The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan

Sönmez, Alper; Harlak, Ali; Kılıç, Selim; Polat, Zülfıkar; Hayat, Levent; Keskın, Onur; Doğru, Teoman; Yılmaz, Mehmet; Açıkel, Cengiz Han; Kocar, Ismail H.

doi:10.1016/j.jinf.2005.01.014

Cited by 29 publications

(40 citation statements)

References 11 publications

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“…38,39 However, other studies have found that compliance with mefloquine is higher than with doxycycline (American Soldiers: 80% versus 60%; Turkish troops: 61% versus 56%; Australian travelers: 78% versus 68%). [40][41][42] However, how compliance is defined is important in interpreting these findings. In the cited studies, estimated compliance rates correspond to taking the medication as prescribed without missing a dose.…”

Section: Discussionmentioning

confidence: 99%

“…This is different than completely stopping the medication, which was only reported between 3% and 5% for either medication among service members. 41,42 Complete cessation of the medication would impact this study more profoundly than missing doses, but this is also expected to occur among a small percentage of subjects. If subjects stopped taking prescribed prophylaxis due to adverse events and if the adverse events resulted in a medical encounter, then it would have been captured and the risk period would have been censored appropriately.…”

Section: Discussionmentioning

confidence: 99%

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Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

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Rohrbeck

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Mefloquine was widely prescribed to U.S. military service members until 2009 when use was limited to personnel with contraindications to doxycycline and no contraindications to mefloquine. The need to estimate the occurrence of neuropsychiatric outcomes (NPOs) in service members prescribed mefloquine warranted a comprehensive evaluation of this issue. Active component service members filling a prescription for mefloquine, doxycycline, or atovaquone/proguanil (A/P) between January 1, 2008 and June 30, 2013, were included in the analysis. The risk of developing incident NPOs and the risk of subsequent NPOs among subjects with a history of the condition were assessed. A total of 367,840 individuals were evaluated (36,538 received mefloquine, 318,421 received doxycycline, and 12,881 received A/P). Among deployed individuals prescribed mefloquine, an increased risk of incident anxiety was seen when compared with doxycycline recipients (incidence rate ratio [IRR] = 1.12 [1.01-1.24]). Among nondeployed mefloquine recipients, an increased risk of posttraumatic stress disorder (PTSD) was seen when compared with A/P recipients (IRR = 1.83 [1. 07-3.14]). An increased risk of tinnitus was seen for both deployed and nondeployed mefloquine recipients compared with A/P recipients (IRR = 1.81 [1.18-2.79]), 1.51 (1.13-2.03), respectively). Six percent of the mefloquine cohort had an NPO in the year before receiving mefloquine. When comparing individuals with a prior neuropsychiatric history to those without, the ratio of relative risks for adjustment disorder, anxiety, insomnia, and PTSD were higher (not statistically significant) for mefloquine compared with doxycycline. These findings emphasize the continued need for physicians prescribing mefloquine to conduct contraindication screening.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

Eick-Cost

Rohrbeck

et al. 2017

The American Society of Tropical Medicine and Hygiene

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“…These findings are consistent with observations from previous studies in both civilian and military populations, identifying daily dosing regimens as significant obstacles to compliance with doxycycline prophylaxis. 7,8 Similarly, long-term use of daily doxycycline for dermatological indications yield lower compliance owing to GI side effects. 15 Although the majority of those not taking DH daily reported simply forgetting to take it, one-third of soldiers reported concerns with side effects as the primary reason for noncompliance.…”

Section: Discussionmentioning

confidence: 99%

“…DH and MQ have been shown to have high rates of AEs and noncompliance in prior clinical studies. 2,3,7,8,16 Because of the poor compliance with doxycycline, theater policy changed during the deployment, and personnel were offered the option of using MQ (Mod 9 to US CENTCOM, Individual Protection and Individual-Unit Deployment Policy, 8 Sep 2008). Given their comparative expense, AP, DHEC, and DM were not routinely used, though AP was taken on a limited basis by aviators, accounting for the small proportion here.…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies of deployed soldiers have demonstrated poor compliance with daily doxycycline prophylaxis. [7][8][9][10][11][12] Although most efficacy trials of DH and DM have shown comparable rates of GI toxicity, AE withdrawals, and noncompliance, it is important to realize that most of the safety and tolerability data are from trials powered for efficacy, not tolerability. 13 Differences in study design, end points, assessment methods, and length of follow-up complicate the comparison of the safety and tolerability of the different dosage forms of doxycycline (Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Safety, Tolerability, and Compliance with Long-Term Antimalarial Chemoprophylaxis in American Soldiers in Afghanistan

Saunders¹,

Garges²,

Manning³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Long-term antimalarial chemoprophylaxis is currently used by deployed U.S. military personnel. Previous small, short-term efficacy studies have shown variable rates of side effects among patients taking various forms of chemoprophylaxis, though reliable safety and tolerability data on long-term use are limited. We conducted a survey of troops returning to Fort Drum, NY following a 12-month deployment to Operation Enduring Freedom, Afghanistan from 2006 to 2007. Of the 2,351 respondents, 95% reported taking at least one form of prophylaxis during their deployment, and 90% were deployed for > 10 months. Compliance with daily doxycycline was poor (60%) compared with 80% with weekly mefloquine (MQ). Adverse events (AEs) were reported by approximately 30% with both MQ and doxycycline, with 10% discontinuing doxycycline compared with 4% of MQ users. Only 6% and 31% of soldiers reported use of bed nets and skin repellents, respectively. Compliance with long-term malaria prophylaxis was poor, and there were substantial tolerability issues based on these anonymous survey results, though fewer with MQ than doxycycline. Given few long-term antimalarial chemoprophylaxis options, there is an unmet medical need for new antimalarials safe for long-term use.

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Mefloquine for preventing malaria during travel to endemic areas

Tickell-Painter

Maayan²,

Saunders

et al. 2017

Cochrane Database of Systematic Reviews

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BackgroundMefloquine 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.ObjectivesTo summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers.Search methodsWe 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 criteriaWe 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 analysisTwo 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 resultsWe 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-proguanilParticipants 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)....

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The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan

Cited by 29 publications

References 11 publications

Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

Safety, Tolerability, and Compliance with Long-Term Antimalarial Chemoprophylaxis in American Soldiers in Afghanistan

Mefloquine for preventing malaria during travel to endemic areas

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