Mefloquine Prophylaxis Research Articles

Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial

BackgroundWhole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes.MethodsIn a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135.ResultsRelatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%).ConclusionsThese CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches.Trial registrationThe trial was registered at ClinicalTrials.gov under identifier NCT03813108.

Development of Resistance Against Mefloquine Prophylaxis in Peace-Keeping Forces in the Central African Republic.

ObjectiveTo record the frequency of malaria-like symptoms in patients who have been given mefloquine as chemoprophylaxis and to determine the effectiveness of antimalarials against these symptoms.MethodologyIt was an observational study that took place at a United Nations Level 1 hospital, Kaga-Bandoro, Central African Republic. The total duration of the study was three months.Patients presenting to the clinic with multiple symptoms despite chemoprophylaxis with mefloquine were assessed through a physical examination and screening test for malaria. Malaria treatment with a six-dose regimen of artemether (20 mg), along with lumefantrine (120 mg) two tablets BD for three days, was given after informed consent to those patients and post-treatment symptoms were observed and recorded.ResultsOut of 61 patients, 93% of them presented with body aches, 92% with headache, 52% with shivering, 44% with vertigo, 38% with fever, sweating, and nausea/vomiting, 18% with diarrhea, and 10% with pain in the abdomen.ConclusionIt had been seen that patients presented with symptoms despite standard mefloquine prophylactic therapy, which were resolved with other antimalarial drugs. The presentation of the symptoms was also not classical.

A cluster of the first reported Plasmodium ovale spp. infections in Peru occuring among returning UN peace-keepers, a review of epidemiology, prevention and diagnostic challenges in nonendemic regions

BackgroundPlasmodium ovale curtisi and Plasmodium ovale wallikeri are regarded as less virulent forms of malaria with a geographic distribution including Southeast Asia, Central and West Africa, and is increasingly reported as an infection in returning travellers. A species of malaria that may have delayed or relapsing presentations similar to Plasmodium vivax, the clinical presentation of P. ovale spp. has been described to have prepatent periods of 2 weeks or slightly longer with reports of relapse following primary infection out to 8–9 months. This presentation may be obscured further in the setting of anti-malarial exposure, with report of delayed primary infection out to 4 years. Presented is a cluster of 4 imported P. ovale spp. cases in returning Peruvian military personnel assigned to United Nations peace-keeping operations in the Central African Republic.Case presentationFrom January to December 2016, Peruvian peace-keepers were deployed in support of United Nations (UN) operations in the Central African Republic (CAR). While serving abroad, Navy, Army, and Air Force members experienced 223 episodes of Plasmodium falciparum malaria following interruption of prophylaxis with mefloquine. Diagnosis was made using rapid diagnostics tests (RDTs) and/or smear with no coinfections identified. Cases of malaria were treated with locally-procured artemether-lumefantrine. Returning to Peru in January 2017, 200 peace-keepers were screened via thick and thin smear while on weekly mefloquine prophylaxis with only 1 showing nucleic acid within red blood cells consistent with Plasmodium spp. and 11 reporting syndromes of ill-defined somatic complaints. Between a period of 5 days to 11 months post return, 4 cases of P. ovale spp. were diagnosed using smear and polymerase chain reaction (PCR) following febrile complaints. All cases were subsequently treated with chloroquine and primaquine, with cure of clinical disease and documented clearance of parasitaemia.ConclusionThese patients represent the first imported cases in Peru of this species of malaria as well as highlight the challenges in implementing population level prophylaxis in a deployed environment, and the steps for timely diagnosis and management in a non-endemic region where risk of introduction for local transmission exists.

A study on mefloquine-associated neuropsychiatric manifestations among Nepalese soldiers posted for United Nations peace mission

Background: Mefloquine is one of the prophylactic medications recommended by the government of Nepal. In areas of intense malaria transmission, prophylaxis with drugs is an important strategy to prevent malaria. During prophylactic use, several neuro-psychiatric and other systemic adverse effects can occur with mefloquine. Notable psychiatric manifestations include anxiety, depression, restlessness, and confusion.
 Objective: To study the psychiatric effects of mefloquine in Nepalese serving soldiers posted in the United Nations peace mission nations of the African continent taking mefloquine prophylaxis.
 Methodology: This prospective descriptive study was conducted among Nepalese soldiers posted for United Nations peace mission in South Sudan over a period of one year. Soldiers of age group 25-55 years posted for peace mission having no past and family history of psychiatric illnesses were enrolled in the study. General Health Questionnaire-12, translated into Nepali by Nepalese Journal of Psychiatry, with a questionnaire about the side effects was used to collect detailed information.
 Results: A total of 524 soldiers posted on peace mission were enrolled in the present study, among which 520 were male and four were female. There were four positive cases with General Health Questionnaire score 3/12 or more. Among the adverse events noted, neuropsychiatric adverse events were more common than non-neuropsychiatric adverse events but none were of life-threatening severity.
 Conclusion: In a malaria endemic region with a high prevalence of malaria, mefloquine can be safely used in an apparently healthy population, judging the risk-benefit.

