Many of those affected were medically evacuated and some were hospitalized because of problems volunteers said were caused by Lariam, also called mefloquine. Others risked contracting malaria when they secretly violated Peace Corps rules and quit taking the drug because side effects bothered them so much. Some say that debilitating problems that began when they started taking the drug have continued for years after they stopped.
"This has been the big story among Peace Corps volunteers for 12 years," said Allen Hoppes, a volunteer in Mali, West Africa, in 1992. That was three years after the Peace Corps began using Lariam, which continues to be the Peace Corps' drug of choice.
"The Peace Corps told us if we did not want to take mefloquine, we did not want to be Peace Corps volunteers," Hoppes said.
Hoppes secretly only took a half pill each week. He said Lariam caused paranoia and hallucinations and he tried to kill a giant imaginary python prowling his floors and confronted a non-existent intruder in his house one night. "I thought he wanted to kill me," Hoppes said.
"I think mefloquine has too many side effects to be considered safe."
Lariam is a product of Hoffmann-La Roche, a giant Swiss pharmaceutical company with U.S. headquarters in Nutley, N.J. In addition to Peace Corps volunteers, U.S. soldiers -- including troops currently in Afghanistan -- State Department employees and civilian vacationers receive the drug, which has been prescribed to 22 million people worldwide since 1985. It was cleared for use in the United States in 1989.
In a recent, two-month investigation of Lariam, United Press International found evidence that the drug can cause mental problems so severe that in a small percentage of cases it has triggered suicide. Thousands of pages of internal Roche safety documents obtained by UPI showed the company tracking suicides and suicidal behavior and acknowledging that depression -- which it said can lead to suicide -- is a known side effect of Lariam.
The Food and Drug Administration told UPI that no action was required because a link with suicide had not been proved, a position maintained by the drug company as well. The FDA also cited the effectiveness of the drug, which has cut cases of deadly cerebral malaria among Peace Corps volunteers by 71 percent since 1989. Lariam is used to prevent and treat malaria, which the FDA says kills 850,000 people a year, mostly children in Africa.
Responses to that story included comments from former Peace Corps volunteers who said the Peace Corps had denied Lariam could cause their health problems. UPI reporters interviewed 33 former volunteers and reviewed 83 e-mail messages from others. Nearly half of the Peace Corps' 7,000 volunteers face malaria risk and more than 83 percent are given mefloquine to prevent the disease, according to Peace Corps medical data obtained by UPI. Many report no troublesome side effects from Lariam.
President George W. Bush has proposed doubling the size of the Peace Corps to some 14,000 volunteers.
Informed of UPI's findings, Sen. Christopher Dodd, D-Conn., who is chairman the subcommittee that oversees the Peace Corps and is a former volunteer, said: "The potential side effects of Lariam that this investigation has uncovered are worrisome and should be looked into by independent medical experts to ensure that the health of Peace Corps volunteers is being adequately safeguarded."
Volunteers interviewed by UPI said they usually received their first pill during orientation in Philadelphia or Washington, just one day prior to departure to their posts. That startled a handful of the volunteers who had done their own research and learned that the manufacturer recommended taking the first dose one week before their exposure to malaria.
-- Volunteers also said they were warned only that the pills could provoke vivid dreams. They said the Peace Corps downplayed possible side effects.
-- Volunteers with a history of mental problems -- considered risky candidates for Lariam according to the drug label from Roche -- were told to take their pills just like other volunteers.
-- The Peace Corps says it offers the antibiotic doxycycline as an alternative drug for volunteers who are not able to take Lariam. Some volunteers said the Peace Corps allowed them to switch. But many said they were not provided alternatives or were discouraged, cajoled or threatened into staying on mefloquine even as their side effects worsened.
-- Volunteers said that Peace Corps medical officials in the field dismissed complaints about mefloquine. They said doctors obtained by the Peace Corps in the United States to treat volunteers who required emergency psychiatric evacuations would not discuss Lariam as a possible cause.
Russell Gerber, the chief of epidemiology at the Peace Corps, said this spring there is no evidence that mental problems among volunteers are caused by Lariam. "We do get people who develop schizophrenia in the Peace Corps, but it is not associated with mefloquine," Gerber said.
