SAN DIEGO (FRONTLINE MEDICAL NEWS) – What causes multiple sclerosis (MS)? A team of Scottish researchers offers a new theory that it’s triggered in part by a one-two punch of infection with pinworm – a common condition in the United States, especially among children – and the Epstein-Barr virus (EBV).

The theory identifies pinworm as the prime suspect to be the “missing link” that explains why EBV and MS are so tightly connected, said Patrick Kearns, MBChB , a graduate student at Harvard T.H. Chan School of Public Health in Boston.

Dr. Kearns is the lead author of two reports about the possible role of pinworm that were presented at ACTRIMS Forum 2018, which is held by the Americas Committee for Treatment and Research in Multiple Sclerosis. He spoke in an interview.

At issue is the nongenetic roots of MS. “The genetics of multiple sclerosis are fascinating and great progress appears to have been made in recent years,” Dr. Kearns said. “But it is clear from the epidemiology that there are still missing environmental factors that contribute to genetically susceptible persons’ developing the disease.”

Dr. Kearns and his colleagues focused on a well-known cluster of MS cases that began to appear in the Faroe Islands – a Danish possession in the North Atlantic – during World War II. The cases began to appear after British troops occupied the islands.

“Many of the occupation soldiers were from the Scottish Highlands, where the MS prevalence is quite high: 90 cases per 100,000, comparable to the northern U.S.,” according to a National MS Society summary about MS clusters.

In a theory that spawned controversy, the late neurologist John Kurtzke, MD, speculated that the British soldiers brought a transmissible agent to the islands, which triggered MS cases.

Could the agent be EBV alone? The authors of the new studies don’t think so, although they note that EBV is “robustly linked” to MS. Indeed, a 2012 meta-analysis reported that the virus “appears to be present in 100% of MS patients,” based on studies considered to be the strongest ( Mult Scler. 2013 Feb;19[2]:162-6 ).

The authors of the new reports note that, while EBV infection “appears necessary,” it is “clearly not sufficient” to cause the disease on its own.

“Certainly almost everyone gets EBV eventually,” Dr. Kearns said. “So mere presence of the virus is certainly not sufficient for causing the disease. But it seems still to be necessary, and timing of infection might be everything.”

So what’s the missing piece of the puzzle?

Dr. Kearns began to think it might be the lowly pinworm after helping a colleague by analyzing data from appendicitis samples in children. He noted that uninflamed samples often had pinworms in them, but the inflamed samples often didn’t, which suggested that “the rate of pinworms in normal appendices must be very high in the healthy pediatric population at any given time.”

More data confirmed this to be true, and medical literature told Dr. Kearns that pinworms were common in high latitudes – places where people often are especially prone to MS.

“Most remarkably, they are known to have very little migration and stay spatially stable in populations over long periods of time,” Dr. Kearns said, “and typically everyone in an affected population will encounter them because their eggs are transmitted in household dust.”

And, he said, “they are known to be common in soldiers who live in military accommodation.”

According to the Centers for Disease Control and Prevention , pinworm prevalence can be as high as 50% in at-risk groups – children, caregivers of infected children, and people who live in institutions. Pinworms, which are spread through ingestion, are often asymptomatic but may cause anal itching and trigger bacterial infections.

The researchers suggest that pinworm infection comes first, followed by EBV infection. This makes sense because “late EBV infection in the form of infectious mononucleosis is known to be a risk factor for MS,” Dr. Kearns said.

The one-two punch of pinworm and then EBV is a plausible theory “because EBV lives in memory B cells, which are known to be important in MS and could be specific for the previous exposure to pinworm,” Dr. Kearns said. “However, this is very speculative and some researchers will argue this is very unlikely to be the case. But I think there is a chance it could explain some of the epidemiology, so I’m keen to try and test the theory if I can.”

What’s next? Dr. Kearns wants to explore data from Scotland in search of areas of high and low MS incidence that could offer insight into environmental triggers.

He added that the development of a serological blood test to prove a history of pinworm infection would be “the most effective way to prove or disprove this theory.”

“I have approached an investigator who has a track record of doing this for other infections and have been encouraged that he thinks that it would be achievable,” he said. “But this will definitely take time and funding.”

No specific funding was reported. The study authors reported no relevant disclosures.

SOURCE: Kearns P et al. ACTRIMS Forum 2018, Abstracts LB257 and LB264 .


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