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

Experiences of general practitioner continuity among women with chronic fatigue syndrome/myalgic encephalomyelitis: a cross-sectional study

Abstract:

BACKGROUND: Continuity of care is important for patients with chronic illness in need of coordinated healthcare services from multiple providers. Little is known about how patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience continuity of GP care. This study explores how women with CFS/ME experience GP care across the three dimensions of continuity: informational, management, and relational continuity.

METHODS: This cross-sectional study uses questionnaire data collected from members of The Norwegian ME Association. Descriptive statistics and logistic regressions were used to estimate experiences of continuity, and associations with age, education, self-rated degree of CFS/ME, duration of the GP relation (GP duration), and number of GP visits for CFS/ME-related issues during the previous year (GP frequency).

RESULTS: Almost two-thirds of participants reported positive experiences across all three dimensions of GP continuity of care; 64.4% for informational, 64.1% for management, and 77.2% for relational continuity. Lower educational attainment was associated with more negative experiences of informational continuity (primary school only compared to university educated: odds ratio [OR] 0.12, confidence interval [CI] 0.03-0.49, p = 0.003). Compared to participants aged 40-59 years, those aged 60+ years were significantly less likely to have experienced poor (negative) management continuity (OR 0.25, CI 0.09-0.76, p = 0.014). A GP relationship of three or more years was associated with positive experiences of relational continuity (OR 2.32, CI 1.09-4.95, p = 0.030). Compared to those with moderate CFS/ME, those who graded their CFS/ME as severe or very severe were significantly more likely to have negative experiences of relational continuity (OR 0.38, CI 0.14-0.99, p = 0.047).

CONCLUSIONS: A large proportion of participants experienced all three aspects of continuity of GP care (especially the relational dimension) positively. Informational and management continuity scores were moderately lower. Our results suggest greater emphasis on information giving, feedback, and better coordination of care to be good strategies for practice improvement for this patient group.

 

Source: Hansen AH, Lian OS. Experiences of general practitioner continuity among women with chronic fatigue syndrome/myalgic encephalomyelitis: a cross-sectional study. BMC Health Serv Res. 2016 Nov 14;16(1):650. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109710/ (Full article)

 

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups.

METHODS: All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization.

RESULTS: Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %.

CONCLUSIONS: This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

 

Source: Bakken IJ, Tveito K, Aaberg KM, Ghaderi S, Gunnes N, Trogstad L, Magnus P, Stoltenberg C, Håberg SE. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway. BMC Fam Pract. 2016 Sep 2;17(1):128. doi: 10.1186/s12875-016-0527-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010760/ (Full article)

 

How do women with chronic fatigue syndrome/myalgic encephalomyelitis rate quality and coordination of healthcare services? A cross-sectional study

Abstract:

OBJECTIVE: To test the association between self-rated health and self-rated degree of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and CFS/ME patients’ assessment of quality of primary care, specialist care and coordination of care.

DESIGN: Cross-sectional study.

SETTING: Self-reported questionnaire data from women members of The Norwegian ME Association obtained in 2013.

PARTICIPANTS: 431 women with CFS/ME aged 16-73 years.

MAIN OUTCOME MEASURE: The participants’ assessment of quality in primary care, specialist care and in coordination of care (good/very good or poor/very poor). Main explanatory variables: self-rated health and self-rated degree of CFS/ME.

RESULTS: Quality of care was rated poor by 60.6% in primary care, by 47.7% in specialist care, and by 71.2% regarding coordination of care. Poorer self-rated health increased the probability of rating quality in primary care poor, particularly among women 40 years and over (OR 2.38, 95% CI 1.63 to 3.49), women with university education (OR 2.57, CI 1.68 to 3.94), and owing to less frequent general practitioner (GP) visits (OR 2.46, CI 1.60 to 3.78). Poorer self-rated health increased the probability of rating quality poor in specialist care (OR 1.38, CI 1.05 to 1.82), but not in coordination of care. A more severe CFS/ME was associated with a higher probability of rating quality in primary care poor (OR 0.61, CI 0.38 to 0.93). Frequent visitors and those with a long GP relationship were less likely to report primary care quality as poor.

CONCLUSIONS: A large proportion of women with CFS/ME rated quality of care poor/very poor in primary care, specialist care and in coordination of care. The dissatisfaction was higher for primary care than for specialist care. Overall, poorer self-rated health and a more severe CFS/ME were associated with lower quality scores in primary and specialist care, but not in coordination of care. Healthcare services, as assessed by women with CFS/ME, do have a large potential for improvement.

