Ten-Week Follow-Up of Monkeypox Case-Patient, Sweden, 2022.

A previously healthy male patient had detectable monkeypox virus DNA in saliva 76 days after laboratory confirmation of infection. A comprehensive characterization of viral kinetics and a detailed follow-up indicated a declining risk for transmission during the weeks after monkeypox symptoms appeared.

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue.

BACKGROUND: Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time. RESULTS: No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffected twins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetected hepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation. CONCLUSIONS: Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.

CNS infections, sepsis and risk of Parkinson's disease.

BACKGROUND: Neuroinflammation may play an important role in the aetiology of Parkinson's disease (PD); however, little is known about infections in relation to future PD risk. METHODS: We conducted a register-based nested case-control study in Sweden to examine infections of the central nervous system (CNS) and sepsis in relation to PD with 18,648 patients and 93,240 matched controls. We defined the index date as the date of first recorded PD diagnosis in the Swedish Patient Register. RESULTS: Overall, PD patients were more likely to have a previous hospitalization for CNS infections [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] or sepsis (OR = 1.6, 95% CI: 1.4-1.7) than controls, largely due to hospitalizations in the year before PD identification (CNS infections: OR = 3.0, 95% CI: 1.6-5.7; sepsis: OR = 3.5, 95% CI: 3.0-4.0). However, we found that subjects with multiple CNS infections at least 5 years before the index date had higher PD occurrence than those without CNS infections (OR = 3.3, 95% CI: 1.4-8.2), whereas the corresponding OR for sepsis was 1.4 (95% CI: 0.8-2.4). After the index date, PD patients were more likely to be hospitalized for CNS infections [hazard ratio (HR) =1.8, 95% CI: 1.2-2.7] or sepsis (HR = 2.2, 95% CI: 2.1-2.4) than controls. CONCLUSIONS: This study provides preliminary evidence for an association between CNS infections, but not sepsis, and a higher future risk of PD. It also shows that PD patients were more prone to CNS infections and sepsis than controls.

Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker.

BACKGROUND: Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. METHODS: Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. FINDINGS: There were no significant differences in gene expression for any transcript. CONCLUSIONS: Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias.

The epidemiology of chronic fatigue in the Swedish Twin Registry.

BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity. METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS. FINDINGS: The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender. INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.

Twin analyses of chronic fatigue in a Swedish national sample.

BACKGROUND: Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits. METHOD: The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42-64 years, 75.68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness. RESULTS: Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects. CONCLUSIONS: Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.

Chronic fatigue in a population sample: definitions and heterogeneity.

BACKGROUND: Numerous nosological decisions are made when moving from the common human symptom of unusual fatigue to the rare chronic fatigue syndrome (CFS). These decisions have infrequently been subjected to rigorous evaluation. METHOD: We obtained telephone interview data on fatiguing symptoms from 31406 individuals twins in the Swedish Twin Registry aged 42-64 years; 5330 subjects who endorsed fatigue and possessed no exclusionary condition formed the analytic group. We evaluated the definition and classification of CFS-like illness using graphical methods, regression models, and latent class analysis. RESULTS: Our results raise fundamental questions about the 1994 Centers for Disease Control criteria as (1) there was no empirical support for the requirement of four of eight cardinal CFS symptoms; (2) these eight symptoms were not equivalent in their capacity to predict fatigue; and (3) no combination of symptoms was markedly more heritable. Critically, latent class analysis identified a syndrome strongly resembling CFS-like illness. CONCLUSIONS: Our data are consistent with the 'existence' of CFS-like illness although the dominant nosological approach captures population-level variation poorly. We suggest that studying a more parsimonious case definition - impairing chronic fatigue not due to a known cause - would represent a way forward.