There is widespread agreement that a variety of infections are capable of precipitating chronic fatigue syndrome (CFS) in susceptible individuals. In l988, Lloyd et al reported that several of their patients had linked the onset of CFS to receiving a vaccination in the absence of any coincidental infection.^l Since then, other anecdotal reports have also linked vaccinations to the onset of CFS.^2,3

The explanation for vaccine-induced CFS may be because the primary purpose of any vaccine is to mimic the effects of infection on the immune system. If an antigenic challenge by infection can precipitate CFS, then it is conceivable that vaccines could act in a very similar manner.

This reasoning is further strengthened by the fact that immunologically based illnesses, such as arthritis, can occur when a susceptible host and an environmental trigger, such as an infection or vaccination, interact.4 It is also interesting to note that vaccinations have been suggested as a possible precipitating factor in the development of Gulf War illness.

Causal vaccines
My research interest in this aspect of developing CFS is largely based on clinical evidence from patients seen in my practice over the past 10 years. As a result, I have gathered details on more than 200 patients with a history of either developing CFS or experiencing a significant relapse/exacerbation of CFS symptoms following a vaccination.

In addition, I have more than 150 reports referring to such a link from members of myalgic enceph-alomyelitis (ME) or CFS self-help support groups and/or their physicians throughout the world.

This data (although unpublished) suggests that tetanus, typhoid, influenza, and hepatitis B are the most commonly implicated vaccines in cases of CFS. I have reports of very few cases involving hepatitis A (using immunoglobulin), polio, or rubella vaccine, or those predominantly given during childhood—-with the possible exception of Bacillus Calmette--Guerin vaccine (three cases).

Almost all of my cases involve adults, and in a significant minority the vaccine was administered when the person had not yet fully recovered from an infective illness such as infectious mononucleosis (known as glandular fever in the U.K.) or had already experienced an adverse reaction to a previous dose of the same vaccine (as is sometimes the case with hepatitis B accine).

About one third of my cases involve vaccine-induced/exacerbated CFS following receiving the hepatitis B vaccine (HBV). Most of these patients are health care workers, particularly nurses. Most of the other patients received HBV for occupational health purposes, often as a condition of employment and without any information on side effects, such as severe neurological reactions.

The prognosis in this group has been poor, with less than 10% of the patients I have personally followed reporting any significant relief of CFS symptoms.

Although chronic debilitating fatigue is the most frequently reported symp-tom of CFS after vaccine administration in this group, around 20% also complained of significant joint pain/arthralgia, a finding consistent with several reports linking HBV to arthritis and other autoimmune disorders.⁵

Less than 5% of the patients also reported neurological complications/side effects such as tremors or one-sided weakness, which appear to be separate from their CFS symptoms.

For instance, one female patient developed an acute disseminated inflammation of the brain and spinal cord (encephalo-myelitis) shortly after the second dose of vaccine. This was followed by the gradual onset of CFS.

Hepatitis vaccines are highly immunogenic compounds, and a number of possible explanations exist as to why they may be more likely to trigger CFS.

One explanation involves a preexisting genetic susceptibility, which after antigenic stimulation with HBV, results in a pathological process (possibly involving immune complex formation) leading to a clinical disease.

Another explanation is that a hypersensitivity reaction occurs to a component of HBV, such as the preservative thimerosal.⁶

Researchers in Canada, who made similar observations of a link between HBV and CFS, hypothesized that this may involve an autoimmune reaction with a microscopic form of demyelination not visible on magnetic resonance imaging.⁷

Despite growing anecdotal evidence from other experienced physicians who also believe that HBV can precipitate CFS,² vaccine manufacturers do not acknowledge any causal link. In fact, a report by an independent working group in Canada that dismissed any such causal link is frequently quoted as a reason for dismissing these claims, even though it contained some very questionable assumptions to support the conclusions.⁸

For example, the report inaccurately states that chronic carriers of hepatitis B infection without signs of ongoing liver damage do not complain of tiredness. The report also uses results from a one-week follow-up study of 700 health care students, which found excessive short-term tiredness in about 14% after vaccination with HBV to refute any link with chronic fatigue.

