chronic fatigue

Chronic fatigue and organophosphate pesticides in sheep farming: a retrospective study amongst people reporting to a UK pharmacovigilance scheme

Abstract:

The Department of Health has recently published a report from the CFS/ME Working Group which concluded that chronic fatigue syndrome (CFS) should be recognized as a chronic illness. Symptoms consistent with CFS are often reported by people who consider their health has been affected by exposure to pesticides, but the Working Group concluded that this type of exposure is not a common trigger for the syndrome.

The Veterinary Medicines Directorate (VMD) collects self-assessed reports of ill health in humans associated with veterinary medicines under their Suspected Adverse Reaction Surveillance Scheme. The reporters have mainly been sheep farmers. These reports were used to investigate the possible relationship between chronic fatigue (CF) and exposure to organophosphate pesticides in sheep farming. The overall aim of the study was to investigate a possible association between exposure to organophosphates and the development of CF amongst people who consider their health has been affected by pesticides in sheep farming. The hypothesis investigated was that repeated exposure to organophosphate pesticides in sheep dip may increase the probability of developing CF. A group of mostly sheep farmers who had reported to the VMD surveillance scheme were identified.

We planned to use a retrospective case-control study design but the initial symptoms reports were not sufficiently reliable to enable this. The study population was asked to complete two questionnaires. The first questionnaire was designed to identify the history of exposure of subjects to organophosphate pesticides, and their exposure was then reconstructed using a metric specifically developed for this purpose. The second questionnaire collected detailed information to identify whether the subjects had CF when they originally reported to the VMD and at the time of the survey.

The questionnaire was sent to a total of 206 subjects, of whom 28 had moved home. A total of 37% of the remaining 178 subjects participated. There was a high prevalence of CF amongst those who completed the questionnaire and this has generally persisted since the subjects reported to the VMD. Higher CF scores were associated with higher exposure to organophosphate pesticides.

CF is very common amongst those who consider their health was affected by pesticides and we have shown there is limited evidence of an association between exposure to organophosphates and CF. Further research is needed to investigate the cause of this syndrome amongst farmers exposed to pesticides.

Source: Tahmaz N, Soutar A, Cherrie JW. Chronic fatigue and organophosphate pesticides in sheep farming: a retrospective study amongst people reporting to a UK pharmacovigilance scheme. Ann Occup Hyg. 2003 Jun;47(4):261-7. http://annhyg.oxfordjournals.org/content/47/4/261.long (Full article)

Chronic fatigue in a population-based study of Gulf War veterans

Abstract:

Fatigue has been associated with illness in veterans of the Gulf War; however, few studies have confirmed self-reported fatigue by using clinical evaluation, and symptomatic veterans have not been evaluated with established criteria for Chronic Fatigue Syndrome (CFS). The authors describe the frequency and clinical characteristics of CFS in a sample of veterans residing in the northwestern United States. The sample was selected randomly from U.S. Department of Defense databases of troops deployed to southwest Asia during the Gulf War. The selected individuals were invited to participate in a clinical case-control study of unexplained illness.

Of 799 survey respondents eligible for clinical evaluation, 178 had fatigue symptoms. Of the 130 veterans who were evaluated clinically, 103 had unexplained fatigue, and 44 veterans met the 1994 U.S. Centers for Disease Control criteria for CFS. In this population, the authors estimated a minimum prevalence of any unexplained fatigue to be 5.1%, and of CFS to be 2.2%. The estimated prevalence was greater among females than among males. Cases were similar to healthy controls, as determined by laboratory tests and physical findings. In comparison to several clinical studies of CFS patients, the authors of this study found a lower proportion of veterans who reported a sudden onset of symptoms (19%) vs. a gradual onset (50%).

Although it has previously been suggested that veterans of the Gulf War suffer from higher rates of chronic fatigue than the general population, the study results described herein–on the basis of clinical examination of a population-based sample of veterans-actually indicate that an increased rate may indeed exist. Gulf War veterans with unexplained fatigue should be encouraged to seek treatment so that the impact of these symptoms on overall quality of life can be reduced.

Source: McCauley LA, Joos SK, Barkhuizen A, Shuell T, Tyree WA, Bourdette DN. Chronic fatigue in a population-based study of Gulf War veterans. Arch Environ Health. 2002 Jul-Aug;57(4):340-8. http://www.ncbi.nlm.nih.gov/pubmed/12530602

Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort

Abstract:

BACKGROUND: Some patients exposed to Q fever (Coxiella burnetii infection) may develop chronic fatigue.

AIM: To determine whether subjects involved in the West Midlands Q fever outbreak of 1989 had increased fatigue, compared to non-exposed controls, 10 years after exposure.

DESIGN: Matched cohort study comparing cases to age-, sex- and smoking-history-matched controls not exposed to Q fever.

