by Dr. Stephn Straus, NIH
Lancet, Volume 353, Number 9148, 16 January 1999
Over 50000 British, Canadian, and American troops returned from battle as changed men. Once-vital young men who left to engage a foreign tyrant began to complain of breathlessness, grinding fatigue, irritability, headache, insomnia, and paraesthesias, rendering 70% of them unfit for further duty.[1] 5 years later, fewer than one in six had recovered fully.[2]
Specialised research units were commissioned and the best medical minds were enlisted to study these men, to formulate therapeutic approaches, and to devise strategies for preventing similar outcomes in future military campaigns. Reports were published of vascular instability, hyperventilation, bacilliuria, and other physiological and laboratory anomalies in the veterans. Some reports claimed that the fear of injury and exposure to poison gas had emotionally crippled these young men, especially those with inherently weak constitutions.[3,4]
The year was 1918. And the medical legacies of service in the Great War, as well as the debates about their origins and management, like those documented for other major campaigns since the Crimean War,[5] are as relevant today as then. On Aug 2, 1990, Iraqi troops invaded Kuwait. After 39 days of preparatory bombing, a multinational coalition launched, on Feb 24, 1991, 4 days of crushing land, sea, and air assaults that neutralised Iraqi resistance, and restored Kuwaiti sovereignty. The campaign included some 697000 US troops, 45000 British, and 4500 Canadian. Analysts predicted as many as 40000 Allied casualties, but only 148 men died in combat and 467 were injured among US units. Many more, though, had been drilled to respond to poison-gas attacks, had been vaccinated to withstand likely biological weapons, had witnessed Iraqi corpses littering the desert, had inhaled the smoke from burning oil wells, and had survived SCUD missile attacks.
In January, 1992, unexplained chronic illnesses were recognised among Gulf War veterans in an army reserve unit based in Indiana, USA.[6] Additional reports of ill veterans precipitated rancorous debates as to the nature of the "Gulf War syndrome" and whether it was being responsibly addressed. Several scholarly committees investigated the problem[7,8] and advised allocation of targeted research funds that, in the USA alone, have by now exceeded $115 000000.
Two papers in this issue of The Lancet are products of that research enterprise. The primary paper, by Catherine Unwin and colleagues, is one of the most definitive epidemiological studies of Gulf War veterans conducted to date. Extensive questionnaires about deployment, exposures, symptoms, and illnesses were mailed to some 4000 Gulf War veterans, and to similar numbers of men who served elsewhere during the same year, and of men who served later in Bosnia. The dominant finding was that the Gulf War veterans were roughly twice as likely as members of the other military cohorts to report chronic fatigue, irritability, headache, and other symptoms, which were remarkably similar to those reported after the Great War. The Gulf War veterans also showed higher levels of psychological distress. Statistical adjustment for such distress did not eliminate the differences between the three cohorts.
These data verify in British troops what had been reported previously in Canadian and US veterans--namely, that service in the Gulf War posed an exceptionally high risk of a long illness. Surprisingly, as debilitating as these illnesses were reported to be, in the aggregate they did not lead to higher rates of divorce or unemployment. Unwin and colleagues' report, however, does show that the increased risk of developing chronic illnesses with physiological and psychological features after Gulf War service extended to all branches of the military and to both active-duty and retired men. Moreover, the risk of illness correlated significantly with potentially harmful exposures. Although members of the other two military cohorts were exposed at lower frequencies to some of the same deleterious factors, for all three cohorts such exposures correlated with increased risk of illness. Among these factors, vaccination against plague and anthrax before deployment to the Gulf correlated highly with illness. The investigators speculate that these vaccines--more so than the routine ones given to service personnel--had unanticipated effects. For instance, knowing that one is being prepared for biological warfare is frightening. Furthermore, vaccines induce the release of potent cytokines, the neuroimmunological effects of which might be most evident in an individual already subjected to other significant physiological and psychological assaults.[9]
The accompanying paper, by Khalida Ismail and colleagues, used factor analysis, a complex statistical method of revealing categories of symptoms referable to particular body systems that best define and contribute most to the severity of an illness. A similar, well-controlled modelling study has been reported by Fukuda and colleagues.[10] Both studies concluded that the types and clustering of symptoms in Gulf War veterans are unlikely to reflect a novel or unique disease. A major feature, however, of Fukuda and colleagues' study was the construction of a case-definition of a chronic multisystem illness among the veterans by incorporation of the key elements that the researchers had found to be most predictive of illness. The researchers then compared the results of physical examinations and extensive laboratory investigations of veterans who met these criteria with those of veterans who did not, and they found that a unique Gulf War syndrome could not be delineated.
The cumulative studies now confirm that there is no unique Gulf War syndrome. Although the possibility of some still unappreciated environmental factor cannot be dismissed entirely, the Gulf War seems to differ from others only in a quantitative sense and in the intensity of public discourse about it. There were highly prevalent exposures that, together with the fear of injury and death from unseen nuclear, chemical, and biological weapons, made service in the Gulf War more hazardous than the mere "body count" would suggest. Perhaps it was the very lack of mutilation and death in that war that permitted the true physical and emotional costs of battle to be revealed.
On the assumption that these conclusions are correct, there are limited means of preventing chronic illness in future wars. Unless those wars are to be fought solely by machines, the human cost of warfare will remain high. The troops must be prepared both physically and emotionally for combat, be provided with routine health surveillance afterwards, and be given a commitment for all necessary care for war-related illness. Military scientists also need to undertake prospective studies to define the pre-existing attributes of an individual and the experiences that contribute most to the risk of long psychological illnesses. The outcomes of such studies will undoubtedly benefit the victims of similar illnesses among the larger civilian population.
Stephen E Straus
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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2. Grant RT. Observations on the after-histories of men suffering from the effort syndrome. Heart 1925; 12: 121-42.
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5. Da Costa JM. On irritable heart: a clinical study of a form of functional cardiac disorder and its consequences. Am J Med Sci 1871; 121: 17-52.
6. DeFraites RF, Wanat ER, Norwood AE, Williams S, Cowen D, Callahan T. Investigation of a suspected outbreak of an unknown disease among veterans of operation Desert Shield/Storm, 123rd Army Reserve Command, Fort Benjamin Harrison, Indiana, April 1992. Washington, DC: Walter Reed Army Institute of Research, 1992.
7. Office of the Under Secretary of Defense for Acquisition and Technology. Report of the Defense Science Board Task Force on Persian Gulf War Health Effects. Washington, DC. June, 1994.
8. Health Consequences of Service during the Persian Gulf War: Recommendations for research and information systems. Washington DC: National Academy Press, 1996.
9. Rook G, Zumla A. Gulf War syndrome: is it due to a systemic shift in cytokine balance towards a Th2 profile? Lancet 1997; 349: 1831-33.
10. Fukuda K, Nisenbaum R, Stewart G, et al. Chronic multisystem illness affecting Air Force veterans of the Gulf War. JAMA 1998; 280: 981-88.
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