Our weekly summary of research paper abstracts that have not already appeared on the MEA website.
Note from Dr Charles Shepherd:
The abstracts from the papers covering Gulf War Syndrome and Hepatitis C infection are included in view of the overlap between these two conditions and ME/CFS.
J Virol. 2011 Oct;85(20):10909-13. Epub 2011 Aug 17.
Phylogenetic analysis of murine leukemia virus sequences from longitudinally sampled chronic fatigue syndrome patients suggests PCR contamination rather than viral evolution.
Katzourakis A, Hué S, Kellam P, Towers GJ.
Department of Zoology, University of Oxford, South Parks Road, Oxford OX13PS, United Kingdom.
Xenotropic murine leukemia virus (MLV)-related virus (XMRV) has been amplified from human prostate cancer and chronic fatigue syndrome (CFS) patient samples. Other studies failed to replicate these findings and suggested PCR contamination with a prostate cancer cell line, 22Rv1, as a likely source. MLV-like sequences have also been detected in CFS patients in longitudinal samples 15 years apart. Here, we tested whether sequence data from these samples are consistent with viral evolution. Our phylogenetic analyses strongly reject a model of within-patient evolution and demonstrate that the sequences from the first and second time points represent distinct endogenous murine retroviruses, suggesting contamination.
Psychiatry Res. 2011 Sep 30;189(2):318-20. Epub 2011 Aug 15.
Cumulative life stress in chronic fatigue syndrome.
Nater UM, Maloney E, Heim C, Reeves WC.
National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control & Prevention, Atlanta, GA, USA.
We studied the impact of cumulative life stress on CFS in a population-based study. We found that exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress. Also, post-traumatic stress disorder was significantly more common in people with CFS. These results not only corroborate findings from other studies but, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias, and c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. Stress may be an important factor in the pathophysiology of CFS. Consequently, future studies should provide a more detailed understanding of the processes that lead from stress to CFS using longitudinal designs.
Published by Elsevier Ireland Ltd.
Am J Epidemiol. 2011 Oct 1;174(7):761-8. Epub 2011 Jul 27.
Longitudinal health study of US 1991 Gulf War veterans: changes in health status at 10-year follow-up.
Li B, Mahan CM, Kang HK, Eisen SA, Engel CC.
Institute for Clinical Research, Inc., Washington DC, USA.
The authors assessed changes in the health status of US 1991 Gulf War-era veterans from a 1995 baseline survey to a 2005 follow-up survey, using repeated measurement data from 5,469 deployed Gulf War veterans and 3,353 non-deployed Gulf War-era veterans who participated in both surveys. Prevalence differences in health status between the 2 surveys were estimated for adverse health indices and chronic diseases for each veteran group. Persistence risk ratios and incidence risk ratios were calculated after adjustment for demographic and military service characteristics through Mantel-Haenszel stratified analysis. At 10-year follow-up, deployed veterans were more likely to report persistent poor health, as measured by the health indices (functional impairment, limitation of activities, repeated clinic visits, recurrent hospitalizations, perception of health as fair or poor, chronic fatigue syndrome-like illness, and posttraumatic stress disorder), than nondeployed veterans. Additionally, deployed veterans were more likely to experience new onset of adverse health (as measured by the indices) and certain chronic diseases than were nondeployed veterans. During the 10-year period from 1995 to 2005, the health of deployed veterans worsened in comparison with nondeployed veterans because of a higher rate of new onset of various health outcomes and greater persistence of previously reported adverse health on the indices.
BMC Med. 2011 Jul 28;9:91.
Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care.
Nacul LC, Lacerda EM, Pheby D, Campion P, Molokhia M, Fayyaz S, Leite JC, Poland F, Howe A, Drachler ML.
Department of Nutrition and Public Health Interventions Research, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Luis.Nacul@lshtm.ac.uk
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or chronic fatigue syndrome (CFS) has been used to name a range of chronic conditions characterized by extreme fatigue and other disabling symptoms. Attempts to estimate the burden of disease have been limited by selection bias, and by lack of diagnostic biomarkers and of agreed reproducible case definitions. We estimated the prevalence and incidence of ME/CFS in three regions in England, and discussed the implications of frequency statistics and the use of different case definitions for health and social care planning and for research.
We compared the clinical presentation, prevalence and incidence of ME/CFS based on a sample of 143,000 individuals aged 18 to 64 years, covered by primary care services in three regions of England. Case ascertainment involved: 1) electronic search for chronic fatigue cases; 2) direct questioning of general practitioners (GPs) on cases not previously identified by the search; and 3) clinical review of identified cases according to CDC-1994, Canadian and Epidemiological Case (ECD) Definitions. This enabled the identification of cases with high validity.
The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD. The overall estimated minimal yearly incidence was 0.015%. The highest rates were found in London and the lowest in East Yorkshire. All but one of the cases conforming to the Canadian criteria also met the CDC-1994 criteria, however presented higher prevalence and severity of symptoms.
ME/CFS is not uncommon in England and represents a significant burden to patients and society. The number of people with chronic fatigue who do not meet specific criteria for ME/CFS is higher still. Both groups have high levels of need for service provision, including health and social care. We suggest combining the use of both the CDC-1994 and Canadian criteria for ascertainment of ME/CFS cases, alongside careful clinical phenotyping of study participants. This combination if used systematically will enable international comparisons, minimization of bias, and the identification and investigation of distinct sub-groups of patients with possibly distinct aetiologies and pathophysiologies, standing a better chance of translation into effective specific treatments.
J Viral Hepat. 2011 Aug;18(8):562-70. doi: 10.1111/j.1365-2893.2010.01339.x. Epub 2010 Jun 23.
Hepatitis C virus enters human peripheral neuroblastoma cells – evidence for extra-hepatic cells sustaining hepatitis C virus penetration.
Bürgel B, Friesland M, Koch A, Manns MP, Wedemeyer H, Weissenborn K, Schulz-Schaeffer WJ, Pietschmann T, Steinmann E, Ciesek S.
Division of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH) and Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Patients with chronic hepatitis C virus (HCV) infection show an increased incidence of nervous system disorders such as chronic fatigue syndrome, depression and cognitive dysfunction. It is unclear whether this is because of HCV replication in the brain and in peripheral neuronal cells or to more indirect effects of HCV infection on the central or peripheral nervous system. The aim of this study was to investigate whether cells originating from these tissues are permissive for HCV cell entry, RNA replication and virus assembly. Among eight cell lines analysed, the human peripheral neuroblastoma cell line SKNMC expressed all HCV entry factors and was efficiently infected with HCV pseudoparticles (HCVpp) independent of the HCV genotype. All remaining cell types including human neuroblastoma and glioblastoma cell lines and microglial cells lacked expression of at least one host factor essential for HCV entry. When transfected with HCV luciferase reporter virus RNA, inoculated with HCV reporter viruses or challenged with high-titre cell culture-derived HCV, none of these cells supported detectable HCV RNA replication. Thus, in conclusion, this comprehensive screening did not reveal evidence directly strengthening the notion that HCV enters and replicates in the central nervous system. However, productive viral entry into the peripheral neuroblastoma cell line SKNMC indicates that HCV may penetrate into certain nonhepatic cell types which may serve as viral reservoirs and could modulate viral pathogenesis.