Use Of Mefloquine Research Articles

Drug Abuse: An Exploration of the Government's Use of Mefloquine at Guantánamo

Mefloquine is an antimalarial drug that has long been known to cause severe neuropsychological adverse effects such as anxiety, paranoia, hallucinations, aggression, psychotic behavior, mood changes, depression, memory impairment, convulsions, loss of coordination (ataxia), suicidal ideation, and possibly suicide, particularly in patients with a history of mental illness. A prescribing physician must exercise caution and informed judgment when weighing the risks and potential benefits of prescribing the drug. To administer this drug with its severe potential side effects without a malaria diagnosis and without taking a patient’s mental health history is not medically justified. Yet as a matter of official policy, the standard operating procedure implemented by the United States military at Guantanamo Bay was to administer high doses of mefloquine to detainees whether or not any use of the drug was medically appropriate and without consideration of the detainees’ mental health. It is clear that the military employed a medically inappropriate treatment regime at Guantanamo Bay (GTMO). It is less clear why, although the available evidence supports several possible conclusions. In view of the continued and unexplained refusal of the government to release full medical records for all detainees, it is not possible to determine whether this conduct was gross malpractice or deliberate misuse of drug. In either case, it does not appear plausible from the available evidence that mefloquine was given to treat malaria. This suggests a darker possibility: that the military gave detainees the drug specifically to bring about the adverse side effects, either as part of enhanced interrogation techniques, experimentation in behavioral modification, or torture for some other purpose. While this Report does not reach a conclusion about the actual conduct, it does explore the legal rules that would apply were it determined that mefloquine was administered not to treat malaria but rather to exploit the neuropsychiatric effects of the drug.

The position of mefloquine as a 21st century malaria chemoprophylaxis.

BackgroundMalaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis.MethodsA literature search to update the status of mefloquine as a malaria chemoprophylaxis.ResultsExcept for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerability of mefloquine and the use of this medication by groups at high risk of malaria.DiscussionUse of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors.ConclusionThe choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline.

Postural orthostatic tachycardia syndrome: a case report of palpitations and dizziness following prophylactic mefloquine use

The antimalarial agent mefloquine has been reported to cause a number of possible side effects. Here we describe a case demonstrating a previously unreported complication, the postural orthostatic tachycardia syndrome (POTS). A 44-year-old woman presented with symptoms of severe orthostatic intolerance (palpitations and dizziness) in combination with postural tachycardia (but no fall in blood pressure) following the use of mefloquine prophylaxis. Investigations revealed evidence of autonomic dysfunction (with loss of ECG R-R interval variation) consistent with POTS. Her symptoms responded well to beta-blockade with propranolol. The possibility of POTS should be considered in patients presenting with symptoms of palpitations, dizziness, presyncope or other features suggestive of autonomic dysfunction following the use of mefloquine.

Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers.

Mefloquine is a 4-quinolinemethanol compound structurally related to quinine. Quinine is mainly metabolized by the cytochrome P450 3A4 isozyme (CYP3A4), whereas rifampin, a potent inducer of CYP3A4, is known to markedly decrease plasma quinine concentration. Our aim was to study the effect of rifampin on the pharmacokinetics of mefloquine, and explore a possible role of CYP3A4 on mefloquine metabolism. In an open, two-phase crossover study, seven healthy Thai male volunteers received a single oral dose of 500 mg mefloquine alone, or 500 mg mefloquine plus a long-term administration of 600 mg rifampin. Blood samples were collected at specific time points over a 56-day period. Plasma mefloquine and its carboxylic acid metabolite were measured by HPLC for pharmacokinetic analysis. The results indicate that rifampin significantly decreased the area under the plasma concentration-time curve (AUC0 - infinity) of mefloquine by 68% (P < 0.01), maximum plasma concentration (Cmax) by 19% (P < 0.001), and elimination half-life (t1/2) by 63% (P < 0.01), whereas the time to reach Cmax (t(max)) of mefloquine was unaffected. The apparent oral clearance (CL) of mefloquine was significantly increased by 281% (P < 0.01). After administration of rifampin, the Cmax of the carboxylic acid metabolite of mefloquine was significantly increased by 47% (P < 0.05), whereas the t1/2 was significantly decreased by 39% (P < 0.01), and t(max) by 76% (P < 0.01). The AUC0 - infinity and CL of the mefloquine metabolite were increased by 30% and 25%, respectively, but were not significantly different from the control phase. The results indicate that rifampin reduces the plasma concentration of a single oral dose of 500 mg mefloquine by increasing metabolism of mefloquine in the liver and gut wall. The CYP3A4 isozyme most likely plays an important role in the enhanced metabolism of mefloquine. Simultaneous use of rifampin and mefloquine should be avoided to optimize the therapeutic efficacy of mefloquine and prevent the risk of Plasmodium falciparum resistance in malarial treatment.

