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Health and exposures of United Kingdom Gulf war veterans
- Malcolm Hooper (6 June 2001)
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Malcolm Hooper, Emeritus Professor of Medicinal Chemistry University of Sunderland
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malcolm.hooper{at}virgin.net Malcolm Hooper
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Editor,- I welcome the publication of recent papers by Cherry and her collaborators.[1] [2] Although they form part of a large number of epidemiological studies, referenced by the authors, based solely on questionnaire data they do add significantly to the understanding of the ill-health of Gulf War Veterans (GWVs). The limitations of such studies are recognised by the authors, for example, the lack of any baseline information prior to the Gulf war, the lack of any exposure data for the period spent in the Gulf, and the absence of many records. Once again there has been found an excess of the numbers and severity of symptoms amongst GWVs compared with a carefully chosen control group. It has been shown that these important and disturbing findings cannot be attributed to either excessive smoking or drinking amongst the veterans. The analysis of the data also clearly shows that the GWVs are reliable and accurate in their recall of information even in the extensive absence of official records. The abject failure in record keeping/preservation by the Ministry of Defence is again identified. However, 10 years after the Gulf War it is cause for considerable concern that only very limited clinical studies of the health of GWVs have been reported in the UK. The first major finding identifies an association of severity of symptoms with pesticide handling in a manner that suggests a causal connection with peripheral neuropathies. This is new and accords with individual eyewitness accounts from the field[3] and some longstanding clinical studies. The second major finding confirms the association of symptoms and severity with the numbers of vaccines administered. It does not support the contentious and highly criticised,[4] and subsequently modified,[5] claim that only vaccines given in theatre were associated with excessive symptoms and severity. The case made by the authors would have been considerably strengthened if they had recognised important clinical studies and investigations already carried out on some GWVs both in this country and the USA. Jamal et al have reported a small clinical study on UK veterans that identified peripheral neuropathy similar to that found in organophosphate-poisoned farmers.[6] [7] Mackness and coworkers have found, across all genotypes, a reduction of approximately 50% in the blood levels of PON 1, an enzyme with a key role in the metabolism organophosphate pesticides.[8] PON 1 plays an important protective role in the cardiovascular system[9] and in the aetiology of diabetes related damage.[10] In the United States Haley, whose epidemiology has been much criticised,[11][12][13] identified three major syndromes[14] [15] two of which, confusion-ataxia and arthro-myo-neuropathy, were associated with adverse reactions to NAPS tablets (pyridostigmine bromide). Arthro-myo-neuropathy syndrome was also strongly associated with the (excessive) use of the insect repellent DEET. Impaired cognition was associated with the wearing of flea collars. All these exposures feature prominently in the analysis carried out by Cherry and her co-workers.[1] [2] Crucially, after his epidemiological survey, Haley investigated the sick veterans clinically. He identified extensive and 'generalised injury to the central, peripheral, and autonomic nervous systems.'[16] More recent papers have shown both functional and structural deficits in the central nervous system including the left basal ganglia, and brain stem.[17] [18] This accords with the 'poor functioning of the central nervous system' associated by Cherry et al with their neurological factor which was not dissected further to explore only central nervous system effects. Haley has also shown significant variations in PON1 enzyme levels, which varied with the genotype.[19] Abou-Donia has shown, in animal studies, that there is synergism between insecticides of different classes, organophosphates and pyrethrins, which is exacerbated with DEET.[20] He has found specific antibodies to neuronal markers in one boy exposed to chlorpyrifos,[21] the major organophosphate used by the Americans in the Gulf. Despite the initial and vehement denial of the use of organophosphates by UK forces it emerged that these had been used extensively,[22] and with very little control.[3] [23] Furthermore the trained operatives were not supplied with effective protective clothing to carry out spraying and dusting with these insecticides.[3] [23] Although UK authorities have strenuously denied any exposure to nerve agents and other chemical warfare agents,[24] it is clear that the Americans now recognise that a substantial number of their troops were exposed to low levels of nerve agents which produced only transient and in some cases no immediate symptoms.[17] [23] [26] Eye witness accounts support this view.[3] [26][27] The 'cholinergic triple whammy' of NAPS, organophosphate insecticides, and nerve agents would be expected to exert severe and extensive effects on the central, peripheral, and autonomic nervous system. The use of NAPS has been heavily criticised,[28] and is consistent with the high incidence of side effects reported: approximately 50% in the army.