WASHINGTON, Feb. 8 (UPI) -- A military doctor who linked brain damage in several soldiers to a controversial malaria drug now says he doesn't know whether the drug played any role in those disorders.
The doctor, Navy Cmdr. Michael Hoffer, said he changed his mind based on new information. Critics of the military's handling of the drug, called Lariam, say it fits a pattern of not acknowledging severe side effects -- and that Hoffer was overruled.
"The military is stonewalling again," said Jeanne Lese of Lariam Action USA, an advocacy group for people who believe they have been harmed by the drug. "These GIs deserve better than this."
Hoffer is co-director of the Pentagon's Spatial Orientation Lab at Naval Medical Center, San Diego. Beginning last spring he diagnosed several service members who served in Iraq and Afghanistan with vestibular -- or balance system -- disorders resulting from damage to a nerve in their brainstem.
Hoffer said then that side effects of Lariam were the likely cause of the damage. He put the terms "Lariam-induced" and "Drug Toxicity Malarials" in two soldiers' medical records reviewed by United Press International.
Hoffer told UPI in an interview Friday that he subsequently learned the soldiers had other risk factors that could explain the brain damage and therefore decided to discontinue citing the drug. The records now state that the disorder is "of unknown origin in individual stationed in Afghanistan or involved in OIF (Operation Iraqi Freedom)."
One soldier said Hoffer told him he was pressured "from the top" to drop all references to Lariam toxicity -- a charge Hoffer called "a lie."
"That's what he told me," said the soldier, who requested anonymity because he feared repercussions. "I asked him, 'Is that your decision or who's telling you that you can't use that any more?' And he told me it comes from 'the top.' When I asked what does the top mean he just said, 'The top.' I said top Navy, Pentagon, DoD? And when I said DoD he just shook his head, like up and down, yes."
"He doesn't agree with it," the soldier added. "He said, 'You as well as I know this is what 99.999 percent caused it.'"
"That's a lie," Hoffer told UPI last week in a telephone interview. "I never told them I was ordered to do that, and I didn't do that. What I did was make the medically appropriate diagnosis when I was seeing different individuals." He said the first few soldiers he diagnosed told him their only possible risk factor was taking Lariam.
"When I started seeing another several individuals, they admitted to a number of other exposures, a number of other things that could have caused their dizziness, things like jet-fuel exposure, things like noise, things like head trauma, et cetera. So of course after about the second or third person I started making the medically appropriate diagnosis of unknown etiology (cause) because there's no way to know which of the many things caused the disorder."
In January Sen. Dianne Feinstein, D-Calif., wrote Secretary of Defense Donald Rumsfeld citing Hoffer's work and asking that it be included in an ongoing Pentagon study of whether malaria drugs, in particular Lariam, have caused health problems in soldiers. She first raised the issue last June, shortly after Hoffer's initial findings of "Lariam toxicity," writing to Health and Human Services Secretary Tommy Thompson that "six U.S. service members have been diagnosed with permanent brainstem and vestibular damage from being given this drug."
Lariam has been at the center of controversy over whether it has caused mental and physical problems among soldiers serving in Afghanistan and Iraq, where it was widely prescribed. The Food and Drug Administration warned in 2003 that it might be linked to suicide, and after the Army largely quit using it in Iraq the number of suicides there fell by at least half in 2004.
The issue of Lariam's side effects in the military first surfaced after three Army Special Forces soldiers who served in Afghanistan killed their wives, and subsequently themselves, after returning to Fort Bragg, N.C., in the summer of 2002. A team from the Army Surgeon General's office ruled out Lariam as a common factor in the rash of deaths, citing two other homicides that occurred that summer involving Army personnel who were not deployed and did not take the drug.
Critics said that was an effort to avoid looking at the effect of the drug on the soldiers who did serve in Afghanistan by expanding the "cluster" of deaths under review. (Last Thursday at Fort Bragg another Special Forces soldier who had been stationed in Afghanistan shot and wounded his ex-wife and her boyfriend, then shot and killed himself, police said.)
Lese, the Lariam Action director, said she sees parallels between that investigation and the military's handling of the vestibular cases in San Diego.
"It's just like Fort Bragg," she said. "By dismissing conclusive results of clinical tests done by their own physicians, the military deprives soldier-patients and their families of vital information about the cause of their illness. This puts these patients at even greater risk of doing themselves more damage and leaves their families in limbo."
