Suzanne D. Vernon, PhD
By Suzanne D. Vernon, PhD
Scientific Director, The CFIDS Association of America
Viruses and bacteria are everywhere and come in many shapes and sizes. Viruses are the tiniest microbes and depend on a cell to survive. Bacteria are unicellular organisms that contain all the necessary ingredients for survival either inside or outside of a cell. The viruses and bacteria that have been identified represent only the tip of the iceberg. Why have so few been identified? Most of the time, viruses and bacteria do not cause health problems, so we do not necessarily look for them. Up until recently, technology has limited our ability to detect many pathogens. Now we have the technologic capabilities to catalogue the all of the microbes in any given setting – this is called the microbiome. The National Institutes of Health funds the Human Microbiome Project to explore how the trillions of microscopic organisms that live in or on our bodies affect our health. Despite the fact that we live in relative harmony with microbes, acute infectious disease outbreaks still wreak public health havoc. Once the acute episodes of sickness caused by these microbes subside, the infectious agent fades from the spotlight back into its environmental niche. But is this the end of the acute outbreak story? Several recent reports document chronic sequelae of acute infections, providing compelling evidence that post-infection CFS is a relatively common consequence precipitated by a variety of pathogens.
In 2006, the British Medical Journal (BMJ) published a paper that followed 253 people after acute infection with three very different agents: Epstein Barr Virus (EBV), a very large DNA virus that causes kissing disease or mononucleosis; Ross River Virus (RRV), a small RNA virus that causes severe joint pain; and Coxiella burnetii (CB), a bacteria-like pathogen that causes Q fever. While each of these pathogens are structurally different and each causes a different type of acute illness, the same proportion of people developed post-infection CFS – about 10% -- regardless of whether the initial disease was caused by EBV, RRV or CB. This study found that the severity of the acute illness, rather than the specific pathogen, was the major determinant for developing post-infection CFS.
Further evidence that severity of acute infection is predictive of post-infection CFS comes from a study just published in BMC Infectious Diseases. The intestinal protozoan Giardia duodenalis was the cause of a 2004 waterborne outbreak of Giardia infection in Bergen, Norway. The investigators found high rates of post-infection fatigue (41%) and abdominal symptoms (38%) among the 1,017 giardiasis cases two years after the outbreak. Protracted and severe giardiasis was determined to be the risk factor for post-infection fatigue and abdominal symptoms.
West Nile Virus (WNV) and severe acute respiratory syndrome (SARS) are two more structurally different viruses that were introduced into naïve human populations causing different acute illnesses. The illness caused by WNV can be an acute fever (febrile) illness, meningitis or encephalitis. In a study published in the Journal of Neuropsychology in 2008, most of the people who had been hospitalized for WNV had returned to independent living, but some had persistent neurocognitive problems for more than 18 months following acute disease. The Journal of Infectious Disease published a paper showing that WNV was detected in the urine of five people who had WNV encephalitis. Four of the 5 WNV positive people reported chronic symptoms including weakness, fatigue, memory loss and loss of coordination (ataxia). Three of these were more than six years past the initial WNV infection. Finally, of 233 SARS survivors in Hong Kong participating in a study of persistent mental health problems and chronic fatigue, 27% met the 1994 CFS case definition. Both psychiatric morbidity and post-SARS CFS continued to cause significant disability four years after the acute infections with SARS.
In contrast to the dramatic introduction of WNV and SARS into human populations, there is evidence that many of us have been exposed to human parvovirus B19. In a study published in Journal of General Virology, antibodies to human parvovirus B19 were measured in the serum of 200 CFS patients compared to 200 healthy controls. Human parvovirus B19 antibodies were detected at similar rates in both groups (75% in CFS and 78% in controls). However, 83 CFS patients had significantly higher rates of antibodies to a specific parvovirus protein called NS1 and 11 of these CFS patients had parvovirus DNA detected in their serum. Antibodies to human parvovirus B19 NS1 protein correlated with higher levels of expression activity of two host genes. This was not found in the controls indicating that immune control of common viral infections may not be efficient in some CFS patients.
Seven different pathogens precipitating seven different acute diseases have been demonstrated to result in one common clinical CFS phenotype, in a subset of cases arising from these infections. Each of these studies implicates possible pathogen and host factors in post-infection CFS. But perhaps most important is the recognition that post-infection CFS is a significant and common consequence of severe acute infection. Increased recognition of these chronic illness outecomes, as well as improved early detection of these severe infectious events, could have a significant impact of decreasing chronic consequences of post-infection CFS.
Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575.
Morch K, Hanevik K, Rortveit G, Wensaas KA, Eide GE, Hausken T, Langeland N. Severity of Giardia infection associated with post-infectious fatigue and abdominal symptoms two years after. BMC Infect Dis. ;9(1):206. [Epub ahead of print]
Sejvar JJ, Curns AT, Welburg L, Jones JF, Lundgren LM, Capuron L, Pape J, Reeves WC, Campbel GL. Neurocognitive and functional outcomes in persons recovering from West Nile virus illness. J Neuropsychol. 2008 Sep;2(Pt 2):477-99.
Murray K, Walker C, Herrington E, Lewis JA, McCormick J, Beasley DW, Tesh RB, Fisher-Hoch S. Persistent infection with West Nile virus years after initial infection. J Infect Dis. 2010 Jan 1;201(1):2-4.
Lam MH, Wing YK, Yu MW, Leung CM, Ma RC, Kong AP, So WY, Fong SY, Lam SP. Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: Long-term follow-up. Arch Intern Med. 2009 Dec 14;169(22):2142-7.
Kerr JR, Gough J, Richards SC, Main J, Enlander D, McCreary M, Komaroff AL, Chia JK. Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME). J Gen Virol.. [Epub ahead of print]
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