Etiology Of Chronic Fatigue Syndrome Research Articles

Mental fatigue and chronic fatigue syndrome in clinical practice

Fatigue is an extremely disabling symptom both in healthy people and in various diseases. Physical fatigue is characterized by limitations in physical functioning, while mental/cognitive fatigue involves difficulties in concentrating and performing cognitive tasks. Mental and physical fatigue exist in both pathological and physiological fatigue. Fatigue is primarily an adaptive physiological process. It is a signal to have a rest and helps conserve energy to prevent injury, which can be useful after intense work, or when the body’s defenses need to be redistributed, for example, during infectious disease. It is important to distinguish between fatigue or tiredness and chronic fatigue syndrome in clinical practice. Chronic fatigue syndrome has multisystem manifestations and affects millions of people globally. Although the exact aetiology of chronic fatigue syndrome is uncertain, the studies point to neurological, immunological, autonomic and energy disorders. The main sings of chronic fatigue syndrome are debilitating fatigue that is worsened by activity, poor exercise tolerance, unrefreshing sleep and cognitive impairment. Reduced information processing speed is the most common cognitive impairment in chronic fatigue syndrome. Other manifestations include decreased reaction time, working memory, and attention. These symptoms must persist for at least 3–6 months for a diagnosis to be made. As there are no specific tests for chronic fatigue syndrome, a diagnosis can be established on the basis of a medical history and physical examination.Although there are no standards-based methods specific to chronic fatigue syndrome, clinicians can reduce the severity of symptoms using pharmacological and non-pharmacological treatment approaches that have proved their efficacy in clinical practice. In particular, nootropics are widely used in asthenic conditions and chronic fatigue syndrome. Fonturacetam is a nootropic drug that directly activates brain integration activities, promotes memory consolidation, and improves concentration and mental activity.

Revealing gut microbiome associations with CFS

The etiology of chronic fatigue syndrome (CFS) is largely unknown. In this issue of Cell Host and Microbe, Guo etal. and Xiong etal. report CFS-associated gut microbiome and metabolomic datasets-implicating dysregulation of immune modulating molecules. This may provide a framework for new therapeutic paradigms and disease origins.

Current knowledge about Chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) causes – summary

Chronic Fatigue Syndrome (CFE) is a severe and disabling disease whose etiology has not yet been elucidated. This implies the lack of a specific biomarker for the diagnosis of PE, and no causal treatment. There are a number of diagnostic criteria that facilitate the diagnosis of PE, but it is still a diagnosis with exclusion. This chapter reviews the scientific literature systematically, summarizing the available knowledge about the probable etiology of Chronic Fatigue Syndrome. The current topic of the influence of SARS-Cov-2 virus infection on the development of symptoms of IPC was also taken into account in particular. A clear explanation of the etiology of PE is necessary for the further development of scientific knowledge about the Chronic Fatigue Syndrome.

Mildronate. Chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a state of constant, impairing quality of life, fatigue, lasting more than 6 months, inexplicable by any of coexisting patient’s pathological conditions. The prevalence of CFS in the world is approximately 2 % of the population (120–140 mln inhabitants of Earth). The etiology of CFS is unknown. Several theories of development of CFS have been proposed (immune, infectious, endocrine, metabolic, neurological, psychiatric), however, none of them fully explains the clinical manifestations of CFS. There is no specific treatment for this condition. This article presents the clinical case of a patient B 45 years old with CFS, who received treatment with regular physical exercises, diet (limiting consumption of coffee and caffeine-containing products, alcohol, salt intake to less than 5 g per day, an increase in the consumption of plant foods and products containing potassium, calcium, magnesium), as well as intake of Mildronat, a positive dynamics was observed, manifested by an increase in productivity at work, decrease in fatigue, a decrease in the daily variability of blood pressure and a decrease in heart rate at rest.

Duvet woman versus action man: the gendered aetiology of Chronic Fatigue Syndrome according to English newspapers

ABSTRACTMedia portrayals of conditions such as Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) demand exploration as the media is a potent source of information and meaning, and as such has the potential to inform public and professional understandings. To date, there is little systematic exploration of print media representations of CFS/ME. In this study, we address that gap by exploring the voices of CFS/ME sufferers in the English print media (1998–2015) from a constructionist feminist perspective. We found that portrayals of CFS/ME differ meaningfully, depending on gender. The psychological and emotional tended to be foregrounded where women were concerned and the scepticism surrounding CFS/ME as a “non disease” was much more evident. On some occasions this was dealt with directly, whilst on others it was “leaked in” or hinted at. This serves to delegitimise the illness in women. In contrast, the physical was usually foregrounded in the case of men suffering from the condition and their experiences were accredited greater legitimacy. We problematise these representations and discuss the potential impact upon public and professional sympathy, treatment options and long-standing, gendered constructions of illness.