Mefloquine for preventing malaria in pregnant women.

Mefloquine for preventing malaria in pregnant women.

Mefloquine for preventing malaria in pregnant women.

Mefloquine for preventing malaria in pregnant women.

Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review.

Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established. We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988). We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment. Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.

A serious nightmare: psychiatric and neurologic adverse reactions to mefloquine are serious adverse reactions.

Mefloquine (originally marketed as Lariam) is a neurotoxic quinoline derivative antimalarial drug that is known to cause serious and potentially lasting neuropsychiatric adverse reactions. Since 2013, drug regulators in several jurisdictions, including the United States, the United Kingdom, Ireland, and Canada, have required their mefloquine labels be updated to warn that when used for malaria prophylaxis the drug should be discontinued at the onset of neurologic or psychiatric symptoms. These recent changes to the international labeling serve to imply that psychiatric and neurologic reactions to mefloquine prophylaxis may be an early warning of an impending more serious reaction that may further jeopardize the patient with continued use of the drug. To prevent these more serious effects, these drug labels now warn that mefloquine should be discontinued and that patients seek immediate medical intervention to obtain an alternative antimalarial drug when psychiatric or neurologic symptoms occur. When used correctly for malaria prophylaxis as the updated labeling now directs, it is reasonable to expect that mefloquine will be discontinued, and an alternative drug substituted, in each patient who develops psychiatric or neurologic symptoms. This opinion discusses the implications of this updated labeling for the reporting of adverse reactions and for the continued use of the drug in malaria prophylaxis.

三日熱マラリアの再発との判別が困難であった 4 カ月以上の潜伏期間の後に発症した四日熱マラリアの 1 例

We report herein on a case of Plasmodium malariae malaria with more than a 4-month incubation period. A 35-year-old Japanese man who first presented to our clinic with fever and history of travel to Papua New Guinea was suspected of having Plasmodium vivax malaria based on peripheral smear results. We admitted him and initiated treatment with mefloquine. After two days of therapy, he became afebrile. We discharged him, and P. vivax was later confirmed with PCR. We started mefloquine prophylaxis for a planned trip to Papua New Guinea. After his return, a standard dose of primaquine (15 mg x 14 days) was prescribed for a radical cure of P. vivax. About 4 months after his last visit to Papua New Guinea, he returned to our clinic with fever. We suspected a relapse of P. vivax malaria and admitted him for a second time. After two days of mefloquine therapy, his symptoms improved. We discharged him and restarted a higher dose of primaquine (30 mg x 14 days) therapy for a radical cure of P. vivax. Subsequently, the PCR test revealed the parasite was P. malariae and not P. vivax. Only 13 cases of Plasmodium malariae malaria have been reported in Japan during the past 10 years. Blood-stage schizonticides such as mefloquine is not active against the liver stage. Therefore, the use of these drugs for prophylaxis will not be effective for prevention of malaria if its liver stage is longer than the duration of effective chemoprophylaxis. Although the incubation period of P. malariae is typically 13 to 28 days, it occasionally lasts for months or even years. Careful attention should be given to the possibility that P. malariae occasionally has a long incubation period even in the absence of the hypnozoite stage.

Plasmodium falciparum Infection during Suppressive Prophylaxis with Mefloquine Does Not Induce an Antibody Response to Merozoite Surface Protein-1(42)

A sensitive biomarker of malaria infection would obviate the need for placebo control arms in clinical trials of malaria prophylactic drugs. Antibodies to the 42-kDa fragment of merozoite surface protein-1 (MSP1(42)) have been identified as a potential marker of malaria exposure in individuals receiving prophylaxis with mefloquine. We conducted an open-label trial to determine the sensitivity of seroconversion to MSP1(42), defined as a fourfold rise in enzyme-linked immunosorbant assay (ELISA) titer, among 23 malaria naïve volunteers receiving mefloquine prophylaxis and 6 controls after Plasmodium falciparum sporozoite challenge. All members of the control cohort but none of the mefloquine cohort developed patent parasitemia. Four of six controls but zero of the mefloquine cohort seroconverted to MSP1(42). We conclude that malaria infection during suppressive prophylaxis does not induce antibody response to the blood-stage antigen MSP1(42) in a malaria-naïve study population.

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.

Caspofungin-Induced Toxic Epidermal Necrolysis; Acute Eosinophilic Pneumonia Secondary to Daptomycin; Catastrophic Complications of Intravenous Promethazine; Separate Episodes of Delirium Caused by Amiodarone and Levetiracetam; Fatal Hemobilia in Advanced Hepatocellular Carcinoma Caused by Sorafenib; Mania Associated with Mefloquine Prophylaxis; Inappropriate Prescribing Predicts Adverse Events in the Elderly

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) Medwatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to Medwatch, please consider sharing the account with our readers.