Mefloquine prescriptions in the presence of contraindications: prevalence among US military personnel deployed to Afghanistan, 2007

Contraindications to mefloquine use include a history of certain prevalent neuropsychiatric disorders, which are thought to increase the risk of severe adverse events including anxiety, paranoia, depression, hallucinations, psychosis, and possibly suicide. Within the US military, the continued availability and use of mefloquine is subject to administrative policies dating to 2002 that require clinicians to exercise added caution during prescribing. This analysis was performed to quantify the effectiveness of these policies in ensuring health care provider compliance with package insert prescribing guidance. A previously identified cohort consisting of 11,725 active duty US military personnel, among whom 1127 (9.6%) had contraindications to mefloquine use identified through medical surveillance and pharmaceutical databases, was examined to identify individuals receiving prescriptions for mefloquine in the 45 days prior to a combat deployment in 2007. Among the 11,725 cohort members, 4505 (38.4% of the cohort) received a prescription for mefloquine. Among the 1127 cohort members with contraindications, 155 (1.3% of the cohort) were prescribed mefloquine, comprising 13.8% of those with contraindications. Despite the longstanding administrative policies meant to reduce such events, approximately one in seven individuals with neuropsychiatric contraindications received a prescription for mefloquine prior to a recent combat deployment, significantly increasing the risk of subsequent adverse events. Given the prevalence of neuropsychiatric disorders among US military personnel and the continued availability of mefloquine, additional study is recommended to describe and quantify the nature and extent of mefloquine-associated adverse events experienced among this group.

Anti-Malaria Drug Mefloquine Induces Motor Learning Deficits in Humans

Mefloquine (a marketed anti-malaria drug) prophylaxis has a high risk of causing adverse events. Interestingly, animal studies have shown that mefloquine imposes a major deficit in motor learning skills by affecting the connexin 36 gap junctions of the inferior olive. We were therefore interested in assessing whether mefloquine might induce similar effects in humans. The main aim of this study was to investigate the effect of mefloquine on olivary-related motor performance and motor learning tasks in humans. We subjected nine participants to voluntary motor timing (dart throwing task), perceptual timing (rhythm perceptual task) and reflex timing tasks (eye-blink task) before and 24 h after the intake of mefloquine. The influence of mefloquine on motor learning was assessed by subjecting participants with and without mefloquine intake (controls: n = 11 vs mefloquine: n = 8) to an eye-blink conditioning task. Voluntary motor performance, perceptual timing, and reflex blinking were not affected by mefloquine use. However, the influence of mefloquine on motor learning was substantial; both learning speed as well as learning capacity was impaired by mefloquine use. Our data suggest that mefloquine disturbs motor learning skills. This adverse effect can have clinical as well as social clinical implications for mefloquine users. Therefore, this side-effect of mefloquine should be further investigated and recognized by clinicians.

Intermittent Treatment for the Prevention of Malaria during Pregnancy in Benin: A Randomized, Open‐Label Equivalence Trial Comparing Sulfadoxine‐Pyrimethamine with Mefloquine

