Epidemic myalgic encephalomyelitis
There have been at least 75 documented outbreaks of myalgic encephalomyelitis and chronic fatigue syndrome since the 1930s. The true number of clusters and outbreaks is likely much higher. Many of these outbreaks occurred in institutions like hospitals and schools, and frequently coincided with outbreaks of poliomyelitis.
The first recorded outbreak of epidemic was in 1934 in Los Angeles and the most recent putative outbreak was in Arizona in 1996.
Prior to the 1980s, while no infectious was ever isolated, the outbreaks were widely thought to be caused by a virus related to poliovirus, i.e., by another, yet-to-be-unidentified enterovirus. After the Incline Village outbreak in 1984, herpesviruses and in particular, Epstein-Barr virus was posited as the cause.
History[edit | edit source]
The first recorded outbreak of epidemic myalgic encephalomyelitis was in 1934 in Los Angeles and was thought to be an outbreak of atypical polio. After the outbreak in Akureyri, Iceland in 1946, the disease came to be called Akureyri Disease or Icelandic disease through much of the 1940s and 1950s. It was named myalgic encephalomyelitis after London's Royal Free Hospital outbreak in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.
After the Incline Village outbreak in Nevada in 1984, the disease came to be called and redefined as Chronic Fatigue Syndrome. The most recent was putative outbreak was in Arizona in 1996.
Onset[edit | edit source]
The incubation period was generally estimated at 4 to 8 days.[1][2][3] The illness generally began with a prodromal period of flu-like symptoms, symptoms of an upper respiratory tract infection, low-grade fever, sore throat or gastrointestinal distress,[4][5][6] followed by a symptom complex involving muscle weakness, muscle fatigability and central nervous system involvement in a significant proportion of cases.[2][7]
Symptoms[edit | edit source]
Reported symptoms could vary considerably from outbreak to outbreak. Common symptoms included:
- muscle fatigability
- muscle weakness / paresis[8][9] (10-80%[10] of cases), commonly occurring in the legs[3][4]
- ataxia
- myalgia[3][8] and neuralgia
- severe headache[4][8][9]
- stiffness of the neck and spine[3][4][8][9]
- tender lymph nodes, spleen and/or liver
- cognitive symptoms including impaired memory[3] and concentration[9]
- sleep disturbances[9]
- sensory symptoms including sensitivity to light and sound, paraesthesiae,[3][8][9] hyperaesthesia
- autonomic symptoms such as tachychardia, coldness of the extremities, sweating
- post-exertional malaise, worsening of symptoms with exertion[3][7][9][11][12] ("fatigue on walking short distances and on the least exertion was prominent"[2])
Findings[edit | edit source]
Findings varied considerably based on the technology of the time and what tests physicians attending to these outbreaks chose or were able to run:
- Low-grade fever[3][8][11][9]
- Abnormal electromyogram showing generalized, mild, lower motor neuron changes indicative of a radiculopathy.[2][13]
- Muscle weakness measured via quantitative muscular-testing[7]
- Normal or minimal cerebrospinal fluid findings[3][7][9][14]
- Normal or mildly increased erythrocyte sedimentation rate[8][9][5]
- Mild increase in white blood cell count[9]
- Autonomic nervous system dysfunction, hypothalamic dysfunction
- Orthostatic tachycardia[9]
- Ulnar neuritis, neuropathy or lesion[1][15][16]
- Microscopic infiltration of nerve roots with lymphocytes and mononuclear cells; patchy damage to the myelin sheaths and axon swellings (in monkeys infected with unidentified virus from the Adelaide outbreak)
- Raised urinary creatine excretion[11][16]
- abnormally high lactic dehydrogenase and glutamic oxaloacetic transaminase[5]
In the majority of early epidemics, no viral or bacterial infectious agent was successfully cultured.[3][8][9] In a small number of epidemics Coxsackie B[17][18] or Bethesda-Ballerup paracolon organism[7] were found. In others, infection of animal models with samples from patients results in identifiable nervous system damage on autopsy and in one case, myocarditis, in spite of being unable to identify the agent.[2][19]
Epidemiology[edit | edit source]
