Serious Infections in Adolescence Linked to Increased MS Risk

Experiencing serious infections during adolescence is tied to an increased risk of developing multiple sclerosis (MS) later in life, but those occurring in childhood don’t increase MS risk, according to a new Swedish study.

The study also found that certain types of infections, especially those that affect the central nervous system, or the brain and spinal cord, are most associated with MS risk.

“Our study provides further evidence that adolescence is a period of heightened susceptibility to exposures linked with MS risk and that there can be many years between exposure and MS diagnosis,” Scott Montgomery, a professor at Örebro University, in Sweden, and the study’s lead author, said in a press release.

“It may be worthwhile considering MS as a potential diagnosis in someone displaying neurological symptoms if they had a serious infection in adolescence,” he added.

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The study, “Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis,” was published in Brain.

MS is caused by the immune system attacking cells in the brain, but the factors that lead to this erroneous immune attack are not well understood. One thought is that infections could predispose a person to develop MS, since the immune system normally attacks infectious invaders and this could lead to the beginning of the autoimmune processes underlying the disease.

Indeed, some specific infections — such as the Epstein-Barr virus (EBV), which causes infectious mononucleosis, known as mono — have been linked with an increased risk of developing MS later in life. However, it’s not clear whether this is an effect of a specific type of infection, or whether such infections, in general, increase MS risk.

Now, researchers in Sweden conducted an analysis to gain better insight into the connection between infections and MS risk. Using national databases, the team identified nearly 2.5 million people who were born between 1970 and 1994. Of these, 4,022 were diagnosed with MS at the age of 20 or later; the average age at diagnosis was around age 30. More females than males developed MS, which is in line with well-established sex-based differences in MS.

Among the analyzed patients, 462, 157 or nearly 20% (19.07%) had a diagnosed infection in adolescence, between the ages of 11 and 19. Meanwhile, 338 ,352 individuals (13.96%) had an infection during childhood — specifically at age 10 or younger.

Of note, because the researchers used databases, they were specifically looking at infections that were diagnosed in a hospital — meaning those that are relatively severe, since a mild infection like a cold is usually unlikely to prompt a hospital visit.

Using statistical analyses, the researchers assessed whether infections in early life were tied to an altered risk of developing MS later on. The results showed there was no link between childhood infections and MS risk.

However, infections in adolescence were associated with a significantly increased risk of MS, by about 33%. An additional analysis — which excluded an infection from EBV and several other well-established infections with a known connection to MS — still showed a statistically significant association between infections in adolescence and MS risk, by about 17%, the researchers noted.

“The association we found between infections in adolescence and increased risk of a subsequent multiple sclerosis diagnosis was not only explained by infections previously linked with multiple sclerosis risk: infectious mononucleosis and pneumonia, nor due to CNS infection, which although not having been previously investigated as a risk factor for multiple sclerosis (to our knowledge), could plausibly affect later multiple sclerosis risk as indicated by this study,” the researchers wrote.

“Thus, other types and sites of infection in adolescence were also risk factors increasing the likelihood of a subsequent multiple sclerosis diagnosis,” they concluded.

The team added that the difference in risk based on age is “consistent with prior studies on other environmental risk factors” for MS, like concussion and vitamin D levels.

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Further analyses showed that the highest MS risk was tied to any infection of the central nervous system or CNS, which comprises the brain and spinal cord. People with CNS infections in adolescence were nearly three times more likely to develop MS, the data showed. Removing EBV did not alter this significant association.

CNS infections in childhood also were associated with a significantly increased MS risk, by about 47%.

Respiratory infections during adolescence increased the risk of MS later on, as did any infection during adolescence of the genitals/urinary tract — though neither type of infection during childhood was tied to a significantly increased MS risk. Gastrointestinal infections in childhood or adolescence showed no significant association with MS risk.

Analyses that looked at viral infections other than EBV showed no significant association with MS risk. However, any bacterial infection — both inside and outside of the CNS — was significantly associated with MS risk.

Additional analyses that looked only at patients diagnosed with MS after age 25 found similar results. This suggests that the results aren’t being complicated by the fact that MS itself can predispose people for infections, even before symptoms are obvious enough for the disease to be diagnosed.

“The next step in our research will be to further investigate whether people who are genetically susceptible to developing MS are more likely to have a more pronounced immune reaction to infections increasing the likelihood of hospital admission,” Montgomery wrote.