UPI obtained copies of Army correspondence that suggests that the Office of the Surgeon General was closely monitoring the San Diego cases and Hoffer's opinion linking the disorders to Lariam, which is known generically as mefloquine. The letter refers to Dr. Paul Cordts, director of health policy and services for the Surgeon General's office.
"We have just been contacted by COL Cordts at OTSG reference Mefloquin (Larium) as an ototoxic (ear-damaging) agent, indicating the information from Balboa (San Diego) concerning this is spurious," read a Dec. 1 letter written by Col. Nancy J. Burt of the Army's Physical Evaluation Board, which rules on disability cases. The letter, to a doctor at a military hospital, recommended "modifications accordingly" in records of one soldier.
A spokesman for the Surgeon General's office did not respond when asked whether anyone from that office pressured Hoffer or his superiors to drop the Lariam reference. But it is clear they did not believe the mention of Lariam was appropriate. In a statement to UPI, the spokesman said:
"There is a difference between making a diagnosis and attributing a cause or causes for that diagnosis. Epidemiologists have the training and expertise to do the latter." Noting that an epidemiology team has since looked at the data, the spokesman said, "Dr. Hoffer's diagnoses are not at issue; our concern is not assigning cause until after the epidemiology study is complete."
That study is complete and is being reviewed, according to Capt. Michael Brady, a spokesman for the Navy Bureau of Medicine and Surgery. Brady said the Department of Defense ordered the study because it was "obviously interested to see if Lariam, or if any substance or any cause or combination of causes, is resulting in vestibular damage to individuals. They convened a group of research experts. The basis of that study was the initial diagnosis that we had learned, and that came from Hoffer, that this could possibly be attributed to Lariam.
"They looked at not only the population of people who presented themselves to Dr. Hoffer but other individuals who had deployed to the Middle East that possibly had taken Lariam, or people that have vestibular problems that didn't take Lariam. All those were factored into that study."
Lariam's official product label, under "Adverse Reactions," lists "vestibular disorders" and "dizziness or vertigo, loss of balance." The presence of those terms on the label, while not "proof" in the sense of a scientific study, show that such events are associated with the drug and that medical providers and patients are on notice they could occur.
The label also states, under general precautions: "Caution should be exercised with regard to activities requiring alertness and fine motor coordination ... as dizziness, a loss of balance, or other disorders of the central or peripheral nervous system have been reported during and following the use of Lariam. ... These effects may occur after therapy is discontinued due to the long half-life of the drug."
Lariam was invented by the Army's Walter Reed Institute of Research in the 1960s, which licensed it to Swiss pharmaceutical giant Hoffmann-La Roche; it has been approved for use in the United States since 1989. Increasing warnings have appeared on the official product label and now include aggression, hallucinations, paranoia and psychosis. The FDA ordered in 2003 that everyone prescribed the drug be given a written caution about potential side effects, including mental problems and reports of suicide. Fewer than 20 drugs come with mandatory written warnings.
In 2003 the Pentagon grew concerned over a spike in suicides in Iraq, where Lariam was prescribed, and sent another team from the Army Surgeon General's office to investigate. That team did not look at Lariam use, but Army officials said it was not a factor in any of the 24 suicides. In the year ending in October 2003 the Pentagon wrote 45,000 prescriptions for Lariam.
The Army largely quit using Lariam in Iraq in 2004 -- citing a lack of malaria risk -- and UPI reported last month that the number of suicides plunged by at least half, from 24 in 2003 to nine in 2004, with three deaths still under investigation. The Army attributed that decline to better mental healthcare and heightened awareness of suicide risks.
A scientist who has advised the military on malaria prevention said that doesn't hold up. He asked not to be named because he holds a sensitive position.
"There really can be no doubt that the decision to drop the use of mefloquine played a large part in the fall in suicide numbers," he said. "This very dangerous drug, of course, should never have been prescribed for Iraq in the first place.
"As the World Health Organization and every book on travel medicine points out, the malaria parasites in that region are sensitive to chloroquine alone -- which is an older and much safer drug." The Centers for Disease Control and Prevention also has long recommended chloroquine as the drug of choice for Iraq.
After a six-week investigation, UPI reported three years ago that mounting evidence suggests that Lariam has led to such severe mental problems that in a number of cases it resulted in suicide. Last year UPI reported that a startling pattern of violence and suicide by Special Forces soldiers followed their use of Lariam.
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