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

Magnus, Per; Gunnes, Nina; Tveito, Kari; Bakken, Inger Johanne; Ghaderi, Sara; Stoltenberg, Camilla; Hornig, Mady; Lipkin, W. Ian; Trogstad, Lill; Håberg, Siri E.

doi:10.1016/j.vaccine.2015.10.018

Cited by 66 publications

(62 citation statements)

References 37 publications

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“…Their estimated incidence rate among women of age 10–14 years was approximately 60 compared to 0.53 among 10–15 years old girls in our study [24] . CFS/SEID has been associated with preceding infections [26] and vaccines, such as the pandemic influenza [26] and the HPV vaccination, but the association between the CFS/SEID with HPV vaccines has not been confirmed [27] .…”

Section: Discussionmentioning

confidence: 99%

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002–2012

Skufca

Ollgren

Ruokokoski

et al. 2017

Papillomavirus Research

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BackgroundIn Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11–12 years with a catchup for girls 13–15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations.MethodsFirst diagnosis of CFS/SEID, GBS and POTS in girls aged 11–15 years were obtained from the National Hospital Discharge Register during 2002–2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI).ResultsIn total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27–1.01) for CFS/SEID, 1.11 (95% CI; 0.71–1.74) for GBS and 4.21 (95%CI; 3.34–5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0–70.3: p=0.029) and POTS (16.5% (95% CI; 7.8–25.9: p<0.05), but not in GBS (5.4% (95% CI; −8.4–21.3: p=0.460).ConclusionsOur findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities.

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Section: Discussionmentioning

confidence: 99%

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002–2012

Skufca

Ollgren

Ruokokoski

et al. 2017

Papillomavirus Research

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“…The vaccination period overlapped with the peak period of the pandemic wave, but a small number of vaccines were also distributed after the peak pandemic wave. [24,25]…”

Section: Exposure Information (Influenza Pandemic Vaccine)mentioning

confidence: 99%

Influenza vaccination and risk for cardiovascular events: a nationwide self-controlled case series study

Sen

Bakken

Govatsmark

et al. 2021

BMC Cardiovasc Disord

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Background US and European guidelines diverge on whether to vaccinate adults who are not at high risk for cardiovascular events against influenza. Here, we investigated the associations between influenza vaccination and risk for acute myocardial infarction, stroke and pulmonary embolism during the 2009 pandemic in Norway, when vaccination was recommended to all adults. Methods Using national registers, we studied all vaccinated Norwegian individuals who suffered AMI, stroke, or pulmonary embolism from May 1, 2009 through September 30, 2010. We defined higher-risk individuals as those using anti-diabetic, anti-obesity, anti-thrombotic, pulmonary or cardiovascular medications (i.e. individuals to whom vaccination was routinely recommended); all other individuals were regarded as having lower-risk. We estimated incidence rate ratios with 95% CI using conditional Poisson regression in the pre-defined risk periods up to 180 days following vaccination compared to an unexposed time-period, with adjustment for season or daily temperature. Results Overall, we observed lower risk for cardiovascular events following influenza vaccination. When stratified by baseline risk, we observed lower risk across all three outcomes in association with vaccination among higher-risk individuals. In this subgroup, relative risks were 0.72 (0.59–0.88) for AMI, 0.77 (0.59–0.99) for stroke, and 0.73 (0.45–1.19) for pulmonary embolism in the period 1–14 days following vaccination when compared to the background period. These associations remained essentially the same up to 180 days after vaccination. In contrast, the corresponding relative risks among subjects not using medications were 4.19 (2.69–6.52), 1.73 (0.91–3.31) and 2.35 (0.78–7.06). Conclusion In this nationwide study, influenza vaccination was associated with overall cardiovascular benefit. This benefit was concentrated among those at higher cardiovascular risk as defined by medication use. In contrast, our results demonstrate no comparable inverse association with thrombosis-related cardiovascular events following vaccination among those free of cardiovascular medications at baseline. These results may inform the risk–benefit balance for universal influenza vaccination.

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“…Others associated infection and vaccination with later CFS onset ( 19 , 20 ). Recently, pandemic influenza A (H1N1) infection was related with a more than two-fold increased CFS risk ( 21 ). A state of low-grade inflammation ( 22 ), as derived from elevated (hs)CRP ( 23 ), interleukin (IL)-6 ( 24 ), IL-1 and tumor necrosis factor (TNF)-α ( 22 ), and/or nuclear factor kappa B (NFκB) ( 25 ) has, however, not consistently been found ( 26 – 28 ), possibly because of differences in experimental approaches and patient conditions ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

Ruiz-Núñez

Tarasse

Vogelaar³

et al. 2018

Front. Endocrinol.

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Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21–69 years, 21 males) and 99 age- and sex-matched controls (19–65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation. Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%). FT3 below the reference range, consistent with the “low T3 syndrome,” was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00–6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of “non-thyroidal illness syndrome” and “low T3 syndrome” experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated.

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

Cited by 66 publications

References 37 publications

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002–2012

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002–2012

Influenza vaccination and risk for cardiovascular events: a nationwide self-controlled case series study

Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

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