In the context of the increasing resistance to sulfadoxine-pyrimethamine (SP), we evaluated the efficacy of mefloquine (MQ) for intermittent preventive treatment during pregnancy (IPTp). A multicenter, open-label equivalence trial was conducted in Benin from July 2005 through April 2008. Women of all gravidities were randomized to receive SP (1500 mg of sulfadoxine and 75 mg of pyrimethamine) or 15 mg/kg MQ in a single intake twice during pregnancy. The primary end point was the proportion of low-birth-weight (LBW) infants (body weight, <2500 g; equivalence margin, 5%). A total of 1601 women were randomized to receive MQ (n=802)or SP (n=799).In the modified intention-to-treat analysis, which assessed only live singleton births, 59 (8%) of 735 women who were given MQ and 72 (9.8%) of 730 women who were given SP gave birth to LBW infants (difference between low birth weights in treatment groups, -1.8%; 95% confidence interval [CI], -4.8% to 1.1%]), establishing equivalence between the drugs. The per-protocol analysis showed consistent results. MQ was more efficacious than SP in preventing placental malaria (prevalence, 1.7% vs 4.4% of women; P = .005),clinical malaria (incidence rate, 26 cases/10,000 person-months vs. 68 cases/10,000 person-months; P = .007) and maternal anemia at delivery (as defined by a hemoglobin level <10 g/dL) (prevalence, 16% vs 20%; marginally significant at P = .09). Adverse events (mainly vomiting, dizziness, tiredness, and nausea) were more commonly associated with the use of MQ (prevalence, 78% vs 32%; P < 10(-3)) One woman in the MQ group had severe neuropsychiatric symptoms. MQ proved to be highly efficacious--both clinically and parasitologically--for use as IPTp. However, its low tolerability might impair its effectiveness and requires further investigations.

Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

BackgroundMefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.Presentation of the hypothesisStudies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.Testing and implications of the hypothesisConsistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.

Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan

BackgroundMefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but its prescribing requires careful attention to rule out contraindications to its use, including a history of certain psychiatric and neurological disorders. The prevalence of these disorders has not been defined in cohorts of U.S. military personnel deployed to areas where long-term malaria chemoprophylaxis is indicated.MethodsMilitary medical surveillance and pharmacosurveillance databases were utilized to identify contraindications to mefloquine use among a cohort of 11,725 active duty U.S. military personnel recently deployed to Afghanistan.ResultsA total of 9.6% of the cohort had evidence of a contraindication. Females were more than twice as likely as males to have a contraindication (OR = 2.48, P < 0.001).ConclusionThese findings underscore the importance of proper systematic screening prior to prescribing and dispensing mefloquine, and the need to provide alternatives to mefloquine suitable for long-term administration among deployed U.S. military personnel.

Use of mefloquine in multidrug-resistant Mycobacterium avium complex pulmonary disease in an HIV-negative patient

Mycobacterium avium complex (MAC) is a leading cause of pulmonary disease (PD), even in those with intact immunity, representing about 30% of the cases of pleuropulmonary mycobacterial infection. Based on previous studies, macrolides are the only agents used in the treatment of MAC disease for which there is a correlation between in vitro susceptibility and in vivo (clinical) response. However, resistance develops rapidly if single-agent treatment is used. Data regarding treatment of macrolide-resistant MAC (MRMAC) and multidrug-resistant MAC (MDRMAC) are sparse. A 50-year-old, HIV-negative white man, weighing 53.6 kg, with severe chronic obstructive pulmonary disease and bronchiectasis was initially on treatment for MAC-PD and MRMAC. The patient was followed between 1999 and 2006. His treatment history revealed that in addition to the multiple drugs administered during the course of his illness, thalidomide, interferon-γ, and mefloquine were also administered. The patient died ~7 years later due to respiratory failure and overwhelming infection This case report describes the use of mefloquine as adjunct treatment in an HIV-negative patient with MDRMAC-PD and discusses the associated outcomes of drug resistance.

Reversible hearing loss in temporal association with chemoprophylactic mefloquine use

A 67 year old Caucasian lady received pre-travel immunizations against tetanus, diphtheria, typhoid fever, hepatitis A, and mefloquine chemoprophylaxis. Left sided hearing loss consequent upon tympanic rupture was present since childhood; she was otherwise in good health and without history of recent upper respiratory tract infection. After 1 dose of mefloquine right sided tinnitus and hearing loss developed; audiometry revealed mixed left sided loss and right sided sensorineural loss (-90db at 1kHz; -70dB at 4kHz). Prednisone, aspirin and omeprazole were prescribed; mefloquine chemoprophylaxis was discontinued. On day 9 of her hearing loss the tinnitus suddenly disappeared, and right sided hearing improved. Audiometry on day 93 revealed normal right sided hearing (-10dB at 1kHz; -10dB at 4kHz). Causality remains undetermined, but it may be prudent to avoid mefloquine chemoprophylaxis in individuals with known hearing impairment.

