52 CEST)
The epidemic of Coronavirus Disease 2019 (COVID-19) have affected all the regions of the world, nevertheless, in some countries there is a lack of studies on its main clinical and epidemiological features. We analyzed the incidence, incidence rates, and evolution of COVID-19 cases in Honduras from February 18-April 24, 2020.Methods: Using daily epidemiological data from surveillance about COVID-19 in Honduras, we calculated the rates of incidence (cases/100,000 population), and developed at national, departmental, and municipal levels GIS-based maps.Results: February 18 - April 24, 2020, a sum of 3,169 suspected COVID-19 cases have been assessed by RT-PCR, 533 (16.8%) of them were positive, for an incidence rate of 5.73 cases/100,000 pop. The highest peak was reached on March 31 (48 cases). The department with the highest number of cases and incidence rate was Cortes (383 cases, 71.9% of the total, 21.45 cases/100,000 pop). Discussion: The pattern and evolution of COVID-19 epidemic in Honduras has been particularly focused in the major urban areas, San Pedro Sula and Tegucigalpa, the capital city. Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of the evolution of the pandemic and monitoring interventions.
REVIEW | doi:10.20944/preprints202004.0155.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; Coronavirus; False-negative; Nucleic Acid Test; Screening; Diagnostic Accuracy; Missed Diagnosis; Epidemic; Infectious Disease
Online: 9 April 2020 (14:37:56 CEST)
Reliable methods to confirm the diagnosis of COVID-19 are essential to the successful management and containment of the virus. Current diagnostic options are limited in type, supply, and reliability. This article explores the controversial unreliability of existing diagnostic methods and maintains that more reliable diagnostic methods, combinations, and sequencing are necessary to effectively assist in reducing the occurrence of discharge of the patient on false negative test results. This reduction would in effect reduce transmission of the disease.
ARTICLE | doi:10.20944/preprints202111.0478.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Long COVID; data acquisition source; post-infectious; longitudinal cohort study; patient-powered
Online: 25 November 2021 (13:51:54 CET)
ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: bed bugs; Cimex spp.; Hong Kong; sleep disturbance; health impact; public health; causal agent; infectious agent; vector
Online: 6 October 2021 (09:09:17 CEST)
Bedbug (Cimex spp.) are a nuisance public-health pest that is on the rise globally, particularly in crowded cities such as Hong Kong. To investigate the health impacts of bedbug infestations among bedbug victims, online surveys were distributed in Hong Kong between June 2019 to July 2020. Data on sociodemographics, self-rated health, average hours of sleep per day, and details of bedbug infestation were collected. Bivariate and multivariable analysis were performed using logistic regression. The survey identified 422 bedbug victims; among them, 223 (52.9%) experienced ≥5 bites in the past month, most bites occurred on the arms (n=202, 47.8%) and legs (n=215, 51%), and the most common reaction to bites were itchiness (n=322, 76.3%), redness, and swelling of the skin (n=246, 58.1%), and difficulties sleeping or restlessness (n=125, 29.6%). Bites usually occurred during sleep (n=230, 54.5%). For impact on daily life in the past month, most bedbug victims reported moderate to severe impact on mental and emotional health (n=223, 52.8%) and sleeping quality (n=239, 56.6%). Lower self-rated health (aOR<1) was independently associated with impact to physical appearance (p=0.008), spending money on medication or doctor consultation (p=0.04), number of bites in the past month (p=0.023), and irregular time of bites (p=0.003). Lower average hours of sleep per day (aOR<1) was independently associated with impact on mental and emotional health (p=0.016). This study brings attention to the neglected issue of bedbug infestation by considering bedbugs as an infectious agent instead of a vector and providing empirical evidence describing its health impacts.
ARTICLE | doi:10.20944/preprints202108.0423.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: longitudinal study; emergency; infectious disease; organizational justice; stress; loneliness; compassion fatigue; meditation; prayer; insomnia; mental health; anaesthetists
Online: 23 August 2021 (10:22:05 CEST)
The COVID-19 pandemic has severely tested the physical and mental health of health care workers (HCWs). The various stages of the epidemic have posed different problems; consequently, only a prospective study can effectively describe the changes in the workers’ health. This repeated cross-sectional study is based on a one-year investigation (spring 2020 to spring 2021) of intensive care physicians in one of the two COVID-19 hub hospitals in Central Italy. Changes in their work activity due to the pandemic were studied anonymously together with their perception of organizational justice, occupational stress, sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and intention to quit. In May-June 2021, one year after the baseline, doctors reported an increased workload, isolation at work and in social life, lack of time for physical activity and meditation and compassion fatigue. Stress was inversely associated with the perception of justice in safety procedures and directly correlated with work isolation. Occupational stress was significantly associated with anxiety, depression, burnout, dissatisfaction, and intention to quit. Procedural justice was significantly associated with happiness. Doctors believed vaccinations would help control the problem; however, this positive attitude had not yet resulted in improved mental health. Doctors reported high levels of distress (73%), sleep problems (28%), anxiety (25%), depression (64%). Interventions to correct the situation are urgently needed.
