thedrifter
02-28-06, 06:49 AM
02.27.2006
Laboratory Rats Suffer Same Fate as Soldiers Who Took Anti-Malarial Drug
By Nathaniel Helms
A half-dozen laboratory rats given Mefloquine, a controversial and some say terribly dangerous anti-malarial drug linked to everything from homicide to suicide in service members who took it in Iraq and Afghanistan and then killed their loved ones and themselves in alarming numbers have displayed the same frightening neurological symptoms.
On March 1 Army scientists are going to release their finding in a medical journal called Antimicrobial Agents and Chemotherapy that says there "may be a biological basis for some of the clinical neurological effects associated with mefloquine." Mefloquine was invented by US Army researchers at Walter Reed Army Hospital and sold to the public under the trade name Lariam by Swiss drug giant F. Hoffman-Roche Ltd.
The research using the rats was conducted by a team of scientists led by Dr. Geoffrey Dow at the Division of Experimental Therapeutics, Walter Reed Army Institute of Research, in Silver Spring, MD.
Mefloquine was developed by the US Army at Walter Reed because some strains of malaria were becoming resistant to chloroquine – a decades old treatment - in the late '70s. It was then licensed to Hoffman-Roche for world-wide distribution. The drug subsequently came under scrutiny when American, Canadian, and Australian service members who took it in Somalia and during the Global War on Terror displayed dangerous neuropsychiatric side effects linked to using it.
Retired US Navy Reserve Commander Bill "Skyman" Manofsky, a highly vocal and visible critic of the drug, said the Department of Defense's response to the so-called "Lariam toxicity" cases said he was not impressed with the news of the study. Manofsky, a former P-3 Orion navigator who suffered adverse symptoms after being prescribed mefloquine while stationed in Kuwait, claims the rat study is too little, too late. He argues there are already 19 service members afflicted with Lariam-related disabilities that could have been studied instead of rats.
Mefloquine was first used to prevent malaria in 1985, and since then approximately 14.5 million people have been prescribed the drug for malaria prevention and 1.6 million for treatment of malaria, according to a study published in the British Journal of General Practice published two years ago.
Since then "Lariam Action" support groups have been formed in Australia, New Zealand, Britain, the US, Canada, Ireland, Denmark, and Switzerland. Lariam-related lawsuits have been filed (though some have been withdrawn) in Ireland, Canada, Denmark, and the US.
An abstract of the Walter Reed study says:
"Mefloquine is one of the drugs approved by the FDA for malaria chemoprophylaxis (chemical prevention). Mefloquine is also approved for the treatment of malaria and is widely used for this purpose in combination with artesunate. However, the clinical utility of the compound has been compromised by reports of adverse neurological effects in some patients. In the present study, the potential neurological effects of mefloquine were investigated with six 7-week-old female rats given a single oral dose of the compound. Potential mefloquine-induced neurological effects were monitored using a standard functional observational battery, automated open field tests, automated spontaneous activity monitoring, a beam traverse task, and histopathology. Plasma mefloquine concentrations were determined 72 h after dosing by using liquid chromatography-mass spectrometry. Mefloquine induced dose-related changes in endpoints associated with spontaneous activity and impairment of motor function and caused degeneration of specific brain stem nuclei (nucleus gracilis). Increased spontaneous motor activity was observed only during the rats' normal sleeping phase, suggesting a correlate to mefloquine-induced sleep disorders. The threshold dose for many of these effects was 187 mg/kg of body weight. This dose yielded plasma mefloquine concentrations after 72 h that are similar to those observed in humans after the treatment dose. Collectively, these data suggest that there may be a biological basis for some of the clinical neurological effects associated with mefloquine."
In other words, the rats suffered brain damage after taking one dose of Mefloquine equal to what a human would take.
Manofsky and eighteen other service members who used the drug have already been diagnosed with the same symptoms displayed in the laboratory rats. In addition to brain damage, the affected servicemen display balance problems generally associated with problems in the inner ear, acute sleep disturbances, and psychological problems similar to behaviors frequently associated with Post Traumatic Stress Disorder, including suicide, aggressive, and manic behavior.
In 2004 the Army quit prescribing Lariam – the name preferred by the Army - in Iraq after published reports linked its usage to depression, hallucinations, psychosis and reports of suicide. It was widely prescribed in Iraq in 2003 when 11 of the 24 confirmed suicides in Iraq were by soldiers in units where the drug was used. The Army's explanation for ceasing to provide Lariam in Iraq was that it had just discovered that the strains of malaria resistant to other, less toxic anti-malarial drugs didn't exist there. The Army still issues the drug in Afghanistan.
