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Meta-Analysis
. 2017 Oct 30;10(10):CD006491.
doi: 10.1002/14651858.CD006491.pub4.

Mefloquine for preventing malaria during travel to endemic areas

Maya Tickell-Painter  1 , Nicola Maayan, Rachel Saunders, Cheryl Pace, David Sinclair
Affiliations
Meta-Analysis

Mefloquine for preventing malaria during travel to endemic areas

Maya Tickell-Painter et al. Cochrane Database Syst Rev. .

Abstract

Background: Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects.

Objectives: To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers.

Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017.

Selection criteria: We included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women.

Data collection and analysis: Two review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach.

Main results: We included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses. Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants). Mefloquine safety versus atovaquone-proguanil Participants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence). There were few serious adverse effects reported with mefloquine (15/2651 travellers) and none with atovaquone-proguanil (940 travellers).One RCT and six cohort studies reported on our prespecified adverse effects. In the RCT with short-term travellers, mefloquine users were more likely to report abnormal dreams (RR 2.04, 95% CI 1.37 to 3.04, moderate-certainty evidence), insomnia (RR 4.42, 95% CI 2.56 to 7.64, moderate-certainty evidence), anxiety (RR 6.12, 95% CI 1.82 to 20.66, moderate-certainty evidence), and depressed mood during travel (RR 5.78, 95% CI 1.71 to 19.61, moderate-certainty evidence). The cohort studies in longer-term travellers were consistent with this finding but most had larger effect sizes. Mefloquine users were also more likely to report nausea (high-certainty evidence) and dizziness (high-certainty evidence).Based on the available evidence, our best estimates of absolute effect sizes for mefloquine versus atovaquone-proguanil are 6% versus 2% for discontinuation of the drug, 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, and 6% versus 1% for depressed mood. Mefloquine safety versus doxycyclineNo difference was found in numbers of serious adverse effects with mefloquine and doxycycline (low-certainty evidence) or numbers of discontinuations due to adverse effects (RR 1.08, 95% CI 0.41 to 2.87; 4 RCTs, 763 participants; low-certainty evidence).Six cohort studies in longer-term occupational travellers reported our prespecified adverse effects; one RCT in military personnel and one cohort study in short-term travellers reported adverse events. Mefloquine users were more likely to report abnormal dreams (RR 10.49, 95% CI 3.79 to 29.10; 4 cohort studies, 2588 participants, very low-certainty evidence), insomnia (RR 4.14, 95% CI 1.19 to 14.44; 4 cohort studies, 3212 participants, very low-certainty evidence), anxiety (RR 18.04, 95% CI 9.32 to 34.93; 3 cohort studies, 2559 participants, very low-certainty evidence), and depressed mood (RR 11.43, 95% CI 5.21 to 25.07; 2 cohort studies, 2445 participants, very low-certainty evidence). The findings of the single cohort study reporting adverse events in short-term international travellers were consistent with this finding but the single RCT in military personnel did not demonstrate a difference between groups in frequencies of abnormal dreams or insomnia.Mefloquine users were less likely to report dyspepsia (RR 0.26, 95% CI 0.09 to 0.74; 5 cohort studies, 5104 participants, low certainty-evidence), photosensitivity (RR 0.08, 95% CI 0.05 to 0.11; 2 cohort studies, 1875 participants, very low-certainty evidence), vomiting (RR 0.18, 95% CI 0.12 to 0.27; 4 cohort studies, 5071 participants, very low-certainty evidence), and vaginal thrush (RR 0.10, 95% CI 0.06 to 0.16; 1 cohort study, 1761 participants, very low-certainty evidence).Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.Additional analyses, including comparisons of mefloquine with chloroquine, added no new information. Subgroup analysis by study design, duration of travel, and military versus non-military participants, provided no conclusive findings.

Authors' conclusions: The absolute risk of malaria during short-term travel appears low with all three established antimalarial agents (mefloquine, doxycycline, and atovaquone-proguanil).The choice of antimalarial agent depends on how individual travellers assess the importance of specific adverse effects, pill burden, and cost. Some travellers will prefer mefloquine for its once-weekly regimen, but this should be balanced against the increased frequency of abnormal dreams, anxiety, insomnia, and depressed mood.

PubMed Disclaimer

Conflict of interest statement

NM was contracted by the Cochrane Infectious Diseases Group (CIDG) as a freelance consultant to work on this review and previously worked for Enhanced Reviews Ltd, a company that conducts systematic reviews mostly for the public sector. NM is currently employed by Cochrane Response, an evidence services unit operated by Cochrane.

CP has been involved in aspects of clinical trial management for trials of antimalarials (other than mefloquine) where the study drug has been supplied free of charge by the manufacturer.

David Sinclair was employed at Liverpool School of Tropical Medicine as an author and editor with the CIDG, funded through a grant from the UK Department for International Development.

RS was employed at Liverpool School of Tropical Medicine as an author with the CIDG, funded through a grant from the UK Department for International Development.

MTP was employed at Liverpool School of Tropical Medicine as an author with the CIDG, funded through a grant from the UK Department for International Development.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary for RCTs: review authors' judgements about each 'Risk of bias' item for each included study.
3
3
'Risk of bias' summary in cohort studies: mefloquine versus placebo/no treatment 1Assesses whether our pre‐defined confounders were measured and balanced across groups.
 2Assesses the non‐response rate of prospective participants.
 3Assesses the risk that participants labelled as taking mefloquine (or another antimalarial) actually took something else.
 4Assesses the risk that participants whose adverse effects are attributed to mefloquine (or another antimalarial) actually took another drug as well.
 5Assesses whether outcome data reasonably complete for most participants and whether intervention status reasonably complete for those in whom it was sought.
 6Assesses whether the outcome measure was subjective, and whether participants and outcome assessors were blinded.
 7Assesses whether it is clear that all information collected within the study has been reported.
 8Assess the risk of bias due to influence by a corporate study sponsor.
4
4
'Risk of bias' summary in cohort studies: mefloquine versus doxycycline 1Assesses whether our pre‐defined confounders are measured and balanced across groups.
 2Assesses the non‐response rate of prospective participants.
 3Assesses the risk that participants labelled as taking mefloquine (or another antimalarial) actually took something else.
 4Assesses the risk that participants whose adverse effects are attributed to mefloquine (or another antimalarial) actually took another drug as well.
 5Assesses whether outcome data reasonably complete for most participants and whether intervention status reasonably complete for those in whom it was sought.
 6Assesses whether the outcome measure was subjective, and whether participants and outcome assessors were blinded.
 7Assesses whether it is clear that all information collected within the study has been reported.
 8Assesses the risk of bias due to influence by a corporate study sponsor.
5
5
'Risk of bias' summary in cohort studies: mefloquine versus atovaquone‐proguanil 1Assesses whether our pre‐defined confounders are measured and balanced across groups.
 2Assesses the non‐response rate of prospective participants.
 3Assesses the risk that participants labelled as taking mefloquine (or another antimalarial) actually took something else.
 4Assesses the risk that participants whose adverse effects are attributed to mefloquine (or another antimalarial) actually took another drug as well.
 5Assesses whether outcome data reasonably complete for most participants and whether intervention status reasonably complete for those in whom it was sought.
 6Assesses whether the outcome measure was subjective, and whether participants and outcome assessors were blinded.
 7Assesses whether it is clear that all information collected within the study has been reported.
 8Assesses the risk of bias due to influence by a corporate study sponsor.
6
6
'Risk of bias' summary in cohort studies: mefloquine versus chloroquine 1Assesses whether our pre‐defined confounders are measured and balanced across groups.
 2Assesses the non‐response rate of prospective participants.
 3Assesses the risk that participants labelled as taking mefloquine (or another antimalarial) actually took something else.
 4Assesses the risk that participants whose adverse effects are attributed to mefloquine (or another antimalarial) actually took another drug as well.
 5Assesses whether outcome data reasonably complete for most participants and whether intervention status reasonably complete for those in whom it was sought.
 6Assesses whether the outcome measure was subjective, and whether participants and outcome assessors were blinded.
 7Assesses whether it is clear that all information collected within the study has been reported.
 8Assesses the risk of bias due to influence by a corporate study sponsor.
1.1
1.1. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 1 Clinical cases of malaria.
1.2
1.2. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 2 Malaria; episodes of parasitaemia in semi‐immune populations.
1.3
1.3. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 3 Serious adverse events or effects (all studies).
1.4
1.4. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 4 Discontinuations due to adverse effects (all studies).
1.5
1.5. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 5 Nausea (all studies).
1.6
1.6. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 6 Vomiting (all studies).
1.7
1.7. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 7 Abdominal pain (all studies).
1.8
1.8. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 8 Diarrhoea (all studies).
1.9
1.9. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 9 Headache (all studies).
1.10
1.10. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 10 Dizziness (all studies).
1.11
1.11. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 11 Abnormal dreams (all studies).
1.12
1.12. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 12 Insomnia (all studies).
1.13
1.13. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 13 Anxiety (all studies).
1.14
1.14. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 14 Depressed mood (all studies).
1.15
1.15. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 15 Abnormal thoughts and perceptions.
1.16
1.16. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 16 Pruritis (all studies).
1.17
1.17. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 17 Visual impairment (all studies).
1.18
1.18. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 18 Vertigo (all studies).
1.19
1.19. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 19 Other adverse events (RCTs).
1.20
1.20. Analysis
Comparison 1 Mefloquine versus placebo/non users, Outcome 20 Other adverse effects (cohort studies).
2.1
2.1. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 1 Clinical cases of malaria (RCTs).
2.2
2.2. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 2 Serious adverse events or effects (all studies).
2.3
2.3. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 3 Discontinuations due to adverse effects (all studies).
2.4
2.4. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 4 Nausea (all studies).
2.5
2.5. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 5 Vomiting (all studies).
2.6
2.6. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 6 Abdominal pain (all studies).
2.7
2.7. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 7 Diarrhoea (all studies).
2.8
2.8. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 8 Dyspepsia (all studies).
2.9
2.9. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 9 Headache (all studies).
2.10
2.10. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 10 Dizziness (all studies).
2.11
2.11. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 11 Abnormal dreams (all studies).
2.12
2.12. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 12 Insomnia (all studies).
2.13
2.13. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 13 Anxiety (all studies).
2.14
2.14. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 14 Depressed mood (all studies).
2.15
2.15. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 15 Abnormal thoughts and perceptions.
2.16
2.16. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 16 Pruritis (all studies).
2.17
2.17. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 17 Photosensitivity (all studies).
2.18
2.18. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 18 Yeast infection (all studies).
2.19
2.19. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 19 Visual impairment (all studies).
2.20
2.20. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 20 Other adverse effects (cohort studies).
2.21
2.21. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 21 Other adverse events (RCTs).
2.22
2.22. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 22 Other adverse events (cohort studies).
2.23
2.23. Analysis
Comparison 2 Mefloquine versus doxycycline, Outcome 23 Adherence (cohort studies).
3.1
3.1. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 1 Clinical cases of malaria (RCTs).
3.2
3.2. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 2 Serious adverse events or effects (all studies).
3.3
3.3. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 3 Discontinuations due to adverse effects (all studies).
3.4
3.4. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 4 Nausea (all studies).
3.5
3.5. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 5 Vomiting (all studies).
3.6
3.6. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 6 Abdominal pain (all studies).
3.7
3.7. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 7 Diarrhoea (all studies).
3.8
3.8. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 8 Mouth ulcers (all studies).
3.9
3.9. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 9 Headache (all studies).
3.10
3.10. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 10 Dizziness (all studies).
3.11
3.11. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 11 Abnormal dreams (all studies).
3.12
3.12. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 12 Insomnia (all studies).
3.13
3.13. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 13 Anxiety (all studies).
3.14
3.14. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 14 Depressed mood (all studies).
3.15
3.15. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 15 Abnormal thoughts and perceptions (all studies).
3.16
3.16. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 16 Pruritis (all studies).
3.17
3.17. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 17 Visual impairment (all studies).
3.18
3.18. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 18 Other adverse effects (cohort studies).
3.19
3.19. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 19 Other adverse events (cohort studies).
3.20
3.20. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 20 Adherence (RCTs).
3.21
3.21. Analysis
Comparison 3 Mefloquine versus atovaquone‐proguanil, Outcome 21 Adherence (cohort studies).
4.1
4.1. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 1 Clinical cases of malaria (RCTs).
4.2
4.2. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 2 Serious adverse events or effects (all studies).
4.3
4.3. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 3 Discontinuations due to adverse effects (all studies).
4.4
4.4. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 4 Nausea (all studies).
4.5
4.5. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 5 Vomiting (all studies).
4.6
4.6. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 6 Abdominal pain (all studies).
4.7
4.7. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 7 Diarrhoea (all studies).
4.8
4.8. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 8 Headache (all studies).
4.9
4.9. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 9 Dizziness (all studies).
4.10
4.10. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 10 Abnormal dreams (all studies).
4.11
4.11. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 11 Insomnia (all studies).
4.12
4.12. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 12 Anxiety (all studies).
4.13
4.13. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 13 Depressed mood (all studies).
4.14
4.14. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 14 Abnormal thoughts and perceptions.
4.15
4.15. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 15 Pruritis (all studies).
4.16
4.16. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 16 Visual impairment (all studies).
4.17
4.17. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 17 Vertigo (all studies).
4.18
4.18. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 18 Cohort studies in travellers; prespecified adverse effects.
4.19
4.19. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 19 Other adverse effects (cohort studies).
4.20
4.20. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 20 Other adverse events (RCTs).
4.21
4.21. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 21 Pregnancy related outcomes (RCTs).
4.22
4.22. Analysis
Comparison 4 Mefloquine versus chloroquine, Outcome 22 Adherence (cohort studies).
5.1
5.1. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 1 Nausea; effects.
5.2
5.2. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 2 Abdominal pain; effects.
5.3
5.3. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 3 Diarrhoea; effects.
5.4
5.4. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 4 Headache; effects.
5.5
5.5. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 5 Dizziness; effects.
5.6
5.6. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 6 Abnormal dreams; effects.
5.7
5.7. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 7 Insomnia; effects.
5.8
5.8. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 8 Anxiety; effects.
5.9
5.9. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 9 Depressed mood; effects.
5.10
5.10. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 10 Abnormal thoughts or perceptions; effects.
5.11
5.11. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 11 Pruritis; effects.
5.12
5.12. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 12 Visual impairment; effects.
5.13
5.13. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 13 Adherence; during travel.
5.14
5.14. Analysis
Comparison 5 Mefloquine versus currently used regimens; by study design, Outcome 14 Adherence; after return.
See this image and copyright information in PMC