Many of these outbreaks occurred at institutions for example, hospitals,[7][20][9] schools, army bases or convents. The pattern of spread suggested a highly infectious agent that spread person to person, rather than through contaminated food or drink or exposure to a single toxic agent.[2][20][12][9]
Outbreaks tended to begin in the summer months, with most initial cases reported from April to September in the Northern hemisphere, October to March in the Southern hemisphere.[9][10]
In outbreaks involving both medical personnel and the general community, medical personnel had a higher attack rate and/or greater central nervous system involvement.[12] A similar pattern was seen in hospital outbreaks, where those in roles that involved more frequent or intimate contact with patients or those working in an infectious disease ward were more affected than other hospital staff.[2][20] A large proportion of recorded outbreaks have taken place in hospital settings.[10]
In many outbreaks including Los Angeles, Akureyri, Rockville, MD, Royal Free Hospital, and Punta Gorda, Florida, women were affected at higher rates.[1][2][7][20][10][12][21][6][8] In other outbreaks, including the 1949-1953 Adelaide outbreak and an outbreak in northern England in 1955, a 1:1 gender ratio was reported.[2] In hospital epidemics, young female nurses were disproportionately affected, but this may have been due to risk factors like higher repeated exposure to the same infection during an epidemic[2] and in some outbreaks, gender-segregated living quarters.[21] However, the higher ratio of women were also reported in outbreaks in the general population.[10] In Akureyri, while the incidence among adults was higher for females, there was no significant difference in incidence between sexes among those under twenty.[1] This comports with patterns of age and sex distribution in sporadic cases.[citation needed]
In most outbreaks, those most affected tended to be adults in their twenties,[2][20][11][9] although cases of young children and adults as old as 80 have been recorded in outbreaks.[10] In Akureyri, the highest attack rate was among ages 15-19.[3]
Melvin Ramsay observed an absence of cases among sedentary people, and postulated that this might explain why hospital staff frequently became affected, while patients in hospital rarely did.[5]
| Outbreak | Type | Peak months | Percent female | Most affected age group | Attack rate |
|---|---|---|---|---|---|
| 1934 Los Angeles | Institution | May to December | 75% | < 30 years | 4.5% |
| 1937 Erstfeld | Institution | July | NA (all male soldier) | 14% | |
| 1948-49 Akureyri | Community | Winter | 50% (< age 20), 70% ( > age 20) [3] | 15-19 years[3] | 6.7% (town), 0.8% (rural)[3] |
| 1949-53 Adelaide | Community | Winter (August) | 50% | ||
| 1950 Louisville | Institution | October | NA (mainly female nurses) | 23% | |
| 1953 Maryland | Institution | July | NA (mainly female nurses) | 13.7% | |
| 1954 Johannesburg | Community | August to March | 72%[8] | ||
| 1955 Dalston | Community | January | 50%[22] | 13.9%[22] | |
| 1955 Durban | Institution | late summer (February) | NA (mainly female nurses) | < 25 years | |
| 1955 London | Institution | July to November | |||
| 1956 Punta Gorda | Mixed | mid-March to June | 74%[12] | 20-49 years[12] | 6.1%[12] (community), 42% (hospital) |
| 1961 New York State | Institution | July to January | NA (all female nuns) | < 30 years | 37.7% |
Pathophysiology[edit | edit source]
Due to limited of objective findings, very little was known about the pathophysiology of the disease. Several investigators postulated damage to the hypothalamus[5] owing to the symptoms of orthostatic tachycardia, abnormal glucose regulation, circulatory impairment, and problems with temperature regulation.
Prognosis[edit | edit source]
Although many patients improved over time, in follow-up studies, a large percentage were still ill months to years later. Many case studies note long periods of convalescence with relapses following exertion[3][7][9][11][12] or before or during menstrual periods.[7][11][12]
| Outbreak | Time after outbreak | Subjective recovery rate | Objective recovery rate |
|---|---|---|---|
| 1948-49 Akureyri outbreak | 7 years | 13%[3] | 31%[3] |
| 1953 Maryland outbreak | 5 months | 0%[7] | |
| 1955 Durban outbreak | 3 years | 89%*[9] | |
| 1961 New York State outbreak | 1 year | 35%[11] |
- Follow-up was with those patients considered disabled. Others may have been more mildly affected.