[2] Recently a tilt table study of the widespread loss of cardiovascular autonomic control among veterans has been announced in the United States.[29] Baumzweiger includes assessment of orthostatic hypotension in his examination and treatment of sick veterans in the United States.[30] All this evidence provides very convincing support for a causal relationship between exposure to NAPS, pesticides, and DEET in the health of the GWVs. The study provides very strong evidence for the reliability and accuracy of the responses by GWVs even in the absence of records-over all only 27.5% of GWVs have any vaccination records. Although the Ministry of Defence has insisted that no more than 10 different vaccines were given to the veterans[24] [28] it is noteworthy that 11% reported receiving 10 or more vaccines. The association of ill health with numbers of vaccines administered is consistent with other studies.[31] What is lacking, along with most of the records, is the time frame for these inoculations. Adverse effects are well known when too many vaccines are administered too close together. The theoretical proposal of Rook and Zumla[32] concerning a possibly severe disturbance of the Th1/Th2 ratios is referred to, but not the work of Nicolson[33][34] and Vodjani[35] who have found mycoplasma species, particularly M fermentans incognitus, in about half of American veterans examined. These are also present in other chronic illnesses, myalgic encephalomyelitis, ME, fibromyalgia, and rheumatoid arthritis where a compromised immune system is thought to play an important role in the pathology. Repeat cycles of powerful antibiotics, with appropriate support for the gut, have proved an effective therapy in some of these cases.[36] A major study is presently under way in the States with doxycycline and ciprofloxacin.[37] An important aspect of the widespread exposure to many and varied toxins in the Gulf is the question of synergy. Can the important data base assembled by these investigators be used to explore this question? Synergy is known for pesticide exposure.[20] The well documented effects of organophosphates on the immune system in man,[38] which were deliberately ignored by the COTS Committee,[39] provide a further example of possible synergistic or at least additive adverse effects. The immune system has suffered from more than the obvious exposure to vaccines. Exposure to oil and smoke was consistently identified with severity (the best indicator) of symptoms but dropped from further consideration of the respiratory factor after allowing for other exposures. It is not clear what these factors are, but NAPS and organophosphates and vaccines are all known to exert profound effects on the respiratory system and would be expected to exert synergistic or additive adverse effects. Adverse effects from exposure to oil and smoke have been reported and would be expected,[40][41][42][43] although official publications deny any such possibilities.[44] Although the authors report a study drawing attention to the importance of gastrointestinal symptoms[45] they do not emphasise the association with such symptoms in their own study. Table 6 in Part I shows that the gastrointestinal factor is significant in all veterans ranging from the essentially well (cluster 2) to the most severely affected (cluster 6). Our own preliminary studies have identified the importance of gastrointestinal dysfunction as a major factor, in a small sample of GWVS, which responds to dietary changes.[46] The arbitrary division of exposures into three factors includes, 'factors reflecting individual susceptibilities'.[2] These encompass 'felt that life was in danger', sought medical attention in Gulf, and experienced side effects from NAPS. A much greater factor in personal susceptibilities is the biochemistry of the individual and his or her capacity for handling external chemical and biological toxic insults. The importance of the varied and extensive cytochrome P-450 enzymes confer remarkable variations in susceptibility to xenobiotics.[47] The association of genetic halotypes with some major chronic autoimmune diseases is well known.[48] This susceptibility could well lead to a range of vaccine induced illnesses. However the conflicting data on PON 1 levels[3][19] illustrates the urgent need for further studies of all these important issues. The very low reporting of possible exposure to depleted uranium (DU) was understandable at the time the questionnaires were completed. However, recent events, including leaks of official military documents and memos,[24] [49][50] as well as the identification of DU in the urine of GWVs,[51] and people living in Yugoslavia,[52] indicate widespread exposure has occurred in areas where DU munitions have been used. An independent report commissioned by the American veterans surveyed 10 000 veterans and found the 75-80% had been in areas where they could have been exposed to DU.[53] [54]
The data and analysis presented in these papers is consistent with
the thesis that the exposure of GWVs to an excessive load of many and
varied chemical and biological toxins is responsible for the adverse
health effects they are now suffering.[6][7] [14][15][16][17] [28] [54]
M Hooper 1. Cherry N, Creed F, Silman A, et al. Health and exposures of United Kingdom Gulf war veterans. Pt I: the pattern and extent of ill health. Occup Environ Med 2001;58:291-8. |
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