Malaria chemoprophylaxis is a mouthful, but it also highly contentious. It is an issue that has concerned the military and travellers alike. Chemoprophylaxis is the use of medication to prevent the development of a disease, in this case malaria. However, for Sheldon Johnston of Sydney, prevention had serious consequences.

Johnston took Lariam as a form of malaria prevention on a trip to Africa in 1995-1996. After taking the medication for two weeks, he experienced a range of side effects, including vomiting, dizziness, pins and needles, insomnia, ringing ears, paranoia and depression.

“The most severe [side effect] was definitely the disturbing mental feelings of a kind of psychosis and depression, and the feeling of shattered nerves,” he recounted. “I have since read a sufferer… describe it as like someone has broken into your mind during the night and rearranged all the furniture.”

It took Johnston the best part of a year for most of the side effects of Lariam to leave his body. However he still experiences tinnitus, ringing in his ears.

Others speak of similar experiences with Lariam.

"I'd give anything if I could feel like I did... to be the person I was before I took Lariam," one person laments on the Lariam Action USA website.

Another describes Lariam as "a complete do-it-yourself Dr. Jekyll and Mr. Hyde kit, all in five little bitty pills. I have been able to experience just about every psychological problem known to mankind in just three short days."

Lariam, also referred to by its generic name, mefloquine, is one drug that can be taken as malaria chemoprophylaxis. Lariam was developed by the United State’s military. Malaria has been a key issue for the armed forces throughout history.

Associate Professor James McCarthy was quick to explain the importance of malaria chemoprophylaxis, as he welcomed me into his cramped office at the Queensland Institute of Medical Research at Herston where he is the Head of Clinical Tropical Medicine.

“If you go back to ancient times, the Romans and the Greeks had major problems with malaria, Napoleon had problems with malaria and the British army had problems with malaria,” Professor McCarthy says earnestly.

He notes that the Australian Defence Force (ADF) works in malarious countries such as the Solomon Islands, East Timor, Papua New Guinea and Afghanistan. Malaria prevention has therefore been a priority for the ADF, with the creation of the Army Malaria Institute (AMI) in the late 1960s. Experts from the AMI advise the military on how to best protect their troops from being bitten by mosquitos, and about which malaria tablets the troops should take, McCarthy explains.

If antimalarials such as Lariam have side effects, what then is the most appropriate drug to use for malaria chemoprophylaxis in the military?

“There’s a wide range of drugs that are available for malaria… Deciding which drug to give someone for prevention of malaria is a complex issue and is one that has generated a lot of controversy,” Professor McCarthy says.

“Mefloquine is a controversial drug,” McCarthy explains. “There’s clearly a small group of people that don’t tolerate the drug and it has a number of significant side effects, including what we call neuropsychiatric side effects. This occurs in a very small minority of people, but in those that it does occur it can cause very disabling side effects.”

Studies conducted in the Netherlands in 2005 link mefloquine to an increased risk of psychiatric events in females and in patients with a history of psychiatric diseases.

Professor McCarthy explains that there was some controversy about Australian troops deployed in East Timor taking mefloquine. When he speaks his voice is matter-of-fact.

“A number of troops did experience bad side effects.” He notes, however, that the side effects were no more common among those that took Lariam compared with those soldiers that took another antimalarial, doxycycline.

An article by Kirchener et al. published in the Medical Journal of Australia confirms that 56 per cent of soldiers taking doxycycline experienced adverse effects, compared with 57 per cent of those taking mefloquine.  “And there were a couple of people that took the drug that shouldn't have taken it because that had a medical reason not to,” McCarthy says.  “So you could argue that… some of the bad effects were actually because they were given the wrong medication, that mefloquine wasn’t the drug for them.”

After soldiers returned from East Timor, Brisbane law firm Quinn and Scattini received significant press coverage when they said they would launch a class action on behalf of ADF personnel who were unhappy with the antimalarials they had been prescribed. A lawyer with Quinn and Scattini, Margaret Brain, stated that the firm did not pursue a class action. However there was “investigation” into the matter.