P01-97 - Mania induced by mefloquine prophylaxis: case description and literature review

ObjectivesMefloquine is being used as malaria prevention by Plasmodium Falciparum in chloroquine-resistant zones. We describe a woman who developed a manic episode with psychotic symptoms during mefloquine treatment.Methods and resultsA 26-year-old Spanish woman had been working in Mali for the last six months and had started antimalarial prevention with mefloquine. In Mali, the clinical picture had a sudden debut and she related: excessive happiness, incapacity to sleep, and megalomania (she believed to have special powers and to be the mother of all the children). She was admitted in a hospital in Mali for seven days and received treatment with haloperidol and chlorpromazine. Then, she was repatriated to Spain without treatment and she continued suffering the same symptoms. After 15 days, she went to our hospital and she was admitted. Treatment started with risperidone (up to 6 mg/day) and clonazepam (up to 1.5 mg/day). At admission Young Mania Rating Scale (YMRS) was 25 points. Physical examination and complementary tests were normal, and was orientated as a manic episode with psychotic symptoms secondary to mefloquine. She had a quick symptomatic improvement (after 7 days of treatment YMRS was 5 points) and was discharged after 15 days.ConclusionMefloquine more frequent adverse neuropsychiatric effects are: dizziness, vivid dreams and insomnia. Others are confusion, and auditory hallucinations. Side effects are dose dependent. Psychotic symptoms are frequently auto-limited when mefloquine is suppressed but treatment with atypical antipsychotics is often needed. MDR1/ABCB1 polymorphisms may play a role in neuropsychiatric side effects

PW01-41 - Mania induced by mefloquine prophylaxis: case description and literature review

ObjectivesMefloquine is being used as malaria prevention by Plasmodium Falciparum in chloroquine-resistant zones. We describe a woman who developed a manic episode with psychotic symptoms during mefloquine treatment.Methods and resultsThe case describes a 26-year-old Spanish woman who had been working in Mali for the last six months and had started antimalarial prevention with mefloquine. In Mali, the clinical picture had a sudden debut and she related: excessive happiness, incapacity to sleep, and megalomania (she believed to have special powers and to be the mother of all the children). She was admitted in a hospital in Mali for seven days and received treatment with haloperidol and chlorpromazine. Then, she was repatriated to Spain without treatment and she continued suffering the same symptoms. After 15 days, she went to our hospital and she was admitted. Treatment started with risperidone (up to 6 mg/day) and clonazepam (up to 1.5 mg/day). At admission Young Mania Rating Scale (YMRS) was 25 points. Physical examination and complementary tests were normal, and was orientated as a manic episode with psychotic symptoms secondary to mefloquine. She had a quick symptomatic improvement (after 7 days of treatment YMRS was 5 points) and was discharged after 15 days.ConclusionMefloquine more frequent adverse neuropsychiatric effects are: dizziness, vivid dreams and insomnia. Others are confusion, and auditory hallucinations. Side effects are dose dependent. Psychotic symptoms are frequently auto-limited when mefloquine is suppressed but treatment with atypical antipsychotics is often needed. MDR1/ABCB1 polymorphisms may play a role in neuropsychiatric side effects.

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.

Analysis of the direct and indirect costs of treatment of imported malaria in the Slovak Republic

This study analyzed the approximate cost of treatment of patients hospitalized with a diagnosis of imported malaria in Slovakia. Between 2003 and 2007, 15 patients with imported malaria were hospitalized. The mean direct cost of the treatment was 970.75 euros and the mean indirect cost was 53.15 euros. For the patient with the highest cost of treatment, the use of mefloquine prophylaxis would have represented only 0.5% of the total direct cost of treating the disease. Despite the partial resistance of plasmodia, malaria chemoprophylaxis is unequivocally a cheaper choice than subsequent treatment of malaria.

Malaria and Mefloquine Prophylaxis Use Among Japan Ground Self‐Defense Force Personnel Deployed in East Timor