Practical advice
Health care providers caring for CFS patients who require vaccinations clearly must weigh the pros (i.e., how effective? how necessary?) and cons (i.e., risks of adverse effects and exacerbation of CFS symptoms) for each individual vaccine. I would advise against having routine nonessential vaccinations if a patient is:

• In the very early stages of CFS, particularly when it obviously follows an infective episode;
• Continuing to experience flulike symptoms, including sore throat, enlarged glands, fevers, and joint pains; or
• Has previously experienced an adverse reaction to that particular vaccine.

If the vaccination is potentially lifesaving, then considerations relating to CFS must take a lower priority. As for some of the more commonly required vaccines, my advice on their use is as follows:

Hepatitis A. Short-lived protection using immuno-globulin does not seem to cause any problems in CFS patients. I have not received any adverse feedback from CFS patients who have used hepatitis A vaccine.

Hepatitis B. If a patient requires HBV for occupational health purposes, clinicians should weigh the pros and cons as previously discussed and then discuss with the patient.

Influenza. If a patient has any medical condition that could be severely affected by an attack of the flu, such as heart disease, asthma, or bronchitis, influenza vaccine should certainly be considered.

My own data indicates approximately 60% of CFS patients experience some form of exacerbation in  their fatigue and flulike symptoms (sometimes quite marked) following an influenza vaccine.

Meningitis C. My feedback from approximately 30 children and adolescents with CFS who have been given the meningitis C vaccine in the U.K. is that there were no serious side effects or exacerbations of CFS symptoms. The only adverse effects reported have been minor exacerbations of fatigue and headache.

Polio and diphtheria. One research study showed evidence that people with CFS do not experience adverse reactions to polio vaccination.⁹ This is also my own impression from feedback received from patients I have advised receive polio boosters in relation to foreign travel.

Polio vaccinations or boosters should clearly be given to patients traveling to countries where polio still occurs. The same advice applies to diphtheria, which is becoming increasingly common in parts of Eastern Europe.

Tetanus. Maintaining up-to-date protection is vital for individuals whose employment (e.g., working on a farm) or leisure activity (e.g., gardening) places them at risk of contracting tetanus.

However, tetanus vaccine can produce side effects in healthy people and may well cause CFS patients to relapse. The pros and cons need to be carefully considered as tetanus vaccine has been reported to precipitate CFS.^1,2

Typhoid. The typhoid vaccine can cause side effects in healthy people. The feedback I received from my CFS patients, however, indicates that the oral form of typhoid vaccine was generally well tolerated.

Whenever vaccinations are considered necessary, they should be given when CFS patients are feeling reasonably well and not under any undue stress. It is also wise to make sure that all travel vaccinations are completed at least two weeks before departure in the event a patient experiences exacerbated symptoms or a relapse.

Not surprisingly, patients with possible vaccine-induced CFS often face considerable difficulty in obtaining disability benefits on the grounds of permanent ill health. However, some of my patients in the U.K. have successfully argued their cases and been awarded injury payments on the grounds that HBV given for occupational health reasons caused their CFS. I am also involved in a number of cases where the debate is likely to be settled in court.

1. Lloyd A et al. What is myalgic encephalomyelitis? Lancet. l988; l: 1286-7.
2. Weir W. The post-viral fatigue syndrome. Current Medical Literature: Infect Dis. l992; 6: 3-8.
3. CIBA Foundation. Chronic Fatigue Syndrome. Eds. Bock GR et al. J Wiley; l993; symposium 173.
4.  Symmons DPM et al. Can immunisation trigger rheumatoid arthritis? Ann Rheum Dis. l993; 52: 843-844.
5. Gross K et al. Arthritis after hepatitis B vaccination. Scand J Rheum. l995; 24: 50-2.
6. Grotto I et al. Major adverse reactions to yeast-derived hepatitis B vaccines—a review. Vaccine. l998; 16: 329-34.
7. Hyde B. The clinical investigation of acute onset ME/CFS and MS following recombinant hepatitis B immunisation. Second World Congress on CFS and Related Disorders, Brussels. 1999; September 9-12.
8. Report of the working group on the possible relationship between hepatitis B vaccination and the chronic fatigue syndrome. Canad Med Assoc J. l993; 149: 314-9.
9. Vedhara K et al. Consequences of live poliovirus vaccine administration in chronic fatigue syndrome. J Neuroimmun. l997; 75: 183-95.

Dr. Charles Shepherd is in private practice in the United Kingdom (U.K.) and is a  member of the Chief Medical Officer’s Working Group on CFS/ME at the U.K. Department of Health.