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environmental factors on sporadic Creutzfeldt-Jakob disease ?

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    environmental factors on sporadic Creutzfeldt-Jakob disease ?

    Eur J Epidemiol. 2023; 38(7): 757–764. Published online 2023 May 16. doi: 10.1007/s10654-023-01004-5 PMCID: PMC10276107PMID: 37191829

    Received: 31 January 2023 / Accepted: 6 April 2023 / Published online: 16 May 2023 © The Author(s) 2023

    The role of environmental factors on sporadic Creutzfeldt-Jakob disease mortality: evidence from an age-period-cohort analysis

    Angéline Denouel1

    · Jean-Philippe Brandel1,2

    · Danielle Seilhean1 · Jean-Louis Laplanche3,4

    · Alexis Elbaz5

    · Stéphane Haik1,2

    Abstract

    Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of prion diseases. The causes of sCJD are still unknown and exogenous factors may play a role. Worldwide, the number of patients with sCJD has progressively increased over time. This increase can be partly explained by increasing life expectancy and better case ascertainment, but a true increase in the number of sCJD cases cannot be excluded. We estimated mortality rates from sCJD in France (1992–2016) and studied variation in mortality rates by age, period, and time.

    We included all cases aged 45–89 years old who died with a probable/definite sCJD diagnosis based on the French national surveillance network. We used age-period-cohort (APC) Poisson regression models to study variation in mortality rates by sex, age, period, and time.

    A total of 2475 sCJD cases aged 45–89 years were included. Mortality rates increased with age, reached a peak between 75 and 79 years, and decreased thereafter. Mortality rates were higher in women than men at younger ages and lower at older ages. The full APC model with a sex×age interaction provided the best fit to the data, thus in favour of sex, age, period, and cohort effects on mortality rates. In particular, mortality rates increased progressively with successive birth cohorts.

    Based on 25 years of active surveillance in France, we show evidence for sex, age, period, and cohort effects on sCJD mortality. The identification of cohort effects suggests that environmental exposures may play a role in sCJD etiology.

    Keywords Age-period-cohort model · Prion · Temporal trend · Sporadic Creutzfeldt-Jakob disease

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    Worldwide, the number of patients with sCJD appears to have progressively increased over time [13]. This increase can be partly explained by increasing life expectancy as well as by better case ascertainment due to improved diagnostic tests and awareness of the disease among clinicians. Indeed, a relationship between surveillance intensity and sCJD incidence has been shown [14]. It cannot be excluded, however, that an actual increase of sCJD cases has occurred, and this hypothesis can be examined using age-period-cohort (APC) models.

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    In this paper, we estimated mortality rates from sCJD in France over a 25-year period (1992–2016) based on data from the French national surveillance network.

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    The overall sCJD mortality rate was 4.58 per 1,000,000 person-years (95% CI=4.39–4.78) (Table S1).

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    Besides risk factors explored in case-control studies, the possibility of zoonotic risk factors remains a possibility that could account for an exogenous origin in some sCJD cases. Research on atypical forms of BSE (L-BSE, H-BSE) has revealed molecular similarities between the L-BSE strain and molecular subtypes of human sCJD, in particular the MV2 subtype [39]. Furthermore, L-BSE has been experimentally transmitted to non-human primates as efficiently as classical BSE responsible for vCJD in humans, and could be even more virulent [40–42]. The zoonotic risk associated with natural sheep scrapie has also been recently updated with the demonstration of an intracerebral transmission of scrapie to mice expressing the human prion protein during serial passages, as well as transmission of scrapie to primates. These observations highlight the possibility of a causal link between exposure to sheep scrapie and sCJD in some cases [43, 44]. A large increase in animal product consumption and the generalization of mechanically separated meat in developed countries over the last century may have contribute to increase the zoonotic prion pressure [45]. It would be of interest to observe the effect of safety measures implemented since the “mad cow crisis” to avoid population prion exposure on sCJD mortality in the next decades.

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    SUNDAY, NOVEMBER 26, 2023

    The role of environmental factors on sporadic Creutzfeldt-Jakob disease mortality: evidence from an age-period-cohort analysis

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