Analysis of the 'epidemic' of multiple sclerosis in the Faroe Islands. II. Biostatistical aspects

A series of biostatistical tests were applied to the data upon which the Faroe epidemic hypothesis was constructed. Temporal, cluster analysis using three commonly applied methods were unsuitable because of the very small size of the sample (32 cases of MS). Methods to detect non-random clusters of disease identified a cluster of 16 cases with date of onset between 1941-1950 (p less than 0.05). However, when 1 questionable case of MS was excluded, the resulting cluster did not support the epidemic hypothesis. The overlapping 95% confidence limits of 5- and 10-year based incidence rates of MS, by date of onset (Poisson distribution) argues against the presence of an epidemic. Analysis of the exposure data, i.e. contacts between the Faroese and the British troops, yielded only borderline statistical significance but changing a single case of MS from the exposed to the unexposed category failed to support the exposure theory. All calculations were also carried out using the probable date of acquisition of the disease, between the ages of 5 and 14 years; these also failed to substantiate the hypotheses of epidemic and transmissibility. Since the validity of statistical analysis to test for the presence of epidemics with small sample sizes is not well established, the lack of concordance between the results of the various approaches leads to the conclusion that there was no epidemic of MS in the Faroes.     

Validity of the epidemics of multiple sclerosis in the Faroe Islands

Concerns have been raised as to our diagnoses, exclusions, case ascertainment, definition of epidemics, and the role of the British occupation in the occurrence of multiple sclerosis among Faroese. We believe none of these points are substantiated, but rather that there did occur three consecutive and decreasing epidemics of clinical neurologic MS (CNMS) among native resident Faroese between 1943 and 1973, with no cases before or (so far) since. We have attributed these occurrences to the introduction into the Faroe islands of what we have called the primary MS affection (PMSA) by the British troops who occupied the islands in World War II. The first Faroese population cohort of PMSA-affected, which included the epidemic I cases, transmitted PMSA to the next cohort of Faroese comprising those attaining age 11 in 1945-1956, and they included the epidemic II cases. The second cohort thereafter similarly transmitted PMSA to the third Faroese cohort with its epidemic III cases. We conclude that PMSA is a single, widespread, specific, systemic infectious disease whose acquisition in virgin populations follows 2 years of exposure starting between age 11 and 45, which then produces CNMS in only a small proportion of the affected after a 6-year incubation period, and which is transmissible only during part or all of this systemic PMSA phase that ends before the usual age of CNMS onset. In endemic MS areas both the exposure and incubation periods may be twice as long, but otherwise PMSA may have there the same characteristics as inferred for the Faroes.     

Multiple sclerosis in the Faroe Islands

Detailed questionnaires were completed in 1978–79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patient's spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no difference, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B, but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls.     

Multiple sclerosis in the Faroe Islands. 5.

Based on 32 cases with clinical onset 1943–73, we previously described the occurrence of clinical neurologic multiple sclerosis (CNMS) on the Faroe Islands as constituting three consecutive epidemics, with 20, 9, and 3 cases respectively. As of 1991 there were seven additional cases of CNMS with clinical onset 1984–1989 constituting the fourth epidemic, as well as three more members of epidemic III. We have proposed that CNMS is the rare late result of infection with PMSA (the primary multiple sclerosis affection), a state requiring some two years of exposure from age 11+ for acquisition by Faroese, and that PMSA was first transmitted during World War II by affected but asymptomatic British troops to Faroese residents; part of this (F1) cohort of affected asymptomatic Faroese transmitted PMSA to the next (F2) cohort comprising Faroese reaching age 11 in the interval when that F1 subset was present, and the F2 cohort similarly transmitted PMSA to the third (F3) cohort. Cases of CNMS defining epidemic I-III were members of the respective F1-F3 cohorts. The existence of epidemic IV within the F4 cohort of Faroese may be taken as validation of our transmission models and of our theses as to the nature of multiple sclerosis.     