Molecular analysis of chloroquine resistance in Plasmodium falciparum in Yunnan Province, China

Resistance of Plasmodium falciparum to chloroquine (CQ) is determined by the mutation at K76T of the P. falciparum chloroquine resistance transporter (pfcrt) gene and modified by other mutations in this gene and in the P. falciparum multidrug resistance 1 (pfmdr1) gene. To determine the extent of polymorphisms in these genes in field P. falciparum isolates from Yunnan province of China, we genotyped the pfcrt codon 76, pfmdr1 codons 86 and 1246. Our results showed that although CQ has been withdrawn from treating falciparum malaria for over two decades, 90.3% of the parasites still carried the pfcrt K76T mutation. In contrast, mutations at pfmdr1 codons 86 and 1246 were rare. Sequencing analysis of the pfcrt gene in 34 parasite field isolates revealed CVIET at positions 72-76 as the major type, consistent with the theory of Southeast Asian origin of CQ resistance in the parasite. In addition, two novel pfcrt haplotypes (75D/144Y/220A and 75E/144Y/220A) were identified. Real-time polymerase chain reaction was used to determine pfmdr1 gene amplification, which is associated with mefloquine resistance. Our result indicated that in agreement with that mefloquine has not been used in this area, most (>90%) of the parasites had one pfmdr1 copy. Genotyping at two hypervariable loci showed relatively low levels of genetic diversity of the parasite population. Meanwhile, 28.4% of cases were found to contain mixed clones, which favour genetic recombination. Furthermore, despite a unique history of antimalarial drugs in Yunnan, its geographical connections with three malarious countries facilitate gene flow among parasite populations and evolution of novel drug-resistant genotypes. Therefore, continuous surveillance of drug resistance in this area is necessary for timely adjustment of local drug policies and more effective malaria control.

Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report

BackgroundConvenient once-a-week dosing has made mefloquine a popular choice as malaria prophylaxis for travel to countries with chloroquine-resistant malaria. However, the increased use of mefloquine over the past decade has resulted in reports of rare, but severe, neuropsychiatric adverse reactions, such as anxiety, depression, hallucinations and psychosis. A direct causality between mefloquine and severe reactions among travelers has been partly confounded by factors associated with foreign travel and, in the case of therapeutic doses of mefloquine, the central nervous system manifestations of Plasmodium infection itself. The present case provides a unique natural history of mefloquine-induced neuropsychiatric toxicity and revisits its dose-dependent nature.Case presentationThis report describes an acute exacerbation of neuropsychiatric symptoms after an unwarranted therapeutic dose (1250 mg) of mefloquine in a 37-year-old male previously on a once-a-week prophylactic regimen. Neuropsychiatric symptoms began as dizziness and insomnia of several days duration, which was followed by one week of escalating anxiety and subtle alterations in behaviour. The patient's anxiety culminated into a panic episode with profound sympathetic activation. One week later, he was hospitalized after developing frank psychosis with psychomotor agitation and paranoid delusions. His psychosis remitted with low-dose quetiapine.ConclusionThis report suggests that an overt mefloquine-induced psychosis can be preceded by a prodromal phase of moderate symptoms such as dizziness, insomnia, and generalized anxiety. It is important that physicians advise patients taking mefloquine prophylaxis and their relatives to recognize such symptoms, especially when they are accompanied by abrupt, but subtle, changes in behaviour. Patients with a history of psychiatric illness, however minor, may be at increased risk for a mefloquine-induced neuropsychiatric toxicity. Physicians must explicitly caution patients not to self-medicate with a therapeutic course of mefloquine when a malaria diagnosis has not been confirmed.