Update of

Comment in

  • Mefloquine revisited.
    Hagmann SHF. Hagmann SHF. Travel Med Infect Dis. 2017 Nov-Dec;20:1-2. doi: 10.1016/j.tmaid.2017.11.006. Epub 2017 Nov 20. Travel Med Infect Dis. 2017. PMID: 29158041 No abstract available.

References

References to studies included in this review

Albright 2002 {published data only}
    1. Albright TA, Binns HJ, Katz BZ. Side effects of and compliance with malaria prophylaxis in children. Journal of Travel Medicine 2002;9(6):289‐92. - PubMed
Andersson 2008 {published data only}
    1. Andersson H, Askling HH, Falck B, Rombo L. Well‐tolerated chemoprophylaxis uniformly prevented Swedish soldiers from Plasmodium falciparum malaria in Liberia, 2004‐2006. Military Medicine 2008;173(12):1194‐8. - PubMed
Arthur 1990 {published data only}
    1. Arthur JD, Echeverria P, Shanks GD, Karwacki J, Bodhidatta L, Brown JE. A comparative study of gastrointestinal infections in United States soldiers receiving doxycycline or mefloquine for malaria prophylaxis. American Journal of Tropical Medicine and Hygiene 1990;43(6):608‐13. - PubMed
Belderok 2013 {published data only}
    1. Belderok SM, Hoek A, Roeffen W, Sauerwein R, Sonder GJ. Adherence to chemoprophylaxis and Plasmodium falciparum anti‐circumsporozoite seroconversion in a prospective cohort study of Dutch short‐term travelers. PLoS ONE 2013;8(2):e56863. - PMC - PubMed
Boudreau 1991 {published data only}
    1. Boudreau EF, Pang LW, Chaikummao S, Witayarut C. Comparison of mefloquine, chloroquine plus pyrimethamine‐sulfadoxine (Fansidar), and chloroquine as malarial prophylaxis in eastern Thailand. Southeast Asian Journal of Tropical Medicine and Public Health 1991; Vol. 22, issue 2:183‐9. - PubMed
Boudreau 1993 {published data only}
    1. Boudreau E, Schuster B, Sanchez J, Novakowski W, Johnson R, Redmond D, et al. Tolerability of prophylactic Lariam regimens. Tropical Medicine and Parasitology 1993;44(3):257‐65. - PubMed
Bunnag 1992 {published data only}
    1. Bunnag D, Malikul S, Chittamas S, Chindanond D, Harinasuta T, Fernex M, et al. Fansimef for prophylaxis of malaria: a double‐blind randomized placebo controlled trial. Southeast Asian Journal of Tropical Medicine and Public Health 1992; Vol. 23, issue 4:777‐82. - PubMed
Corominas 1997 {published data only}
    1. Corominas N, Gascon J, Mejias T, Caparros F, Quinto L, Codina C, et al. Adverse drug reactions associated to the antimalarial chemoprophylaxis. Medicina Clinica 1997;108(20):772‐5. - PubMed
Cunningham 2014 {published and unpublished data}
    1. Cunningham J, Horsley J, Patel D, Tunbridge A, Lalloo DG. Compliance with long‐term malaria prophylaxis in British expatriates. Travel Medicine and Infectious Disease 2014;12(4):341‐8. - PubMed
Davis 1996 {published data only}
    1. Davis TM, Dembo LG, Kaye‐Eddie SA, Hewitt BJ, Hislop RG, Batty KT. Neurological, cardiovascular and metabolic effects of mefloquine in healthy volunteers: a double‐blind, placebo‐controlled trial. British Journal of Clinical Pharmacology 1996;42(4):415‐21. - PMC - PubMed
Eick‐Cost 2017 {published data only}
    1. Eick‐Cost A, Hu Z, Rohrbeck P, Clark L. Neuropsychiatric outcomes after mefloquine exposure among U.S. military service members. American Journal of Tropical Medicine and Hygiene 2017;96(1):159‐66. - PMC - PubMed
Goodyer 2011 {published data only}
    1. Goodyer L, Rice L, Martin A. Choice of and adherence to prophylactic antimalarials. Journal of Travel Medicine 2011;18(4):245‐9. - PubMed
Hale 2003 {published data only}
    1. Hale BR, Owusu‐Agyei S, Fryauff DJ, Koram KA, Adjuik M, Oduro AR, et al. A randomized, double‐blind, placebo‐controlled, dose‐ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. Clinical Infectious Diseases 2003;36(5):541‐9. - PubMed
Hill 2000 {published data only}
    1. Hill DR. Health problems in a large cohort of Americans traveling to developing countries. Journal of Travel Medicine 2000;7(5):259‐66. - PubMed
Hoebe 1997 {published data only}
    1. Hoebe C, Munter J, Thijs C. Adverse effects and compliance with mefloquine or proguanil antimalarial chemoprophylaxis. European Journal of Clinical Pharmacology 1997;52(4):269‐75. - PubMed
Jute 2007 {published data only}
    1. Jute S, Toovey S. Knowledge, attitudes and practices of expatriates towards malaria chemoprophylaxis and personal protection measures on a mine in Mali. American Journal of Tropical Medicine and Hygiene 2007;5(1):40‐3. - PubMed
Kato 2013 {published and unpublished data}
    1. Kato T, Okuda J, Ide D, Amano K, Takei Y, Yamaguchi Y. Questionnaire‐based analysis of atovaquone‐proguanil compared with mefloquine in the chemoprophylaxis of malaria in non‐immune Japanese travelers. Journal of Infection and Chemotherapy 2013;19(1):20‐3. - PubMed
Korhonen 2007 {published and unpublished data}
    1. Korhonen C, Peterson K, Bruder C, Jung P. Self‐reported adverse events associated with antimalarial chemoprophylaxis in peace corps volunteers. American Journal of Preventine Medicine 2007;33(3):194‐9. - PubMed
Kuhner 2005 {published data only}
    1. Kuhner S, Drager‐Hoppe HS, Dreesman J. Malaria chemoprophylaxis ‐ A survey on drug‐related adverse events. Medizinische Welt 2005;56(1‐2):51‐5.
Landman 2015 {published data only}
    1. Landman KZ, Tan KR, Arguin PM. Adherence to malaria prophylaxis among Peace Corps volunteers in the Africa region, 2013. Travel Medicine and Infectious Disease 2015;13(1):61‐8. - PMC - PubMed
    1. Landman KZ, Tan KR, Arguin PM. Knowledge, attitudes, and practices regarding antimalarial chemoprophylaxis in U.S. Peace Corps volunteers ‐ Africa, 2013. Morbidity and Mortality Weekly Report 2014;63(23):516‐7. - PMC - PubMed
Laver 2001 {published data only}
    1. Laver SM, Wetzels J, Behrens RH. Knowledge of malaria, risk perception, and compliance with prophylaxis and personal and environmental preventive measures in travelers exiting Zimbabwe from Harare and Victoria Falls International airport. Journal of Travel Medicine 2001;8(6):298‐303. - PubMed
Laverone 2006 {published data only}
    1. Laverone E, Boccalini S, Bechini A, Belli S, Santini MG, Baretti S, et al. Travelers' compliance to prophylactic measures and behavior during stay abroad: Results of a retrospective study of subjects returning to a travel medicine center in Italy. Journal of Travel Medicine 2006;13(6):338‐44. - PubMed
Lobel 2001 {published data only}
    1. Lobel HO, Baker MA, Gras FA, Stennies GM, Meerburg P, Hiemstra E, et al. Use of malaria prevention measures by North American and European travelers to East Africa. Journal of Travel Medicine 2001;8(4):167‐72. - PubMed
Mavrogordato 2012 {published data only}
    1. Mavrogordato A, Lever AM. A cluster of Plasmodium vivax malaria in an expedition group to Ethiopia: Prophylactic efficacy of atovaquone/proguanil on liver stages of P. vivax. Journal of Infection 2012;65(3):269‐74. - PubMed
Meier 2004 {published data only}
    1. Meier CR, Wilcock K, Jick SS. The risk of severe depression, psychosis or panic attacks with prophylactic antimalarials. Drug Safety 2004;27(3):203‐13. - PubMed
Napoletano 2007 {published data only}
    1. Napoletano G, Bissoli P, Bisoffi Z, Todescato A, Gottardello L, Costa S, et al. Malaria chemoprophylaxis ‐ Follow up of returned travellers of Veneto Region, Italy. Giornale Italiano di Medicina Tropicale 2007;12(1‐4):13‐9.
Nosten 1994 {published data only}
    1. Nosten F, Ter Kuile F, Maelankiri L, Chongsuphajaisiddhi T, Nopdonrattakoon L, Tangkitchot S, et al. Mefloquine prophylaxis prevents malaria during pregnancy: A double‐blind, placebo‐controlled study. Journal of Infectious Diseases 1994;169(3):595‐603. - PubMed
Ohrt 1997 {published data only}
    1. Ohrt C, Richie TL, Widjaja H, Shanks GD, Fitriadi J, Fryauff DJ, et al. Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double‐blind, placebo‐controlled trial. Annals of Internal Medicine 1997; Vol. 126, issue 12:963‐72. - PubMed
Overbosch 2001 {published data only}
    1. Overbosch D, Schilthuis H, Bienzle U, Behrens RH, Kain KC, Clarke PD, et al. Atovaquone‐proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double‐blind study. Clinical Infectious Diseases 2001;33(7):1015‐21. - PubMed
Pearlman 1980 {published data only}
    1. Pearlman EJ, Doberstyn EB, Sudsok S, Thiemanun W, Kennedy RS, Canfield CJ. Chemosuppressive field trials in Thailand. IV. The suppression of Plasmodium falciparum and Plasmodium vivax parasitemias by mefloquine (WR 142,490, A 4‐quinolinemethanol). Americal Journal of Tropical Medicine and Hygiene 1980;29(6):1131‐7. - PubMed
Petersen 2000 {published data only}
    1. Petersen E, Ronne T, Ronn A, Bygbjerg I, Larsen SO. Reported side effects to chloroquine, chloroquine plus proguanil, and mefloquine as chemoprophylaxis against malaria in Danish travelers. Journal of Travel Medicine 2000;7(2):79‐84. - PubMed
Philips 1996 {published data only}
    1. Phillips MA, Kass RB. User acceptability patterns for mefloquine and doxycycline malaria chemoprophylaxis. Journal of Travel Medicine 1996;3(1):40‐5. - PubMed