Some comments on the occurrence of multiple sclerosis in the Faroe Islands

Summary Some factors which might be related to the marked increase in multiple sclerosis in the Faroe Islands in mid-century were studied. Of these, only the occupation by British troops in World War II was found to be significant. A vague relationship with industrial changes earlier in the century was also found. These findings are discussed with caution with respect to the close association between population on the one hand and all features tested as well as multiple sclerosis on the other.Supported by the Hermann and Lilly-Schilling foundation in the Stifterverband für die Deutsche Wissenschaft, Essen, Federal Republic of Germany     

Multiple sclerosis in the Faroe Islands. 8. Notifiable diseases

Wallin MT, Heltberg A, Kurtzke JF. Multiple sclerosis in the Faroe Islands. 8. Notifiable diseases.
Acta Neurol Scand: 2010: 122: 102–109.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To seek evidence for a possible infectious origin of the type 1 epidemic of multiple sclerosis (MS) in the Faroe Islands. This began in 1943 coincident with their British military occupation throughout World War II. Materials and methods – Data obtained from the Danish National Health Service were assessed for all notifiable diseases in the Faroe Islands reported from 1900 to 1977. Results – Among 38 disorders, selective increases were found for acute infectious gastroenteritis (AIGE) and paradysentery, with outbreaks in late 1940 and in 1943 shortly after the introduction and later marked influx, respectively, of British troops. Five other infections showed elevated numbers in 1941 and 1942. Conclusions – There is a temporal association of AIGE and paradysentery in the Faroe Islands with the first arrival and later marked augmentation of British forces stationed there during the war. Rises in the incidence of other diseases in 1941–1942 seem more likely a consequence of increased foreign commercial travel by Faroese at that time.     

Incidence of amyotrophic lateral sclerosis in the Faroe Islands

Joensen P. Incidence of amyotrophic lateral sclerosis in the Faroe Islands.
Acta Neurol Scand: 2012: 126: 62–66.
© 2011 John Wiley & Sons A/S. Objectives – The establishment of variations in the incidence of amyotrophic lateral sclerosis (ALS) in the Faroese population from that found in other general populations may point to risk factors for the development of this disease among the Faroese. The aim of this study was to estimate the annual incidence of ALS during the period 1987–2009 and to compare the occurrence of ALS in the Faroe Islands with data from three European countries. Method – All Faroese patients diagnosed with ALS in this period are documented in the current longitudinal prospective study. Results – The incidence of ALS in the Faroe Islands during the period 1987–2009 is 2.6 (1.7–3.7) per 100,000 annually. The results yielded no strong evidence of a difference (P = 0.09) in the incidence of ALS between Faroe Islands and Europe. The sample population is small, and this, of course, impacts the statistical precision of the findings. Conclusion – The data clearly suggest, however, that the Faroese population is probably not subject to an increased risk of ALS, even though certain risk factors are present in the general population: (i) a fish‐based diet contaminated with mercury and polychlorinated biphenyl; (ii) the high occurrence of the recessive carnitine transporter genetic defect; and (iii) the anticipated high degree of inbreeding at the fifth generation.     

Multiple sclerosis in the Faroe Islands. II. Clinical update, transmission, and the nature of MS

In this century, 41 Faroese with MS were ascertained. One subset, after living in Denmark for 2 years between ages 11 and 31, had MS onset an average of 6 years later. In the Faroes, MS occurred as three separate and decreasing epidemics beginning in 1943 and ending in 1973. We believe that asymptomatic British troops introduced the first epidemic during 1941 to 1942, with the later epidemics resulting from transmission by affected but asymptomatic Faroese. We conclude that "MS" is a widespread, systemic, specific infectious disease only rarely causing neurologic symptoms and transmissible at most from ages 13 to 26.     

Multiple sclerosis in the Faroe Islands and the lack of protection by exposure in infancy.