Steve Weinberg, associate director for volunteer support, noted that the Centers for Disease Control and Prevention advises the Peace Corps on malaria prevention. He said, "The CDC has been behind mefloquine pretty much 100 percent. They just love it. They are the leading expert and we rely heavily on them."
After interviewing volunteers who said they had Lariam problems, UPI in May scheduled follow-up interviews with Gerber and Weinberg, but Peace Corps spokeswoman Ellen Field canceled them.
Field and Peace Corps Director Gaddi Vasquez did not answer written questions from UPI or agree to interviews. "I want to get the Peace Corps out of this story," Field told UPI.
The Walter Army Institute of Research invented the drug, along with Roche. After it was approved, key studies of Lariam's safety and effectiveness were conducted on Peace Corps volunteers by the CDC, which reported that no serious side effects were observed and that psychiatric reactions were most likely due to travel stress or mental illness.
But among the more than 100 volunteers who contacted UPI with similar symptoms, several said their particular experiences show that travel stress and mental illness did not cause their problems.
Staci Bolton had been a volunteer for a year and a half on the Caribbean island of St. Lucia, where there is no malaria risk, when the Peace Corps gave her Lariam in the winter of 1998 for a two-week vacation to Venezuela.
Bolton said the Peace Corps handed her the pills in a white envelope with no warnings, but that soon after she returned to St. Lucia she was hospitalized with vomiting, chills, sudden bouts of crying and weakness so bad she could not walk. Bolton said she suffered intense anxiety and unexplained chest pain. "I was convinced I was going to die," Bolton said.
Bolton also said she nearly threw herself out a third-story window of the Peace Corps headquarters in St. Lucia while waiting to be evacuated to Washington. "I remember thinking, 'I should jump off that balcony.' I saw huge, human-sized butterflies. I wasn't afraid of them. I don't know if I was thinking I should go after those butterflies or...I don't know what I was thinking.
"Talk about people committing suicide. I can totally understand that," Bolton said.
The Peace Corps sent Bolton to the Virginian Suites hotel just outside Washington. There, the Peace Corps rents a block of rooms where volunteers who do not require immediate hospitalization are sent for a maximum of 45 days to see doctors obtained by the agency. The Peace Corps also maintains a contract with the Psychiatric Institute of Washington to handle volunteers who do require immediate hospitalization for mental problems.
Bolton said that the doctor in the hospital in St. Lucia determined that Lariam might have caused her problems, but that the doctors the Peace Corps provided in Washington would not discuss Lariam. Bolton said her medical chart from Washington says the cause of her problems was undetermined.
"I know that is what it was," Bolton said. " They just wanted to avoid the whole discussion. I do not know why they would not agree"
She said her symptoms cleared up soon after stopping Lariam, and she was able to return to service.
Another Peace Corps volunteer served in Lithuania in the early 1990s but said the considerable stress of his assignment caused no serious mental problems. The volunteer, who requested anonymity, later took Lariam on his own during a vacation to Zimbabwe two years ago and tried to commit suicide by overdosing on Xanax after taking his sixth pill of Lariam. He said he believes his suicide attempt "absolutely" was connected to Lariam.
Kevin Lee Croft, who served in Togo, West Africa, in 1992, also ruled out stress and said Lariam made him hallucinate plate-sized butterflies coming out of the walls of his house, and when he looked in the mirror, his face had no eyes. He says he suffered severe paranoia and still has troubling anxiety he thinks is left over from taking the drug.
Croft acknowledged Africa is "a difficult place to be." Asked if travel stress could have triggered the problems he experienced, Croft said, "Hell, no. I've worked in some of the nastiest places on the face of the Earth. I've spent time in south and central Mexico. I have lived and worked in Belfast. Exposure to danger is not new to me. I've always been able to keep a pretty cool perspective on all of that.
"In none of those places did butterflies come out of the walls."
Other volunteers said they believe Lariam caused their bizarre hallucinations and other harrowing reactions because symptoms would reappear when they started taking the drug again after a break.
