scholarly journals HMOX1 genetic polymorphisms and outcomes in infectious disease: a systematic review

2021 ◽  
Author(s):  
Fergus W Hamilton ◽  
Julia Somers ◽  
Ruth E Mitchell ◽  
Peter Ghazal ◽  
Nicholas J Timpson
Keyword(s):  
Infectious Disease ◽  
Severe Malaria ◽  
Distress Syndrome ◽  
Repeat Length ◽  
Heme Oxygenase 1 ◽  
Potential Association ◽  
Wide Range ◽  
Strength Of Association ◽  
Citation Screening ◽  
Stress Response Gene

Introduction: Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans. Methods: A search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection. Results 1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies. In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes. Conclusions Despite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive. The most promising data supports a potential association with protection from severe malaria, although this was not found in all studies.  

scholarly journals The clinical and histopathological aspect of the liver, lung, and kidney in Malaria

2019 ◽  
Vol 3 (2) ◽  
pp. 123
Author(s):  
Syafarinah Nur Hidayah Akil
Keyword(s):  
Infectious Disease ◽  
Severe Malaria ◽  
Distress Syndrome ◽  
Portal Tract ◽  
Clinical Importance ◽  
Kidney Injury ◽  
Histopathological Change ◽  
Worldwide Distribution ◽  
Liver And Kidney ◽  
Lung And Kidney

Malaria is an infectious disease with worldwide distribution. The symptom ranges from asymptomatic to severe malaria that could cause mortality. Sequestration and rosetting in the capillaries of several organs in combination with the host inflammatory and immune response could cause multi-organ dysfunction including brain, liver, lung, kidney, etc. This review is to summarize the clinical and histopathological aspect of the disease, especially in lung, liver, and kidney. The clinical importance of severe malaria in the lung are acute lung injury or acute respiratory distress syndrome, jaundice in the liver, and acute kidney injury in the kidney. The histopathological change, in general, is the sequestration of infected erythrocytes in the capillaries of the organ. In the lung, the main changes are seen especially the septa. While in the liver, there are various changes including Kupffer cells hyperplasia, the proliferation of portal tract and bile duct, etc. In the kidney, the changes are in the glomerulus, tubules, and interstitial.

scholarly journals Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Marcelo L. M. Pereira ◽  
Luana S. Ortolan ◽  
Michelle K. Sercundes ◽  
Daniela Debone ◽  
Oscar Murillo ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Plasmodium Berghei ◽  
Distress Syndrome ◽  
Clinical Signs ◽  
Heme Oxygenase 1 ◽  
Lung Protection ◽  
Clinical Complications ◽  
Respiratory Parameters ◽  
Mrna And Protein Expression ◽  
Serious Disease

Malaria is a serious disease, caused by the parasite of the genusPlasmodium, which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected withPlasmodium bergheiANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans.

scholarly journals Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

2021 ◽  
pp. 074873042098732
Author(s):  
N. Kronfeld-Schor ◽  
T. J. Stevenson ◽  
S. Nickbakhsh ◽  
E. S. Schernhammer ◽  
X. C. Dopico ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Multidisciplinary Approach ◽  
Preliminary Assessment ◽  
Epidemiological Evidence ◽  
Wide Range ◽  
Human Coronaviruses ◽  
Induced Changes ◽  
And Behavior ◽  
Timing Phase

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

scholarly journals Contagion Management at the Méditerranée Infection University Hospital Institute

2021 ◽  
Vol 10 (12) ◽  
pp. 2627
Author(s):  
Pierre-Edouard Fournier ◽  
Sophie Edouard ◽  
Nathalie Wurtz ◽  
Justine Raclot ◽  
Marion Bechet ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Early Diagnosis ◽  
Personal Protective Equipment ◽  
Early Stage ◽  
Point Of Care ◽  
University Hospital ◽  
Protective Equipment ◽  
Monitoring Point ◽  
Epidemiological Monitoring ◽  
Wide Range

The Méditerranée Infection University Hospital Institute (IHU) is located in a recent building, which includes experts on a wide range of infectious disease. The IHU strategy is to develop innovative tools, including epidemiological monitoring, point-of-care laboratories, and the ability to mass screen the population. In this study, we review the strategy and guidelines proposed by the IHU and its application to the COVID-19 pandemic and summarise the various challenges it raises. Early diagnosis enables contagious patients to be isolated and treatment to be initiated at an early stage to reduce the microbial load and contagiousness. In the context of the COVID-19 pandemic, we had to deal with a shortage of personal protective equipment and reagents and a massive influx of patients. Between 27 January 2020 and 5 January 2021, 434,925 nasopharyngeal samples were tested for the presence of SARS-CoV-2. Of them, 12,055 patients with COVID-19 were followed up in our out-patient clinic, and 1888 patients were hospitalised in the Institute. By constantly adapting our strategy to the ongoing situation, the IHU has succeeded in expanding and upgrading its equipment and improving circuits and flows to better manage infected patients.

scholarly journals Determinants of vitamin D status in Kenyan calves

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rebecca Callaby ◽  
Emma Hurst ◽  
Ian Handel ◽  
Phil Toye ◽  
Barend M. de C. Bronsvoort ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Vitamin D ◽  
Health Outcomes ◽  
Critical Role ◽  
Subsequent Development ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Skeletal Health ◽  
A Genome ◽  
Wide Range