Relationship to polio[edit | edit source]
Prior to the poliovirus vaccine, several outbreaks of what later came to be called myalgic encephalomyelitis coincided with confirmed outbreaks of poliomyelitis including the 1934 Los Angeles outbreak, the 1948 Akureyri, Iceland outbreak, and 1949 outbreak in Adelaide, Australia.[4] Many outbreaks were initially misinterpreted as clusters of poliomyelitis or abortive poliomyelitis, hence one of ME's earliest names, atypical polio. It is not known whether there is a direct relationship between polio outbreaks and ME or if outbreaks of ME were more likely to be reported when public health authorities were already mobilized for an earlier crisis.
No serological evidence of polio was ever found in these outbreaks and the ultimate pattern of the outbreaks differed in significant ways, chief among them the higher attack rate, the tendency to affect adults rather than children, and the higher morbidity than poliomyelitis but no mortality.[2][10] Findings in several outbreaks seemed to suggest that symptoms were caused by an enterovirus distinct from but related to polio: findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio, i.e., the rise in cases during summer months.[2][10]
There is indirect evidence of cross-immunity between poliovirus and the unidentified virus or viruses in epidemic myalgic encephalomyelitis outbreaks. After the Akureyri outbreak, children in areas that had been affected responded to poliomyelitis vaccination with higher antibody titres, as if these children had already been exposed to an agent immunologically similar to the poliovirus.[2][23] During the outbreak in Adelaide, cases of classic poliomyelitis dropped by 43%.[24]
Controversy[edit | edit source]
In 1970, a paper by Colin P. McEvedy and AW Beard claimed that the 1955 Royal Free Hospital outbreak was actually mass hysteria[25][26] despite never examining patients.[27]
Outbreaks of the 1980s and 1990s[edit | edit source]
The case reports of the 1980s and 1990s differed substantially from those of earlier decades. Whereas reports from the 1930s-1960s focused heavily on neurological and muscle symptoms and findings, and compared and contrasted the disease to poliomyelitis, reports of the 1980s focused far more heavily on fatigue and the possible relationship to herpesviruses.
See also[edit | edit source]
- Ramsay definition
- Enterovirus
- List of enterovirus infection studies
- List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks
- Non-cytolytic enterovirus
- Eightfold increase in ME/CFS incidence in the 1980s
Learn more[edit | edit source]
- In the Bughouse - The New Yorker by Berton Roueché[28]
- Osler's Web by Hillary Johnson
References[edit | edit source]
- ↑ 1.0 1.1 1.2 1.3 Sigurdsson, B (September 1950). "A disease epidemic in Iceland simulating poliomyelitis". American Journal of Hygiene. 52: 222–38.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 Parish, JG (1978). "Early outbreaks of 'epidemic neuromyasthenia'". Postgraduate Medical Journal. 54: 711–7. PMC 2425322. PMID 370810.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 Sigurdsson, B (May 1956). "The Lancet". Clinical findings six years after outbreak of Akureyri disease. 270: 766–7.
- ↑ 4.0 4.1 4.2 4.3 4.4 Pellew, R.A. (June 30, 1951). "A Clinical Description of a Disease resembling Poliomyelitis, seen in Adelaide, 1949-1951". Medical Journal of Australia. 1 (26): 944–6.
- ↑ 5.0 5.1 5.2 5.3 5.4 Ramsay, A. Melvin (November 1978). "Epidemic neuromyasthenia' 1955-1978". Postgraduate Medical Journal. 54: 718–721. PMC 2425324. PMID 746017.
- ↑ 6.0 6.1 Levine, P. H.; Snow, P. G.; Ranum, B. A.; Paul, C.; Holmes, M. J. (April 14, 1997). "Epidemic neuromyasthenia and chronic fatigue syndrome in west Otago, New Zealand. A 10-year follow-up". Archives of Internal Medicine. 157 (7): 750–754. ISSN 0003-9926. PMID 9125006.
