Date: 5th March 1995
INTRODUCTION
A recently published survey by Hubert & Lison 1 has shown that pre-treatment with low level doses of the anti chemical warfare agent, PYRIDOSTIGMINE BROMIDE (PYR) causes muscular damage in experimental animals. Under normal conditions, no muscle damage occurs at the 30% Acetylcholine Esterase (ACE) inhibition level used to protect troops from possible chemical weapon attack. However, when the same PYR treated animals experimental animals are exercised strenuously, extensive muscle damage occurred.
Pyridostigmine (3x30 mg/day) was given to UK Gulf personnel and to USA personnel (n = 400000) as part of the NAPs anti-chemical weapon package. Some of the USA and Coalition personnel (GWVs) would inevitably be involved in heavy physical activity and most would be subject to varying degrees of heat stress.
The reported major long term adverse symptoms in affected UK Gulf War Veterans (n = 150) include: headaches, and short term memory loss (43%), chronic fatigue on moderate exercise (27%), gastric reflux (22%), henieric diarrhoea (16%) and a smaller incidence of other symptoms. This is very similar to the symptoms reported by sheep farmers (n = 400) showing adverse reactions to OPs sheep dip.
There is little evidence of extensive exposure of GWVs by organophosphate (OP) chemical warfare agents: Tabun, Sarin, Soman or VX. Though this possibility should not be totally discarded. Other exposures to OPs include heavily insecticidal treated clothing and tentage. For USA forces the major insecticide was DEET which acts synergistically with the carbamate pyridostigmine. Both carbamates and OPs inhibit acetylcholinesterase (ACE), by binding to the same site on the enzyme required to recycle the neuro-transmitter, acetylcholine. This neuro-transmitter is present in peripheral nerve synapses, neuromuscular synapses, gastric and intestinal glands and the brain.
My preliminary research shows the presence of OP antibodies in the blood of affected sheep farmers. As OP molecules are too small to be antigenic it is presumed that when OPs bind to a number of protein esterases and serine proteases, they become antigenic. This will lead to the production of antibodies. This is the case in the rare muscle fatigue disease MYASTHENIA GRAVIS where auto-antibodies are present in the blood, against the acetylcholine receptor proteins on muscle membranes.
The expected muscle damage induced by PYR in exercise stressed GWVs, will release nerve and muscle proteins into the bloodstream. In some patients auto antibodies may be produced to nerve and muscle tissue. As a first step, MYASTHENIA GRAVIS auto antibody tests could be made on GWVs reporting chronic fatigue on exercise. If no acetylcholine receptor auto-antibodies are present the auto antibody screening could be extended to a range of muscle and nerve proteins.
If PYR functions immunologically, in a similar way to OPs in affected sheep farmers, then PYR antibodies may be present in affected GWVs and could be tested for. Antibodies to the OPs: Diazinon and Propetamphos were present in affected sheep farmers but not in the majority of control subjects. PYR may link to nerve and muscle proteins to become antigenic though this has yet to be tested experimentally. Tests for nerve and muscle auto antibodies are more routine and are available at specialist centres in the UK.
It is likely that other immunological changes are present in GWVs. In OP exposed farmers there are increased rates of non Hodgkin Lymphoma and soft tissue Sarcomas. Changes in numbers of special classes of immune cells are probably responsible for these carcinomas and an study Natural Killer Cells and T lymphocytes etc. in GWVs should be examined.
A number of auto-immune diseases are recognised with rheumatoid arthritis perhaps the most common. If auto antibodies are present in GWVs then a range of immune suppressing drugs may be candidates for the control of the condition. It is outside of my expertise to suggest which drugs may be effective but as in rheumatoid arthritis immune suppressants have varying degrees of efficacy.
In the case of OP exposed farmers and their families it appears that mild exercises (swimming) and good nutrition may help to alleviate the chronic fatigue symptoms. Mineral supplements containing zinc and calcium, the B complex vitamins (B6, B12, folate), and essential fatty acids (evening primrose oil and fish liver oils) are inexpensive and readily available. This may be a useful option, while more detailed pharmacological interventions are examined.
1) Study of muscular effects of short term pyridostigmine treatment in resting and exercising rats.
Herbert M & Lison D human & Experimental toxicology (1995) 14 pp 49-54
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