Could chronic infection underlie my M.E.?

Published in InterAction 50, Winter 2004

We regret that our medical adviser cannot respond to individual enquiries.

Dear Doctor: Could chronic infection underlie my M.E ?

Given my infective-type symptoms whenever I start to tire (swollen glands, feeling fluey and as if I have a temperature) I cannot help wondering if I have an undiagnosed chronic infection that’s contributing to or underlying my M.E . I’ve read about many different infections being implicated, from bacterial ones like borreliosis and mycoplasma to viral ones like glandular fever, and also parasites. I’ve met people with M.E. who have improved on long courses of antibiotics and am desperate to try and find the underlying cause of my symptoms so I can get them treated.

I managed to get an antibody screen on the N H S which included the chlamydia group and mycoplasma. The results came back that I had antibodies for both meaning that at some time I had been ex posed to them. However, there was no evidence to support current infection. What I would specifically like to know is: Do people with M.E. have viruses or infections that persist and cause typical symptoms of the illness? And if there is evidence of this, what can be done medically (e.g. a trial of antibiotics)? Also, can an initial infectious trigger cause long-term problems to someone who has M.E. even if the virus/bacteria is no longer detectable?

LKS, East Sussex

Clinical Immunologist and AfME Principal Medical Advisor Professor Tony Pinching responded:

For many years, the idea that CFS /M.E. was due to a single chronic infection was widely tested, and very many viral, bacterial and other organisms were considered. However, no consistent and reproducible sign of any specific chronic infection has been found to explain the illness and most investigators now think this idea is not compatible with the data.

The evidence strongly suggests that the same condition can be triggered by many different infections, and also by other non-infective triggers. The infections that can do this include the various viruses that cause glandular fever, as well as enteroviruses and hepatitis viruses; certain bacteria, including Salmonella; and other organisms such as Toxoplasma. In all these cases, there is no indication that the organism persists any differently in people with CFS /M.E. Indeed, if such chronic active infection were found, the diagnosis would not be CFS /M.E., but something else.

Most of the symptoms that we get with active infections such as fever, flu-like feelings, and swollen glands are side-effects of our anti-infective immune defences wheeling into action. Once they have done their job, they normally subside, as do the accompanying symptoms. In CFS/M.E., it is as if these symptoms of immune activation persist, even though the bug has been sorted. Many studies have shown non-specific evidence of such activation, although we don’t yet know if this is primary, or a consequence of something else. [Interestingly, this activation of antiviral immune mechanisms may explain why quite a few people with CFS/M.E. don’t get colds etc, as well as explaining why, if they do get them, they get them worse!]

A useful analogy is that of ripples in a pond after a stone has been thrown in. The symptoms are effects of the ripples, and taking the stone out again will not solve the problem.

The changes in the immune system seen in CFS/M.E. are not ones that would significantly affect the immune markers (e.g. antibody tests) that are used to help diagnose some infections, so tests for persistent infection should still work normally.

Most patients with CFS/M.E. see no benefit in their chronic symptoms from the use of antibiotics (for example during the treatment of other infections that they get), and many find that they temporarily make some symptoms worse. There are, however, a few patients who find that some of their symptoms reduce during or after use of certain antibiotics (though individuals vary in which ones they respond to). I believe this is probably due to effects of the antibiotics other than their action in suppressing bacteria, as antibiotics have a range of side-effects on human body systems, including the immune system.

No large scale trials of antibiotics have been done (and small pilot studies have not been
encouraging ). Furthermore, several large studies of antiviral agents in people with CFS/M.E. following virus infection have not demonstrated any beneficial effect.

CFS Physician Dr Andrew Wright commented:

Based on current published evidence we cannot say that persistent infection is the cause of CFS/M.E. However we can hypothesise about the cause by drawing together several strands of information.

For instance, work from the Vascular Biology Unit at Dundee has shown measurable problems with blood flow in CFS/M.E. patients and in the functioning and shorter life span in the blood of neutrophils (a type of scavenger white cell that is important in fighting infection). These results taken together, plus the findings previously that other white cells i.e. lymphocytes and natural killer cells also don’t work as well and ‘die young’ in M.E. patients, do support the possibility of persistent infection or toxin damage, while not providing definitive proof.

Other researchers have reported finding persistent infections such as chlamydia, mycoplasma and staphylococci. These though are probably opportunistic infections resulting from the imbalanced immunity seen in CFS/M.E. rather than its prime cause. Similarly, I sometimes find moderately high numbers of the glandular fever virus as an active infection and I believe that the effect of M.E. on the immune system causes the virus to reactivate - though not at high enough levels to cause all the symptoms experienced.

I see both people who respond well to antibiotics and those who are made worse by them. However, it may be that the latter reaction is a side effect of bacteria being killed off and so releasing toxic substances into the bloodstream (known as ‘die-off’).

If bacteria exist they are certainly not easily detected and they must also be able to explain the immunological, blood vessel abnormalities and other features of this illness in order to merit closer examination. The unresolved issue is whether symptoms experienced by patients are as a result of persistent infection or an as-yet unexplained autoimmune process triggered by the initial infection. I think myself after looking at the evidence so far available that it is the former, and that one type of bacteria called borrelia may fit all the above criteria as the symptoms of chronic borrelia infection are identical to those of CFS/M.E.

There are 300 types of borrelia so it wont be easy to find out how many may be implicated, and in addition many people may test positive but have few or no symptoms. Other factors such as co-infections, genetic and environmental factors, and how you yourself react to the presence of a bacteria in your system will also prove very important. In order to look at this I have put together a research team with academic and clinical microbiologists to study this possibility, and then maybe one day I can answer the reader’s question more defnitively!

InterAction commentator Dr Kelly Morris concluded:

M.E./CFS is a mixed bag of conditions, so one diagnosis is never going to fit all. However, several groups have implicated chronic infections in the pathogenesis (disease process) of some cases of M.E./CFS and related conditions like fibromyalgia. This hypothesis must be distinguished from the common situation when a bacterial or viral infection is a trigger to the condition, and perhaps sets off chronic immune changes as if the infection does persist.

Two infections that have been implicated by more than one research group are parvovirus B19 and mycoplasmas. But even if the presence of a chronic infection is suspected, this infection could be the cause of symptoms (in which case, strictly speaking, the diagnosis is chronic infection and not M.E./CFS), or it could be a consequence of immune impairment or a secondary factor in precipitating relapse.

What is interesting is that the immune chemicals (cytokines) produced by the body during infections are now known to affect the way in which the brain produces serotonin, a chemical messenger that is important in mood and energy.

Abnormal levels of serotonin have been linked with depression-like symptoms and fatigue, while the build-up of secondary products has been implicated in cognitive changes like brain fog. This pathway is important in developing symptoms seen in flu, for example, and is suggested to have evolved so that people with infections become less mobile and sociable, thus having less chance of passing the infection onto others.

I have had success with long courses of antibiotics to improve fatigue and other symptoms in two people who showed clear evidence of chronic infections (swabs from one person grew a bacterium called Staphaureus, while the other had evidence of an undiagnosed chronic sexual infection that did not respond to usual short-course antibiotics). But I am sure that these anecdotes are not typical of most people with CFS/M.E. and related illnesses.

A recent trial of a year’s treatment for mycoplasma in Gulf War illness found no benefit of antibiotics, and more side-effects than the dummy treatment. I’d suggest that strong clinical evidence of chronic infection and a discussion of potential harms is required before embarking on such an experimental treatment.