Potasman 2002 {published data only}
    1. Potasman I, Weller B. Does mefloquine prophylaxis affect electroencephalographic patterns?. American Journal of Medicine 2002;112(2):147‐9. - PubMed
Rack 2005 {published data only}
    1. Rack J, Wichmann O, Kamara B, Gunther M, Cramer J, Schonfeld C, et al. Risk and spectrum of diseases in travelers to popular tourist destinations. Journal of Travel Medicine 2005;12(5):248‐53. - PubMed
Rieckmann 1993 {published data only}
    1. Rieckmann KH, Yeo AE, Davis DR, Hutton DC, Wheatley PF, Simpson R. Recent military experience with malaria chemoprophylaxis. Medical Journal of Australia 1993;158(7):446‐9. - PubMed
Rietz 2002 {published data only}
    1. Rietz G, Petersson H, Odenholt I. Many travellers suffer of side‐effects of malaria prophylaxis. Lakartidningen 2002;99(26‐7):2939‐44. - PubMed
Salako 1992 {published data only}
    1. Salako LA, Adio RA, Walker O, Sowunmi A, Sturchler D, Mittelholzer ML, et al. Mefloquine‐sulphadoxine‐pyrimethamine (Fansimef, Roche) in the prophylaxis of Plasmodium falciparum malaria: A double‐blind, comparative, placebo‐controlled study. Annals of Tropical Medicine and Parasitology 1992;86(6):575‐81. - PubMed
Santos 1993 {published data only}
    1. Santos JB, Prata A, Wanssa E. Mefloquine chemoprophylaxis of malaria in the Brazilian Amazonia. Revista da Sociedade Brasileira de Medicina Tropical 1993;26(3):157‐62. - PubMed
Saunders 2015 {published data only}
    1. Saunders DL, Garges E, Manning JE, Bennett K, Schaffer S, Kosmowski AJ, et al. Safety, tolerability, and compliance with long‐term antimalarial chemoprophylaxis in American soldiers in Afghanistan. American Journal of Tropical Medicine and Hygiene 2015;93(3):584‐90. - PMC - PubMed
Schlagenhauf 1997 {published data only}
    1. Schlagenhauf P, Lobel H, Steffen R, Johnson R, Popp K, Tschopp A, et al. Tolerance of mefloquine by SwissAir trainee pilots. American Journal of Tropical Medicine and Hygiene 1997;56(2):235‐40. - PubMed
Schlagenhauf 2003 {published data only}
    1. Schlagenhauf P, Johnson R, Schwartz E, Nothdurft HD, Steffen R. Evaluation of mood profiles during malaria chemoprophylaxis: a randomized, double‐blind, four‐arm study. Journal of Travel Medicine 2009;16(1):42‐45. - PubMed
    1. Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, et al. Tolerability of malaria chemoprophylaxis in non‐immune travellers to sub‐Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ 2003;327(7423):1078. - PMC - PubMed
Schneider 2013 {published data only}
    1. Schneider C, Adamcova M, Jick SS, Schlagenhauf P, Miller MK, Rhein HG, et al. Antimalarial chemoprophylaxis and the risk of neuropsychiatric disorders. Travel Medicine and Infectious Disease 2013;11(2):71‐80. - PubMed
    1. Schneider C, Adamcova M, Jick SS, Schlagenhauf P, Miller MK, Rhein HG, et al. Use of anti‐malarial drugs and the risk of developing eye disorders. Travel Medicine and Infectious Disease 2014;12(1):40‐7. - PubMed
Schwartz 1999 {published data only}
    1. Schwartz E, Regev‐Yochay G. Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline. Clinical Infectious Diseases 1999;29(6):1502‐6. - PubMed
Shamiss 1996 {published data only}
    1. Shamiss A, Atar E, Zohar L, Cain Y. Mefloquine versus doxycycline for malaria prophylaxis in intermittent exposure of Israeli Air Force aircrew in Rwanda. Aviation, Space, and Environmental Medicine 1996;67(9):872‐3. - PubMed
Sharafeldin 2010 {published data only}
    1. Sharafeldin E, Soonawala D, Vandenbroucke JP, Hack E, Visser LG. Health risks encountered by Dutch medical students during an elective in the tropics and the quality and comprehensiveness of pre‐and post‐travel care. BMC Medical Education 2010;10:89. - PMC - PubMed
Sonmez 2005 {published data only}
    1. Sonmez A, Harlak A, Kilic S, Polat Z, Hayat L, Keskin O, et al. The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan. Journal of Infectious Diseases 2005;51(3):253‐8. - PubMed
Sossouhounto 1995 {published data only}
    1. Sossouhounto RT, Soro BN, Coulibaly A, Mittelholzer ML, Stuerchler D, Haller L. Mefloquine in the prophylaxis of P. Falciparum malaria. Journal of Travel Medicine 1995;2(4):221‐4. - PubMed
Steffen 1993 {published data only}
    1. Handschin JC, Wall M, Steffen R, Sturchler D. Tolerability and effectiveness of malaria chemoprophylaxis with mefloquine or chloroquine with or without co‐medication. Journal of Travel Medicine 1997;4(3):121‐7. - PubMed
    1. Steffen R, Fuchs E, Schildknecht J, Naef U, Funk M, Schlagenhauf P, et al. Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting east Africa. Lancet 1993;341(8856):1299‐303. - PubMed
    1. Steffen R, Heusser R, Machler R, Bruppacher R, Naef U, Chen D, et al. Malaria chemoprophylaxis among European tourists in tropical Africa: use, adverse reactions, and efficacy. Bulletin of the World Health Organization 1990;68(3):313‐22. - PMC - PubMed
Steketee 1996 {published data only}
    1. Steketee RW, Wirima JJ, Hightower AW, Slutsker L, Heymann DL, Breman JG. The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi. American Journal of Tropical Medicine and Hygiene 1996;55(Suppl 1):33‐41. - PubMed
    1. Steketee RW, Wirima JJ, Slutsker L, Breman JG, Heymann DL. Comparability of treatment groups and risk factors for parasitemia at the first antenatal clinic visit in a study of malaria treatment and prevention in pregnancy in rural Malawi. American Journal of Tropical Medicine and Hygiene 1996;55(Suppl 1):17‐23. - PubMed
    1. Steketee RW, Wirima JJ, Slutsker L, Khoromana CO, Heymann DL, Breman JG. Malaria treatment and prevention in pregnancy: Indications for use and adverse events associated with use of chloroquine or mefloquine. American Journal of Tropical Medicine and Hygiene 1996;55(Suppl 1):50‐6. - PubMed
    1. Steketee RW, Wirima JJ, Slutsker L, Roberts JM, Khoromana CO, Heymann DL, et al. Malaria parasite infection during pregnancy and at delivery in mother, placenta, and newborn: efficacy of chloroquine and mefloquine in rural Malawi. American Journal of Tropical Medicine and Hygiene 1996;55(Suppl 1):24‐32. - PubMed
    1. Steketee RW, Wirima JJ, Slutsker WL, Khoromana CO, Breman JG, Heymann DL. Objectives and methodology in a study of malaria treatment and prevention in pregnancy in rural Malawi: the Mangochi Malaria Research Project. American Journal of Tropical Medicine and Hygiene 1996;55(Suppl 1):8‐16. - PubMed
Stoney 2016 {published data only}
    1. Stoney RJ, Chen LH, Jentes ES, Wilson ME, Han PV, Benoit CM, et al. Malaria prevention strategies: adherence among Boston area travelers visiting malaria‐endemic countries. American Journal of Tropical Medicine and Hygiene 2016;94(1):136‐42. - PMC - PubMed
Tan 2017 {published data only}
    1. Tan KR, Henderson S, Williamson J, Ferguson RW, Wilkinson TM, Jung P, et al. Long term health outcomes among returned Peace Corps volunteers after malaria prophylaxis, 1995‐2014. Travel Medicine and Infectious Disease 2017;17:50‐55. - PMC - PubMed
Terrell 2015 {published data only}
    1. Terrell AG, Forde ME, Firth R, Ross DA. Malaria chemoprophylaxis and self‐reported impact on ability to work: mefloquine versus doxycycline. Journal of Travel Medicine 2015;22(6):383‐8. - PubMed
Tuck 2016 {published data only}
    1. Tuck J, Williams J. Malaria protection in Sierra Leone during the Ebola outbreak 2014/15; The UK military experience with malaria chemoprophylaxis Sep 14‐Feb 15. Travel Medicine and Infectious Diseases 2016;14(5):471‐4. - PubMed
van Riemsdijk 1997 {published data only}
    1. Riemsdijk MM, Klauw MM, Heest JA, Reedeker FR, Ligthelm RJ, Herings RM, et al. Neuro‐psychiatric effects of antimalarials. European Journal of Clinical Pharmacology 1997;52(1):1‐6. - PubMed
van Riemsdijk 2002 {published data only}
    1. Riemsdijk MM, Sturkenboom MC, Ditters JM, Ligthelm RJ, Overbosch D, Stricker BH. Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: a focus on neuropsychiatric adverse events. Clinical Pharmacology and Therapeutics 2002;72(3):294‐301. - PubMed
Vuurman 1996 {published data only}
    1. Vuurman EF, Muntjewerff ND, Uiterwijk MM, Veggel LM, Crevoisier C, Haglund L, et al. Effects of mefloquine alone and with alcohol on psychomotor and driving performance. European Journal of Clinical Pharmacology 1996;50(6):475‐82. - PubMed
Waner 1999 {published data only}
    1. Waner S, Durrhiem D, Braack LE, Gammon S. Malaria protection measures used by in‐flight travelers to South African game parks. Journal of Travel Medicine 1999;6(4):254‐7. - PubMed
Weiss 1995 {published data only}
    1. Weiss WR, Oloo AJ, Johnson A, Koech D, Hoffman SL. Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: Comparison with mefloquine, doxycycline, and chloroquine plus proguanil. Journal of Infectious Disease 1995;171(6):1569‐75. - PubMed
Wells 2006 {published data only}
    1. Wells TS, Smith TC, Smith B, Wang LZ, Hansen CJ, Reed RJ, et al. Mefloquine use and hospitalizations among US service members, 2002‐2004. American Journal of Tropical Medicine and Hygiene 2006;74(5):744‐9. - PubMed

