HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway

Abstract:

Background: Vaccination has been suggested to be involved in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). HPV vaccine was introduced in the Norwegian Childhood Immunisation Programme and offered 12 year old girls from 2009. We studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake.

Methods: Individual data from national registries, including the Norwegian Population Registry, the Norwegian Patient Registry and the Norwegian Immunisation Registry were linked using the unique personal identification number. Yearly incidence rates of CFS/ME for 2009–2014 were calculated among the 824,133 boys and girls, aged 10–17 living in Norway during these 6 years. A total of 176,453 girls born 1997–2002 were eligible for HPV vaccination and included in further analyses. Hazard ratios (HRs) of CFS/ME were estimated using Cox regression. Risk differences (RDs) of vaccine uptake were estimated with binomial regression.

Results: A similar yearly increase in incidence rate of CFS/ME was observed among girls and boys, IRR = 1.15 (95% confidence interval (CI) 1.10–1.19) and 1.15 (95% CI 1.09–1.22), respectively. HPV vaccination was not associated with CFS/ME, HR = 0.86 (95% CI 0.69–1.08) for the entire follow-up period and 0.96 (95% CI 0.64–1.43) for the first two years after vaccination. The risk of CFS/ME increased with increasing number of previous hospital contacts, HR = 5.23 (95% CI 3.66–7.49) for 7 or more contacts as compared to no contacts. Girls with 7 or more hospital contacts were less likely to be vaccinated than girls with no previous hospital contacts, RD = −5.5% (95% CI −6.7% to −4.2%).

Conclusions: No indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.

Source: Berit Feiring, Ida Laake, Inger Johanne Bakken, Margrethe Greve-Isdahl, Vegard Bruun Wyller, Siri E. Haberg, Per Magnus, Lill Trogstad. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine, June 23, 2017. http://www.sciencedirect.com/science/article/pii/S0264410X17308083

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS

Abstract:

BACKGROUND: There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS are unclear, evidence suggests that deterioration in cognitive function is widely prevalent in patients with either condition. Little is known about differing risk factors or exposures, which may lead to severe cognitive or sleep symptoms. This study aims to gauge the extent of cognitive and sleep symptoms in ME/CFS and MS patients participating in the UK ME/CFS Biobank and identify the characteristics of those experiencing severe symptoms.

METHODS: This was a cross-sectional study of 395 UK ME/CFS Biobank participants, recruited from primary care and the community, using similar standardised protocols, and matched by age, sex and geographical area. Data were collected from participants using a standardized written questionnaire at clinical visits. Cognitive symptoms included problems with short-term memory, attention, and executive function. Sleep symptoms included unrefreshing sleep and poor quality or inadequate duration of sleep. All participants reported symptoms based on an ordinal severity scale. Multivariable logistic regression was carried out in the ME/CFS group to investigate socio-demographic factors associated with severe symptoms.

RESULTS: All cognitive and sleep symptoms were more prevalent in the ME/CFS group, with 'trouble concentrating' (98.3%) the most commonly reported symptom. Severe symptoms were also more commonly reported in the ME/CFS group, with 55% reporting 'severe, unrefreshing sleep'. Similarly, in the MS group, the most commonly reported severe symptoms were sleep-related. Logistic regression analysis revealed that ME/CFS patients aged over 50 years were more than three times as likely to experience severe symptoms than those younger than 30 (OR 3.23, p = 0.031). Current smoking was associated with severe symptoms, increasing the risk by approximately three times (OR 2.93, p = 0.003) and those with household incomes of more than £15,000 per year were less likely to experience severe symptoms compared to those earning less than this (OR 0.31, p = 0.017).

CONCLUSIONS:Cognitive and sleep symptoms are more common in ME/CFS patients than in MS patients and healthy controls, providing further support for existing evidence of central nervous system abnormalities in ME/CFS. Our findings suggest that people with ME/CFS who are smokers, or have a low income, are more likely to report severe cognitive and sleep symptoms. Future research should aim to develop strategies to prevent the progression of severe cognitive and sleep symptoms through early interventions that prioritise patients identified as being at highest risk.

Source: Jain V, Arunkumar A, Kingdon C, Lacerda E, Nacul L. Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS. BMC Neurol. 2017 Jun 20;17(1):117. doi: 10.1186/s12883-017-0896-0. https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-017-0896-0 (Full article)

Stressful Events in the Onset of Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a complex and multifactorial disease. Stressful situations experienced could be related to the presentation of the disease. Few studies have determined which factors could trigger CFS. The main objective of this study was to explore the stressful situations which can be associated with CFS presentation.