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 Shelokov, Alexis; Habel, Karl; Verder, Elizabeth; Welsh, William (August 1957). "Epidemic Neuromyasthenia — An Outbreak of Poliomyelitis-like Illness in Student Nurses". New England Journal of Medicine (257): 345-355. doi:10.1056/NEJM195708222570801.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Jackson, B (May 1957). "A disease resembling poliomyelitis; report of an outbreak in Johannesburg". South African Medical Journal. 31: 514–517.
- ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 Hill, RC (April 4, 1959). "Epidemic myalgic encephalomyelopathy: the Durban outbreak". The Lancet. 1: 689–693.
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 Acheson, E.D. (1959), "The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia" (PDF), American Journal of Medicine, 26 (4): 569–595
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 Albrecht, Robert (March 21, 1964). "Epidemic Neuromyasthenia Outbreak in a Convent in New York State". Journal of the American Medical Association. 187: 904–907.
- ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 12.8 Poskanzer, David C.; Henderson, Donald A.; Kunkle, E. Charles; Kalter, Seymour S.; Clement, Walter B.; Bond, James O. (1957). "Epidemic Neuromyasthenia — An Outbreak in Punta Gorda, Florida". New England Journal of Medicine (257): 356-364. doi:10.1056/NEJM195708222570802. PMID 13464939.
- ↑ Marinacci, AA (October 1965). "The value of the electromyogram in the diagnosis of Iceland disease". Electromyography. 5: 241–51.
- ↑ Ramsay, Melvin; O'Sullivan, E (May 26, 1956). "Encephalomyelitis simulating poliomyelitis". The Lancet. 270: 761–764.
- ↑ Levine, PH (January 1994). "Epidemic neuromyasthenia and chronic fatigue syndrome: epidemiological importance of a cluster definition". Clinical Infectious Diseases. 18: S16-20. PMID 8148446.
- ↑ 16.0 16.1 White, D; Burtch, Robert (July 1, 1954). "Iceland Disease: A New Infection Simulating Acute Anterior Poliomyelitis". Neurology. 4.
- ↑ Fegan, KG; Behan, PO; Bell, EJ (June 1, 1983). "Myalgic encephalomyelitis — report of an epidemic". J R Coll Gen Pract. 33 (251): 335–337. PMID 6310104.
- ↑ Calder, BD; Warnock, PJ (January 1984). "Coxsackie B infection in a Scottish general practice". Jrnl Royal Coll Gen Pract. 34 (258): 15–19. PMID 6319691.
- ↑ Pellew, R.A.A. (September 24, 1955). "Further Investigations on a Disease Resembling Poliomyelitis Seen in Adelaide". The Medical Journal of Australia. 2: 480–2.
- ↑ 20.0 20.1 20.2 20.3 20.4 Gilliam, A.G. (1938). "Epidemiological Study Of An Epidemic, Diagnosed As Poliomyelitis, Occurring Among The Personnel Of The Los Angeles County General Hospital During The Summer Of 1934". Public health bulletin, 1936-1938 (231–240).
- ↑ 21.0 21.1 An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital
- ↑ 22.0 22.1 Wallis, A.L. (1957). An investigation into an unusual disease seen in epidemic and sporadic form in a general practice in Cumberland in 1955 and subsequent years, M.D. Thesis. University of Edinburgh.
- ↑ Sigurdsson, B (February 15, 1958). "Response to poliomyelitis vaccination". The Lancet. 1: 370–1.
- ↑ "Poliomyelitis in 1953"". Bulletin of the World Health Organization. 12 (4): 595–649. 1955. PMC 2542300.
- ↑ McEvedy, Colin P.; Beard, A.W. (January 3, 1970). "Royal Free Epidemic of 1955: A Reconsideration". British Medical Journal. 1 (5687): 7–11. ISSN 0007-1447. PMC 1700894. PMID 5411611.
- ↑ Shepherd, Charles (December 7, 2015). "It's time for doctors to apologise to their ME patients". The Telegraph.
- ↑ Speight, Nigel (2013). "Myalgic encephalomyelitis/chronic fatigue syndrome: Review of history, clinical features, and controversies". Saudi Journal of Medicine and Medical Sciences. 1 (1): 11. doi:10.4103/1658-631x.112905. ISSN 1658-631X.
- ↑ Roueché, Berton (November 19, 1965). "In The Bughouse". 41 (Part 6). The New Yorker. p. 208.