New Diagnostic Biomarkers for Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without symptoms of infection or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months. The pathogenesis of CFS is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of CFS and diagnostic uncertainty. We performed comprehensive metabolomic analyses of blood samples obtained from patients with CFS and healthy controls to establish an objective diagnosis of CFS. Here, we review previous findings concerning the immune, endocrine, and metabolic system in animal models for CFS and the patients, and present our results which may contribute to the development of a diagnostic biomarker for CFS.

The Association Between Borna Disease Virus and Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis

Context: Several studies have controversial results regarding the association between Borna disease virus (BDV) and chronic fatigue syndrome (CFS). The present systematic review and meta-analysis investigated the association between CFS and BDV. Evidence Acquisition: The present study was conducted based on the PRISMA guidelines for systematic review and meta-analysis studies. To avoid bias, all procedures of the study were performed by two researchers independently. A comprehensive search was performed using online databases, including PubMed, Scopus, Embase, PsycINFO, science Direct, Cochrane Library, web of science, and Google scholar using the MeSH keywords until December 12th, 2016. Heterogeneity among studies was evaluated using Cochran's Q test I2 Index. Finally, the random effect model was used for combined Odds Ratio (OR) using Review Manger software version 5.3.5. Results: Among 9 eligible studies comprising 610 cases and 2176 controls, the total OR for association between BDV and CFS was estimated to be 10.41 (95% confidence interval [CI]: 4.24 - 25.55, P < 0.0001). For subgroup analysis by the diagnostic methods (ELISA, RT-PCR, and Western blot), OR was 2.47 (95% CI: 0.77 - 7.96, P=0.13), 12.20 (95% CI: 1.66 - 89.57, P=0.01), and 28.36 (95% CI: 3.76-213.85, P=0.001), respectively (test for subgroup differences: P=0.08; I2=59.5). Subgroup analysis for BDV and CFS association by antigens and antibodies had an OR of 12.20 (1.66, 89.57) and 8.20 (3.32, 20.22), respectively (test for subgroup differences: P=0.72; I2=0). Conclusions: This study supports the association between BDV and CFS and shows the role of viral agents in etiology of CFS. Therefore, viral agents may play a role in the etiology of neuropsychiatric disorders.

Differential effects of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome

ObjectiveThere is wide consensus that childhood trauma plays an important role in the aetiology of chronic fatigue syndrome (CFS). The current study examines the differential effects of childhood trauma subtypes on fatigue and physical functioning in individuals suffering from CFS. MethodsParticipants were 155 well-documented adult, predominantly female CFS patients receiving treatment at the outpatient treatment centre for CFS of the Antwerp University Hospital in Belgium. Stepwise regression analyses were conducted with outcomes of the total score of the Checklist Individual Strength (CIS) measuring fatigue and the scores on the physical functioning subscale of the Medical Outcomes Short Form 36 Health Status Survey (SF-36) as the dependent variables, and the scores on the five subscales of the Traumatic Experiences Checklist (TEC) as the independent variables. ResultsThe patients' fatigue (β=1.38; p=0.025) and physical functioning scores (β=−1.79; p=0.034) were significantly predicted by childhood sexual harassment. There were no significant effects of emotional neglect, emotional abuse, bodily threat, or sexual abuse during childhood. ConclusionOf the childhood trauma subtypes investigated, sexual harassment emerged as the most important predictor of fatigue and poor physical functioning in the CFS patients assessed. These findings have to be taken into account in further clinical research and in the assessment and treatment of individuals coping with chronic fatigue syndrome.

Acupuncture and moxibustion for chronic fatigue syndrome in traditional Chinese medicine: a systematic review and meta-analysis

