Role Of Fever Research Articles

ThermoPCD: a database of molecular dynamics trajectories of antibody-antigen complexes at physiologic and fever-range temperatures.

Progression of various cancers and autoimmune diseases is associated with changes in systemic or local tissue temperatures, which may impact current therapies. The role of fever and acute inflammation-range temperatures on the stability and activity of antibodies relevant for cancers and autoimmunity is unknown. To produce molecular dynamics (MD) trajectories of immune complexes at relevant temperatures, we used the Research Collaboratory for Structural Bioinformatics (RCSB) database to identify 50 antibody:antigen complexes of interest, in addition to single antibodies and antigens, and deployed Groningen Machine for Chemical Simulations (GROMACS) to prepare and run the structures at different temperatures for 100-500ns, in single or multiple random seeds. MD trajectories are freely available. Processed data include Protein Data Bank outputs for all files obtained every 50ns, and free binding energy calculations for some of the immune complexes. Protocols for using the data are also available. Individual datasets contain unique DOIs. We created a web interface, ThermoPCD, as a platform to explore the data. The outputs of ThermoPCD allow the users to relate thermally-dependent changes in epitopes:paratopes interfaces to their free binding energies, or against own experimentally derived binding affinities. ThermoPCD is a free to use database of immune complexes' trajectories at different temperatures that does not require registration and allows for all the data to be available for download. Database URL: https://sites.google.com/view/thermopcd/home.

Fever as a Predictor of COVID-19 Outcomes in Hospitalized Patients.

With the advent of the COVID-19 pandemic, numerous questions have arisen regarding the screening, diagnosis, treatment, and prognosis of infected patients. Among these, screening infected patients through body temperature measurement has proven ineffective. However, doubts persist regarding the role of fever as a prognostic factor in the disease. To assess the prevalence of fever and its relevance as a marker of mortality in COVID-19. This prospective and longitudinal cohort study was conducted between April 2020 and December 2021 and analyzed 1400 COVID-19 patients systematically admitted to the emergency department of a reference hospital during the period from April 2020 to December 2021, in the city of Curitiba, Brazil. [LG1]The study evaluated [LG2]the presence of fever (body temperature above 37,7ºC) upon admission and/or during hospitalization, patient profiles, and outcomes (in-hospital death, discharge, admission at the intensive care unit, need of mechanical ventilation). Fever was present in 128 participants (9.1%), with a higher prevalence in males (71%) and obese individuals (42.9%). Among the febrile patients, 39 required intubation (30.4%), with two intubated upon admission (1.5%), 104 were discharged (81.2%), and 24 deceased (18.7%). Fever was not associated with a higher mortality rate. Fever showed low prevalence, is more common in males and obese individuals, and is not related to worse clinical outcomes.

Fever and antibiotic use in maternal urinary tract infections during pregnancy and risk of congenital heart defects: Findings from the National Birth Defects Prevention Study.

Previous studies report an association between prenatal maternal urinary tract infections (UTI) and specific congenital heart defects (CHDs); however, the role of fever and antibiotic use on this association is poorly understood. Using data from the National Birth Defects Prevention Study, we examined whether the relationship between maternal UTIs during the periconceptional period and occurrence of CHDs is modified by the presence of fever due to UTI and corresponding antibiotic use among 11,704 CHD case infants and 11,636 live-born control infants. Information on UTIs, fever associated with UTI and antibiotic use (sulfonamides, nitrofurantoin, cephalosporins, penicillin, macrolides, and quinolones) during pregnancy were obtained using a computer-assisted telephone interview. Using unconditional multivariable logistic regression, we calculated adjusted odds ratios (ORs) to determine the association between maternal UTIs and subtypes of CHDs. Analyses were stratified by the presence of fever and medication use associated with UTI. The prevalence of UTIs during the periconceptional period was 7.6% in control mothers, and 8.7% in case mothers. In the absence of fever, UTI was associated with secundum atrial septal defects (ASD) (OR 1.3; 95% confidence interval [CI] 1.1-1.5) and in the absence of antibiotics, UTI was associated with conotruncal defects as a group and for four specific CHDs. When fever and UTI occurred concomitantly, no significantly elevated odds ratios were noticed for any subtypes of CHD. Among women with UTIs who used antibiotics, an elevated but statistically non-significant estimate was observed for secundum ASD (OR 1.4; 95% CI 1.0-2.0). Findings in the present study suggest that fever due to UTI and corresponding maternal antibiotic use do not substantially modify the association between maternal UTIs and specific CHDs in offspring. Further studies with larger sample sizes are warranted to guide clinical management of UTIs during the periconceptional period.