Malaria poses a significant threat to military personnel stationed in endemic areas; therefore, it is important to examine the risks of military operations, particularly in areas where malaria-related data are scarce. The recent deployment of Japan Ground Self-Defense Force (JGSDF) for a peacekeeping operation in East Timor provided an opportunity to investigate these risks. The results of these studies may be translated into chemoprophylactic strategies for travelers. A total of 1,876 members were deployed between April 2002 and September 2003. They consisted of three battalions; each remained for 6 months and was put on mefloquine prophylaxis. Malaria infection was investigated, including exposure to Plasmodium falciparum sporozoites, assessed by seroconversion for anticircumsporozoite (anti-CS) protein antibodies. Adherence to and adverse events (AEs) of mefloquine were studied via questionnaires. Four members were evacuated: one each with optic neuritis, lung cancer with brain metastasis, IgA nephropathy, and psychotic reactions that may have been precipitated by mefloquine. Six clinical episodes of Plasmodium vivax occurred, including one relapse, but there were no clinical cases of P falciparum, yielding a crude malaria attack rate of 0.32% for the 6-month period. Overall, 3.1% of the study population seroconverted for the anti-CS protein antibodies, with some regional differences noted. About 24% of questionnaire respondents, reported AEs; however, none of the AEs was severe. The AEs tended to emerge during the initial doses of chemoprophylaxis. The implementation of mefloquine prophylaxis among JGSDF personnel in East Timor, where P falciparum constitutes a moderate risk, appears to have been a success. Mefloquine prophylaxis was generally safe for Japanese unless predisposed to neuropsychiatric illness. However, given that mefloquine is the only chemoprophylactic agent available, a risk-benefit analysis tailored to the traveler is required for visits to countries such as East Timor.

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.

Suicide spectaculaire lié à une prise de méfloquine

We present a case in which suicide was a severe neuropsychiatric reaction to treatment with mefloquine. Physicians must be aware of these serious psychiatric complications and bear them in mind when faced with atypical behavior or suspected suicide. The body of a 27-year-old man was discovered at his home, covered with multiple knife wounds. The autopsy report concluded that death was due to a craniocerebral wound from a violent blow. Homicide was initially suspected. Suicide during acute psychosis associated with mefloquine was suggested, and toxicologic analyses confirmed this hypothesis. Serious neurologic and psychiatric adverse events associated with mefloquine (Lariam) have been reported since its introduction in 1985. Mefloquine prophylaxis is recommended for travelers to high-risk areas of chloroquine-resistant plasmodium falciparum. The risk of malarial infection and the proven efficacy of mefloquine to prevent malaria should be weighed against the risk of drug-associated adverse events. Physicians must nonetheless be aware of these serious psychiatric complications, especially when faced with atypical behavior and atypical suicides. The patient's' family and friends should be asked about a possible trips abroad that might have entailed antimalaria treatment, even several months earlier. Testing for mefloquine during toxicological examinations is then essential. The World Health Organization recommendations and contraindications must be followed in prescribing mefloquine.

Malaria in Brazilian military personnel deployed to Angola.

Malaria represents one of the most important infectious disease threats to deployed military forces; most personnel from developed countries are nonimmune personnel and are at high risk of infection and clinical malaria. This is especially true for forces deployed to highly-endemic areas in Africa and Southeast Asia where drug-resistant malaria is common. We conducted an outbreak investigation of malaria cases in Angola where a total of 439 nonimmune Brazilian troops were deployed for a 6-month period in 1995-1996. A post-travel medical evaluation was also performed on 338 (77%) of the 439 soldiers upon return to Brazil. Questionnaire, medical record, thick/thin smear, and serum anti-Plasmodium falciparum antibody titer (by IFA) data were obtained. Peak serum mefloquine (M) and methylmefloquine (MM) metabolite levels were measured in a subsample of 66 soldiers (42 cases, 24 nonmalaria controls) who were taking weekly mefloquine prophylaxis (250 mg). Seventy-eight cases of malaria occurred among the 439 personnel initially interviewed in Angola (attack rate = 18%). Four soldiers were hospitalized, and 3 subsequently died of cerebral malaria. Upon return to Brazil, 63 (19%) of 338 soldiers evaluated were documented to have had clinical symptoms and a diagnosis of malaria while in Angola. In addition, 37 (11%) asymptomatically infected individuals were detected upon return (< 1% parasitemia). Elevated, post-travel anti-P. falciparum IFA titers (> or = 1:64) were seen in 101 (35%) of 292 soldiers tested, and was associated with a prior history of malaria in-country (OR = 3.67, 95% CI 1.98-6.82, p <.001). Noncompliance with weekly mefloquine prophylaxis (250 mg) was associated with a malaria diagnosis in Angola (OR = 3.75, 95% CI 0.97-17.41, p =.03) but not with recent P. falciparum infection (by IFA titer). Mean peak levels (and ratios) of serum M and MM were also found to be lower in those who gave a history of malaria while in Angola. Malaria was a significant cause of morbidity among Brazilian Army military personnel deployed to Angola. Mefloquine prophylaxis appeared to protect soldiers from clinical, but not subclinical, P. falciparum infections. Mefloquine noncompliance and an erratic chemoprophylaxis prevention policy contributed to this large outbreak in nonimmune personnel. This report highlights the pressing need for development of newer, more efficacious and practical, prophylactic drug regimens that will reduce the malaria threat to military forces and travelers.