Yellow Fever Vaccine May Increase Risk of Relapse in MS Patients

Patient Expert

Vaccinations are an important part of life individually and for our society.   Vaccines provide important protections against disease, some potentially devastating.   The Center of Disease Control and Prevention (CDC) provides information regarding recommended vaccines for children and adults.

The most familiar vaccine we encounter each year is the influenza vaccine, the flu shot.   Although it is a bit early to think about the annual flu vaccine, I will urge you to get the flu vaccine when it becomes available in the fall and to always practice good hygiene.

MS and Common Vaccines

If you are concerned, as an MS patient, that the flu vaccine might increase your risk of MS relapse, research shows that it does not increase risk.   A recent study published in the Journal of Neurology (July 2011) provides a systemic review and meta-analysis of the role vaccines may have in the risk of development multiple sclerosis or MS exacerbation.

Researchers found that the risk of developing multiple sclerosis remained unchanged after BCG (tuberculosis), Hepatitis B, Influenza, MMR (measles-mumps-rubella), Polio and Typhoid fever immunization, whereas diphtheria and tetanus vaccinations may be associated with a decreased risk of MS.   Further research is needed for the remaining vaccines, according to the report.

MS and the Yellow Fever Vaccine

Although common vaccines are safe for use in multiple sclerosis, a recent study in the Archives of Neurology (online June 2011) indicates that the Yellow Fever vaccine can increase relapse rate in travelers with MS.   This study was conducted by the same researchers who undertook the meta-analysis referenced above.

Seven patients with RRMS who were traveling to areas where yellow fever is endemic received the yellow fever vaccine and were observed for two years.   To serve as controls, 21 additional patients were included: seven healthy individuals who were age- and sex-matched, seven MS patients who received flu vaccines according to WHO (World Health Organization) recommendations, and seven MS patients who receive no vaccines.

Patients were told to report exacerbations within 72 hours, otherwise they were examined every three months for two years.   MRI scans were conducted three months and nine months following the vaccination, and the scans were compared to scans conducted 12 months prior to the beginning of the study.   Relapses were analyzed both during the "at risk period" between one and five weeks following vaccination and the "non-risk period" which was the remaining time of weeks six to 104.   Since the yellow fever vaccine contains a live virus, researchers began measuring the ARP one full week after vaccination.

For the entire two-year time period, the annual relapse rate was 0.99 with five (of seven) patients experiencing 14 exacerbations.   There were five relapses during the at-risk period (annualized relapse rate of 8.57) and nine relapses during the non-risk period (annualized relapse rate of 0.67).   The exacerbation rate was 12.778 times higher [emphasis mine] during the at-risk period.   Patients also had more lesions three months after immunization as compared to 12 months before the study and during the two-year follow-up.   Two of the seven patients in the test group had no relapses or additional lesions at any time during the study.

Of the five patients who did have relapses following vaccination, four patients had significant increases in EDSS (Expanded Disability Status Score) of 2-3 points as determined by neurological evaluations conducted 12 months following the at-risk period relapse.   The fifth patient did not experience an increase in EDSS score.   The two patients who experienced no relapses or new lesions did not have an increase in EDSS score.

All seven vaccinated MS patients were on disease-modifying treatment.   Their ages ranged from 33-40 years with disease duration from 36-62 months.   EDSS scores at the beginning of the study ranged from 1.0-2.0 and at the end of the study, 1.5-4.0.   One person who began with the lowest EDSS score (1.0) completed the study with the highest EDSS score (4.0).   She was the quickest to relapse at only 15 days following the yellow fever vaccination.   (see the chart at the bottom of the post)

What is Yellow Fever?

Yellow Fever is a virus which is transmitted through the bite of infected mosquitoes in sub-Saharan Africa and tropical South America.   Symptoms of yellow fever include arrhythmias (irregular heartbeat), bleeding, coma, decreased urination, delirium, fever, headache, jaundice, muscle aches, seizures, vomiting, and red eyes, face, or tongue.   Signs of advanced yellow fever include liver failure, renal (kidney) failure, and shock.

There is no treatment for yellow fever itself, but for the symptoms (ie. dialysis, fluids, blood products).   Prognosis is not very good in severe cases.   Yellow fever is a potentially fatal disease affecting approximately 200,000 people annually and causing an estimated 30,000 deaths per year.   This is the reason vaccination is required for visitors traveling to certain countries.

The CDC shares that "from 1970 through 2010, a total of nine cases of yellow fever were reported in unvaccinated travelers from the United States and Europe who traveled to West Africa (five cases) or South America (four cases). Eight (88 percent) of these nine travelers died. There has been only one documented case of yellow fever in a vaccinated traveler. This nonfatal case occurred in a traveler from Spain who visited several West African countries during 1988."


Although this study is small and limited, a casual link between the yellow fever vaccine and MS relapses can be indirectly inferred by the timing of relapses, the strength of relapses observed, and the likelihood of a biological link, say the authors.   In four of seven patients, the yellow fever vaccination did lead to relapse and worsening of disease.   However immunization against influenza in the same patients and during the same follow-up period showed no effect on the annual exacerbation rate or lesion load.

If you plan to travel to a location known to have yellow fever epidemics, and based on information such as length of stay, time of year, and other factors which may increase your risk of contracting yellow fever, discuss with your doctor the pros and cons of receiving the vaccine.   Carefully balance the risk of MS exacerbation and the likelihood of exposure to the virus.