Correspondence
Health Advice for Travelers
N Engl J Med 2000; 343:1045-1046October 5, 2000
- Article
To the Editor:
In their recommendations for travelers, Ryan and Kain (June 8 issue)1 unfortunately do not include sufficient information about the adverse effects of mefloquine (Lariam). Recent studies from Spain, Sweden, and California2-4 found that one in five people discontinues use of this drug because of neuropsychological symptoms. A study from Denmark found that the rate of central nervous system symptoms was higher in people taking mefloquine than in those taking other drugs as prophylaxis against malaria and that “when symptoms develop, they are perceived as more severe.”5 Last year, the product information for Lariam was completely revised and expanded to include a new section with advice for patients, new recommendations for use of the drug in children, and an expanded discussion of reported adverse reactions, with coverage of many new adverse effects.
The implications of the latest information on mefloquine are important. According to the Centers for Disease Control and Prevention (CDC), doxycycline is just as effective as mefloquine in preventing malaria and has far fewer adverse effects. It is time for the CDC to reexamine its recommendation of mefloquine as the drug of choice for prophylaxis against malaria.
5 ReferencesLora Abell, M.D.
Midwest Health Center, Lake St. Louis, MO 633671
Ryan ET ,Kain KC . Health advice and immunizations for travelers. N Engl J Med 2000;342:1716-1725
Full Text | Web of Science | Medline2
Micheo C, Arias C, Rovira A. Adverse effects and compliance with mefloquine or chloroquine plus proguanil malaria chemoprophylaxis. Presented at the Second European Conference on Travel Medicine, Venice, Italy, March 2000. abstract.
3
Norrbohm O, Vepsalainen S, Bjorkman A, Ministry of Foreign Affairs, Stockholm, Sweden. Mild side effects and their causality during mefloquine prophylaxis. Presented at the International Society of Travel Medicine, Montreal, June 1999.
4
Ward B, Mathison D, Scripps Clinic Travel Clinic. Adverse events experienced with mefloquine chemoprophylaxis in travelers from one USA travel clinic, La Jolla, California. Presented at the International Society of Travel Medicine, Montreal, June 1999.
5
Petersen E ,Ronne T ,Ronn A ,Bygberg I ,Larsen SO . Reported side effects to chloroquine, chloroquine plus proguanil, and mefloquine as chemoprophylaxis against malaria in Danish travelers. J Travel Med 2000;7:79-84
CrossRef | Web of Science | Medline
To the Editor:
On the basis of our systematic review of the literature,1 we would like to add three comments to the advice given by Ryan and Kain for people traveling to high altitudes. First, acetazolamide is indeed effective as prophylaxis against acute mountain sickness, and the risk of minor adverse drug reactions is low. The optimal dose, however, has been shown to be 750 mg per day; lower doses do not work and should therefore not be used. Second, 8 mg of dexamethasone per day is about as effective as 750 mg of acetazolamide per day; however, adverse effects from weaning (such as depression) may limit its usefulness. Third, when the rate of ascent is less than 500 m per day, prophylaxis is not worthwhile, since then the underlying risk of acute mountain sickness is very low.
1 ReferencesLionel Dumont, M.D.
Chahé Mardirosoff, M.D.
Martin R. Tramèr, M.D., D.Phil.
Geneva University Hospital, CH-1211 Geneva 14, Switzerland1
Dumont L ,Mardirosoff C ,Tramer MR . Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systematic review. BMJ 2000;321:267-272
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Author/Editor Response
The authors reply:
To the Editor: As we mention in our review, mefloquine has been associated with neuropsychiatric adverse events and should not be used by persons with seizure disorders or psychiatric conditions. We focused on randomized, controlled trials since they provide the best evidence on which to base advice on chemoprophylaxis. To date, well-designed trials have not found significant differences in the rates of adverse events or drug discontinuation between subjects taking mefloquine and those taking other antimalarial drugs; the rates of discontinuation of these drugs because of neuropsychiatric events have been reported to be 5 percent or less.1,2 Once the full reports are published, we look forward to reviewing in detail the studies in abstract form cited by Abell. In the open, nonrandomized study of Danish travelers by Petersen et al., which is cited by Abell, neuropsychiatric adverse events were reported significantly more frequently by subjects taking mefloquine than by those taking chloroquine; however, widespread resistance to chloroquine limits the usefulness of this agent. The subjects taking a combination of chloroquine and proguanil reported depression significantly more frequently than did those taking chloroquine alone.
Although doxycycline is as effective as mefloquine in the prevention of malaria, doxycycline should not be used by pregnant women or by children younger than eight years of age. The CDC does not state that doxycycline has fewer adverse effects than mefloquine. Adverse events associated with the use of doxycycline include photosensitivity, vaginal moniliasis, and intestinal upset, and its use may decrease the efficacy of hormonal contraceptive agents. The recent approval of a fixed combination of atovaquone and proguanil by the Food and Drug Administration increases the options available for preventing malaria.
Although 750 mg of acetazolamide per day is perhaps the best-studied regimen for preventing acute mountain sickness, double-blind, placebo-controlled trials have shown that 500 mg of acetazolamide per day is also effective.3,4 Even lower doses are often recommended to lessen the likelihood of adverse events, which may include paresthesia and alterations in the taste of carbonated beverages.5 However, the optimal dose is unknown, and studies comparing various doses and durations of therapy are warranted. We agree that dexamethasone is an effective agent in the prevention of acute mountain sickness, but that adverse effects limit its use.
5 ReferencesEdward T. Ryan, M.D.
Massachusetts General Hospital, Boston, MA 02114-2696Kevin C. Kain, M.D.
Toronto General Hospital, Toronto, ON M5G 2C4, Canada1
Lobel HO ,Kozarsky PE . Update on prevention of malaria for travelers. JAMA 1997;278:1767-1771
CrossRef | Web of Science | Medline2
Croft A ,Garner P . Mefloquine to prevent malaria: a systematic review of trials. BMJ 1997;315:1412-1416
CrossRef | Web of Science | Medline3
Acetazolamide in control of acute mountain sicknessLancet 1981;1:180-183
Web of Science | Medline4
Greene MK ,Kerr AM ,McIntosh IB ,Prescott RJ . Acetazolamide in prevention of acute mountain sickness: a double-blind controlled cross-over study. BMJ 1981;283:811-813
CrossRef | Web of Science | Medline5
Meyer BH . The use of low-dose acetazolamide to prevent mountain sickness. S Afr Med J 1995;85:792-793
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