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

 

Source: Hansen AH, Lian OS. How do women with chronic fatigue syndrome/myalgic encephalomyelitis rate quality and coordination of healthcare services? A cross-sectional study. BMJ Open. 2016 Apr 4;6(4):e010277. doi: 10.1136/bmjopen-2015-010277. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823449/ (Full article)

 

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

 

Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012

Abstract:

BACKGROUND: The aim of the current study was to estimate sex- and age-specific incidence rates of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) using population-based registry data. CFS/ME is a debilitating condition with large impact on patients and their families. The etiology is unknown, and the distribution of the disease in the general population has not been well described.

METHODS: Cases of CFS/ME were identified in the Norwegian Patient Register (NPR) for the years 2008 to 2012. The NPR is nationwide and contains diagnoses assigned by specialist health care services (hospitals and outpatient clinics). We estimated sex- and age-specific incidence rates by dividing the number of new cases of CFS/ME in each category by the number of person years at risk. Incidence rate ratios were estimated by Poisson regression with sex, age categories, and year of diagnosis as covariates.

RESULTS: A total of 5,809 patients were registered with CFS/ME during 2008 to 2012. The overall incidence rate was 25.8 per 100,000 person years (95% confidence interval (CI): 25.2 to 26.5). The female to male incidence rate ratio of CFS/ME was 3.2 (95% CI: 3.0 to 3.4). The incidence rate varied strongly with age for both sexes, with a first peak in the age group 10 to 19 years and a second peak in the age group 30 to 39 years.

CONCLUSIONS: Early etiological clues can sometimes be gained from examination of disease patterns. The strong female preponderance and the two age peaks suggest that sex- and age-specific factors may modulate the risk of CFS/ME.

 

Source: Bakken IJ, Tveito K, Gunnes N, Ghaderi S, Stoltenberg C, Trogstad L, Håberg SE, Magnus P. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012. BMC Med. 2014 Oct 1;12:167. doi: 10.1186/s12916-014-0167-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189623/ (full article)

Comment:

CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation

Abstract:

Aim. To estimate number of children being diagnosed with chronic fatigue syndrome (CFS). Methods. For a period of 10 years (2002-2011) data from children being referred for fatigue symptoms were collected retrospectively.

Results. Thirty-seven children were referred. Four were excluded due to incorrect coding. Six (18%) patients received other diagnoses at the end of evaluation time. Of the 27 who received the diagnosis G93.3, four had a previous chronic illness, while 23 patients were previously healthy. All patients reported onset of fatigue symptom in relation to an infection, and all tested positive for IgG to either Epstein-Barr virus, cytomegalovirus or borrelia, indicating previous infection. There were 16 (59%) boys among the 27 patients. The mean age at the debut of fatigue symptoms was 141 months (SD 30) for boys and 136 months (SD 31) for girls, respectively. Being underweight, defined as BMI < 17.5, was found in 12 (44%) patients.

Conclusion. An increasing number of children and adolescents are evaluated for CFS. The clinical assessment of children and adolescents with possible CFS need systematically evaluation. Nutritional status, possible eating disorder, and psychosocial issues need to be addressed and evaluated carefully. A multidisciplinary approach is essential when assessing CFS in children and adolescents. There is a need for European guidelines.

 

Source: Elgen I, Hikmat O, Aspevik TN, Hagen EM. CFS in Children and Adolescent: Ten Years of Retrospective Clinical Evaluation. Int J Pediatr. 2013;2013:270373. doi: 10.1155/2013/270373. Epub 2013 Jun 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697308/ (Full article)

 

Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course

Abstract:

BACKGROUND: A high prevalence of chronic fatigue has previously been reported following giardiasis after a large waterborne outbreak in Bergen, Norway in 2004. The aim of this study was to describe and evaluate differential diagnoses and natural course of fatigue five years after giardiasis among patients who reported chronic fatigue three years after the infection.

METHODS: Patients who three years after Giardia infection met Chalder’s criteria for chronic fatigue (n=347) in a questionnaire study among all patients who had laboratory confirmed giardiasis during the Bergen outbreak (n=1252) were invited to participate in this study five years after the infection (n=253). Structured interviews and clinical examination were performed by specialists in psychiatry, neurology and internal medicine/infectious diseases. Fukuda et al’s 1994 criteria were used to diagnose chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF). Self-reported fatigue recorded with Chalder Fatigue Questionnaire three and five years after infection were compared.

