Microsoft powerpoint - jack melling presentation 9 may final

Overview from USA & UK
research programs
Dr Jack Melling
• Director, UK Microbiological Research Authority, Porton Down• Director, Salk Institute Biologics Development Center, Pennsylvania Consultant:
• United States Government Accountability Office• US Dept. of Veterans Affairs Research Advisory Committee on GWI• International AIDS Vaccine Initiative Research Investment
• US Government investment in research into Gulf War illnesses up to end of 2005exceeds $370 What is the Scope of the Illness?
How Widespread is the Problem?
• Numbers of ill veterans exceed numbers of ill control • Pennsylvania air guard >30% (Fukuda et al 1998) • Kansas veterans >26% (Steele 2000) • New England army veterans >32% (Proctor etAl 2001) • 179,000 US Gulf veterans have Service connected What is the Nature of the Illness?
Is it Physiological or Psychological?
76% of ill Gulf veterans have no identifiable
psychiatric condition (Ismail et al 2002)
Improved tests of autonomic regulation have shown
that an important element of GWI is neurological
• Cognitive functioning in treatment-seeking Gulf War veterans: pridostigmine bromide use & PTSD (Sullivan et al 2003) • Physiological & genetic aspects of autonomic dysfunction in Gulf War veterans (Sastre 2003) Comparison of Evidence Relating to
Exposures. What was the Cause or Causes of
the Illness?
Exposures: Questions to Consider
What evidence is there for “Exposure X” to have
contributed to the chronic symptoms affecting Gulf
War veterans?

• Potential role in combination with other exposures • Potential for a subset of individuals to have been particularly affected due to their location or occupation • Potential for some individuals to have greater Gulf War Exposures in Relation to GWI:
Summary of Evidence
Pattern of exposure compatible with patterns of GWI?
Higher in Ground Troops
Greater exp. In 1990/91 GW
Psychological stressors
Chemical weapons
Oil well fires
Vaccines: anthrax
Number of vaccines
Gulf War Exposures in Relation to GWI:
Summary of Epidemiologic Evidence
Evidence consistently indicates not associated Two studies support sign. Association, higher or with more severe illness: s/r exposure problematic Results inconsistent, may relate to proximity/duration of exposure Very little clear information: s/r problematic, little control for confounding Little information, 1 strong study suggests association Exposures & GWI: Strongest
Evidence for Association
Strongest evidence from epidemiologic studies supports pesticides and PB as causal factors – Animal studies support plausibility, especially when PB combined with – Overall pattern of exposures also support association Two studies support positive association with chemical weapons, but s/r exposure questionable in one – Unknown if exposure extensive enough to explain large proportion of – Brain cancer/Khamisiyah findings could be due to nerve agents, – Animal studies support physiological effects of low dose nerve agent – Neurological impairment 4-5 years after Khamisiyah exposure Exposures & GWI: Little/Poor
Evidence of Association
Very little useful information concerning associations between vaccines and GWI – Significant associations generally modest– Little animal or human research informs plausibility Almost no information concerning likely associations between DU and GWI – Animal studies suggest possible neuro effects– Unknown if similar conditions seen in other deployments with Oil well fires, overall unlikely to be primary cause of GWI – 2 studies identifying higher exposure levels show sign association– Little information re. possible synergism with other exposures– May be associated with diagnosed asthma & other respiratory Consistent findings that psych stressors not associated with GWI – Animal studies suggest possible synergism with other exposures Treatments
No Specific Treatments
Chronic Fatigue Syndrome
USA Department of
Veterans Affairs
Research Advisory Committee on
Gulf War Veterans’ Illnesses
Neurotoxic Substances
published since 2000 showed exposure to a combination of NTS synergistically increased neurotoxicity Chemical Weapons
OSAGWI report indicates potential for very low-level exposures to ~100,000 following Khamisiyah demolitions Multiple reports of other incidents; 80% of chemical targets destroyed More commonly reported by ground troops; UK similar Exposure fairly unique to 1990-91 Gulf War Known Toxic Effects:
Chemical Weapons
• Little known re. low-level chronic effects in humans – Japanese studies indicate chronic symptoms, subtle neuro • Animal studies have identified persistent neurological & immune effects following low-level exposures • Few animal studies have evaluated interaction of sarin Nerve Agents
Animal Data – 16 studies on low-dose sarin exposure Neurological impairment 4-5 years after Khamisiyah exposure Long term effects on survivors of Tokyo terrorist attacks in 1994 Delayed effects in German CW workers from 1930’s Pesticide Exposures
• Multiple compounds used; DOD identified 37; 15 of • Diverse applications: skin, uniforms, tents, bedding, area • OSAGWI report indicates 41,000 potentially • Studies indicate highly correlated use of multiple pesticides, i.e. those who used high levels of one pesticide likely to use higher levels of others • RAND study found higher pesticide use correlated with Known Toxic Effects:
Acute poisoning produces diverse symptoms, delayed neurological Large body of toxicological research on adverse effects of different Community and occupational studies indicate chronic, low-level exposures associated with higher symptom levels Animal studies demonstrate synergistic effects of DEET, OP and Genetic variation (PON1, BCHE, NTE) linked individual
• Military did successfully protect service people • 41,000 Service members may have been • Overexposure may contribute to unexplained Pyridostigmine Bromide Exposures
• More commonly reported by ground troops • Exposure to PB unique to 1990-91 Gulf War Pyridostigmine Bromide
• 7 Epidemiological Studies – 4 since 2000 - have shown association between PB & elevated rates • Rand Review (1999) concluded that PB could Pyridostigmine Bromide (PB)
Known Toxic Effects
• Used for many years to treat myasthenia gravis, • Acute side effects (mostly GI) reported to have affected about 33% of those taking PB during the Gulf War • Animal studies indicate synergy with DEET, permethrin • Preliminary evidence of PB causing severe difficulty for Vaccine Exposures – US Troops
• US combat troops reported most likely to have received Vaccines
• Epidemiological evidence linking multiple • Anthrax Vaccine – Different vaccines for UK



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