METHODS: A postal questionnaire was sent to subjects at home, followed by further assessment in hospital, including a physical examination and blood tests.

RESULTS: Of 108 Q-exposed subjects, 70 (64.8%) had fatigue, 37 idiopathic chronic fatigue (ICF) (34.3%), vs. 29/80 (36.3%) and 12 (15.0%), respectively, in controls. In 77 matched pairs, fatigue was commoner in Q-exposed subjects than in controls: 50 (64.9%) vs. 27 (35.1%), p<0.0001. ICF was found in 25 (32.5%) of Q-exposed patients and 11(14.3%) of controls (p=0.01). There were 36 (46.8%) GHQ cases in Q-exposed subjects, vs. 18 (23.4%) controls (p=0.004). A matched analysis of those more intensively studied showed fatigue in 48 (66.7%) Q-exposed patients and 25 (34.7%) controls, (p<0.0001), ICF in 25 (34.7%) Q-exposed and 10 (13.9%) controls (p=0.004), and chronic fatigue syndrome (CFS) in 14 (19.4%) Q-exposed patients and three (4.2%) controls (p=0.003). Thirty-four (47.2%) Q-exposed patients were GHQ cases compared to 17 (23.6%) controls (p=0.004).

DISCUSSION: Subjects who were exposed to Coxiella in 1989 had more fatigue than did controls, and some fulfilled the criteria for CFS. Whether this is due to ongoing antigen persistence or to the psychological effects of prolonged medical follow-up is uncertain.

Comment in: Q fever: still a mysterious disease. [QJM. 2002]

Source: Wildman MJ, Smith EG, Groves J, Beattie JM, Caul EO, Ayres JG. Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort. QJM. 2002 Aug;95(8):527-38. http://qjmed.oxfordjournals.org/content/95/8/527.long (Full article)

Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance

Abstract:

OBJECTIVES: To measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance.

STUDY DESIGN: We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing. Beat-to-beat arterial pressure was monitored by Finapres.

RESULTS: Orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing.

CONCLUSIONS: Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria of chronic fatigue without orthostatic intolerance.

Comment in:

Chronic fatigue syndrome and Addison’s disease. [J Pediatr. 2003]

Orthostatic intolerance and chronic fatigue syndrome: new light on an old problem. [J Pediatr. 2002]

Source: Tanaka H, Matsushima R, Tamai H, Kajimoto Y. Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. J Pediatr. 2002 Apr;140(4):412-7. http://www.ncbi.nlm.nih.gov/pubmed/12006954

A twin study of chronic fatigue

Abstract:

OBJECTIVE: The etiology of chronic fatigue syndrome is unknown, but genetic influences may be important in its expression. Our objective was to assess the role of genetic and environmental factors in unexplained chronic fatigue.

METHODS: A classic twin study was conducted using 146 female-female twin pairs, of whom at least one member reported > or =6 months of fatigue. After completing questionnaires on symptoms, zygosity, physical health, and a psychiatric interview, twins were classified using three increasingly stringent definitions: 1) chronic fatigue for > or =6 months, 2) chronic fatigue not explained by exclusionary medical conditions, and 3) idiopathic chronic fatigue not explained by medical or psychiatric exclusionary criteria of the chronic fatigue syndrome case definition. Concordance rates in monozygotic and dizygotic twins were calculated for each fatigue definition along with estimates of the relative magnitude of genetic and environmental influences on chronic fatigue.

RESULTS: The concordance rate was higher in monozygotic than dizygotic twins for each definition of chronic fatigue. For idiopathic chronic fatigue, the concordance rates were 55% in monozygotic and 19% in dizygotic twins (p =.042). The estimated heritability in liability was 19% (95% confidence interval = 0-56) for chronic fatigue > or =6 months, 30% (95% confidence interval = 0-81) for chronic fatigue not explained by medical conditions, and 51% (95% confidence interval = 7-96) for idiopathic chronic fatigue.

CONCLUSIONS: These results provide evidence supporting the familial aggregation of fatigue and suggest that genes may play a role in the etiology of chronic fatigue syndrome.

Source: Buchwald D, Herrell R, Ashton S, Belcourt M, Schmaling K, Sullivan P, Neale M, Goldberg J. A twin study of chronic fatigue. Psychosom Med. 2001 Nov-Dec;63(6):936-43. http://www.ncbi.nlm.nih.gov/pubmed/11719632

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

Abstract:

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50).

At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months).

In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275).

Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.