Leading reasons for antibiotic prescriptions in pediatric respiratory infections: influence of fever in a primary care setting

BackgroundAntibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription.MethodsWe conducted a prospective observational study that evaluated preschool children aged 0–5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections.ResultsAmoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics.ConclusionOur findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas.

Exploring Latino Perspectives in Childhood Fever: Beliefs, Practices, and Needs.

Latino parents have significant knowledge gaps and misconceptions about fever. In this study, we explored Latino beliefs and practices around fever and its impact on their care decisions. A qualitative-focused ethnography was conducted with 21 Latino parents. Semi-structured interviews were completed, and inductive thematic analysis was used to identify themes and subthemes. Three major themes emerged: (a) the meaning of fever; (b) seeking guidance; and (c) navigating fever. Subthemes included: a sign of folk illness, a sign of infection, trust in health care providers, watchful waiting, and barriers and needs. Latino parents have significant knowledge gaps about the role of fever in illness. They engage multiple systems of care but rarely share their fears with health care providers. Culturally-sensitive interventions incorporating traditional and biomedical approaches are needed. Findings can help inform future interventions targeting knowledge gaps in this population.

Il sintomo febbre: l'interpretazione e la corretta gestione

In paediatric age, fever represents one of the main reasons for parental concern and the main cause of access to the emergency room. Against "fever phobia", it is essential that the paediatrician spends some time explaining to parents that fever is a defence mechanism against infection and that it should be treated rationally, with the objective of making the child feel better and not making them heal faster. Furthermore, it is useful to provide parents with indications on how to measure body temperature and advice on clinical signs to pay attention to, besides fever. Indeed, in addition to temperature, there are other parameters to evaluate in a febrile child, some clearly measurable, others for which it is necessary for the doctor to evaluate the child "face to face". It is on this issue that the main guidelines on the management of febrile children are based, whose objective is to help the paediatrician to identify those few children who have a severe disease and therefore deserve prompt treatment and investigations. The article shows current evidence on the role of fever, the most correct methods for its measurement, the reasonable use of drugs for the symptomatic control of fever and the approach to be followed in the management of fever in the child aged less than 5 years.

Risk of attention-deficit hyperactivity disorder in offspring of mothers with infections during pregnancy.

Maternal infections during pregnancy are common events that have been suggested to be risk factors for Attention-deficit hyperactivity disorder (ADHD) in offspring. Only a few studies have been conducted to date and results are conflicting. The current study investigates the associations between specific groups of prenatal maternal infections and offspring ADHD, considering timing of exposure and the role of fever. We used data from the prospective Norwegian Mother, Father and Child Cohort Study (MoBa), including more than 112,000 pregnancies, linked with data from the Medical Birth Registry of Norway and the Norwegian Patient Registry to estimate odds ratios for the likelihood that children develop ADHD after being exposed to maternal infections during gestation. Children exposed to any maternal infection during pregnancy showed increased risk of receiving an ADHD diagnosis (OR=1.15, CI=1.03-1.27). Specifically, increased ADHD risk was observed after exposure to genitourinary infections in second (OR=1.42, CI=1.06-1.90) or third trimester (OR=2.04, CI=1.19-3.49), and to respiratory infections in second trimester (OR=1.31, CI=1.12-1.54), provided these infections were accompanied by episodes of fever. Increased ADHD risk was also observed after exposure to diarrhea without fever in the third trimester (OR=1.25, CI=1.07-1.46). Overall, our results suggest that prenatal exposure to maternal infections, particularly with co-occurring episodes of fever, are risk factors for ADHD. Fever (or severity of the infection) appears to be more important in mid-pregnancy associations. Our results indicate that type of infection and timing of exposure might influence the associations, but small effect sizes require careful interpretations. The association between infection and ADHD should be estimated using discordant siblings or other negative control designs that give better adjustment for unmeasured familial confounding.

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever.

BackgroundMost COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear.MethodsWe compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation.ResultsAmong 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus, were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis.ConclusionGut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.

NSP2 Is Important for Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus to Trigger High Fever-Related COX-2-PGE2 Pathway in Pigs.