BackgroundAs the etiology of chronic fatigue syndrome (CFS) is unclear and the treatment is still a big issue. There exists a wide range of literature about acupuncture and moxibustion (AM) for CFS in traditional Chinese medicine (TCM). But there are certain doubts as well in the effectiveness of its treatment due to the lack of a comprehensive and evidence-based medical proof to dispel the misgivings. Current study evaluated systematically the effectiveness of acupuncture and moxibustion treatments on CFS, and clarified the difference among them and Chinese herbal medicine, western medicine and sham-acupuncture.MethodsWe comprehensively reviewed literature including PubMed, EMBASE, Cochrane library, CBM (Chinese Biomedical Literature Database) and CNKI (China National Knowledge Infrastructure) up to May 2016, for RCT clinical research on CFS treated by acupuncture and moxibustion. Traditional direct meta-analysis was adopted to analyze the difference between AM and other treatments. Analysis was performed based on the treatment in experiment and control groups. Network meta-analysis was adopted to make comprehensive comparisons between any two kinds of treatments. The primary outcome was total effective rate, while relative risks (RR) and 95% confidence intervals (CI) were used as the final pooled statistics.ResultsA total of 31 randomized controlled trials (RCTs) were enrolled in analyses. In traditional direct meta-analysis, we found that in comparison to Chinese herbal medicine, CbAM (combined acupuncture and moxibustion, which meant two or more types of acupuncture and moxibustion were adopted) had a higher total effective rate (RR (95% CI), 1.17 (1.09 ~ 1.25)). Compared with Chinese herbal medicine, western medicine and sham-acupuncture, SAM (single acupuncture or single moxibustion) had a higher total effective rate, with RR (95% CI) of 1.22 (1.14 ~ 1.30), 1.51 (1.31–1.74), 5.90 (3.64–9.56). In addition, compared with SAM, CbAM had a higher total effective rate (RR (95% CI), 1.23 (1.12 ~ 1.36)). In network meta-analyses, similar results were recorded. Subsequently, we ranked all treatments from high to low effective rate and the order was CbAM, SAM, Chinese herbal medicine, western medicine and sham-acupuncture.ConclusionsIn the treatment of CFS, CbAM and SAM may have better effect than other treatments. However, the included trials have relatively poor quality, hence high quality studies are needed to confirm our finding.

Chronic fatigue syndrome – revisited

Chronic fatigue syndrome (CFS) is a common and disabling problem; although most likely of biopsychosocial origin. The nature of the pathophysiological components remains unclear. It is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear. Celiac disease can present with neurological symptoms in the absence of gastrointestinal symptoms; therefore, celiac disease should be included in the differential diagnosis of CFS.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.326-328

Persistent Burnout Theory of Chronic Fatigue Syndrome

There is no agreement on the etiology of chronic fatigue syndrome (CFS), and the main theories (behavioural and viral/immune) do not satisfactorily explain the condition. A growing body of evidence suggests that CFS may be caused by a dysfunction of the stress system—and the hypothalamic-pituitary-adrenal (HPA) axis in particular—as a result of chronic stress. CFS shares many similarities to occupational burnout, including similar symptoms, physiological abnormalities and triggers. After a brief review of the science of stress, burnout, central fatigue and CFS, I propose a model of CFS based on a state of persistent burnout that remains after the initial stressors have been removed. This persistence may be due to a combination of a dysregulation of the HPA axis, and behavioural factors. A novel treatment approach based on self-efficacy and positive goals is proposed.

Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle.

The etiology of chronic fatigue syndrome (CFS) is unknown. Myalgic encephalomyelitis (ME) has been recently postulated to be the cause of CFS. Orthostatic intolerance (OI) has been known as an important symptom in predicting quality of life in CFS patients. Cardiac function may be impaired in patients with ME. The presence or absence of OI was determined both symptomatically and by using a 10-min stand-up test in 40 ME patients. Left ventricular (LV) dimensions and function were determined echocardiographically in the ME patients compared to 40 control subjects. OI was noted in 35 (97%) of the 36 ME patients who could stand up quickly. The mean values for the cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic diameter (EDD), LV end-systolic diameter, stroke volume index, cardiac index and LV mass index were all significantly smaller in the ME group than in the controls. Both a small LVEDD (<40 mm, 45 vs. 3%) and a low cardiac index (<2 l/ min/mm2, 53 vs. 8%) were significantly more common in the ME group than in the controls. Both heart rate and LV ejection fraction were similar between the groups. In conclusion, a small LV size with a low cardiac output was common in ME patients, in whom OI was extremely common. Cardiac dysfunction with a small heart appears to be related to the symptoms of ME.

Mitochondrial Dysfunction and Chronic Fatigue Syndromes: Issues in Clinical Care (modified version)

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear. Despite considerable worldwide efforts, no single etiology has been identified to explain the development of chronic fatigue syndrome (CFS). It is likely that multiple factors promote its development, sometimes with the same factors both causing and being caused by the syndrome. However, a number of recent studies have shown oxidative stress may be involved in its pathogenesis. Any dysfunction in the Mitochondria, the key organelle responsible for cellular energy production can result in the excess fatigue and other symptoms that are common complaints in almost every chronic disease. Several components of this system require routine replacement, and this need can be facilitated with natural supplements. A detailed review of the literature suggests a number of marginal nutritional deficiencies may have etiologic relevance. In this review article an attempt has been made to look into these factors in relation to chronic fatigue syndrome.