ARTICLE | doi:10.20944/preprints202102.0253.v1
Subject: Biology And Life Sciences, Virology Keywords: airborne pathogens; animal production; infectious animal disease; livestock health; mass balance; swine diseases; viral aerosol; virus isolation
Online: 10 February 2021 (11:41:43 CET)
Porcine reproductive and respiratory syndrome virus (PRRSV) infections cause significant economic losses to swine producers every year. Aerosols containing infectious PRRSV are an important route of transmission, and proper treatment of air could mitigate the airborne spread of the virus within and between barns. Previous bioaerosol studies focused on the microbiology of PRRSV aerosols; thus, the current study addressed the engineering aspects of virus aerosolization and collection. Specific objectives were to (1) build and test a virus aerosolization system, (2) achieve a uniform and repeatable aerosol generation and collection throughout all replicates, (3) identify and minimize sources of variation, (4) verify that the collection system (impingers) performed similarly. The system for virus aerosolization was built and tested (Obj. 1). The uniform airflow distribution was confirmed using a physical tracer (<12% relative standard deviation) for all treatments and sound engineering control of flow rates (Obj. 2). Theoretical uncertainty analyses and mass balance calculations showed <3% loss of air mass flow rate between the inlet and outlet (Obj. 3). A comparison of TCID50 values among impinger fluids showed no statistical difference between any two of the three trials (p-value = 0.148, 0.357, 0.846) (Obj. 4). These results showed that the readiness of the system for research on virus aerosolization and treatment (e.g., by ultraviolet light), as well as its potential use for research on other types of airborne pathogens and their mitigation on a laboratory scale.
ARTICLE | doi:10.20944/preprints202301.0408.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: feline coronavirus; feline infectious peritonitis; FIP prevention; GS-441524; chronic enteritis; inflammatory bowel disease; IBD; antiviral; diarrhea; itraconazole.
Online: 23 January 2023 (09:43:21 CET)
After an incubation period of weeks to months up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats: 27 households were identified containing 147 cats; 13 cats were treated for FIP and 109 others shed FCoV. A 4-7 day course of oral GS-441524 antiviral stopped faecal virus shedding. Follow-up was from 6 months to 3.5 years: 11 of 147 cats died, but none developed FIP. No FIP-recovered cat relapsed. Cats from 8 households recovered from chronic FCoV enteropathy. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group: 37 of 820 cats developed FIP: the difference was statistically significant (p = 0.0038). Conclusions: early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household then FIP can result. Further work is required to establish the role of FCoV in cats with inflammatory bowel disease.
ARTICLE | doi:10.20944/preprints202304.1195.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19 pandemic; antimicrobial resistance; infectious diseases consultation; multi-drug resistant bacteria; infection prevention and control group; antibiotic stewardship
Online: 29 April 2023 (03:23:00 CEST)
Introduction: The reduced implementation of surveillance programs and limited bedside infectious diseases consultations due to the pressure of COVID-19 pandemic in healthcare systems led to increased rates of irrational use of antimicrobials and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). Material-Methods: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram positive and negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the Intensive Care Unit (ICU). Additionally, bloodstream infections with requested infectious diseases consultation were reported (n=400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization and clinical outcome were analysed. Results: A total of 4569 strains of Gram positive and negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious diseases consultations were carried out, while during the period 2020-2022 154, with the percentage of telephone consultations 15% and 76% respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic and 28-day mortality was significantly reduced in cases with bedside consultations. Conclusion: Empowering of infectious diseases surveillance programs and committees, rational use of antimicrobials agents and bedside infectious diseases consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.
REVIEW | doi:10.20944/preprints202205.0166.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Antimicrobial Peptides (AMPs); Alzheimer’s Disease (AD); infectious hypothesis; beta-amyloid (Ab); lactoferrin; defensins; cystatins; thymosin β4; histatin 1; statherin
Online: 12 May 2022 (09:40:33 CEST)
Alzheimer's Disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD) - whose causes are not completely understood - and familial (FAD) - with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Ab) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of Antimicrobial Peptides (AMPs) in this pathology. Literature also demonstrates that Ab can be considered itself as an AMP thus representing a type of innate immune defense peptide that protect the host against a variety of pathogens. Beyond Ab, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1 and statherin have been shown to be involved in AD. Here we have summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD.
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: acute coronary syndromes; myocardial infarction; STEMI; Covid-19, infectious disease; respiratory infections; pathophysiology; percutaneous coronary intervention; thrombolysis; drug treatment
Online: 7 May 2020 (12:49:39 CEST)
Since association between myocardial infarction (MI) and respiratory infections has been described for influenza-viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. First data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss: pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; what emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.
