"Medical history was associated with increased risk of CFS/ME"

The paper by Berit Feiring and colleagues [1] (open-access) is the source blogging material today covering an area that I was previously unaware of: "to study the association between HPV [human papillomavirus] vaccination and risk of CFS/ME [chronic fatigue syndrome/myalgic encephalomyelitis] among girls eligible for HPV vaccination in the national immunisation programme in Norway."

A quick trawl of PubMed to look-see whether there was any previous peer-reviewed science in this area revealed some inklings about a possible *association* between use of the HPV vaccine and some symptoms that may follow a diagnosis of ME/CFS [2] but not much to say that risk of an actual diagnosis of CFS/ME was significantly heightened [3] following HPV immunisation. On the topic of postural tachycardia syndrome (PoTS) and HPV vaccination, I had been aware of some, limited peer-reviewed discussions (see here).

As it happens, Feiring et al did not observe any population-wide links between HPV vaccination and increased risk of CFS/ME based on their analysis of "176,453 girls born 1997–2002 [who] were eligible for HPV vaccination." They tempered their conclusions slightly given that they "did not have access to patient records for verification of the CFS/ME diagnoses" derived from the Norwegian Patient Registry (NPR) but for all intents and purposes, their data is compelling based on sample size and how well Scandinavian countries tend to treat their population data.

A few other, rather interesting aspects to the Feiring data are also apparent: "we observed an increase in the incidence of CFS/ME among adolescents aged 10–17 in Norway, during 2009–2014" and: "Medical history was associated with both increased risk of CFS/ME and lower uptake of HPV vaccine." The idea that numbers of cases of CFS/ME is on the up in Norway is an interesting one and perhaps contrasts with other data from here in Blighty for example (see here) bearing in mind the age groups analysed. I was however specifically drawn to the idea that: "The risk of CFS/ME increased with increasing number of previous hospital contacts."

Looking at hazard ratios (HRs) for a diagnosis of CFS/ME based on how many times a girl had had hospital contact, a rather interesting dose-dependent pattern emerged. So, examining the entire follow-up period, the (adjusted) HR for CFS/ME diagnosis for those with only one hospital contact was 1.64 (1.22–2.19). For those with seven or more hospital contacts, the HR jumped to 5.23 (3.66–7.49). Also potentially important were the possible reason(s) for hospital contact and risk of CFS/ME: "According to ICD-10 diagnoses, the highest risk of CFS/ME was found among girls with diagnoses in chapters I00-I99 (Diseases of the circulatory system)..., A00-B99 (Certain infectious and parasitic diseases)... and R00-R99 (Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified)."

Other discussions on data also from Norway (indeed, from some of the same authors) has talked about medical history around CFS/ME and what conditions seem to be 'over-represented' (see here). On that research occasion [3] they concluded that: "Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway." Said previous findings are not so dissimilar from the current ones reported by Feiring and colleagues.

Insofar as the next steps on from the Feiring data, well one might - assuming independent replication and the like - see a way forward where a potential early warning system for possible CFS/ME screening might be put in place on the basis of patterns of hospital visits and the types/patterns of diagnosis that are given. I appreciate that there is quite a lot of heterogeneity when it comes to CFS/ME (possibly even another label ripe for pluralisation or spectrum-ing?) so I don't want to get too ahead of myself here but there is potential. Whilst HPV vaccination did not seem to be connected to later CFS/ME diagnosis in the Feiring cohort, the question about what factors could be driving the increase in cases remains open: "The reasons for the increase in CFS/ME in Norway are unknown."

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[1] Feiring B. et al. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine. 2017. June 23.

[2] Brinth LS. et al. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus. Vaccine. 2015 May 21;33(22):2602-5.

[3] Donegan K. et al. Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK. Vaccine. 2013 Oct 9;31(43):4961-7.

[4] Bakken IJ. et al. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway. BMC Family Practice. 2016; 17: 128.

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