Impaired cardiac function due to small heart and orthostatic intolerance in patients with myalgic encephalomyelitis

Purpose: The etiology of chronic fatigue syndrome (CFS) remains unclarified. Recently, dysfunction of central nervous system by myalgic encephalomyelitis (ME) has been postulated as the cause of CFS. International Consensus Criteria identify patients with ME who are more physically debilitated and have greater physical and cognitive impairments. Orthostatic intolerance (OI) with symptoms of disabling fatigue, dizziness, diminished concentration, tremulousness and nausea while standing, appears to be a core symptom of ME, impairing the most basic activities of daily living. Cardiovascular dysfunction in association with a small heart or a small left ventricle (LV) and low cardiac output may be related to the pathophysiology of ME. Methods: Consecutive 40 patients who fullfilled the International Consensus Criteria for ME (14 males and 26 females, 31±10 years of age) and 40 age- and sex- matched sedentary control subjects (Controls) were studied. OI was determined either by subjective symptoms or by 10-min standing test. LV dimensions and function were determined echocardiographically. Results: OI was prevalent (95%) in ME. The mean heart rate was not significantly different between ME and Controls (68±11 vs. 70±11 beats/min, NS). The mean values of cardiothoracic ratio (39±5 vs. 43±4%, p<0.01), systolic (109±9 vs. 120±10 mmHg, p<0.05) and diastolic pressures (68±9 vs. 78±8 mmHg, p<0.05), LV end-diastolic (41±6 vs. 44±3 mm, p<0.01) and end-systolic (25±5 vs. 27±3 mm, p<0.05) dimensions, stroke volume index (32±8 vs. 38±6 ml/m2, p<0.01), cardiac index (2.1±0.4 vs. 2.7±0.5 ml/min/m2, p<0.01) and LV mass index (57±16 vs. 70±17 g/m2, p<0.01) were all significantly smaller in ME than in Controls. A smaller LV end-diastolic dimension (<40 mm) was significantly more prevalently noted in ME than in Controls (45% vs. 3%, p<0.01). A lower cardiac index (< 2 l/min/m2) was more prevalent in ME than in Controls (53% vs. 8%, p<0.01). The mean values of both LV fractional shortening (39±6 vs. 39±4%, NS) and LV ejection fraction (69±7 vs. 69±4%, NS) were quite comparable between the groups. Conclusions: OI was prevalent in ME. Both systolic and diastolic blood pressures were low in ME. A small size of LV associated with low cardiac output due to diminished stroke volume was frequently observed in ME. A small heart appears to be related to the genesis of ME via both cerebral and systemic hypoperfusion, which could make it difficult for patients to meet the demands of everyday activity. A small heart with impaired cardiac performance due to decreased preload appears to be an important target for the treatment of ME.

Chronic fatigue syndrome from vagus nerve infection: A psychoneuroimmunological hypothesis

Chronic fatigue syndrome (CFS) is an often-debilitating condition of unknown origin. There is a general consensus among CFS researchers that the symptoms seem to reflect an ongoing immune response, perhaps due to viral infection. Thus, most CFS research has focused upon trying to uncover that putative immune system dysfunction or specific pathogenic agent. However, no single causative agent has been found. In this speculative article, I describe a new hypothesis for the etiology of CFS: infection of the vagus nerve. When immune cells of otherwise healthy individuals detect any peripheral infection, they release proinflammatory cytokines. Chemoreceptors of the sensory vagus nerve detect these localized proinflammatory cytokines, and send a signal to the brain to initiate sickness behavior. Sickness behavior is an involuntary response that includes fatigue, fever, myalgia, depression, and other symptoms that overlap with CFS. The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria. Drawing upon relevant findings from the neuropathic pain literature, I explain how pathogen-activated glial cells can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen. The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies.

