Around 4% of soldiers returning from the first Gulf War have presented an array of symptoms that includes fatigue, psychological distress, post-traumatic stress reaction, a perception of poor health, and reduced physical functioning.

These have become collectively termed Gulf War syndrome. This condition, some believe, has been caused by the harsh vaccination regimen given before combat, which for many included pyridostigmine bromide (PB) to protect against nerve agents. However, initial findings from an ongoing study have not yet found any evidence of a causal link.

"The main findings, albeit preliminary, for the whole project are that we didn't see any marked short-term effects that are associated with vaccination," said Leah Scott, group leader of biomedical sciences at the Defence Science and Technology Laboratory in Porton Down, UK.

But she is confident that the careful experimental design will give a sound test of the hypothesized link. "If these combinations of vaccines and PB have an effect, we'll see it in this model," Scott asserted.

The model species is the common marmoset, Callithrix jacchus, a primate that Porton Down has extensive experience working with. The experimental design consists of four treatments: controls receiving just saline; those getting a cocktail of vaccines and saline; another group being given PB and saline; and a final cohort treated with both the vaccines and PB to represent the worst-case insult that a soldier's immune system would have been subject to.

The marmosets are being monitored for changes in body mass, behavior, sleep pattern, brain activity, muscle function, endocrinology, and immunological status for a period of 18 months. Three months after treatment, the marmosets are doing well and not showing any significant changes that can be attributed to the vaccinations.

"The Porton Down studies are welcome because they're tightly controlled," said Simon Wessely of the Gulf War Illness Research Unit at Guy's, King's and St Thomas' School of Medicine in London. "On the other hand, marmosets are not men," he said.

Wessely has led UK epidemiological research suggesting that veterans of the first Gulf conflict who were immunized out in the Gulf, or "in theater", were more likely to suffer from these illnesses than those that had been vaccinated before deployment. "The pattern of multiple anthrax vaccination in theater is weakly associated with the symptoms," said Wessely.

In theory, the stress experienced by troops in situ could have elevated their cortisol levels, says Wessely, rendering their immune systems less able to deal with the immune challenge of vaccination. "In a setting of high cortisol, you get a Th1 to Th2 shift," he said. Although yet to be replicated, Wessely told BioMedNet News that in the current Gulf conflict, the UK Ministry of Defence (MOD) tried to take this research on board. "As a precautionary measure, the MOD did try to vaccinate before theater in a more planned, calm setting," he said.

When all the Porton Down marmosets have completed 15 months of the 18-month experiment, their immune systems will be faced with a previously unseen antigen. "We want to test the competence of the different treatment groups to respond to a challenge," said Rebecca Hornby, who presented results of her immunological analysis in a poster at the 3rd International meeting of the Edward Jenner Institute for Vaccine Research held here in Oxford.

Another poster was presented recently at the annual meeting of the British Toxicology Society, which revealed the initial analysis of the marmoset behaviour, sleep patterns, brain activity, muscle function, and body weight. No significant differences between the four treatment groups were found.

The study will have finished by the end of the year, says group leader Scott, who thinks the results will be of huge interest in both the UK and US. "Congress knows about this ... and is keenly awaiting the results," she said.

US Department of Defense .