Roche concedes that Lariam can cause severe neuropsychiatric disorders, including manic behavior, acute psychosis with delusions, and aggressive mood swings, in a very small number of cases. To make sure its customers understand the drug's dangers it issued a warning letter in September of 2002 alerting clinicians among other things that:
"During prophylactic (preventative) use, if psychiatric symptoms such as acute anxiety, depression, restlessness or confusion occur, these may be considered prodromal (predictive) to a more serious event. In these cases the drug must be discontinued and an alternative medication should be substituted."
The letter also said "Lariam should not be prescribed for prophylaxis (preventative) in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis or schizophrenia or other major psychiatric disorders, or with a history of convulsions."
It was not the first time alarm bells had rung. A 1997 Canadian government inquiry into the effects of Lariam on Canadian soldiers who served in Somalia in 1993 did not conclusively link Lariam to psychotic behavior in a group of soldiers who beat to death a Somali teenager named Shidane Arone. But it certainly found plenty of anecdotal evidence from Canadian soldiers who reported finding themselves becoming wildly aggressive after taking their weekly 250 milligram dose of mefloquine.
One Canadian army major reportedly said that the men in his unit used to joke that "if you get somebody angry, he's just going to walk into the old church tower and waste 20 people" and then say, "Oh, sorry, bad mefloquine trip."
Canadians in Somalia got their weekly dose of mefloquine on Wednesdays. The U.S. soldiers took their Lariam pill on Tuesdays, prompting some members of the U.S. forces to dub that day of the week "Psycho Tuesdays," the soldiers testified. Other American soldiers dubbed pill day in Somalia, and later in Iraq and Afghanistan, as "Wacky Wednesday" and "Manic Monday" as well, depending on what day they were given their weekly pill. Ironically, the fact the soldiers only had to take mefloquine once a week is one reason it was originally so attractive to the Army because it allowed easier drug management among the troops.
In 2002 an group of four soldiers returning home to Ft. Bragg, NC after service in Afghanistan killed their wives and in two instances themselves after taking Lariam. The Army investigated their deaths and then issued a report that Lariam was not the cause.
The report, issued in November, 2002, said the Pentagon, joined by the U.S. Centers for Disease Control and Prevention, sent a group of medical experts to Ft. Bragg to determine if a link existed between the homicides and Lariam.
Sgt. Rigoberto Nieves, Master Sgt. William Wright, Sgt. Cedric Griffin and Sgt. Brandon Floyd murdered their wives (Nieves and Floyd also shot and killed themselves) within a six-week span in the summer of 2002. Authorities immediately discovered that three of the four men might have been taking Lariam. Subsequently the Army said that the side effects of Lariam had been ruled out. Ultimately the Army concluded the men had serious marital problems.
Since then more American soldiers have displayed bizarre and occasionally fatal behaviors. Within the last two years three 10th Special Forces Group soldiers stationed at Ft. Carson, CO displayed equally deadly behavior after taking Lariam. Chief Warrant Officer William Howell, an SF operator, Sgt. 1st Class Andre McDaniel, an accountant, and Spc. Jeremy Wilson, an electronics technician, committed suicide shortly after returning home from Afghanistan, all within about a 17-month period, the Army said
Sue Rose, an attorney and professor of public health at George Washington University, is another vocal critic of Lariam and the Department of Defense policies that dictate its use among service members. Rose lobbies for change in Lariam Action USA , that has a web site devoted to keeping an eye on Lariam-related issues. Rose said the problems are not the military's alone.
Rose became involved when a friend of hers who is a demographer suffered "very weird symptoms" from using Lariam while on a trip to Africa. The woman found she wanted to jump out the window of her Nigerian hotel room. Alarmed, her friend asked around about what might cause her to suffer such life threatening delusions and discovered other world travelers already knew about Lariam user's bizarre symptoms and shied away from taking it, Rose said.
Rose added that the entire idea of using such a dangerous drug to prevent a handful of malaria related deaths is in itself a stupid policy.
"Fewer than 10 Americans die of malaria a year. Malaria is treatable. Compare that to a drug that costs $100 a prescription that has a 29 to 42 percent chance of harming you," Rose said. "Scientists have to catch up to where the people have been for a long time. They need to substantiate it and treat it. Lariam is designed to persist in the body with a half-life of 14 - 29 days. People can react adversely after taking one dose. "
The Army may change its tune after the newest study is absorbed and acted upon by scientists researching the potentially life-
threatening attributes of the Army's super drug, Rose said, but not yet.
In late February, 2004 Dr. William Winkenwerder (R), Deputy Secretary of Defense for Health Affairs, told Congress that all is well in Lariam Land. He hasn't since changed his tune.
"Investigation has not established mefloquine as a cause in DoD murders or suicides," Winkenwerder assured the members.
