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
Pesticides
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
• Fibromyalgia
• Chronic Fatigue Syndrome
USA Department of
Veterans Affairs
Research Advisory Committee on
Gulf War Veterans’ Illnesses
website: www.va.gov/RAC-GWVI
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:
Pesticides
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
Pesticides
• 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

Source: http://www.britishlegion.org.uk/media/33801/conf07profjackmelling.pdf