AbstractVitamin D plays a critical role in calcium homeostasis and in the maintenance and development of skeletal health. Vitamin D status has increasingly been linked to non-skeletal health outcomes such as all-cause mortality, infectious diseases and reproductive outcomes in both humans and veterinary species. We have previously demonstrated a relationship between vitamin D status, assessed by the measurement of serum concentrations of the major vitamin D metabolite 25 hydroxyvitamin D (25(OH)D), and a wide range of non-skeletal health outcomes in companion and wild animals. The aims of this study were to define the host and environmental factors associated with vitamin D status in a cohort of 527 calves from Western Kenya which were part of the Infectious Disease of East African Livestock (IDEAL) cohort. A secondary aim was to explore the relationship between serum 25(OH)D concentrations measured in 7-day old calves and subsequent health outcomes over the following 12 months. A genome wide association study demonstrated that both dietary and endogenously produced vitamin D metabolites were under polygenic control in African calves. In addition, we found that neonatal vitamin D status was not predictive of the subsequent development of an infectious disease event or mortality over the 12 month follow up period.

scholarly journals Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Samir Awasthi ◽  
Tyler Wagner ◽  
A. J. Venkatakrishnan ◽  
Arjun Puranik ◽  
Matthew Hurchik ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Cell Types ◽  
Specific Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Rna Seq ◽  
Future Studies ◽  
Icu Length Of Stay ◽  
Potential Association ◽  
Clinical Trial Results

AbstractIntensive care unit (ICU) admissions and mortality in severe COVID-19 patients are driven by “cytokine storms” and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids (p-value = 0.0024). Given this potential association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the glucocorticoid receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single-cell RNA-seq data from BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.

scholarly journals Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Heme Oxygenase 1 ◽  
Wide Range ◽  
Significant Burden ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Effect

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

Main approaches to treatment of hypoxia in acute respiratory distress syndrome, bacterial and viral pneumonia (part III)

2021 ◽  
pp. 38-55
Author(s):  
A. V. Vlasenko ◽  
E. A. Evdokimov ◽  
E. P. Rodionov
Keyword(s):  
Respiratory Failure ◽  
Distress Syndrome ◽  
Experimental Studies ◽  
Viral Pneumonia ◽  
Medical Technologies ◽  
Clinical Observations ◽  
Wide Range ◽  
Prevention And Treatment ◽  
High Degree

The paper summarizes data on modern approaches to the diagnosis, prevention and treatment of severe acute parenchymal respiratory failure of various origins, including ARDS due to bacterial viral pneumonia. The work is based on the data of modern well-organized studies, analysis of international clinical guidelines with a high degree of evidence, as well as the results of our own long-term experimental studies and clinical observations of the treatment of patients with ARDS of various origins, including viral pneumonia of 2009, 2016, 2020. Scientifically grounded algorithms for prevention, differential diagnosis and personalized therapy of severe acute respiratory failure using innovative medical technologies and a wide range of respiratory and adjuvant treatment methods have been formulated. The authors tried to adapt as much as possible the existing current recommendations for the daily clinical practice of anesthesiologists and resuscitators.

scholarly journals Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Chaker El Kalamouni ◽  
Etienne Frumence ◽  
Sandra Bos ◽  
Jonathan Turpin ◽  
Brice Nativel ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Heme Oxygenase ◽  
Zika Virus ◽  
Fluorescent Protein ◽  
Human Cells ◽  
Heme Oxygenase 1 ◽  
Viral Inhibition ◽  
Reporter Protein ◽  
Wide Range ◽  
Rna Replicon

Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced in response to a wide range of stress conditions. HO-1 exerts antiviral activity against a broad range of viruses, including the Hepatitis C virus, the human immunodeficiency virus, and the dengue virus by inhibiting viral growth. It has been reported that HO-1 displays antiviral activity against the Zika virus (ZIKV) but the mechanisms of viral inhibition remain largely unknown. Using a ZIKV RNA replicon with the Green Fluorescent Protein (GFP) as a reporter protein, we were able to show that HO-1 expression resulted in the inhibition of viral RNA replication. Conversely, we observed a decrease in HO-1 expression in cells replicating the ZIKV RNA replicon. The study of human cells infected with ZIKV showed that the HO-1 expression level was significantly lower once viral replication was established, thereby limiting the antiviral effect of HO-1. Our work highlights the capacity of ZIKV to thwart the anti-replicative activity of HO-1 in human cells. Therefore, the modulation of HO-1 as a novel therapeutic strategy against ZIKV infection may display limited effect.

scholarly journals How College Students Assess the Threat of Infectious Diseases: Implications for University Leaders and Health Communicators

2021 ◽  
Vol 4 ◽  
pp. 129-164
Author(s):  
Yan Jin ◽  
Yen-I Lee ◽  
Brooke Fisher Liu ◽  
Lucinda Austin ◽  
Seoyeon Kim
Keyword(s):  
Infectious Disease ◽  
College Students ◽  
Online Survey ◽  
Protective Action ◽  
Sexually Transmitted ◽  
Wide Range ◽  
External Attribution ◽  
Action Taking ◽  
University Leaders ◽  
The Relationship

Higher education institutions and their students face a wide range of infectious disease threats (IDTs). However, there is a lack of theory-driven research on how to provide communication for multiple IDTs to motivate protective action taking. To close this gap, this study focuses on college students and two IDT types: respiratory and sexually transmitted infections. We tested an IDT appraisal model with data from an online survey conducted at two U.S. universities with 842 students. Findings indicate that IDT type led to different patterns of threat appraisal and protective action taking intentions. More specifically, participants perceived sexually transmitted threats as significantly more predictable and more controllable than respiratory threats. Participants also had higher intention to take protective action in response to respiratory threats than sexually-transmitted threats. We also found that external attribution-dependent (EAD) emotions (i.e., anger, sadness, surprise, and confusion) and an internal-attribution-dependent (IAD) emotion (i.e., hope) were sequential mediators in the relationship between IDT appraisal and protective action taking intentions for both infectious disease types. Implications for IDT communication research and practice are discussed.

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