WASHINGTON, Oct. 27 (UPI) -- Preliminary studies obtained by United Press International show serious and potential life-threatening problems with a potential anthrax treatment the U.S. government is developing.
Anthrax immune globulin, which the government is developing as a possible treatment in the event of a bioterror attack, protects animals from death if given prior to exposure to toxins from Bacillus anthracis, the anthrax bacterium, but if the compound is formulated incorrectly it can be fatal and it did not prevent death when given after exposure.
Some anthrax immune globulin, or AIG, already may have been placed in the Strategic National Stockpile for emergency use, but at least one expert warned that the research data show the compound does not appear to be effective and actually could kill people.
The Centers for Disease Control and Prevention in Atlanta initiated the animal studies last year, and the Department of Health and Human Services recently awarded a contract to Cangene, a Canadian biotech company, for approximately $428,000 to supply 10 grams of AIG for further testing. HHS researchers have been given a year to finish the studies and decide if the government should order up to 100,000 doses.
The government is interested in developing AIG as an alternative anthrax treatment due to the high mortality rate from the 2001 anthrax letters that killed five people. The death rate was 45 percent, even when intensive-care treatment and antibiotics were administered, and future bioterror attacks could involve anthrax that has been genetically engineered to evade current antibiotics, the CDC noted in its report on the animal studies.
The CDC published a notice in June in the Federal Register that the results of the studies were available, but the agency, for reasons it has not explained, delayed sending the results to UPI until this week -- more than four months after the Federal Register notice and several weeks after HHS awarded the contract to Cangene. The biotech firm, based in Winnipeg, Manitoba, said it was not involved in the animal studies and would not be involved in the additional studies being conducted by HHS.
CDC spokesman Dave Daigle requested that UPI e-mail him questions about the studies, but then did not respond with comment.
"Obviously they can't use this stuff," said Dr. Meryl Nass, an anthrax expert and a physician in Bar Harbor, Maine, adding she would become concerned if officials tried to use it on an emergency basis in the event of another anthrax attack.
"It might kill people," Nass told UPI.
AIG is obtained from the plasma of soldiers who have been inoculated with the anthrax vaccine, which has had a controversial history. The military requires all servicemen to receive the vaccination, but some have objected because they claimed it caused chronic health problems, including dizziness, muscle and joint pain and sleep disruption. Others have said the vaccine may have played a role in causing Gulf War Syndrome. Federal officials, including some in the military, have insisted the vaccine is safe.
In the AIG studies, rats that received a high-enough dose of the compound prior to being injected with anthrax "were completely protected," concluded the CDC report -- which does not cite the names of the researchers who wrote it. The animals survived until the end of the study, which lasted 48 hours.
AIG administered after exposure to anthrax may not confer much protection, however. Rats that received the compound 5, 10 or 20 minutes after being injected with anthrax died within approximately three hours. Only those given AIG immediately after the anthrax injection survived the entire 48-hour study period.
Nass said a study period of 48 hours was short and "very odd." With most animals, it takes a few days before they die from anthrax, so this raises the question whether the rats that were alive after 48 hours would have continued to survive if the study had gone on longer, she said.
Nass also questioned the rationale for administering AIG only up until 20 minutes after the anthrax exposure.
"That means it doesn't work," she said. "You're never going to give it to a human that fast."
Under real-life conditions, a person probably would not become aware of the exposure and the need for treatment lasting a day or two, she said.
The CDC studies also indicate AIG can be deadly under certain circumstances. A separate experiment in rabbits found that a high dose was fatal in all the animals the received it.
"Since there were deaths among 100 percent of rabbits receiving 40 mg/kg AIG intravenously ... a thorough safety evaluation has been initiated," the report stated.
The investigators determined the likely problem was a change in formulation of AIG. The concentration had been doubled from 5 percent to 10 percent for the rabbit study. This was done to increase the potency of the compound and to reduce the amount needed to protect the animals.
"Evidence suggests that this likely clogged the renal tubules, causing an acute toxic nephropathy (acute tubular necrosis) that was seen on necropsy in the dead rabbits," the CDC team concluded in the study.
The problem appeared to be the higher concentration of AIG combined with the fact that it was prepared in a freeze-dried formulation meant it required more time to dissolve into solution.
A less-concentrated dose of AIG still may cause problems, however. In one study, all four animals that received a less-concentrated formula "experienced rapid breathing and (one of the four) experienced diarrhea," the report noted.
The final sentence of the report said the CDC decided that switching the AIG formulation to a 5 percent liquid version may avert some of the dangers of the compound, and the agency "is currently planning animal studies to evaluate AIG dosage and efficacy."
The report does not mention whether those studies ever were conducted or what the results were.
John Langstaff, president of Cangene, told UPI his company recently shipped a supply of AIG to the CDC, which "still has some ongoing activities."
The HHS studies of AIG involve "testing to see if it's safe," Langstaff said.
Cangene was not participating in those studies, but the company would be involved in human clinical trials if HHS elects to pursue development of AIG, he said.