Nathaniel R. Helms is the Editor of DefenseWatch Magazine. He can be reached at natshouse1@charter.net. Please send all comments to DWFeedback@yahoo.com
Ellie
Laboratory Rats Suffer Same Fate as Soldiers Who Took Anti-Malarial Drug
By Nathaniel Helms
A half-dozen laboratory rats given Mefloquine, a controversial and some say terribly dangerous anti-malarial drug linked to everything from homicide to suicide in service members who took it in Iraq and Afghanistan and then killed their loved ones and themselves in alarming numbers have displayed the same frightening neurological symptoms.
On March 1 Army scientists are going to release their finding in a medical journal called Antimicrobial Agents and Chemotherapy that says there "may be a biological basis for some of the clinical neurological effects associated with mefloquine." Mefloquine was invented by US Army researchers at Walter Reed Army Hospital and sold to the public under the trade name Lariam by Swiss drug giant F. Hoffman-Roche Ltd.
The research using the rats was conducted by a team of scientists led by Dr. Geoffrey Dow at the Division of Experimental Therapeutics, Walter Reed Army Institute of Research, in Silver Spring, MD.
Mefloquine was developed by the US Army at Walter Reed because some strains of malaria were becoming resistant to chloroquine – a decades old treatment - in the late '70s. It was then licensed to Hoffman-Roche for world-wide distribution. The drug subsequently came under scrutiny when American, Canadian, and Australian service members who took it in Somalia and during the Global War on Terror displayed dangerous neuropsychiatric side effects linked to using it.
Retired US Navy Reserve Commander Bill "Skyman" Manofsky, a highly vocal and visible critic of the drug, said the Department of Defense's response to the so-called "Lariam toxicity" cases said he was not impressed with the news of the study. Manofsky, a former P-3 Orion navigator who suffered adverse symptoms after being prescribed mefloquine while stationed in Kuwait, claims the rat study is too little, too late. He argues there are already 19 service members afflicted with Lariam-related disabilities that could have been studied instead of rats.
Mefloquine was first used to prevent malaria in 1985, and since then approximately 14.5 million people have been prescribed the drug for malaria prevention and 1.6 million for treatment of malaria, according to a study published in the British Journal of General Practice published two years ago.
Since then "Lariam Action" support groups have been formed in Australia, New Zealand, Britain, the US, Canada, Ireland, Denmark, and Switzerland. Lariam-related lawsuits have been filed (though some have been withdrawn) in Ireland, Canada, Denmark, and the US.
An abstract of the Walter Reed study says:
"Mefloquine is one of the drugs approved by the FDA for malaria chemoprophylaxis (chemical prevention). Mefloquine is also approved for the treatment of malaria and is widely used for this purpose in combination with artesunate. However, the clinical utility of the compound has been compromised by reports of adverse neurological effects in some patients. In the present study, the potential neurological effects of mefloquine were investigated with six 7-week-old female rats given a single oral dose of the compound. Potential mefloquine-induced neurological effects were monitored using a standard functional observational battery, automated open field tests, automated spontaneous activity monitoring, a beam traverse task, and histopathology. Plasma mefloquine concentrations were determined 72 h after dosing by using liquid chromatography-mass spectrometry. Mefloquine induced dose-related changes in endpoints associated with spontaneous activity and impairment of motor function and caused degeneration of specific brain stem nuclei (nucleus gracilis). Increased spontaneous motor activity was observed only during the rats' normal sleeping phase, suggesting a correlate to mefloquine-induced sleep disorders. The threshold dose for many of these effects was 187 mg/kg of body weight. This dose yielded plasma mefloquine concentrations after 72 h that are similar to those observed in humans after the treatment dose. Collectively, these data suggest that there may be a biological basis for some of the clinical neurological effects associated with mefloquine."
In other words, the rats suffered brain damage after taking one dose of Mefloquine equal to what a human would take.
Manofsky and eighteen other service members who used the drug have already been diagnosed with the same symptoms displayed in the laboratory rats. In addition to brain damage, the affected servicemen display balance problems generally associated with problems in the inner ear, acute sleep disturbances, and psychological problems similar to behaviors frequently associated with Post Traumatic Stress Disorder, including suicide, aggressive, and manic behavior.
In 2004 the Army quit prescribing Lariam – the name preferred by the Army - in Iraq after published reports linked its usage to depression, hallucinations, psychosis and reports of suicide. It was widely prescribed in Iraq in 2003 when 11 of the 24 confirmed suicides in Iraq were by soldiers in units where the drug was used. The Army's explanation for ceasing to provide Lariam in Iraq was that it had just discovered that the strains of malaria resistant to other, less toxic anti-malarial drugs didn't exist there. The Army still issues the drug in Afghanistan.