References to studies excluded from this review

Abraham 1999 {published data only}
    1. Abraham C, Clift S, Grabowski P. Cognitive predicators of adherence to malaria prophylaxis regimens on return from a malarious region: protective study. Social Science and Medicine 1999;48(11):1641‐54. - PubMed
Adera 1995 {published data only}
    1. Adera T, Wolfe MS, McGuire‐Rugh K, Calhoun N, Marum L. Risk factors for malaria among expatriates living in Kampala, Uganda: The need for adherence to chemoprophylactic regimens. American Journal of Tropical Medicine and Hygiene 1995;52(3):207‐12. - PubMed
Adshead 2014 {published data only}
    1. Adshead S. The adverse effects of mefloquine in deployed military personnel. Journal of the Royal Naval Medical Service 2014;100(3):232‐7. - PubMed
Angelin 2014 {published data only}
    1. Angelin M, Evengard B, Palmgren H. Travel health advice: Benefits, compliance, and outcome. Scandinavian Journal of Infectious Diseases 2014;46(6):447‐53. - PubMed
Anonymous 1991 {published data only}
    1. Anonymous. Mefloquine ‐ A new antimalarial. Drug and Therapeutics Bulletin 1991;29(13):51‐2. - PubMed
Anonymous 1998 {published data only}
    1. Anonymous. Medication‐associated depression. WHO Drug Information 1998;12(2):81.
Anonymous 1998a {published data only}
    1. Anonymous. Mefloquine effectiveness impaired by high withdrawal rates. WHO Drug Information 1998;12(1):7‐8.
Anonymous 2005 {published data only}
    1. Anonymous. Mefloquine: Revised patient information. WHO Drug Information 2005;19(2):119.
Anonymous 2009 {published data only}
    1. Anonymous. Mefloquine: interstitial pneumonia: rare events. Prescrire International 2009;18(102):167. - PubMed
Artaso 2004 {published data only}
    1. Artaso Irigoyen B, Langarica Eseverri M, Campos Mangas MC. Mefloquine‐induced acute psychosis. Psiquiatria Biologica 2004;11(4):164‐6.
Arthur 1990a {published data only}
    1. Arthur JD, Shanks GD, Echeverria P. Mefloquine prophylaxis. Lancet 1990;335(8695):972. - PubMed
Banerjee 2001 {published data only}
    1. Banerjee D, Stanley PJ. Malaria chemoprophylaxis in UK general practitioners traveling to South Asia. Journal of Travel Medicine 2001;8(4):173‐5. - PubMed
Barbero Gonzalez 2003 {published data only}
    1. Barbero Gonzalez A, Alvarez de Toledo Saavedra F, Esteban Fernandez J, Pastor‐Sanchez R, Gil de Miguel A, Rodriguez Barrios JM, et al. Management of vaccinations and prophylaxis of international travellers from community pharmacy (VINTAF Study). Atencion Primaria 2003;32(5):276‐81. - PMC - PubMed
Barrett 1996 {published data only}
    1. Barrett PJ, Emmins PD, Clarke PD, Bradley DJ. Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travelers. British Medical Journal 1996;313(7056):525‐8. - PMC - PubMed
Berger 1998 {published data only}
    1. Berger A. Science commentary: protection against malaria. British Medical Journal 1998;317(7171):1508. - PMC - PubMed
Berman 2004 {published data only}
    1. Berman J. Toxicity of commonly‐used antimalarial drugs. Travel Medicine and Infectious Disease 2004;2(3‐4):171‐84. - PubMed
Bernado 1994 {published data only}
    1. Bernardo M, Parellada E. Mefloquine and severe psychiatric disorder. Medicina Clinica 1994;102(15):596. - PubMed
Bijker 2014 {published data only}
    1. Bijker EM, Schats R, Obiero JM, Behet MC, Gemert GJ, Vegte‐Bolmer M, et al. Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe, immunogenic and protective: a double‐blind randomized controlled clinical trial. PLoS ONE 2014;9(11):e112910. - PMC - PubMed
Bjorkman 1991 {published data only}
    1. Bjorkman A, Steffen R, Armengaud M, Picot N, Piccoli S. Malaria chemoprophylaxis with mefloquine. Lancet 1991;337(8755):1479‐80. - PubMed
Black 2007 {published data only}
    1. Black J. Lariam and Halfan. Journal of the Royal Society of Medicine 2007;100(8):355‐6. - PMC - PubMed
Blanke 2003 {published data only}
    1. Blanke CH. Increased malaria‐morbidity of long‐term travellers due to inappropriate chemoprophylaxis recommendations. Tropical Doctor 2003;33(2):117‐9. - PubMed
Botella de Maglia 1999 {published data only}
    1. Botella de Maglia J, Espacio Casanovas A. Prevention of malaria. Revista Clínica Española 1999;199(8):549‐50. - PubMed
Bourgeade 1990 {published data only}
    1. Bourgeade A, Tonin V, Keudjian F, Levy PY, Faugere B. Accidental mefloquine poisoning. Presse Medicale 1990;19(41):1903. - PubMed
Brenier‐Pinchart 2000 {published data only}
    1. Brenier‐Pinchart MP, Brion JP, Issartel B, Barro C, Pinel C, Ambroise‐Thomas P. Glucose‐6‐phosphate dehydrogenase deficiency and hemoglobinuric biliary fever after taking mefloquine. Presse Medicale 2000;29(3):142. - PubMed
Brisson 2012 {published data only}
    1. Brisson M, Brisson P. Compliance with antimalaria chemoprophylaxis in a combat zone. American Journal of Tropical Medicine and Hygiene 2012;86(4):587‐90. - PMC - PubMed
Bruguera 2007 {published data only}
    1. Bruguera M, Herrera S. Acute hepatitis associated with mefloquine therapy. Gastroenterologie Hepatologie 2007;30(2):102‐3. - PubMed
Burke 1993 {published data only}
    1. Burke BM. Mefloquine. Lancet 1993;341(8860):1605‐6. - PubMed
Caillon 1992 {published data only}
    1. Caillon E, Schmitt L, Moron P. Acute depressive symptoms after mefloquine treatment. American Jounal of Psychiatry 1992;149(5):712. - PubMed
Carme 1997 {published data only}
    1. Carme B, Peguet C, Nevez G. Compliance with and tolerance of mefloquine and chloroquine + proguanil malaria chemoprophylaxis in French short‐term travellers to sub‐Saharan Africa. Tropical Medicine and International Health 1997;2(10):953‐6. - PubMed
    1. Carme B, Peguet C, Nevez G. Malaria chemoprophylaxis: tolerance and compliance with mefloquine and proguanil/chloroquine combination in French tourists. Bulletin de la Societe de Pathologie Exotique 1997;90(4):273‐6. - PubMed
Castot 1988 {published data only}
    1. Castot A, Garnier R. The secondary effects of mefloquine. Concours Medical 1988;110(43):4003.
Cave 2003 {published data only}
    1. Cave W, Pandey P, Osrin D, Shlim DR. Chemoprophylaxis use and the risk of malaria in travelers to Nepal. Journal of Travel Medicine 2003;10(2):100‐5. - PubMed
Charles 2007 {published data only}
    1. Charles BG, Blomgren A, Nasveld PE, Kitchener SJ, Jensen A, Gregory RM, et al. Population pharmacokinetics of mefloquine in military personnel for prophylaxis against malaria infection during field deployment. European Journal of Clinical Pharmacology 2007;63(3):271‐8. - PubMed
Chin 2016 {published data only}
    1. Chin BS, Kim JY, Gianella S, Lee M. Travel pattern and prescription analysis at a single travel clinic specialized for yellow fever vaccination in South Korea. Infection and Chemotherapy 2016;48(1):20‐30. - PMC - PubMed
Clifford 2009 {published data only}
    1. Clifford D, Brew B, Cinque P, Gorelik L, Bennett D, Panzara MA, et al. Design of a clinical trial of mefloquine in patients with progressive multifocal leukoencephalopathy. 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; 2009 Sep 9‐12; Dusseldorf Germany. Dusseldorf, 2009:S87.
Clift 1996 {published data only}
    1. Clift S, Grabowski P. Malaria prophylaxis and the media. Lancet 1996;348(9023):344. - PubMed
Clyde 1976 {published data only}
    1. Clyde DF, McCarthy VC, Miller RM, Hornick RB. Suppressive activity of mefloquine in sporozoite‐induced human malaria. Antimicrobial Agents and Chemotherapy 1976;9(3):384‐6. - PMC - PubMed
Cobelens 1997 {published data only}
    1. Cobelens FG, Thiel PP. There is no evidence of more symptoms with mefloquine than with other drugs in malaria prophylaxis. Nederlands Tijdschrift voor Geneeskunde 1997;141(16):794‐5; author reply 796. - PubMed
Cohen 1997 {published data only}
    1. Cohen J. Mefloquine prophylaxis ‐ revisited. Australian Family Physician 1997;26(8):909. - PubMed
Conget 1993 {published data only}
    1. Conget JJ, Navarro M, Navarro P, Corachan M. Prophylaxis with mefloquine and changes in thyroidal hormones. Medicina Clinica 1993;100(13):516. - PubMed
Conrad 1997 {published data only}
