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Original Contributions |

Yellow Fever Vaccination and Increased Relapse Rate in Travelers With Multiple Sclerosis

Mauricio F. Farez, MD, MPH; Jorge Correale, MD
Arch Neurol. 2011;68(10):1267-1271. doi:10.1001/archneurol.2011.131.
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Published online

Objective To investigate the effect of yellow fever (YF) immunization on the subsequent multiple sclerosis (MS) relapse risk.

Design Self-controlled case series study.

Setting An MS outpatient clinic.

Patients Seven patients with clinical relapsing-remitting MS traveling to endemic YF areas who received the YF 17D-204 vaccine were studied.

Intervention The YF 17D-204 vaccine.

Main Outcome Measure Number of relapses. Secondary outcomes included the number of new lesions on magnetic resonance imaging and peripheral mononuclear cell cytokine and chemokine production.

Results The annual exacerbation rate during risk periods following immunization was 8.57, while the relapse rate outside the risk period was only 0.67 (rate ratio = 12.778; P < .001). Three months after immunization, patients showed a significant increase in new or enlarging T2-weighted lesions and gadolinium-enhancing lesions compared with 12 months prior to vaccination and 9 months after immunization (both P < .001). Moreover, blood myelin basic protein and myelin oligodendrocyte glycoprotein responses showed significant increases in interferon γ–induced protein 10 kDa–, interferon γ–, interleukin 1α–, interleukin 1β–, and tumor necrosis factor–secreting cell numbers as well as complement component C1qB production after YF vaccination in patients with MS compared with unvaccinated patients with MS, patients with MS vaccinated against influenza, and healthy control subjects (P = .01 and P < .001, respectively).

Conclusion For patients with MS traveling to endemic YF areas, vaccination should be recommended on the basis of carefully weighing the risk of exacerbation against the likelihood of exposure to the YF virus.

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Figure 1. Annual exacerbation rate during the at-risk period (ARP) and nonrisk period.

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Figure 2. Number of myelin basic protein 83-102–specific peripheral blood mononuclear cells (PBMCs) producing interleukin 1α (IL-1α) (A), IL-1β (B), interferon γ (IFN-γ) (C), tumor necrosis factor (TNF) (D), and IFN-γ–induced protein 10 kDa (IP-10) (E) from yellow fever (YF)–vaccinated patients with multiple sclerosis (MS), unvaccinated patients with MS, influenza-vaccinated patients with MS, and healthy controls. Cytokine- and chemokine-secreting cell numbers were calculated by subtracting the number of spots obtained in control cultures without antigen stimulation from the number of spots obtained in cultures exposed to stimulating antigens. Results are reported as number of spots per 105 PBMCs. F, Production of complement component C1qB by PBMCs after lipopolysaccharide stimulation in the same groups of patients assessed by enzyme-linked immunosorbent assay. Data indicate mean values from 7 subjects studied in each group. Error bars indicate SD, shown for YF-vaccinated patients with MS exclusively. All other group variation comparisons were below 2 SDs and therefore considered to lack statistical significance.

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