HYPOTHESIS | doi:10.20944/preprints202002.0147.v4
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Coronavirus; SARS-CoV-2; COVID-19; interferon; IFN; superinfection therapy; SIT; infectious bursal disease virus; IBDV; R903/78; safety; treatment
Online: 1 February 2021 (16:07:55 CET)
Currently, SARS-CoV-2 infection which is the causative agent for COVID-19 disease is a worldwide pandemic with more than 100 million global cases and more than 2.0 million deaths (as of January, 2021). While several vaccines for prevention of COVID-19 have already been registered by the regulatory authorities, the problem is that the substitution rate of this virus is estimated to be one change per 2 weeks, thus mutations could arise that threaten the efficacy of vaccines. Unfortunately, there is no current evidence from random clinical trials to recommend any specific post-exposure treatment for patients with suspected or confirmed COVID-19 disease. Here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated harmless viruses might interact in patients infected with pathogenic virus. During SIT, the patient benefits from superinfection with an apathogenic double-stranded RNA (dsRNA) virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). The safety of orally administered acid-resistant IBDV strain R903/78 reverse engineered viral drug candidate was demonstrated in 10 stage IV cancer patients who exhausted all conventional therapy. Following repeated oral administration of the virus up to 109 infectious units (IU)/ dose, only mild flu-like side effects were reported in some patients. Proof-of-principle efficacy was demonstrated in an early COVID-19 patient who was successfully treated with 3x106 IU of an attenuated IBDV vaccine. A small scale dose-finding Phase I safety study is proposed.
ARTICLE | doi:10.20944/preprints202211.0148.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: COVID-19 pandemic; Infectious diseases; Global diffusion; Environmental factors; Compartmental models; Epidemiologic models; Outlook; Prediction; Preparedness; Surveillance; Health policy; Crisis management; Strategies.
Online: 8 November 2022 (08:40:47 CET)
One of the most important problems in the presence of epidemics and pandemics is an accurate prediction and preparedness. Scholars and experts argue that future pandemics and/or epidemics are almost inevitable events and is not whether next pandemics will happen, but when a new heath emergency will emerge. Epidemiologic models for prediction of Coronavirus Disease 2019 (COVID-19) have shown many limitations because of unpredictable dynamics of the new viral agent SARS-CoV-2 in environment and society. The main goals of this study are twofold: first, the analysis of anthropogenic activities and factors that may trigger pandemic threats; second, the planning of new directions for strategies to reduce risks that a pandemic threat emerges and/or in the initial phase to reduce vast diffusion and negative impact of new viral agents that can generate hazards and problems in public health, environment and socioeconomic systems. In particular, the investigation and understanding of sources and driving factors concerning the emergence and diffusion of new pandemics have critical aspects for strategic actions of forecast, prevention and preparation of effective policy responses to cope with next pandemic crises and health emergencies. Insights here endeavor, whenever possible, to clarify these problems to increase the knowledge of the sources and factor determining the emergence of new viral agents in order to design optimal response policies to face next pandemic diseases similar to COVID-19. .
ARTICLE | doi:10.20944/preprints202207.0339.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Infectious disease testing; public health preparedness; point-of-care testing (POCT); molecular diagnostics; therapeutic turnaround time (TTAT); acute medical challenges; geographic information systems; antimicrobial stewardship
Online: 22 July 2022 (13:13:53 CEST)
Our primary objectives were a) to determine the need for, and the availability of point-of-care testing (POCT) for infectious diseases and b) to recommend point-of-care testing strategies and spatial care paths (SCPs) that enhance public health preparedness in regional districts of Thua Thien Hue Province (TTHP), Central Vietnam, where we conducted field surveys. Medical professionals in 7 community health centers (CHCs), 7 district hospitals (DHs) and 1 provincial hospital (PH) participated. Survey questions (English and Vietnamese) determined the status of diagnostic testing capabilities for infectious diseases and other acute medical challenges in TTHP. Infectious disease testing was limited: 6 of 7 CHCs (86%) lacked infectious disease tests. One CHC (14%, 1/7) had two forms of diagnostic tests available for the detection of Malaria. All CHCs lacked adequate microbiology laboratories. District hospitals had few diagnostic tests for infectious diseases (Tuberculosis, Syphilis), blood culture (29%, 2/7), and pathogen culture (57%, 4/7) available. The PH had broader diagnostic testing capabilities but lacked preparedness for highly infectious disease threats (e.g., Ebola, MERS-CoV, SARS, Zika, and Monkeypox). All sites reported having COVID-19 rapid antigen tests; COVID-19 RT-PCR tests were limited to higher tier hospitals. We conclude that infectious disease diagnostic testing should be improved and POC tests must be supplied near patients’ homes and in primary care settings for the early detection of infected individuals and mitigation of the spread of new COVID-19 variants and other highly infectious diseases.