In 2006, atypical porcine reproductive and respiratory syndrome (PRRS) caused by a highly pathogenic PRRSV (HP-PRRSV) strain broke out in China. Atypical PRRS is characterized by extremely high fever and high mortality in pigs of all ages. Prostaglandin E2 (PGE2) derived from arachidonic acid through the activation of the rate-limiting enzyme cyclooxygenase type 1/2 (COX-1/2) plays an important role in fever. Here, we showed that HP-PRRSV infection increased PGE2 production in microglia via COX-2 up-regulation depending on the activation of MEK1-ERK1/2-C/EBPβ signaling pathways. Then, we screened HP-PRRSV proteins and demonstrated that HP-PRRSV nonstructural protein 2 (NSP2) activated MEK1-ERK1/2-C/EBPβ signaling pathways by interacting with 14-3-3ζ to promote COX-2 expression, leading to PGE2 production. Furthermore, we identified that the amino acid residues 500-596 and 658-777 in HP-PRRSV NSP2 were essential to up-regulate COX-2 expression and PGE2 production. Finally, we made mutant HP-PRRS viruses with the deletion of residues 500-596 and/or 658-777, and found out that these viruses had impaired ability to up-regulate COX-2 and PGE2 production in vitro and in vivo. Importantly, pigs infected with the mutant viruses had relieved fever, clinical symptoms, and mortality. These data might help us understand the molecular mechanisms underlying the high fever and provide clues for the development of HP-PRRSV attenuated vaccines.

The role of Fever in Covid-19

We are living with a lot of diseases related to fevers with different names like Chikungunya fever, West Nile fever, rheumatic fever, Relapsing fever, Rat-bite fever (sodoku), Haver hill fever, Dengue fever, Typhoid fever, Scarlet fever, Viral hemorrhagic fever, etc.

The Important Role of Fever during Infection and the Use of Fever for Treatment of Coronavirus Patients

The Important Role of Fever during Infection and the Use of Fever for Treatment of Coronavirus Patients

Biological Chemistry and Physiopathology of Metabolism During Fever

Physiopathology determines the causes and conditions of pathological processes, in other words, of aetiology, as well as the mechanisms of their production, namely pathogenesis; this discipline studies the general reactions of the organism, regardless of the form of the disease by which they would manifest themselves; it also studies the general rules for the occurrence and evolution of the disorders of the functions of different systems which depend on the properties of the whole organism. The tasks of physiopathology become clearer when we compare it with the tasks of the clinical investigation. Physiopathology clarifies the causes and the mechanism of the onset of a thermal reaction of the body, such as fever; the clinical part, in this case, deals with certain well-defined forms of febrile disorders, especially of infectious origin. Physiopathology studies the general rules of occurrence and development of the inflammatory process, while the clinical disciplines investigate a number of diseases caused by different forms of inflammation. Physiopathology is closely related to biology. The personal clinical study was carried out during the period 2016-2018 on a sample of 362 patients, who showed changes in the functions of different systems and organs during fever. The problem of the influence of fever, seen as a general reaction of the organism to the action of infectious agents, is of major importance in clarifying the role of fever as a reaction of adaptation in the fight of the body against infection, and it largely determines its treatment. Excessive temperature increase, as well as a sudden drop, can exert a harmful effect on the body.

Post-immunisation fever and the antibody response to measles-containing vaccines.

Fever is a common adverse event following measles vaccination, more frequent among older children and those receiving Measles-Mumps-Rubella-Varicella vaccine vs. Measles-Mumps-Rubella vaccine, two factors associated with a better antibody response. However, the role of fever in the immunogenicity of measles-containing vaccines (MCV) is unclear. We performed a post-hoc pooled analysis of data of 5 216 11 to 22 month-old children receiving MCV from 2004 to 2012 in Europe and USA to evaluate the association between post-immunisation fever and antibody response, measured by geometric mean concentrations (GMCs). We further evaluated fever as an effect modifier or a mediator in the associations between the type of MCV or the age at first vaccination and vaccine immunogenicity. After the first dose, fever was associated with 60% higher GMCs (95% CI 1.51-1.68). For children vaccinated at ⩾12 months, the fever did not modify and minimally mediated (2% to 3%) the association between age and antibody response. Fever mediated 18% of the association between type of MCV and GMCs. In a model including fever, age and type of vaccine, fever was the strongest predictor of GMCs. These results suggest that fever is associated with a stronger measles antibody response independently of age and type of MCV.

Fabry Disease in Internal Medicine: The Role of Fever and Hyperthermia in Diagnosis

Fabry Disease in Internal Medicine: The Role of Fever and Hyperthermia in Diagnosis

Autoimmune and inflammatory epilepsies

The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies.