RESULTS: 53 patients were included. CFS was diagnosed in 41.5% (22/53) and ICF in 13.2% (7/53). Chronic fatigue caused by other aetiology was diagnosed in 24.5% (13/53); five of these patients had sleep apnoea/hypopnoea syndrome, six had depression and five anxiety disorder, and among these two had more than one diagnosis. Fatigue had resolved in 20.8% (11/53). Self-reported fatigue score in the cohort was significantly reduced at five years compared to three years (p<0.001).

CONCLUSION: The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection. Obstructive sleep apnoea/hypopnoea syndrome, depression and anxiety were important differential diagnoses, or possibly comorbidities, to post-infectious fatigue in this study. Improvement of chronic fatigue in the period from three to five years after giardiasis was found.

 

Source: Mørch K, Hanevik K, Rivenes AC, Bødtker JE, Næss H, Stubhaug B, Wensaas KA, Rortveit G, Eide GE, Hausken T, Langeland N. Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course. BMC Gastroenterol. 2013 Feb 12;13:28. doi: 10.1186/1471-230X-13-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598369/ (Full article)

 

Comparison of chronic fatigue syndrome/myalgic encephalopathy with other disorders: an observational study

Abstract:

OBJECTIVES: To examine the level of activity in online discussion forums for chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) compared to other disorders. We hypothesized the level of activity to be higher in CFS/ME online discussion forums.

DESIGN: Observational study

SETTING: Norway, which has more than 80% household coverage in internet access, September 2009

PARTICIPANTS: Twelve Norwegian disorder-related online discussion forums

MAIN OUTCOME MEASURES: Number of registered users and number of posted messages on each discussion forum

RESULTS: Two forums were targeted towards individuals with CFS/ME. These forums had the highest number of registered users per estimated 1,000 cases in the population (50.5 per 1,000 and 29.7 per 1,000), followed by a site for drug dependency (5.4 per 1,000). Counting the number of posted messages per 1,000 cases gave similar indications of high online activity in the CFS/ME discussion forums.

CONCLUSIONS: CFS/ME online forums had more than ten times the relative activity of any other disorder or condition related forum. This high level of activity may have multiple explanations. Individuals suffering from a stigmatized condition of unknown aetiology may use the internet to look for explanations of symptoms or to seek out alternative treatments. Internet forum activity may also be reinforced by the creation of in-group identity and pre-morbid personality traits. More knowledge on the type and quality of information provided in online forums is urgently needed.

 

Source: Knudsen A, Lervik L, Harvey S, Løvvik C, Omenås A, Mykletun A. Comparison of chronic fatigue syndrome/myalgic encephalopathy with other disorders: an observational study. JRSM Short Rep. 2012 May;3(5):32. doi: 10.1258/shorts.2011.011167. Epub 2012 May 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365790/ (Full article)

 

Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms

Abstract:

BACKGROUND: The pathophysiology of chronic fatigue syndrome (CFS) in adolescents is unknown, and the clinical course and prognosis is still questioned. Recent research indicates that abnormalities of autonomic cardiovascular control may play an important role. The aim of this research project was to perform a follow-up study of adolescents with chronic fatigue syndrome, focusing on clinical symptoms and autonomic cardiovascular control.

METHODS: 47 adolescents (12-18 years old) with CFS were recruited from the outpatient clinic at the Department of Pediatrics, Oslo University Hospital. In a primary visit and a follow-up visit (3-17 months later), we evaluated: a) a wide range of complaints and symptoms and b) cardiovascular variables at baseline and during a 20° head-up tilt-test (HUT).

RESULTS: At the second visit, patients reported significant improvement regarding functional impairments, fatigue severity, muscular pain, concentration problems, post-exertional malaise and the problem of non-relieving rest. Also, at the second visit, baseline heart rate (HR), blood pressure, total peripheral resistance index (TPRI) and LF/HF (low-frequency:high-frequency heart rate variability ratio, an index of sinus node sympathovagal balance derived from spectral analyses of heart rate) were significant lower, and the increases in HR, mean blood pressure (MBP), diastolic blood pressure (DBP) and TPRI during tilt were significantly less pronounced as compared to the first visit. There was a significant correlation between changes in autonomic symptom score, fatigue severity score and functional impairment score from the first to the second visit.

CONCLUSIONS: The majority of adolescents with CFS experienced an improvement over time in functional impairment, self-reported fatigue and additional symptoms, and a concurrent improvement of autonomic cardiovascular control. A possible connection between clinical symptoms and abnormal autonomic control in CFS might represent a focus for further research.

 

Source: Sulheim D, Hurum H, Helland IB, Thaulow E, Wyller VB. Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms. Biopsychosoc Med. 2012 Mar 21;6:10. doi: 10.1186/1751-0759-6-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337799/ (Full article)