Chronic Fatigue and Personality: A Twin Study of Causal Pathways and Shared Liabilities

The etiology of chronic fatigue syndrome (CFS) remains unknown. Personality traits influence well-being and may play a role in CFS and unexplained chronic fatigue. This study aimed to examine the association of emotional instability and extraversion with chronic fatigue and CFS in a genetically informative sample. We evaluated 245 twin pairs for two definitions of chronic fatigue. They completed the Neuroticism and Extraversion subscales of the NEO Five Factor Inventory. Using a co-twin control design, we examined the association between personality and chronic fatigue. Higher emotional instability was associated with both definitions of chronic fatigue and was confounded by shared genetics. Lower extraversion was also associated with both definitions of fatigue, but was not confounded by familial factors. Both emotional instability and extraversion are related to chronic fatigue and CFS. Whereas emotional instability and chronic fatigue are linked by shared genetic mechanisms, the relationship with extraversion may be causal and bidirectional.

Emotional processing and chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is characterised by severe fatigue and is associated with functional impairment. Somatic symptoms are often present. Although much debate exists about the aetiology of CFS, misinterpretations in the cognitive processing of emotions has been suggested as a causal factor in vulnerable individuals. The rehabilitative treatments of cognitive behavioural therapy and graded exercise therapy have been shown to be effective in improving fatigue and disability in CFS. To date these are the only evidence-based treatments, but effect sizes are modest. Some patients may benefit from receiving more emotion-focused treatments once their functioning has improved. The aim of this paper is to explore the literature on emotional expression and processing in the context of CFS.

Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome

The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI. Small heart is associated with OI in patients with CFS. Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(-) according to the presence or absence of OI. In addition, 11 OI patients and 27 age- and sex-matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically. The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic dimension, LV end-systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(-) patients and healthy controls, and also in OI patients than in controls. A smaller LV end-diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(-) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm(2)) was more prevalent in CFSOI(+) (65%) than in CFSOI(-) (5%, P<0.01), OI (27%), and controls (11%, P<0.01). A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.

Evidence for a heritable predisposition to Chronic Fatigue Syndrome

BackgroundChronic Fatigue Syndrome (CFS) came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV) or other murine leukemia related retroviruses (MLV) might also suggest underlying genetic implications within the host immune system.MethodsWe present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases.ResultsWe observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p <0.001) and distant relationships (p = 0.010). We also observed significant excess CFS relative risk among first (2.70, 95% CI: 1.56-4.66), second (2.34, 95% CI: 1.31-4.19), and third degree relatives (1.93, 95% CI: 1.21-3.07).ConclusionsThese analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.

Sleep and fatigue in mice infected with murine gammaherpesvirus 68

Fatigue, a common symptom of many acute and chronic medical conditions, reduces both quality of life and workplace productivity and can be disabling. However, the pathophysiologic mechanisms that underlie fatigue can be difficult to study in human populations due to the patient heterogeneity, the variety of underlying causes and potential triggering events, and an inability to collect samples that may be essential to elucidation of mechanisms (e.g., brain). Although the etiology of chronic fatigue syndrome (CFS) remains elusive, some studies have implicated viral infections, including Epstein-Barr virus (EBV), a human gammaherpesvirus, as a potential factor in the pathogenesis of CFS. Murine gammaherpesvirus 68 (γHV68) is a mouse pathogen that shares many similarities with human γHVs, including EBV. In this study, we use γHV68-infected C57BL/6J mice as a model system for studying the impact of chronic viral infection on sleep–wake behavior, activity patterns, and body temperature profiles. Our data show that γHV68 alters sleep, activity, and temperature in a manner suggestive of fatigue. In mice infected with the highest dose used in this study (40,000plaque forming units), food intake, body weight, wheel running, body temperature, and sleep were normal until approximately 7days after infection. These parameters were significantly altered during days 7 through 11, returned to baseline levels at day 12 after infection, and remained within the normal range for the remainder of the 30-day period after inoculation. At that time, both infected and uninfected mice were injected with lipopolysaccharide (LPS), and their responses monitored. Uninfected mice given LPS developed a modest and transient febrile response during the initial light phase (hours 12 through 24) after injection. In contrast, infected mice developed changes in core body temperatures that persisted for at least 5days. Infected mice showed an initial hypothermia that lasted for approximately 12h, followed by a modest fever that persisted for several hours. For the remainder of the 5-day recording period, they showed mild hypothermia during the dark phase. Running wheel activity of infected mice was reduced for at least 5days after injection of LPS, but for only 12h in uninfected mice. Collectively, these observations indicate that (1) physiologic and behavioral processes in mice are altered and recover during an early phase of infection, and (2) mice with latent γHV68 infection have an exacerbated response to challenge with LPS. These findings indicate that laboratory mice with γHV68 infections may provide a useful model for the study of fatigue and other physiologic and behavioral perturbations that may occur during acute and chronic infection with gammaherpesviruses.