Despite the possible side effects, Professor McCarthy is adamant about the importance of antimalarials. Malaria can be lethal. The World Health Organisation (WHO) reports that approximately 40 per cent of the world is at risk of contracting malaria. A child dies of malaria every thirty seconds, and more than one million people die from malaria every year. A hint of frustration comes through as he speaks.

“Sometimes I think the wrong message gets conveyed about the risks of drugs versus the risk of dying of malaria, which is certainly a real possibility in some of the areas where the Australian defence forces are deployed.”

The ADF declined to comment; however, military documents highlight their approach to malaria chemoprophylaxis. Doxycycline, a broad-spectrum antibiotic, is the preferred first-line drug, the documents reveal. A relatively new medication, called malarone, is the preferred second-line drug for defence personnel who are unable to take doxycycline. Lariam has also been used for individuals who are intolerant to doxycycline. The documents state that Lariam is not to be taken by personnel who have a history of mental illness or epileptic seizures, or by individuals in aviation-related occupations or who are required to drive vehicles.

Lariam is distributed by Roche Pharmaceuticals. In 2002, two additional paragraphs were added to the warning section in the Lariam Product Information. This reveals that the company acknowledge the dangerous side effects associated with the drug. “Mefloquine may cause psychiatric symptoms in a number of patients, ranging from anxiety, paranoia and depression, to hallucinations and psychotic behaviour,” the warning states. “On occasions, these symptoms have been reported to continue long after mefloquine has been stopped.” Roche recognise that mefloquine has been linked to suicides. The warning notes that “rare cases of suicide ideation and suicide have been reported, though no relationship to drug administration has been confirmed”.

Protest groups have been established in response to Lariam’s side effects. Lariam Action USA was created as an offshoot from the original Lariam Action group in the United Kingdom. The Directors of Lariam Action USA, Sue Rose and Jeanne Lese, explain that the organisation’s primary focus is to provide information to the public and the medical community about the side effects of Lariam and to force regulatory bodies such as the Food and Drugs Administration to re-evaluate the use of mefloquine.

“Mefloquine can cause brain damage,” the Directors state. “This is an unacceptable risk for a drug primarily given to healthy people.” Ms Rose and Ms Lese staunchly maintain that the drug should be reserved to treat malaria, not used for prevention. “It is not sensible to continue to use a drug with such a toxic history when there are other equally effective drugs available.” Which drugs are they referring to? Doxycycline and malarone.

Despite the existence of safer, alternative drugs, the US army continues to prescribe mefloquine in areas where malaria is endemic, the Directors note. Iraq is the one exception. At the beginning of the war, mefloquine was prescribed to soldiers. Ms Rose and Ms Lese remarked that within a year there was a huge jump in military suicides. “The Pentagon suddenly discovered that mefloquine was never needed in Iraq, something the Centres for Disease Control could have confirmed had they bothered to ask.”

Dr G. Richard Olds, Chairman of the Department of Medicine at the Medical College of Wisconsin, remarked that the US soldiers could have taken chloroquine in Iraq. “Perhaps the same intelligence service that thought there were weapons of mass destruction also checked on whether malaria in Iraq was chloroquine resistant or not,” he noted, wryly.

Dr Olds has had extensive experience monitoring the effects of mefloquine on civilians. He stated that there is currently only speculation as to the problems that a soldier might experience taking Lariam. He warned that Lariam interferes with fine motor function. “The most common complaint I see is vivid dreams and sleep disturbances. In some trials up to a third of people who have taken this drug for a year, stop it due to side effects.” Is he concerned about the impact Lariam could have on soldiers? “I’m not sure that I would like a soldier who has to do night patrols with an M14 taking this drug,” he said. “[Does] firing a M14 require 'fine motor function?'”

Professor McCarthy described malaria chemoprophylaxis as a cost-benefit analysis. For some unlucky people, the cost has outweighed the benefit.

The video of the interview with Prof James McCarthy is available online at No Idea Magazine:

http://community.livejournal.com/noidea_magazine/

image by Kim Pierro
Courtesy of Creative Commons