Methodological Concerns Regarding the Relation Between Mefloquine and Serious Psychiatric Events in Females

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.Sir: van Riemsdijk et al.1 report the results of a case-control study of serious psychiatric events related to mefloquine use among Dutch travelers. A highlighted result is a (startling) odds ratio (OR) of 47.1 (with very wide 95% CI of 3.8 to 578.6) for such events in females taking mefloquine.While the basic case-control methodology of this study appears sound, we have concerns that would erode confidence in this study: (1) The overall response rate from cases and controls is felt, by the authors, to be high enough ("almost 70%") to avoid selection bias.†‹

Amplification ofPlasmodium falciparumMultidrug Resistance Gene 1 in Isolates from Gabon

The study of molecular markers of drug resistance is particularly important in surveillance studies of drugs, such as mefloquine, that still retain efficacy in sub-Saharan Africa yet have encountered resistance elsewhere. In a recent study in Thailand, we identified amplification of the Plasmodium falciparum multidrug resistance gene 1 (pfmdr1) as being the most important predictor of in vitro drug resistance and in vivo failure of mefloquine monotherapy. Here we report amplification of pfmdr1 in >5% of patient samples from Lambarene, Gabon, collected in 1995. None of the samples collected 7 years later showed pfmdr1 amplification, suggesting that parasites with increased numbers of pfmdr1 copies have not substantially spread through the population. Nevertheless, the detection of multicopy pfmdr1 in African parasites suggests a high potential for rapid selection for resistance, implying that mefloquine use in Africa should be considered only as part of combination therapy.

Assessment of Risks Associated with Short-Term Use of Mefloquine in Canadian Forces Members: A Descriptive Cross-Sectional Study

Background: Media reports have implicated mefloquine as a contributor to adverse health effects experienced by military members serving in areas where chloroquine-resistant malaria is endemic. A systematic retrospective review has been undertaken to evaluate the health effects seen in members who received mefloquine for chemoprophylaxis against malaria. Methods: Medical records of Regular Canadian Forces (CF) personnel who served in Somalia between 1992 and 1993 were reviewed by trained data extractors. All health effects recorded during treatment with mefloquine were assigned ICD-10-CA codes. Data extractors also noted if the effect has been reported with mefloquine, and rated the severity of the effect. Cohen's kappa was calculated to determine concordance between extractors, and descriptive statistics used to report the health effects seen. Results: The majority of the 1413 subjects identified were male (96%). A total of 5019 adverse health effects were recorded in the medical records, most of which were mild in severity. At least one adverse effect which could potentially have been related to mefloquine was reported in 74.7% ( n = 1056) of subjects. Of the adverse effects recorded, 21 were classified by the data extractors as major (18 cases affecting the nervous system and 3 cardiovascular system effects). These results are consistent with those reported in other populations. Conclusions: The results of this study have been applied to guide development of policies governing the provision of chemoprophylaxis during subsequent military missions. In particular, resources have been allocated to formalize the counselling provided to members regarding antimalarials and prevention of malaria infection.

Treatment of imported malaria in adults: a multicentre study in France

Data about anti-malarial drugs prescription practices in Europe and the safety of imported malaria treatments are scanty. In 1999, a French consensus development conference published guidelines for the prevention and treatment of imported P. falciparum malaria. The impact of these guidelines has not been evaluated. To investigate the impact of these guidelines on the prescription of anti-malarials, and to evaluate the incidence of acute drug events (ADEs) leading to discontinuation of treatment. Cross-sectional survey. Members of the medical staff in 14 French infectious and tropical disease wards completed a standardized form for each patient treated for imported malaria in 2001. A propensity score matching technique was used to estimate the risk of ADEs leading to discontinuation of the regimen. In the 474 patients studied, quinine was the first-line anti-malarial most often prescribed. Only 3% of patients received halofantrine. Mefloquine was associated with a RR of 4.9 (95%CI 3.2-7.4, p < 0.00001) risk of discontinuation of treatment due to ADEs. The very limited use of halofantrine indicates that the main practice recommendations of the guidelines have been taken into account. Mefloquine was associated with a substantial risk of discontinuing the treatment because of ADEs. This is a serious limitation for the use of mefloquine in the treatment of out-patients with imported malaria.