    1. Conrad KA, Kiser WR. Response to doxycycline vs. mefloquine. Military Medicine 1997;162(6):iii. - PubMed
Corbett 1996 {published data only}
    1. Corbett EL, Doherty JF, Behrens RH. Adverse events associated with mefloquine. Study in returned travelers confirms authors' findings. British Medical Journal 1996;313(7071):1552. - PMC - PubMed
Coulaud 1986 {published data only}
    1. Coulaud JP. Chemoprophylaxis of malaria. Medecine et Maladies Infectieuses 1986;16(12):746.
Croft 1996 {published data only}
    1. Croft AM, World MJ. Neuropsychiatric reactions with mefloquine chemoprophylaxis. Lancet 1996;347(8997):326. - PubMed
Croft 1997 {published data only}
    1. Croft AM, Clayton TC, World MJ. Side effects of mefloquine prophylaxis for malaria: an independent randomized controlled trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 1997;91(2):199‐203. - PubMed
Del Cacho 2001 {published data only}
    1. Cacho Ma E, Martinez M, Tuset M, Biarnes C, Mejias T, Gascon J, et al. Advice program for travelers about antimalarial prohilaxis. Atencion Farmaceutica 2001;3(3):171‐6.
Dia 2010 {published data only}
    1. Dia A, Gautret P, Adheossi E, Bienaime A, Gaillard C, Simon F, et al. Illness in French travelers to Senegal: Prospective cohort follow‐up and sentinel surveillance data. Journal of Travel Medicine 2010;17(5):296‐302. - PubMed
Durrheim 1999 {published data only}
    1. Durrheim DN, Gammon S, Waner S, Braack LE. Antimalarial prophylaxis‐‐use and adverse events in visitors to the Kruger National Park. Suid‐Afrikaanse Tydskrif vir Geneeskunde 1999;89(2):170‐5. - PubMed
Eamsila 1993 {published data only}
    1. Eamsila C, Singharaj P, Yooyen P, Chatnugrob P, Nopavong Na Ayuthya A, Webster HK, et al. Prevention of Plasmodium falciparum malaria by Fansimef and Lariam in the northeastern part of Thailand. Southeast Asian Journal of Tropical Medicine and Public Health 1993;24(4):672‐6. - PubMed
El Jaoudi 2010 {published data only}
    1. Jaoudi R, Benziane H, Khabbal Y, Elomri N, Lamsaouri J, Cherrah Y. Long‐term malaria prophylaxis with mefloquine: a study of adverse drug reactions. Therapie 2010;65(5):439‐45. - PubMed
Fernando 2016 {published data only}
    1. Fernando SD, Dharmawardana P, Semege S, Epasinghe G, Senanayake N, Rodrigo C, et al. The risk of imported malaria in security forces personnel returning from overseas missions in the context of prevention of re‐introduction of malaria to Sri Lanka. Malaria Journal 2016;15(1):144. - PMC - PubMed
Fujii 2007 {published data only}
    1. Fujii T, Kaku K, Jelinek T, Kimura M. Malaria and mefloquine prophylaxis use among Japan ground self‐defense force personnel deployed in East Timor. Journal of Travel Medicine 2007;14(4):226‐32. - PubMed
Hamer 2008 {published data only}
    1. Hamer DH, Ruffing R, Callahan MV, Lyons SH, Abdullah AS. Knowledge and use of measures to reduce health risks by corporate expatriate employees in western Ghana. Journal of Travel Medicine 2008;15(4):237‐42. - PubMed
Hellgren 1990 {published data only}
    1. Hellgren U, Angel VH, Bergqvist Y, Arvidsson A, Forero‐Gomez J, Rombo L. Plasma concentrations of sulfadoxine‐pyrimethamine and of mefloquine during regular long term malaria prophylaxis. Transactions of the Royal Society of Tropical Medicine and Hygiene 1990;84(1):46‐9. - PubMed
Hopperus 1996 {published data only}
    1. Hopperus Buma AP, Thiel PP, Lobel HO, Ohrt C, Ameijden EJ, Veltink RL, et al. Long‐term malaria chemoprophylaxis with mefloquine in Dutch marines in Cambodia. Journal of Infectious Diseases 1996;173(6):1506‐9. - PubMed
Jaspers 1996 {published data only}
    1. Jaspers CA, Hopperus Buma AP, Thiel PP, Hulst RA, Kager PA. Tolerance of mefloquine chemoprophylaxis in Dutch military personnel. American Journal of Tropical Medicine and Hygiene 1996;55(2):230‐4. - PubMed
Jensen 1998 {published data only}
    1. Jensen JJ. Mefloquine: neuropsychiatric adverse effects are often severe and persistent long after withdrawal of the drug. Ugeskrift for Laeger 1998;160(16):2413. - PubMed
Karbwang 1991 {published data only}
    1. Karbwang J, Molunto P, Bangchang KN, Banmairuroi V, Bunnag D, Harinasuta T. Pharmacokinetics of prophylactic mefloquine. Southeast Asian Journal of Tropical Medicine and Public Health 1991;22(4):519‐22. - PubMed
Karbwang 1991a {published data only}
    1. Karbwang J, Bangchang KN, Supapojana A, Bunnag D, Harinasuta T. Pharmacokinetics of prophylactic mefloquine in Thai healthy volunteers. Southeast Asian Journal of Tropical Medicine and Public Health 1991;22(1):68‐71. - PubMed
Khaliq 2001 {published data only}
    1. Khaliq Y, Gallicano K, Carignan CT, Cooper C, McCarthy A. Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers. British Journal of Clinical Pharmacology 2001;51(6):591‐600. - PMC - PubMed
Kimura 2006 {published data only}
    1. Kimura M, Kawakami K, Hashimoto M, Hamada M. Malaria prevention and stand‐by emergency treatment among Japanese travelers. Travel Medicine and Infectious Disease 2006;4(2):81‐5. - PubMed
Kitchener 2003 {published data only}
    1. Kitchener S, Nasveld P, Russell B, Elmes N. An outbreak of malaria in a forward battalion on active service in East Timor. Military Medicine 2003;168(6):457‐9. - PubMed
Kitchener 2005 {published data only}
    1. Kitchener SJ, Nasveld PE, Gregory RM, Edstein MD. Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor. Medical Journal of Australia 2005;182(4):168‐71. - PubMed
Kok 1997 {published data only}
    1. Kok PW, Puls FT, Zonderland HD. Not more symptoms with mefloquine use than with other drugs in malaria prophylaxis. Nederlands Tijdschrift Voor Geneeskunde 1997;141(18):898. - PubMed
Kollaritsch 2000 {published data only}
    1. Kollaritsch H, Karbwang J, Wiedermann G, Mikolasek A, Na‐Bangchang K, Wernsdorfer WH. Mefloquine concentration profiles during prophylactic dose regimens. Wiener Klinische Wochenschrift 2000;112(10):441‐7. - PubMed
Kozarsky 1993 {published data only}
    1. Kozarsky P, Eaton M. Use of mefloquine for malarial chemoprophylaxis in its first year of availability in the United States. Clinical Infectious Diseases 1993;16(1):185‐6. - PubMed
Landry 2006 {published data only}
    1. Landry P, Iorillo D, Darioli R, Burnier M, Genton B. Do travelers really take their mefloquine malaria chemoprophylaxis? Estimation of adherence by an electronic pillbox. Journal of Travel Medicine 2006;13(1):8‐14. - PubMed
Lapierre 1983 {published data only}
    1. Lapierre J, Devant J, Coquelin B, Faurant C, Galal AA. Results of an experiment on chemoprophylaxis of malaria using mefloquine in Cambodia (Cambodia‐Thai border region). Bulletin de la Societe de Pathologie Exotique et de ses Filiales 1983;76(4):357‐63. - PubMed
Lim 2005 {published data only}
    1. Lim DS. Dermatology in the military: An East Timor study. International Journal of Dermatology 2005;44(4):304‐11. - PubMed
Lobel 1993 {published data only}
    1. Lobel HO, Bernard KW, Williams SL, Hightower AW, Patchen LC, Campbell C. Effectiveness and tolerance of long‐term malaria prophylaxis with mefloquine. Need for a better dosing regimen. JAMA 1991;265(3):361‐4. - PubMed
    1. Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC. Long‐term malaria prophylaxis with weekly mefloquine. Lancet 1993;341(8849):848‐51. - PubMed
Looareesuwan 1987 {published data only}
    1. Looareesuwan S, White NJ, Warrell DA, Forgo I, Schwartz DE, et al. Studies of mefloquine bioavailability and kinetics using a stable isotope technique: comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers. British Journal of Clinical Pharmacology 1987;24(1):37‐42. - PMC - PubMed
MacArthur 2002 {published data only}
    1. MacArthur JR, Parise ME, Steketee RW. Relationships between mefloquine blood levels, gender, and adverse reactions. American Journal of Tropical Medicine and Hygiene 2002;66(5):445; author reply 446‐7. - PubMed
Malvy 2006 {published data only}
    1. Malvy D, Pistone T, Rezvani A, Lancon F, Vatan R, Receveur MC, et al. Risk of malaria among French adult travellers. Travel Medicine and Infectious Disease 2006;4(5):259‐69. - PubMed