METHODS: Retrospective observational case-control study with CFS diagnosed patients according to the Fukuda’s criteria. Controls were matched to cases by sex, age and educational level with a 1:1 ratio. Participants aged between 18 and 75 years from the province of Lleida. Information was obtained through personal questionnaires. The measure of association was the odds ratio.

RESULTS: In total, 77 cases and 77 controls were included. Association found between stressful life events and presentation of disease were pregnancy ORa=31.7 (CI95%:2.2-456.7), spousal abuse ORa= 10.2 (CI95%:1.2-88.4) and mobbing ORa=6.9 (CI95%:1.3-36.9), eating disorders=7.5 (CI95%:1.3-42.1), car accident ORa=5.5 (CI95%:1.7-17 9), economic problems ORa=5.1 (CI95%:2.1-12.6) and changes in sleep habits ORa=2.8 (CI95%:1.1-7.5).

CONCLUSIONS: Stressful life events as pregnancy, spousal abuse, mobbing, eating disorders, car accident, economic problems and changes in sleep habits felt by those affected must be taken into consideration when compiling background information related to the onset of Chronic Fatigue Syndrome. Adequate identification of these stressful life events in risk people could contribute to early diagnosis of Chronic Fatigue Syndrome.

 

Source: Gimeno Pi I, Guitard Sein-Echaluce ML, Rosselló Aubach L, Torres Puig-Gros J, Fernández Solà J. Stressful Events in the Onset of Chronic Fatigue Syndrome. Rev Esp Salud Publica. 2016 Aug 18;90:e1-7. [Article in English, Spanish; Abstract available in Spanish from the publisher] https://www.ncbi.nlm.nih.gov/pubmed/27535808

 

Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study

Abstract:

OBJECTIVE: The common concurrence of migraine and chronic fatigue syndrome (CFS) has been reported but whether migraine poses a higher risk of CFS remains unknown. In this retrospective case-control study, we examined the association between the 2 disorders by using a nationwide, population-based database in Taiwan.

METHODS: The data were retrieved and analyzed from the National Health Insurance Research Database (NHIRD) of Taiwan; 6902 newly diagnosed migraine cases from 2006-2010 were identified in a subset of the NHIRD, and 27,608 migraine-free individuals were randomly selected as the comparison cohort. The multivariate Cox proportional hazards regression model was used to investigate the risk of CFS in migraineurs after adjustment for demographic characteristics and comorbidities.

RESULTS: After adjustment for the covariates, the risk of CFS was 1.5-fold higher in the migraine cohort than in the comparison cohort (52.72 vs. 28.85 per 10,000 person-years). Intriguingly, the risk was most prominent in the oldest group (≥ 65 years), with a 2.11-fold increased risk (95% confidence interval 1.31-3.41) of CFS. In addition, the adjusted cumulative incidence of CFS in the follow-up years was higher in the migraine group (log-rank test, P < .0001), and CFS incidence appeared to increase with the frequency of migraine diagnoses.

CONCLUSION: The current study demonstrated an increased risk of CFS in migraineurs. Proposed mechanisms in previous studies such as mitochondrial dysfunction and central sensitization may underlie the shared pathophysiology of these seemingly distinct but potentially overlapping disorders.

Copyright © 2015 Elsevier Inc. All rights reserved.

 

Source: Lau CI, Lin CC, Chen WH, Wang HC, Kao CH. Increased risk of chronic fatigue syndrome in patients with migraine: A retrospective cohort study. J Psychosom Res. 2015 Dec;79(6):514-8. doi: 10.1016/j.jpsychores.2015.10.005. Epub 2015 Oct 20. https://www.ncbi.nlm.nih.gov/pubmed/26505533

 

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination.

METHODS: Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression.

RESULTS: The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period.

CONCLUSIONS: Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.

Copyright © 2015 Elsevier Ltd. All rights reserved.

 

Source: Magnus P, Gunnes N, Tveito K, Bakken IJ, Ghaderi S, Stoltenberg C, Hornig M, Lipkin WI, Trogstad L, Håberg SE. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine. 2015 Nov 17;33(46):6173-7. doi: 10.1016/j.vaccine.2015.10.018. Epub 2015 Oct 17. https://www.ncbi.nlm.nih.gov/pubmed/26475444

 

Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study

Abstract:

Several hypotheses have been proposed to explain the etiopathogenesis of chronic fatigue syndrome (CFS), including immune dysregulation. However, few population-based prospective cohort studies have been conducted on CFS and atopy.

We investigated the relationship between atopy and CFS by using a population-based cohort study. In this prospective, population-based cohort study of the National Health Insurance Research Database, we identified 42,558 patients with atopy and 170,232 patients without atopy from 2005 to 2007 with follow-up to 2011. The incidence rates and risks for CFS were estimated using Cox proportion hazards regression.