The Peace Corps evacuated Leah Rabin from Burkina Faso, West Africa, in August 2001 after she hallucinated "man-sized spiders" on her bed at night and suffered depression she said was severe and triggered by Lariam. Rabin first had to stop taking Lariam in June 2000 after her third pill but the Peace Corps put her back on Lariam following a bout with malaria in November of 2000.
Scientists consider the reappearance of symptoms once a drug has been restarted a strong indication of causality -- the technical term is "re-challenge."
While it took months for some volunteers to find Lariam's side effects intolerable, several said the third pill was trouble. Voluntary Service Overseas, the world's biggest volunteer-sending organization, relies on the advice of the U.K. Advisory Committee on Malaria Prevention, which warns travelers who do chose Lariam to take doses for three weeks before leaving, "thus taking the third dose early enough to make a change if they encounter adverse reactions," according to the committee's guidelines. The guidelines also list a bevy of possible side effects for Lariam, including "frankly psychotic episodes."
After being evacuated, Rabin said, the doctors the Peace Corps arranged to treat her while she stayed at the Virginian Suites would not discuss Lariam.
"The psychotherapist did not want to deal with this (nor did any) of the psychotherapists the Peace Corps assigned to me," Rabin said. "The psychotherapist I went to did not have any opinion on the matter whatsoever. She said her role was really to deal with things as they were now."
Lariam is not mentioned as a possible cause of mental problems in a special report in 1999 issued by the Peace Corps Office of Medical Services, which examined mental health medical evacuations in 1996, 1997, and 1998. The report, prepared by Gerber, the epidemiology chief, along with analytical epidemiologist Anne Rimion, said 240 volunteers had been medically evacuated during the period with a mental health condition as the primary diagnosis, predominantly anxiety, adjustment reaction, bipolar disease, depression and psychosis.
A Peace Corps report on the health of volunteers during 2001 notes that mental health complaints are the third most common health issue among volunteers and increased 78 percent since 1993.
Lariam's FDA-regulated label that doctors and pharmacists receive does warn about most of the side effects that volunteers described, but the agency relies on doctors to tell patients of possible side effects.
"I think the label makes it pretty clear that adverse events, and specifically neuropsychiatric events, do occur," said Dr. Leonard Sacks, a medical officer at the FDA. "Our feeling is that people should be getting the information. I do not know what the Peace Corps' agenda is in not giving that information. ... I think you would have to discuss that with them."
In refusing to pay worker's compensation for one volunteer who said Lariam caused her psychiatric problems, the Labor Department and the National Institutes of Health said the drug could not be at fault.
"What the current available data seem to show is mefloquine is not associated with the occurrence of any significant neuropsychiatric symptoms when used at doses recommended for prophylaxis," wrote Dr. Charles Kaelber of NIH in a 1998 letter to the Peace Corps that was cited in denying the claim.
Kaelber cited scientific studies -- including two studies on Peace Corps volunteers by the CDC in the 1990's -- showing no problems from the drug.
Peace Corps volunteers told UPI that the CDC's findings were wrong, mostly because people lied and did not take the drug or tinkered with the dosage.
Mark Ames, who served in Benin, West Africa, from 1992 to 1995 when one CDC study was ongoing, said he heard at the time he was part of a study.
"If there was one, then it is absolutely useless," he told UPI. "Nobody was taking it the way they were supposed to." Thirty to 40 percent of volunteers cut the pill in half, quit taking it or otherwise secretly adjusted the prescribed dose, he estimated. "Everybody had their own modification of it."
The CDC said it stood by the studies, and noted they were peer-reviewed.
The guide on malaria prevention used by Peace Corps medical officers in the field says about Lariam only that "minor side effects (gastrointestinal disturbance and dizziness) tend to be transient and self-limited. Side effects tend to decrease over time, and rarely lead to discontinuation of the drug...Mefloquine is appropriate for long-term use and has not been associated with delayed side effects."
Those who say they still do suffer side effects wonder whether they will ever be the same.
"I'm a lot more nervous than I used to be," said Croft, the Togo volunteer who saw butterflies fly out of the wall 10 years ago. "I still wake up in the middle of the night not knowing where I am, just sure that something bad is about to happen to me. I'll roll out of bed and grab my baseball bat.
"It is one of the long-term effects I deal with. I don't know what it is going to turn into."