Using data from 32 patients with symptom onset between 1943 and 1973, we described the occurrence of clinical neurologic multiple sclerosis (CNMS) in the Faroe Islands as then constituting three epidemics. We concluded that CNMS is the rare late result of infection with the primary MS affection (PMSA), a state requiring some 2 years of exposure for acquisition by Faroese. Our theses are that PMSA was first transmitted during World War II by affected by asymptomatic British troops to Faroese aged 11-45; that this (F1) cohort of affected asymptomatic Faroese under age 27 in 1945 transmitted PMSA to the next (F2) cohort of Faroese comprising those attaining age 11 each year from 1945 until F1 input ceased; that the F2 cohort similarly transmitted PMSA to the third (F3) cohort of Faroese. Cases of CNMS defining epidemics I-III were members of the respective F1-F3 cohorts. Within the F4 cohort of Faroese there is now a fourth epidemic of CNMS, with 7 patients with symptom onset between 1984 and 1989. Intermittency of the year of birth for CNMS cases is thus a reflection of membership in these separate population cohorts, and does not indicate 'protection' in infancy or childhood. There is no evidence for an extra-Faroese source of MS after the first epidemic. No model of acute infection with short transmissibility fits the data.     

Multiple sclerosis in the Faroe Islands: transmission across four epidemics

As of 1991 we had ascertained 42 native resident Faroese plus 12 non-resident "migrant" Faroese with clinical onset of MS in this century. The resident series comprised four successive epidemics beginning in 1943 and then at 13-year intervals thereafter, a separation of very high statistical significance (p < 0.00001). We concluded that the first epidemic in the Faroes resulted from the introduction of a specific but unknown infection which we call the "primary MS affection" (PMSA) by occupying British troops during World War II. Clinical neurologic MS (CNMS) is then the rare late sequel of infection with PMSA. The first epidemic defined age of susceptibility to PMSA as age 11 to 45 at onset of exposure. Models of transmission used for the first three epidemics included the need for two years of exposure before PMSA acquisition and limitation of transmissibility of PMSA to age 13 to 26. With these conditions successive cohorts of susceptible Faroese were defined to account for the second and third epidemics, and they also predicted the occurrence of the fourth epidemic. Further consideration of these models suggests transmissibility is even more limited, perhaps to age 20 to 26 or so.     

Multiple sclerosis in relation to industrial and commercial activities in the Faroe Islands

The distribution of MS cases in the Faroe Islands according to place at birth and place at onset was tested for a possible association with differing industries in 1930 and 1960, respectively. The MS patients originated predominantly from communities where commercial fisheries were prominent, whereas a weaker association was found with wood-processing plants. Both associations might, however, be confounded by the factor population as such, since patients were born mostly in the larger communities. No association with any kind of industry was found when residences during World War II were evaluated with respect to industries in 1960. Further studies into the conditions of life, with special reference to the social background of commercial fisheries in the early 20th century in the Faroe Islands, might be useful.     

Dietary changes in temporal relation to multiple sclerosis in the Faroe Islands: an evaluation of literary sources

In order to generate additional hypotheses on a possible role of dietary factors in the etiology of multiple sclerosis, the ethnographic literature and other relevant sources from the Faroe Islands were reviewed. A transitory occurrence in the first half of the 20th century was evident for the extended consumption of oat products, of fulmars possibly infected with ornithosis virus, and of foodstuffs treated with wood smoke or smoke condensates. The hypothetical basis of these considerations must be emphasized.     

Multiple sclerosis in the Faroe Islands III. An alternative assessment of the three epidemics

Among 32 resident Faroese, clinical MS began between 1943 and 1973 and comprised 3 epidemics, each one significantly later in time and lower in incidence than the preceding. This is confirmed by the present division of the cases of the epidemics according to the calendar time when the patients attained age 11. The risk of MS for Faroese of Epidemic I, (those who acquired the disease from asymptomatic British troops in the World War II occupation), was 18 per 10,000. Depending on the minimum population number required for transmission, the MS risk for Epidemic II was 15 per 18 per 10,000, and for Epidemic III (under our second model) 9 or 11 per 10,000, none differing significantly from Epidemic I. We conclude that the primary MS affection (PMSA) is a single, widespread, specific, systemic infectious disease whose acquisition in virgin populations follows 2 years of exposure starting between age 11 and 45, which then produces clinical neurologic MS (CNMS) in only a small proportion of the affected after an incubation period of 6 (virgin populace) or 12 (endemic areas) years, and which is transmissible only during part or all of this systemic PMSA phase that ends by age 27 or younger.