Source: Kerr JR, Barah F, Mattey DL, Laing I, Hopkins SJ, Hutchinson IV, Tyrrell DA. Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol. 2001 Dec;82(Pt 12):3011-9. http://www.ncbi.nlm.nih.gov/pubmed/11714978

The possibility that fatigue may be an early manifestation of a serious medical illness not elicited through blood testing has been investigated by monitoring fatigued patients prospectively over time for the development of new diagnoses. At 1 year of follow-up, one study 3 showed no significant differences in new diagnoses, the incidences of diagnosed cancers, number of physician visits, or number of hospital admissions or hospital days.

This gives more weight to the conclusion that patients with chronic fatigue who otherwise have normal histories and no abnormalities on physical examination do not require extensive workups for occult medical illnesses.

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071607/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071607/

Source: Stevens DL. Chronic fatigue. West J Med. 2001 Nov;175(5):315-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071607/ (Full article)

A twin study of the etiology of prolonged fatigue and immune activation

Abstract:

Risk factors to prolonged fatigue syndromes (PFS) are controversial. Pre-morbid and/or current psychiatric disturbance, and/or disturbed cell-mediated immunity (CMI), have been proposed as etiologic factors.

Self-report measures of fatigue and psychologic distress and three in vitro measures of CMI were collected from 124 twin pairs. Crosstwin-crosstrait correlations were estimated for the complete monozygotic (MZ; 79 pairs) and dizygotic (DZ; 45 pairs) twin groups. Multivariate genetic and environmental models were fitted to explore the patterns of covariation between etiologic factors. For fatigue, the MZ correlation was more than double the DZ correlation (0.49 versus 0.16) indicating strong genetic control of familial aggregation.

By contrast, for in vitro immune activation measures MZ and DZ correlations were similar (0.49-0.69 versus 0.42-0.53) indicating the etiologic role of shared environments. As small univariate associations were noted between prolonged fatigue and the in vitro immune measures (r = -0.07 to -0.12), multivariate models were fitted. Relevant etiologic factors included: a common genetic factor accounting for 48% of the variance in fatigue which also accounted for 4%, 6% and 8% reductions in immune activation; specific genetic factors for each of the in vitro immune measures; a shared environment factor influencing the three immune activation measures; and, most interestingly, unique environmental influences which increased fatigue but also increased markers of immune activation.

PFS that are associated with in vitro measures of immune activation are most likely to be the consequence of current environmental rather than genetic factors. Such environmental factors could include physical agents such as infection and/or psychologic stress.

Source: Hickie IB, Bansal AS, Kirk KM, Lloyd AR, Martin NG. A twin study of the etiology of prolonged fatigue and immune activation. Twin Res. 2001 Apr;4(2):94-102. http://www.ncbi.nlm.nih.gov/pubmed/11665341

Chronic fatigue: symptom and syndrome

Abstract:

Chronic fatigue is common, is difficult to measure, can be associated with considerable morbidity, and is rarely a subject of controversy. The chronic fatigue syndrome also presents problems in definition and measurement, is associated with even more morbidity than chronic fatigue itself, and is often controversial. Particularly unclear is the way in which chronic fatigue and the chronic fatigue syndrome relate to each other: Is one the severe form of the other, or are they qualitatively and quantitatively different? We know that many things can cause chronic fatigue, and this is probably true for the chronic fatigue syndrome, too. We can anticipate that discrete causes of the chronic fatigue syndrome will be found in the future, even if these causes are unlikely to fall neatly along the physical-psychological divide that some expect. The causes of chronic fatigue are undoubtedly many, both in a population and in any individual person, even when a discrete cause, such as depression or cancer, is identified. Social, behavioral, and psychological variables are important in both chronic fatigue and the chronic fatigue syndrome. Interventions that address these general variables can be successful, and currently they are often more successful than interventions directed at specific causes.

Source: Wessely S. Chronic fatigue: symptom and syndrome. Ann Intern Med. 2001 May 1;134(9 Pt 2):838-43. http://www.ncbi.nlm.nih.gov/pubmed/11346319

Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report

Abstract:

The foci of this brief report are to (1) describe the prevalence of chemical sensitivity (CS) and chronic fatigue (CF) symptomatology and of presumptive multiple CS and CF syndrome diagnoses, and (2) explore the potential overlap between one purported case definition (i.e., chronic multi-symptom illness) and these unexplained symptom syndromes in a well-characterized group of Gulf War veterans. The number of subjects with CS and CF symptomatology and presumptive multiple CS and CF syndrome diagnoses was higher in the Gulf War-deployed group compared with a group deployed to Germany during the Gulf War. However, the percent differences were not significant when comparing the presumptive diagnoses of multiple CS and CF syndrome. The characteristic differences between the groups and the overlap with chronic multi-symptom illness are also discussed.

Source: Proctor SP, Heaton KJ, White RF, Wolfe J. Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report. J Occup Environ Med. 2001 Mar;43(3):259-64. http://www.ncbi.nlm.nih.gov/pubmed/11285874