Marcy 1996 {published data only}
    1. Marcy SM, Wilson ME. Malaria prophylaxis in young children and pregnant women. Pediatric Infectious Disease Journal 1996;15(1):101‐2.
Massey 2007 {published data only}
    1. Massey P, Durrheim DN, Speare R. Inadequate chemoprophylaxis and the risk of malaria. Australian Family Physician 2007;36(12):1058‐60. - PubMed
Matsumura 2005 {published data only}
    1. Matsumura T, Fujii T, Miura T, Koibuchi T, Endo T, Nakamura H, et al. Questionnaire‐based analysis of mefloquine chemoprophylaxis for malaria in a Japanese population. Journal of Infection and Chemotherapy 2005;11(4):196‐8. - PubMed
Meszaros 1996 {published data only}
    1. Meszaros K. Acute psychosis caused by mefloquine prophylaxis?. Canadian Journal of Psychiatry 1996;41(3):196. - PubMed
Michel 2007 {published data only}
    1. Michel R, Ollivier L, Meynard JB, Guette C, Migliani R, Boutin JP. Outbreak of malaria among policemen in French Guiana. Military Medicine 2007;172(9):977‐81. - PubMed
Mimica 1983 {published data only}
    1. Mimica I, Fry W, Eckert G, Schwartz DE. Multiple‐dose kinetic study of mefloquine in healthy male volunteers. Chemotherapy 1983;29(3):184‐7. - PubMed
Mizuno 2006 {published data only}
    1. Mizuno Y, Kudo K, Kano S. Chemoprophylaxis according to the guidelines on malaria prevention for Japanese overseas travellers. Southeast Asian Journal of Tropical Medicine and Public Health 2006;37(Suppl 3):11‐4. - PubMed
Mizuno 2010 {published data only}
    1. Mizuno Y, Kudo K, Kano S. Mefloquine chemoprophylaxis against malaria in Japanese travelers: Results of a study on adverse effects. Tropical Medicine and Health 2010;38(3):103‐6.
Moon 2011 {published data only}
    1. Moon J, Deye G, Miller L, Fracisco S, Miller RS, Tosh D, et al. Malaria infection in individuals taking mefloquine does not induce antibody response to MSP142. 58th Annual Meeting of the American Society of Tropical Medicine and Hygiene; 2009 November 18‐22; Washington, USA. Washington, USA: American Journal of Tropical Medicine and Hygiene, 2009; Vol. 81:156‐7.
    1. Moon JE, Deye GA, Miller L, Fracisco S, Miller RS, Tosh D, et al. Plasmodium falciparum infection during suppressive prophylaxis with mefloquine does not induce an antibody response to merozoite surface protein‐1(42). American Journal of Tropical Medicine and Hygiene 2011;84(5):825‐29. - PMC - PubMed
Morales de Naime 1989 {published data only}
    1. Morales de Naime L, Kosidub H, Martínez Iturriza L. Prophylactic malaria with pyrimethamine, sulfadoxine and mefloquine [Paludismo tratamiento profiláctico con pirimetamina, sulfadoxina y mefloquina]. Medicina Interna 1989;5(3‐4):125‐37.
Munawar 2012 {published data only}
    1. Munawar CM, Khan TP, Hyder MF. Effect of mefloquine on eye. Pakistan Journal of Medical and Health Sciences 2012;6(2):340‐2.
Mølle 2000 {published data only}
    1. Mølle I, Christensen KL, Hansen PS, Dragsted UB, Aarup M, Mads Buhl R. Use of medical chemoprophylaxis and antimosquito precautions in Danish malaria patients and their traveling companions. Journal of Travel Medicine 2000;7(5):253‐8. - PubMed
Namikawa 2008 {published data only}
    1. Namikawa K, Kikuchi H, Kato S, Takizawa Y, Konta A, Iida T, et al. Knowledge, attitudes, and practices of Japanese travelers towards malaria prevention during overseas travel. Travel Medicine and Infectious Disease 2008;6(3):137‐41. - PubMed
Nasveld 2010 {published data only}
    1. Dow GS, McCarthy WF, Reid M, Smith B, Tang D, Shanks GD. A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti‐malarials in non‐immune individuals during deployment to a malaria‐endemic area. Malaria Journal 2014;13(1):49. - PMC - PubMed
    1. Nasveld PE, Edstein MD, Reid M, Brennan L, Harris IE, Kitchener SJ, et al. Randomized, double‐blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrobial Agents and Chemotherapy 2010;54(2):792‐8. - PMC - PubMed
Nevin 2010 {published data only}
    1. Nevin RL. Mefloquine prescriptions in the presence of contraindications: Prevalence among US military personnel deployed to Afghanistan, 2007. Pharmacoepidemiology and Drug Safety 2010;19(2):206‐10. - PubMed
Nevin 2012 {published data only}
    1. Nevin RL. Biased measurement of neuropsychiatric adverse effects of pediatric mefloquine treatment. Pediatric Infectious Diseases Journal 2012;31(1):102; author reply 102‐3. - PubMed
Nosten 1990 {published data only}
    1. Nosten F, Karbwang J, White NJ, Honeymoon, Na Bangchang K, Bunnag D, et al. Mefloquine antimalarial prophylaxis in pregnancy: dose finding and pharmacokinetic study. British Journal of Clinical Pharmacology 1990;30(1):79‐85. - PMC - PubMed
Nosten 1999 {published data only}
    1. Nosten F, Vincenti M, Simpson J, Yei P, Thwai KL, Vries A, et al. The effects of mefloquine treatment in pregnancy. Clinical Infectious Diseases 1999;28(4):808‐15. - PubMed
Nwokolo 2001 {published data only}
    1. Nwokolo C, Wambebe C, Akinyanju O, Raji AA, Audu BS, Emodi IJ, et al. Mefloquine versus proguanil in short‐term malaria chemoprophylaxis in sickle cell anaemia. Clinical Drug Investigation 2001;21(8):537‐44.
Olanrewaju 2000 {published data only}
    1. Olanrewaju I W, Lin L. Mefloquine chemoprophylaxis in Chinese railway workers on contract in Nigeria. Journal of Travel Medicine 2000;7(3):116‐9. - PubMed
Ollivier 2004 {published data only}
    1. Ollivier L, Tifratene K, Josse R, Keundjian A, Boutin JP. The relationship between body weight and tolerance to mefloquine prophylaxis in non‐immune adults: results of a questionnaire‐based study. Annals of Tropical Medicine and Parasitology 2004;98(6):639‐41. - PubMed
Peetermans 2001 {published data only}
    1. Peetermans WE, Wijngaerden E. Implementation of pretravel advice: Good for malaria, bad for diarrhoea. Acta Clinica Belgica 2001;56(5):284‐8. - PubMed
Peragallo 1999 {published data only}
    1. Peragallo MS, Sabatinelli G, Sarnicola G. Compliance and tolerability of mefloquine and chloroquine plus proguanil for long‐term malaria chemoprophylaxis in groups at particular risk (the military). Transactions of the Royal Society of Tropical Medicine and Hygiene 1999;93(1):73‐7. - PubMed
Peragallo 2002 {published data only}
    1. Peragallo MS, Croft AM, Kitchener SJ. Malaria during a multinational military deployment: the comparative experience of the Italian, British and Australian Armed Forces in East Timor. Transactions of the Royal Society of Tropical Medicine and Hygiene 2002;96(5):481‐2. - PubMed
Peragallo 2014 {published data only}
    1. Peragallo MS, Sarnicola G, Boccolini D, Romi R, Mammana G. Risk assessment and prevention of malaria among Italian troops in Afghanistan, 2002 to 2011. Journal of Travel Medicine 2014;21(1):24‐32. - PubMed
Philips 1994 {published data only}
    1. Phillips M. Antimalarial mefloquine. Medical Journal of Australia 1994;161(3):227‐8. - PubMed
Phillips 1996 {published data only}
    1. Phillips M. Adverse events associated with mefloquine. Women may be more susceptible to adverse events. British Medical Journal 1996;313(7071):1552‐3. - PMC - PubMed
Phillips‐Howard 1998 {published data only}
    1. Phillips‐Howard PA, Steffen R, Kerr L, Vanhauwere B, Schildknecht J, Fuchs E, et al. Safety of mefloquine and other antimalarial agents in the first trimester of pregnancy. Journal Travel Medicine 1998;5(3):121‐6. - PubMed
Pistone 2007 {published data only}
    1. Pistone T, Guibert P, Gay F, Malvy D, Ezzedine K, Receveur MC, et al. Malaria risk perception, knowledge and prophylaxis practices among travellers of African ethnicity living in Paris and visiting their country of origin in sub‐Saharan Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 2007;101(10):990‐5. - PubMed
Port 2011 {published data only}
    1. Port A, Cottrell G, Dechavanne C, Briand V, Bouraima A, Guerra J, et al. Prevention of malaria during pregnancy: assessing the effect of the distribution of IPTp through the national policy in Benin. American Journal of Tropical Medicine and Hygiene 2011;84(2):270‐5. - PMC - PubMed