A43 The effect of hydrocortisone on the growth of preterm infants on prolonged mechanical ventilation

Background and Aims: Heart rate is known to increase by approximately 10 beats per minute (bpm) per degree centigrade increase in body temperature in children. A higher heart rate than would be expected for a given level of fever may therefore be more suspicious for an infection compared to conventional heart rate cut-off values. Very few data exist on the relationship between temperature and heart rate in newborns. We aimed to evaluate the role of fever on heart rate in newborns during the first three days of life. Methods: We included all newborns hospitalised at our tertiary care teaching neonatal intensive care unit within the first three days of life during a four-year period. Temperature was measured every two to four hours and heart rate was recorded continuously. Results: Of 863 newborns included 69 (8%) had fever during the first three days of life (rectal temperature >38.5°C), 45 of them had culture proven and clinical early onset sepsis (65%). There was a positive correlation between temperature and heart rate (r = .314, p = .009) with an increment in heart rate by 17.5 bpm (CI 95% 4.6–30.4) with each 1°C increment in temperature. In the subgroup of sepsis positive newborns the increment in heart rate was higher compared to sepsis negative newborns (21.5 bpm (4.9–38.1) vs. 10.5 bpm (−11.7–32.6), respectively). Conclusions: Our results suggest a relationship between pulse rate and temperature in febrile newborns. Further studies might better explore the possible utility of a temperature dependent interpretation of heart rate in this age group.

Role of Sadyo Vamana in dental abscess (danta arbuda)

Sadyo Vamana is a type of purificatory measure mentioned in Ayurveda, which to expel the pus and morbid factors present in a dental abscess without opening it. However, Sadyo Vamana's role in fever and pus filled dental abscess has not been reported so far. I report a case of dental abscess with fever. A 24-year-old male patient with a pus filled dental abscess. His fever and dental abscess didn’t respond to antibiotic and analgesic treatment for 10 days. The patient was given Sadyo Vamana (instant therapeutic emesis) to expel the accumulated pus in dental abscess without opening it. The patient got complete relief from fever and dental abscess after Sadyo Vamana. The patient not gave internal medication.

Prostaglandin D 2 sustains the pyrogenic effect of prostaglandin E 2

Prostaglandin D 2 (PGD 2) is involved in a variety of physiological and pathophysiological processes, but its role in fever is poorly understood. Here we investigated the effects of central PGD 2 administration on body temperature and prostaglandin levels in the cerebrospinal fluid (CSF) of rats. Administration of PGD 2 into the cisterna magna (i.c.m) evoked a delayed fever response that was paralleled by increased levels of prostaglandin E 2 (PGE 2) in the CSF. The elevated PGE 2 levels were not caused by an increased expression of cyclooxygenase 2 or microsomal prostaglandin E synthase-1 in the hypothalamus. Interestingly, i.c.m. pretreatment of animals with PGD 2 considerably sustained the pyrogenic effects of i.c.m. administered PGE 2. These data indicate that PGD 2 might control the availability of PGE 2 in the CSF and suggest that centrally produced PGD 2 may play a role in the maintenance of fever.

Central nervous action of interleukin‐1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide

Although receptors for the pro-inflammatory cytokine interleukin-1 have long been known to be expressed in the brain, their role in fever and behavioural depression observed during the acute phase response (APR) to tissue infection remains unclear. This may in part be due to the fact that interleukin-1 in the brain is bioactive only several hours after peripheral administration of bacterial lipopolysaccharide (LPS). To study the role of cerebral interleukin-1 action in temperature and behavioural changes, and activation of brain structures during the APR, interleukin-1 receptor antagonist (IL-1ra; 100 microg) was infused into the lateral brain ventricle 4 h after intraperitoneal (i.p.) LPS injection (250 microg/kg) in rats. I.p. LPS administration induced interleukin-1beta (IL-1beta) production in systemic circulation as well as in brain circumventricular organs and the choroid plexus. Intracerebroventricular (i.c.v.) infusion of IL-1ra 4 h after i.p. LPS injection attenuated the reduction in social interaction, a cardinal sign of behavioural depression during sickness, and c-Fos expression in the amygdala and bed nucleus of the stria terminalis. However, LPS-induced fever, rises in plasma corticosterone, body weight loss and c-Fos expression in the hypothalamus and caudal brainstem were not altered by i.c.v. infusion of IL-1ra. These findings, together with our previous observations showing that i.c.v. infused IL-1ra diffuses throughout perivascular spaces, where macrophages express interleukin-1 receptors, can be interpreted to suggest that circulating or locally produced brain IL-1beta acts on these cells to bring about behavioural depression and activation of limbic structures during the APR after peripheral LPS administration.

Melanom und Atopie

331 melanoma patients (206 females; 125 males) and 380 control subjects (205 females; 175 males) were questioned about symptoms of atopy (eczema, allergic rhinitis, allergic asthma). Among the melanoma patients there were 14 (10 females, 4 males; 4.2%) with atopy, while in the control group there were 38 (23 females, 15 males; 10%). The influence of age, sex, socio-economic status and other risk factors for melanoma were analysed with the Mantel-Haenszell test, which indicated that melanoma patients had fewer atopic symptoms than subjects in the control group (p less than 0.05). The role of fever may be an explanation of this finding. Among melanoma patients there were fewer feverish infections, while patients with atopy had more feverish complications of their symptoms.