Roche concedes that Lariam can cause severe neuropsychiatric disorders, including manic behavior, acute psychosis with delusions, and aggressive mood swings, in a very small number of cases. To make sure its customers understand the drug's dangers it issued a warning letter in September of 2002 alerting clinicians among other things that:
"During prophylactic (preventative) use, if psychiatric symptoms such as acute anxiety, depression, restlessness or confusion occur, these may be considered prodromal (predictive) to a more serious event. In these cases the drug must be discontinued and an alternative medication should be substituted."
The letter also said "Lariam should not be prescribed for prophylaxis (preventative) in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis or schizophrenia or other major psychiatric disorders, or with a history of convulsions."
It was not the first time alarm bells had rung. A 1997 Canadian government inquiry into the effects of Lariam on Canadian soldiers who served in Somalia in 1993 did not conclusively link Lariam to psychotic behavior in a group of soldiers who beat to death a Somali teenager named Shidane Arone. But it certainly found plenty of anecdotal evidence from Canadian soldiers who reported finding themselves becoming wildly aggressive after taking their weekly 250 milligram dose of mefloquine.
One Canadian army major reportedly said that the men in his unit used to joke that "if you get somebody angry, he's just going to walk into the old church tower and waste 20 people" and then say, "Oh, sorry, bad mefloquine trip."
Canadians in Somalia got their weekly dose of mefloquine on Wednesdays. The U.S. soldiers took their Lariam pill on Tuesdays, prompting some members of the U.S. forces to dub that day of the week "Psycho Tuesdays," the soldiers testified. Other American soldiers dubbed pill day in Somalia, and later in Iraq and Afghanistan, as "Wacky Wednesday" and "Manic Monday" as well, depending on what day they were given their weekly pill. Ironically, the fact the soldiers only had to take mefloquine once a week is one reason it was originally so attractive to the Army because it allowed easier drug management among the troops.
In 2002 an group of four soldiers returning home to Ft. Bragg, NC after service in Afghanistan killed their wives and in two instances themselves after taking Lariam. The Army investigated their deaths and then issued a report that Lariam was not the cause.
The report, issued in November, 2002, said the Pentagon, joined by the U.S. Centers for Disease Control and Prevention, sent a group of medical experts to Ft. Bragg to determine if a link existed between the homicides and Lariam.
Sgt. Rigoberto Nieves, Master Sgt. William Wright, Sgt. Cedric Griffin and Sgt. Brandon Floyd murdered their wives (Nieves and Floyd also shot and killed themselves) within a six-week span in the summer of 2002. Authorities immediately discovered that three of the four men might have been taking Lariam. Subsequently the Army said that the side effects of Lariam had been ruled out. Ultimately the Army concluded the men had serious marital problems.
Since then more American soldiers have displayed bizarre and occasionally fatal behaviors. Within the last two years three 10th Special Forces Group soldiers stationed at Ft. Carson, CO displayed equally deadly behavior after taking Lariam. Chief Warrant Officer William Howell, an SF operator, Sgt. 1st Class Andre McDaniel, an accountant, and Spc. Jeremy Wilson, an electronics technician, committed suicide shortly after returning home from Afghanistan, all within about a 17-month period, the Army said
Sue Rose, an attorney and professor of public health at George Washington University, is another vocal critic of Lariam and the Department of Defense policies that dictate its use among service members. Rose lobbies for change in Lariam Action USA , that has a web site devoted to keeping an eye on Lariam-related issues. Rose said the problems are not the military's alone.
Rose became involved when a friend of hers who is a demographer suffered "very weird symptoms" from using Lariam while on a trip to Africa. The woman found she wanted to jump out the window of her Nigerian hotel room. Alarmed, her friend asked around about what might cause her to suffer such life threatening delusions and discovered other world travelers already knew about Lariam user's bizarre symptoms and shied away from taking it, Rose said.
Rose added that the entire idea of using such a dangerous drug to prevent a handful of malaria related deaths is in itself a stupid policy.
"Fewer than 10 Americans die of malaria a year. Malaria is treatable. Compare that to a drug that costs $100 a prescription that has a 29 to 42 percent chance of harming you," Rose said. "Scientists have to catch up to where the people have been for a long time. They need to substantiate it and treat it. Lariam is designed to persist in the body with a half-life of 14 - 29 days. People can react adversely after taking one dose. "
The Army may change its tune after the newest study is absorbed and acted upon by scientists researching the potentially life-
threatening attributes of the Army's super drug, Rose said, but not yet.
In late February, 2004 Dr. William Winkenwerder (R), Deputy Secretary of Defense for Health Affairs, told Congress that all is well in Lariam Land. He hasn't since changed his tune.
"Investigation has not established mefloquine as a cause in DoD murders or suicides," Winkenwerder assured the members.
Nathaniel R. Helms is the Editor of DefenseWatch Magazine. He can be reached at natshouse1@charter.net. Please send all comments to DWFeedback@yahoo.com
Ellie