Mefloquine Increases the Risk of Serious Psychiatric Events During Travel Abroad

Psychiatric events during travel abroad account for a large percentage of medical repatriations arranged by insurance companies. Several risk factors have been proposed for such events, one of these being use of mefloquine. We investigated the risk of psychiatric events during use of mefloquine. We performed a nationwide case control study using medical records from 4 large alarm centers in the Netherlands. Cases were patients contacting the alarm centers because of psychiatric events, according to International Code Primary Care code P (all psychiatric symptoms) or International Classification of Diseases, Ninth Edition, codes 290-319 (all psychiatric syndromes). To every case we matched up to 6 controls by alarm center, calendar time, and continent of travel. All controls had contacted the alarm centers because of nonpsychiatric medical reasons. Shortly after the anticipated day of return, cases and controls received a questionnaire regarding travel characteristics, gender, age, marital status, education, weight, height, general health, history of psychiatric diseases, use of medicines, smoking status, alcohol intake, coffee intake, and use of malaria prophylaxis. Dates of travel for the source population were between September 1, 1997, and June 1, 2000. The study population consisted of 111 cases and 453 controls. The risk of psychiatric events during the use of mefloquine was 3.5 (95% CI = 1.4 to 8.7). In females, the risk was strongly increased, with an odds ratio of 47.1 (95% CI = 3.8 to 578.6). Stratification for history of psychiatric diseases showed that the risk of psychiatric events during use of mefloquine in cases without a history of psychiatric diseases was 3.8 (95% CI = 1.4 to 10.1), whereas the risk in cases with a history of psychiatric diseases was 8.0 (95% CI = 1.8 to 35.8). The use of mefloquine is associated with an increased risk of psychiatric events in females and in patients with a history of psychiatric diseases.

Efficacy of antimalarial chemoprophylaxis among French residents travelling to Africa

Controversy exists about which antimalarial chemoprophylaxis regimen should be used among travellers to Africa: the WHO and other experts recommend the use of mefloquine throughout sub-Saharan Africa, whereas French experts still support the combination of chloroquine and proguanil in most of West Africa (the so-called zone 2 countries). In this case–control study based at a travel clinic, we examined the compliance with antimalarial chemoprophylaxis and its efficacy among travellers to tropical areas. Cases were patients with Plasmodium falciparum malaria ( n = 131). Controls were patients who had a negative malaria film ( n = 158). Of all controls, only 36 (22.8%) were adequately protected (i.e. compliant with an adapted regimen of chemoprophylaxis). In zone 2 countries, the efficacy of the combined chloroquine and proguanil was 58% (95% CI 22–78%) for all users, but increased to 100% (95% CI 89–100%) for compliant users. In zone 3 countries, the efficacy of mefloquine was 90% (95% CI 51–98%) and 100% (95% CI 58–100%) for all users and compliant users, respectively.

Data mining analysis of psychosis with mefloquine and other antimalarial drugs

Purpose Mefloquine is used for treatment and prophylaxis of chloroquine-resistant malaria. In 2003, thirteen years after its introduction into the US market, the manufacturer strengthened the warnings about psychiatric reactions. Although this signal was detected early, over the years there was great debate and publicity over the strength of its association with mefloquine use. To add to the body of evidence, we applied data mining methods to evaluate the early, pre-publicity safety signals collected in the Food and Drug Administration's (FDA) Adverse Events Reporting System (AERS) database. Methods A data mining system, using the Multi-Item Gamma-Poisson Shrinker (MGPS) methodology, has been recently developed at the Center for Drug Evaluation and Research/FDA, for improving the early detection of safety signals from the AERS database. We used our data mining system to examine the progression of higher-than-expected psychiatric signal scores with mefloquine and other anti-malarial drugs. Results A strong signal score for psychosis (about 30 times over expected) was seen the first year of mefloquine's marketing in the US. An association with psychosis was also seen with quinacrine, but not with other anti-malarial drugs. Conclusion MGPS identified that mefloquine's signal of psychosis appeared prior to widespread publicity. This signal was not identified with other quinoline antimalarials. MGPS also identified known class and therapeutic effects with antimalarial drugs. Clinical Pharmacology & Therapeutics (2004) 75, P77–P77; doi: 10.1016/j.clpt.2003.11.290