Intended for healthcare professionals

Rapid response to:


Chronic fatigue syndrome or myalgic encephalomyelitis

BMJ 2007; 335 doi: (Published 30 August 2007) Cite this as: BMJ 2007;335:411

Rapid Response:

Chlamydia pneumoniae infection a treatable cause of Chronic Fatigue Syndrome

The Editor
British Medical Journal


In your Editorial (BMJ 2007; 335: 411-2), relating to the NICE
clinical guidelines which appeared later in the Journal, you state “We
remain unsure of the causes”. In the guidelines also there is no mention
of the possibility of an infective cause, or of the possible role of
antibiotics in the treatment. NICE remarks that the attending physician
does not need to look for evidence of bacterial or viral infection unless
there has been clinical evidence of such an infection. However, such
evidence can be so mild as to escape mention by the patient. There is
evidence in the literature (1,2,3,4) and considerable anecdotal evidence
(See website that Chlamydia pneumoniae (Cpn) infection
may be the cause in some cases of Chronic Fatigue Syndrome and of the
linked syndrome Polymyalgia Rheumatica (Fibromyalgia), and also that a
trial course of antibiotics is worthwhile(3,4).

Cpn infection is common and frequently involves more than one member
of the family. It exists in two forms. In the initial stage it is
transmitted in an extra cellular form by coughing and may give rise to flu
-like attacks, separated by weeks of continual coughing, often resulting
in chronic laryngitis. In the later stage it changes to being an
intracellular infection, which may be asymptomatic, persisting for life,
or may give rise to symptoms. In the intracellular form the organisms,
coccal in shape, multiply within vacuoles; their cell walls are deficient.
They act on mitochondria, depriving them of ATP; this curtails production
of energy, resulting in symptoms dependent on the cells affected - in
brain and muscle cells, this could result in Chronic Fatigue Syndrome and
in the CNS result in Multiple Sclerosis(5). If present in an inflamed area
such as in muscles, it can
increase the degree of inflammation by up to 5 times, thus causing painful

Because its cell wall is deficient, the antigenic response is low
giving rise to only minimal levels of antibodies. In consequence;
serological tests for diagnosis are unreliable at this stage. This would
explain the negative serology in some reports(6).

Treatment with antibiotics is difficult because drugs have to
penetrate the host cell wall as well as the intracellular organisms.
Treatment needs to be prolonged and pulsed, because of continual
replication of the intracellular forms. Until adequate diagnostic
facilities are readily available treatment needs to be in two stages: the
first stage, which is diagnostic, involves the use of two long-term
bacteriostatic antibiotics for 6 weeks, and the second, meant to be
curative, involves the introduction of a third bactericidal antibiotic.

One possible choice of antibiotics for the first stage is a
combination of Doxycycline and Azithromycin. Initially, the Doxycyline
needs to be given alone in low dosage for two weeks, because of the risk
of a Herxheimer reaction resulting from the release of toxins by damaged
bacteria. Such reactions are usually mild and short-lived. If stable after
two weeks, Azithromycin in low dosage is added for 4 weeks.
Roxithromycin can be used in place of Azithromycin. . Improvement of
symptoms, or the occurrence of a Herxheimer reaction, confirms the

If the diagnosis is confirmed, the second stage involves long-term
pulsed treatment with the above antibiotics, plus the cautious addition of
a third bactericidal antibiotic (e.g. Metronidazole or Tinidazole), with
an appropriate break in giving the third antibiotic if the patient should
have a severe Herxheimer reaction. Mild Herxheimer reactions usually
settle spontaneously and need not interrupt treatment.

The above suggested treatment is based on the David Wheldon Protocol
for Multiple Sclerosis, available on the Internet (Wheldon
protocol/ pneumoniae).


1) Machtey I. Chlamydia pneumoniae antibodies in Myalgia of unknown
cause (including fibromyalgia). J Rheumatol 1997; 36: 1134.

2) Elling P, Olsson AT, Elling H. Synchronous variations of the incidence
of temporal arteritis and polymyalgia rheumatica in different regions of
Denmarj; association with epidemics of Mycoplasma pneumoniae infection. Br
J Rheumatol 1996; 23: 112-9.

3) Chia JK, Chia LY. Chronic Chlamydia pneumoniae infection: A treatable
cause of chronic fatigue syndrome. Clin Infect Dis 1999; 29: 452-3.

4) Moling O, Pegoretti S, Rielli M, Rimenti G, Vedovelli C, Pristera R,
Mian P. Chlamydia pneumoniae – Reactive arthritis and persistent
infection. Br J Rheumatol 1996; 35: 1189-90.

5) Stratton CW, Wheldon DB. Multiple Sclerosis: an infectious syndrome
involving Chlamydophila pneumoniae. Trends Microbiol 2006; 14: 474-9.

6) Komaroff AL, Wang SP, Lee J, Grayston JT. No association of chronic
Chlamydia pneumoniae infection with chronic fatigue syndrome. J Infect Dis
1992; 165: 184.

John Tovey

Retired Clinical Pathologist

Worthing BN12 4NE

Competing interests:
None declared

Competing interests: No competing interests

24 October 2007
John E Tovey
Consultant Pathologist