Potasman 2000 {published data only}
    1. Potasman I, Beny A, Seligmann H. Neuropsychiatric problems in 2,500 long‐term young travelers to the tropics. Journal of Travel Medicine 2000;7(1):5‐9. - PubMed
Quinn 2016 {published data only}
    1. Quinn JC. Better approach needed to detect and treat military personnel with adverse effects from mefloquine. BMJ 2016;352:i838. - PubMed
Reisinger 1989 {published data only}
    1. Reisinger EC, Horstmann RD, Dietrich M. Tolerance of mefloquine alone and in combination with sulfadoxine‐pyrimethamine in the prophylaxis of malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1989;83(4):474‐7. - PubMed
Rieckmann 1974 {published data only}
    1. Rieckmann KH, Trenholme GM, Williams RL, Carson PE, Frischer H, Desjardins RE. Prophylactic activity of mefloquine hydrochloride (WR 142490) in drug‐resistant malaria. Bulletin of the World Health Organization 1974;51(4):375‐7. - PMC - PubMed
Rieke 1993 {published data only}
    1. Rieke B, Fleischer K. Permanent health impairment after staying in malaria areas. Versicherungsmedizin 1993;45(6):197‐202. - PubMed
Ries 1993 {published data only}
    1. Ries S. Cerebral spasm during malaria prophylaxis with mefloquine. Deutsche Medizinische Wochenschrift 1993;118(51‐2):1911‐2. - PubMed
Ringqvist 2015 {published data only}
    1. Ringqvist A, Bech P, Glenthøj B, Petersen E. Acute and long‐term psychiatric side effects of mefloquine: a follow‐up on Danish adverse event reports. Travel Medicine and Infectious Disease 2015;13(1):80‐8. - PubMed
Rombo 1993 {published data only}
    1. Rombo L, Angel VH, Friman G, Hellgren U, Mittelholzer ML, Sturchler D. Comparative tolerability and kinetics during long‐term intake of Lariam and Fansidar for malaria prophylaxis in nonimmune volunteers. Tropical Medicine and Parasitology 1993;44(3):254‐6. - PubMed
Rønn 1998 {published data only}
    1. Rønn AM, Rønne‐Rasmussen J, Gøtzsche PC, Bygbjerg IC. Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: comparing a retrospective and a prospective study. Tropical Medicine and International Health 1998;3(2):83‐8. - PubMed
Sallent 1997 {published data only}
    1. Sallent LV. Anti‐malarial prophylaxis: The role of the general practitioner. Atencion Primaria 1997;20(10):558‐62. - PubMed
Schlagenhauf 1996 {published data only}
    1. Schlagenhauf P, Steffen R, Lobel H, Johnson R, Letz R, Tschopp A, et al. Mefloquine tolerability during chemoprophylaxis: focus on adverse event assessments, stereochemistry and compliance. Tropical Medicine and International Health 1996;1(4):485‐94. - PubMed
Scott 1993 {published data only}
    1. Scott R. Malaria chemoprophylaxis. South African Medical Journal 1993;83(11):861. - PubMed
Smail 1991 {published data only}
    1. Smail A, Ducroix JP, Cohen G, Baillet J. Current malaria prophylactic therapy for travellers servicemen. La Semaine des Hopitaux de Paris 1991;67(40‐41):1824‐7.
Smoak 1997 {published data only}
    1. Smoak BL, Writer JV, Keep LW, Cowan J, Chantelois JL. The effects of inadvertent exposure of mefloquine chemoprophylaxis on pregnancy outcomes and infants of US Army servicewomen. Journal of Infectious Disease 1997;176(3):831‐3. - PubMed
Suriyamongkol 1991 {published data only}
    1. Suriyamongkol V, Timsaad S, Shanks GD. Mefloquine chemoprophylaxis of soldiers on the Thai‐Cambodian border. Southeast Asian Journal of Tropical Medicine and Public Health 1991;22(4):515‐8. - PubMed
Tansley 2010 {published data only}
    1. Tansley R, Lotharius J, Priestley A, Bull F, Duparc S, Mohrle J. A randomized, double‐blind, placebo‐controlled study to investigate the safety, tolerability, and pharmacokinetics of single enantiomer (+)‐mefloquine compared with racemic mefloquine in healthy persons. American Journal of Tropical Medicine and Hygiene 2010;83(6):1195‐201. - PMC - PubMed
ter Kuile 1993 {published data only}
    1. ter Kuile FO, Nosten F, Luxemburger C, White NJ. Mefloquine prophylaxis. Lancet 1993;342(8870):551. - PubMed
Todd 1997 {published data only}
    1. Todd GD, Hopperus Buma AP, Green MD, Jaspers CA, Lobel HO. Comparison of whole blood and serum levels of mefloquine and its carboxylic acid metabolite. American Journal of Tropical Medicine and Hygiene 1997;57(4):399‐402. - PubMed
Turner 2014 {published data only}
    1. Turner C, Sabin C, Chiodini P, Bhagani S, Johnson M, Zuckerman J. Cross‐sectional study investigating the prescription, adherence and tolerability of malaria prophylaxis in HIV‐positive travellers. 3rd Joint Conference of the British HIV Association, BHIVA with the British Association for Sexual Health and HIV, BASHH Liverpool United Kingdom; 2014 April 1‐4; Liverpool, UK. Liverpool, UK: HIV Medicine, 2014; Vol. 15:127.
Valerio 2005 {published data only}
    1. Valerio L, Martinez O, Sabria M, Esteve M, Urbiztondo L, Roca C. High‐risk travel abroad overtook low‐risk travel from 1999 to 2004: Characterization and trends in 2,622 Spanish travelers. Journal of Travel Medicine 2005;12(6):327‐31. - PubMed
Van Genderen 2007 {published data only}
    1. Genderen PJ, Koene HR, Spong K, Overbosch D. Atovaquone‐proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: Results from a randomized, double‐blind study. Journal of Travel Medicine 2007;14(2):92‐5.
Van Grootheest 1999 {published data only}
    1. Grootheest AC, Puijenbroek EP, Heeringa M. Adverse effects of mefloquine: Agitation undermines objective assessment. Pharmaceutisch Weekblad 1999;134(4):114‐6.
van Riemsdijk 2004 {published data only}
    1. Aarnoudse AL, Schaik RH, Dieleman J, Molokhia M, Riemsdijk MM, Ligthelm RJ, et al. MDR1 gene polymorphisms are associated with neuropsychiatric adverse effects of mefloquine. Clinical Pharmacology and Therapeutics 2006;80(4):367‐74. - PubMed
    1. Riemsdijk MM, Ditters JM, Sturkenboom MC, Tulen JH, Ligthelm RJ, Overbosch D, et al. Neuropsychiatric events during prophylactic use of mefloquine before travelling. British Journal of Clinical Pharmacology 2002;58(6):441‐5. - PubMed
    1. Riemsdijk MM, Sturkenboom MC, Ditters JM, Tulen JH, Ligthelm RJ, Overbosch D, et al. Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine. British Journal of Clinical Pharmacology 2004;57(4):506‐12. - PMC - PubMed
Venturini 2011 {published data only}
    1. Venturini E, Chiappini E, Mannelli F, Bonsignori F, Galli L, Martino M. Malaria prophylaxis in African and Asiatic children traveling to their parents' home country: A Florentine study. Journal of Travel Medicine 2011;18(3):161‐4. - PubMed
Wagner 1986 {published data only}
    1. Wagner WH. Fight against malaria ‐ chemotherapy and immunoprophylaxis. Part 1. Chemotherapy. Arzneimittel Forschung 1986;36(1):1‐9. - PubMed
Wallace 1996 {published data only}
    1. Sánchez JL, DeFraites RF, Sharp TW, Hanson RK. Mefloquine or doxycycline prophylaxis in US troops in Somalia. Lancet 1993;341(8851):1021‐2. - PubMed
    1. Wallace MR. Malaria among United States troops in Somalia. American Journal of Medicine 1996;100(1):49‐55. - PubMed
Weinke 1991 {published data only}
    1. Weinke T, Trautmann M, Held T, Weber G, Eichenlaub D, Fleischer K, et al. Neuropsychiatric side effects after the use of mefloquine. American Journal of Tropical Medicine and Hygiene 1991;45(1):86‐91. - PubMed
White 2016 {published data only}
    1. White C. UK troops to continue to receive mefloquine despite concern over adverse events. BMJ 2016;354:i5030. - PubMed
Win 1985 {published data only}
    1. Win K, Thwe Y, Lwin TT, Win K. Combination of mefloquine with sulfadoxine‐pyrimethamine compared with two sulfadoxine‐pyrimethamine combinations in malaria chemoprophylaxis. Lancet 1985;2(8457):694‐5. - PubMed
Winstanley 1999 {published data only}
    1. Winstanley P, Behrens R. Malaria prophylaxis with mefloquine: Neurological and psychiatric adverse drug reactions. Prescribers' Journal 1999;39(3):161‐5.
Wolters 1997 {published data only}
    1. Wolters BA, Bosje T, Luinstra‐Passchier MJ. Not more problems with mefloquine compared to other antimalarial prophylactics. Nederlands Tijdschrift voor Geneeskunde 1997;141(7):331‐4. - PubMed