The overall incidence rate of CFS was higher in the atopy cohort compared with the nonatopy cohort (1.37 versus 0.87 per 1000 person-year), with an adjusted hazard ratio of 1.48 (95% confidence interval 1.30-1.69). The risk of CFS in the atopy cohort increased 1.47- to 1.50-fold for each nonexisting comorbidity. Patients with numerous atopic symptoms exhibited a biological gradient of increasing risk for CFS, and the risk changed significantly after adjustment for age, sex, and comorbidities, increasing from 1.46- to 2.59-fold.

We revealed that atopy is associated with CFS, particularly in patients with numerous atopic syndromes. The actual mechanism for CFS development in patients with atopy remains unclear and requires further investigation. We recommend researching the subsequent fatigue symptom in patients with atopy, particularly those with multiple atopic syndromes.

 

Source: Yang TY, Kuo HT, Chen HJ, Chen CS, Lin WM, Tsai SY, Kuo CN, Kao CH. Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based Study. Medicine (Baltimore). 2015 Jul;94(29):e1211. doi: 10.1097/MD.0000000000001211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603016/ (Full article)

 

Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances

Abstract:

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5 kb (CCTTT) n as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects.

Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5 kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5 kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI.

 

Source: De Luca C, Gugliandolo A, Calabrò C, Currò M, Ientile R, Raskovic D, Korkina L, Caccamo D. Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances. Mediators Inflamm. 2015;2015:245308. doi: 10.1155/2015/245308. Epub 2015 Mar 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387900/ (Full article)

 

An investigation of symptoms predating CFS onset

Abstract:

The Fukuda et al. (1994) criteria for chronic fatigue syndrome (CFS) specifies that a symptom can only be included within a diagnosis if it is experienced concurrently or following the onset of fatigue. In order to investigate this issue, participants provided information on persisting symptoms (lasting greater than six months) and whether those symptoms occurred prior to, concurrently, or following the onset of their fatigue.

More symptoms were experienced after the fatigue onset than prior to the fatigue onset; however, a considerable number of participants reported experiencing persisting symptoms prior to the onset of CFS. Particularly, rates of hay fever and asthma were higher prior to the illness. Investigating symptoms prior to the onset of the illness might provide investigators with ways to better understand the etiology of this illness.

 

Source: Evans M, Barry M, Im Y, Brown A, Jason LA. An investigation of symptoms predating CFS onset. J Prev Interv Community. 2015;43(1):54-61. doi: 10.1080/10852352.2014.973240. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830334/ (Full article)

 

Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis

Abstract:

OBJECTIVE: To examine the effect of early clinical and demographic factors on occupational outcome, return to work or awarded permanent disability pension in young patients with chronic fatigue syndrome (CFS).

DESIGN: Longitudinal cohort study.

INTERVENTION: A written self-management programme including a description of active coping strategies for daily life was provided.

SETTING, PARTICIPANTS: Patients with CFS after mononucleosis were evaluated at Department of Neurology, Haukeland University Hospital during 1996-2006 (contact 1). In 2009 self-report questionnaires were sent to all patients (contact 2).

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measure was employment status at contact 2. Secondary measures included clinical symptoms, and Fatigue Severity Scale (FSS) scores on both contacts, and Work and Social Adjustment Scale (WSAS) at contact 2.

RESULTS: Of 111 patients at contact 1, 92 (83%) patients returned the questionnaire at contact 2. Mean disease duration at contact 1 was 4.7 years and at contact 2 11.4 years. At contact 1, 9 (10%) were part-time or full-time employed. At contact 2, 49 (55%) were part-time or full-time employed. Logical regression analysis showed that FSS≥5 at contact 2 was associated with depression, arthralgia and long disease duration (all at contact 1).

CONCLUSIONS: About half of younger patients with CFS with long-term incapacity for work experienced marked improvement including full-time or part-time employment showing better outcomes than expected. Risk factors for transition to permanent disability were depression, arthralgia and disease duration.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

 

Source: Nyland M, Naess H, Birkeland JS, Nyland H. Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis. BMJ Open. 2014 Nov 26;4(11):e005798. doi: 10.1136/bmjopen-2014-005798. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248085/ (Full article)

 

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA)

Abstract:

The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination.

Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients.

The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria.

This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk factors. ASIA criteria were fulfilled in all patients eluding the plausible link between ASIA and CFS/FM.

 

Source: Agmon-Levin N, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA). Immunol Res. 2014 Dec;60(2-3):376-83. doi: 10.1007/s12026-014-8604-2. https://www.ncbi.nlm.nih.gov/pubmed/25427994