Eight Swallows

Barts-MS rose-tinted-odometer: ★★★★★

How many swallows make a summer? Is eight enough? 

If MS is caused by EBV you would expect there to be clusters of MS potentially linked to a specific subtype of the virus. The best-studied MS cluster is the one from Fjelsø, a small village of 74 families in rural Denmark, where eight people closely linked to each other all developed MS within 13 years of each other. All the subjects had attended the same school. Interestingly all of the people who developed MS had attended the scouts together. 

Danish investigators then typed the variant of EBV these subjects had been infected with and to their surprise, they all had the same subtype of EBV, which importantly was different from controls that were selected from schoolmates and family members. This raises the question of being a scout in Denmark resulted in the transmission of EBV between these subjects. None of these eight subjects reported having had infectious mononucleosis.

What are the chances of getting an eight-person cluster of MS from a group of scouts in a tiny rural village in Denmark? Then on top of this what are the chances of all eight of these people with MS having the same EBV subtype when their family members and schoolmates did not? I suspect the chances are very low.

I don’t think eight swallows are enough to make a summer, but you can’t ignore this cluster when all the other epidemiological evidence points to EBV being causally linked to MS.

The two linked studies below are just a small piece of a large jigsaw puzzle that is gradually being built that I predict will eventually prove EBV is the cause of MS. In the centre of this large jigsaw puzzle are the bespoke pieces for the EBV antiviral and vaccine studies. 

Haahr et al. Cluster of multiple sclerosis patients from Danish community. Lancet. 1997 Mar 29;349(9056):923.

Cluster: We report a cluster of MS in which eight people with verified MS originated from a small Danish community called Fjelsø. All eight had lived within a 2.75 km2 area (2.5 km×1.1 km), where 74 single-family houses, including some farms, were located. The community had a stable population with few migrations into and out of the area. During a 13-year period, all the patients had for 7 years attended the same elementary school with 70-80 pupils. The school had 145 pupils during this period. All those who developed MS had been scouts together, with the older ones being scoutmasters for the younger ones and some of the older ones had also looked after the younger ones. Two cases were siblings and two were aunt and nephew, but MS had not been observed in any of the ancestors of the eight cases or among the school teachers. All cases of MS developed, at various ages and with variable courses, after the eight had left Fjelsø. None of the eight could recall symptoms of infectious mononucleosis.

Munch et al. A single subtype of Epstein-Barr virus in members of multiple sclerosis clusters. Acta Neurol Scand. 1998 Dec;98(6):395-9.

Objectives: Epidemiological studies strongly indicate an infectious involvement in multiple sclerosis (MS). Epstein-Barr virus (EBV), to which all multiple sclerosis patients are seropositive, is also interesting from an epidemiological point of view. We have reported a cluster of MS patients with 8 members from a small Danish community called Fjelsø. To further evaluate the role of EBV in MS we have investigated the distribution of EBV subtypes in cluster members and in control cohorts.

Materials and methods: Blood mononuclear cells were isolated from cluster members, unrelated MS patients, healthy controls, including healthy schoolmates to the Fjelsø cluster patients and finally from persons with autoimmune diseases in order to investigate the number of 39 bp repeats in the EBNA 6-coding region in the EBV seropositive individuals.

Results: We observed a preponderance of the subtype with 3 39 bp repeats in the EBNA 6-coding region both in the MS patients and the healthy controls. In the Fjelsø cluster, all 8 cluster members were harbouring this subtype, which is significantly different from the finding in healthy controls (n = 16), which include 8 schoolmates to the cluster members and 8 randomly selected healthy persons (Fischer’s exact test P = 0.0047), and also compared to all non-clustered individuals studied (P = 0.017).

Conclusion: Infection with the same subtype of EBV links together the 8 persons from the Fjelsø cluster who later developed MS. This finding adds to the possibility that the development of MS is linked to infection with EBV.

CoI: multiple

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