Additional references

ACROBAT‐NSRI tool
    1. Sterne JAC, Higgins JPT, Reeves BC on behalf of the development group for ACROBAT‐NRSI. A Cochrane Risk Of Bias Assessment Tool: for Non‐Randomized Studies of Interventions (ACROBAT‐NRSI). Version 1.0.0 [September 2014]. Available from: http://www.riskofbias.info [Accessed September 2017].
Behrens 2015
    1. Behrens R, Neave P, Jones P. Imported malaria among people who travel to visit friends and relatives: is current UK policy effective or does it need a strategic change?. Malaria Journal 2015;14:149. - PMC - PubMed
Briand 2009
    1. Briand V, Bottero J, Noël H, Masse V, Cordel H, Guerra J, et al. Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open‐label equivalence trial comparing sulfadoxine‐pyrimethamine with mefloquine. Journal of Infectious Diseases 2009;200(6):991‐1001. - PubMed
Bukiwra 2014
    1. Bukirwa H, Unnikrishnan B, Kramer CV, Sinclair D, Nair S, Tharyan P. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database of Systematic Reviews 2014, Issue 3. [DOI: 10.1002/14651858.CD006404.pub2] - DOI - PMC - PubMed
CDC 2015a
    1. Centers for Disease Control and Prevention. Malaria biology. 2015. www.cdc.gov/malaria/about/biology (accessed September 2017).
CDC 2015b
    1. Centers for Disease Control and Prevention. Drugs for malaria prevention table. Travelers' health. 2015. Yellow book. wwwnc.cdc.gov/travel/diseases/malaria (accessed September 2017).
Covidence 2017 [Computer program]
    1. Veritas Health Innovation. Covidence. Version accessed prior to 4 October 2017. Melbourne, Australia: Veritas Health Innovation, 2017.
Croft 2005
    1. Croft AM. Malaria: prevention in travellers. BMJ Clinical Evidence 2010;2010:0903. - PMC - PubMed
EMA 2014
    1. European Medicines Agency. PRAC recommendations on signals adopted at the PRAC meeting of 3‐6 March 2014. EMA/PRAC/65788/2014. ema.europa.eu/docs/en_GB/document_library/PRAC_recommendation_on_signal/... (accessed prior to 19 September 2017).
eMC 2015a
    1. electronic Medicines Compendium. Summary of product characteristics: Larium. medicines.org.uk/emc/medicine/1701#UNDESIRABLE_EFFECTS 2015 (accessed September 2017).
eMC 2015b
    1. electronic Medicines Compendium. Glossary. medicines.org.uk/emc/glossary/#SPC 2015 (accessed September 2017).
FDA 2013
    1. USA Food, Drug Administration. FDA drug safety communication: mefloquine. fda.gov/drugs/drugsafety/ucm362227.htm 2013 (accessed September 2017).
González 2014
    1. González R, Hellgren U, Greenwood B, Menéndez C. Mefloquine safety and tolerability in pregnancy: a systematic literature review. Malaria Journal 2014;13:75. - PMC - PubMed
González 2014a
    1. González R, Mombo‐Ngoma G, Ouédraogo S, Kakolwa MA, Abdulla S, Accrombessi M, et al. Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV‐negative women: a multicentre randomized controlled trial. PLoS Medicine 2014;11(9):e1001733. - PMC - PubMed
Handschin 1997
    1. Handschin JC, Wall M, Steffen R, Stürchler D. Tolerability and effectiveness of malaria chemoprophylaxis with mefloquine or chloroquine with or without co‐medication. Journal of Travel Medicine 1997;4(3):121‐7. - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 [updated March 2011]. http://training.cochrane.org/handbook. The Cochrane Collaboration, 2011. Available at www.cochrane‐handbook.org, (accessed prior to 19 September 2017).
Høgh 2000
    1. Høgh B, Clarke PD, Camus D, et al. Atovaquone‐proguanil versus chloroquine‐proguanil for malaria prophylaxis in non‐immune travellers: a randomised, double‐blind study. Lancet 2000;356:1888‐94. - PubMed
ICH 1994
    1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Clinical safety data management: definitions and standards for expedited reporting E2A. 1994. ICH harmonised tripartite guideline. https://www.imim.cat/media/upload/arxius/MEDIA436.pdf (accessed prior to 19 September 2017).
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0 [updated March 2011]. training.cochrane.org/handbook (accessed prior to 19 September 2017).
Loke 2007
    1. Loke YK, Price D, Herxheimer A. Systematic reviews of adverse effects: framework for a structured approach. BMC Medical Research Methodology 2007;7:32. - PMC - PubMed
Loke 2011
    1. Loke YK, Price D, Herxheimer A. Chapter 14: Adverse effects. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 [updated March 2011]. training.cochrane.org/handbook. The Cochrane Collaboration, 2011. Available at www.cochrane‐handbook.org, (accessed prior to 19 September 2017).
McCarthy 2015
    1. McCarthy S. Malaria prevention, mefloquine neurotoxicity, neuropsychiatric illness, and risk‐benefit analysis in the Australian Defence Force. Journal of Parasitology Research 2015;2015:287651. [DOI: 10.1155/2015/287651] - DOI - PMC - PubMed
MedDRA 2016
    1. Medical Dictionary for Regulatory Activities. Introductory guide MedDRA version 19.0. 2016. International Federation of Pharmaceutical Manufacturers and Associations. meddra.org/sites/default/files/guidance/file/intguide_19_0_english.pdf (accessed September 2017).
Meremikwu 2008
    1. Meremikwu MM, Donegan S, Esu E. Chemoprophylaxis and intermittent treatment for preventing malaria in children. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD003756.pub3] - DOI - PubMed
Muanda 2015
    1. Muanda FT, Chaabane S, Boukhris T, Santos F, Sheehy O, Perreault S, et al. Antimalarial drugs for preventing malaria during pregnancy and the risk of low birthweight: a systematic review and meta‐analysis of randomized and quasi‐randomized trials. BMC Medicine 2015;13:193. [DOI: 10.1186/s12916-015-0429-x] - DOI - PMC - PubMed
Murray 2014
    1. Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384(9947):1005‐70. - PMC - PubMed
Nevin 2015
    1. Nevin R. Rational risk‐benefit decision‐making in the setting of military mefloquine policy. Journal of Parasitology Research 2015;2015:260106. [DOI: 10.1155/2015/260106] - DOI - PMC - PubMed
Oniyangi 2006
    1. Oniyangi O, Omari AA. Malaria chemoprophylaxis in sickle cell disease. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/14651858.CD003489.pub2] - DOI - PMC - PubMed
PHAC 2014
    1. Public Health Agency of Canada. Canadian recommendations for the prevention and treatment of malaria. Canada Communicable Disease Report. 2014. publications.gc.ca/collections/collection_2014/aspc‐phac/HP40‐102‐2014‐e... (accessed September 2017).
PHE 2015
    1. Public Health England Advisory Committee for Malaria Prevention for UK Travellers. Guidelines for malaria prevention in travellers from the UK. 2015. gov.uk/government/publications/malaria‐prevention‐guidelines‐for‐travell... (accessed September 2017).
Radeva‐Petrova 2014
    1. Radeva‐Petrova D, Kayentao K, ter Kuile F, Sinclair D, Garner P. Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment. Cochrane Database of Systematic Reviews 2014, Issue 10. [DOI: 10.1002/14651858.CD000169.pub3] - DOI - PMC - PubMed
Reeves 2011
    1. Reeves BC, Deeks JJ, Higgins JPT, Wells GA. Chapter 13: Including non‐randomized studies. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 [updated March 2011]. training.cochrane.org/handbook (accessed prior to 19 September 2017).
RevMan 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rodrigo 2016
    1. Rodrigo C, Rajapakse S, Fernando S. Primaquine or tafenoquine for preventing malaria in people travelling to or living in endemic areas. Cochrane Database of Systematic Reviews 2016, Issue 6. [DOI: 10.1002/14651858.CD012242] - DOI
Schlagenhauf 2003
    1. Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, et al. Tolerability of malaria chemoprophylaxis in non‐immune travellers to sub‐Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ 2003;327(7423):1078. - PMC - PubMed
Schlagenhauf 1999
    1. Schlagenhauf P. Mefloquine for malaria chemoprophylaxis 1992‐1998: a review. Journal of Travel Medicine 1999;6(2):122‐33. - PubMed
Schlagenhauf 2010
    1. Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG. The position of mefloquine as a 21st century malaria chemoprophylaxis. Malaria Journal 2010;9:357. - PMC - PubMed
Shanks 2005
    1. Shanks GD, Edstein MD. Modern malaria chemoprophylaxis. Drugs 2005;65(12):2091‐110. - PubMed
Tickell‐Painter 2017
    1. Tickell‐Painter M, Saunders R, Mayaan N, Lutje V, Mateo‐Urdiales A, Garner P. Deaths and parasuicides associated with mefloquine chemoprophylaxis: a systematic review. Travel Medicine and Infectious Disease (in press). - PubMed
Treiber 2010
    1. Treiber M, Wernsdorfer G, Wiedermann U, Congpuong K, Wernsdorfer WH. Sensitivity to artemisinin, mefloquine and quinine of Plasmodium falciparum in northwestern Thailand. Wiener Klinische Wochenschrift 2010;122(Suppl 3):52‐6. - PubMed
Treiber 2011
    1. Treiber M, Wernsdorfer G, Wiedermann U, Congpuong K, Sirichaisinthop J, Wernsdorfer WH. Sensitivity of Plasmodium vivax to chloroquine, mefloquine, artemisinin and atovaquone in north‐western Thailand. Wiener Klinische Wochenschrift 2011;123(Suppl 1):20‐5. - PubMed
UK Parliament 2016
    1. UK Parliament 2016. Commons select committee, UK Parliament. 'Larium should be 'drug of last resort' for troops'. parliament.uk/business/committees/committees‐a‐z/commons‐select/defence‐... (accessed September 2017).
Warrell 2002
    1. Warrell D, Gilles H. Essential Malariology. 4th Edition. New York: CRC Press, 2002.
WHO 2015
    1. World Health Organization. Guidelines for the treatment of malaria. 2015. who.int/malaria/publications/atoz/9789241549127/en/ (accessed September 2017).
WHO 2016
    1. World Health Organization. World malaria report 2016. http://www.who.int/malaria/publications/world‐malaria‐report‐2016/en/ (accessed September 2017).
WHO 2017
    1. World Health Organization. Malaria, International travel and health. Chapter 7. who.int/ith/2017‐ith‐chapter7.pdf?ua=1 2017 (accessed 19 September 2017).
WHO‐ART 2008
    1. Uppsala Monitoring Centre. WHO adverse reaction terminology (WHO‐ART). https://www.who‐umc.org/vigibase/services/learn‐more‐about‐who‐art/ (accessed prior to 19 September 2017).

References to other published versions of this review

Jacquerioz 2007
    1. Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database of Systematic Reviews 2007, Issue 2. [DOI: 10.1002/14651858.CD006491] - DOI - PubMed
Jacquerioz 2009
    1. Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database of Systematic Reviews 2009, Issue 10. [DOI: 10.1002/14651858.CD006491.pub2] - DOI - PubMed
Jacquerioz 2015
    1. Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database of Systematic Reviews 2015, Issue 10. [DOI: 10.1002/14651858.CD006491.pub3] - DOI - PubMed

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