- Case report
- Open Access
Failure of malaria chemoprophylaxis with mefloquine in an oversize traveller to Mozambique
© Gobbi et al.; licensee BioMed Central Ltd. 2013
- Received: 23 July 2013
- Accepted: 16 December 2013
- Published: 18 December 2013
A case of failure of mefloquine prophylaxis in an oversize traveller, who correctly took the drug. This case seems to be attributed to mefloquine resistance, however it is suggested that mefloquine dosage should be modulated by body weight, as is already indicated by some authorities.
Dosage of mefloquine tablet (250 mg) in Swiss/Austrian malaria prophylaxis recommendations
> 120 kg
2 tablets (twice weekly on tablet: e.g. Mon & Thu)
> 90 kg
1 and ½ tablets (twice weekly on tablet: e.g. Mon & Thu)
> 60 kg
< 10 kg
5 mg /kg
A case is presented of mefloquine failure in an oversize traveller, that was initially attributed to insufficient dosage.
A 50-year-old Italian patient was admitted to the Centre for Tropical Diseases (CTD) with fever (39°C) and diarrhoea since three days. He reported having visited many Catholic missions over several years (he is a priest) in sub-Saharan Africa, Asia and Latin America. The average length of stay was between 10 and 14 days. He had been vaccinated against yellow fever, hepatitis A and B, and typhoid fever. From 20th to 31st March 2012, he had travelled to Mozambique, regularly taking malaria chemoprophylaxis with mefloquine, one tablet (250 mg) weekly, starting one week before travelling and continuing for four weeks after return: he took the last tablet on 24th April. He presented to CTD on May 18th 2012. His weight was 144 kg. He had no history of alcohol, tobacco or illicit drugs abuse. He was not under any long-term medication. The hearth rate was 90 beats per minute and the blood pressure 140/70 mm Hg. Physical examination was unremarkable, except for a distended abdomen. Quantitative buffy coat (QBC), antigen malarial test and blood smears resulted positive for Plasmodium falciparum malaria, with a parasitaemia of 0.13% (6330 /μl). The blood tests showed 7430 WBC/μl, C reactive protein 142 mg/L. The patient was treated with artemether (tablet 50 mg), eight tablets the first day, then three tablets/day until the fifth day, followed by four tablets of sulphamethoxypyrazine/pyrimethamine 500 mg/25 mg (artemisinin-based combination artemisinin-based combination therapies were not yet available). After two days of treatment, blood films resulted negative and remained so at follow-up, one month later.
Whole blood and plasma mefloquine concentrations were retrospectively evaluated on cryo- preserved (-80°C) samples taken on admission (25 days after the last mefloquine intake), by high pressure liquid chromatography (HPLC) coupled with ultraviolet diode-array detection [10, 11].
Whole blood and plasma mefloquine concentrations were 516 and 320 ng/mL, respectively.
Despite a correct anti-malarial chemoprophylaxis, the patient developed P. falciparum malaria. Therefore, it was concluded that either the strain of P. falciparum was resistant to mefloquine, or its dose was insufficient according to the patient’s body weight. At first, the failure was attributed to an insufficient dosage according to the patient’s weight (144 kg), but later mefloquine concentration was assessed on pre-treatment plasma and blood samples that had been stored.
The mefloquine level in the patient’s bloodstream at admission was within the expected range, considering the breakthrough mefloquine levels >620 ng/ml and a half-life of 21 days (Product information Lariam®, Roche, the Netherlands). Considering these data, P. falciparum resistance to mefloquine was more probable, despite the limitation of a single point in time determination.
Papers describing mefloquine prophylaxis failure in travellers to Africa
Country of infection
Symptoms onset (before return)
Symptoms onset (days after return)
40, 12, 9
F, M, F
63, 77, 91
31, 22, 30, 26, 25
M, M, M, F, M
Niger, Sierra Leone, Cameroon, RCA
3, 30, 28, 22, 40, 44, 23, 23, 27
F, M, M, M, M, M, M, M, M
Senegal, Burkina Faso, Niger, Nigeria, Mali, Ivory Coast, Togo
3, 4, 6, 13, 15, 19, 21, 25, 26
5, 28, 34, 37
M, M, M, M,
Burkina Faso, RCA, Madagascar, Togo
19, 26, 31, 32
Senegal, Ivory coast
6, 34, 40, 45, 50
M, M, M, M, F
Mali, Sierra Leone, Senegal, RCA
7, 30, 45, 46, 61
In relation to the first suspicion, there is no agreement on the need to adjust mefloquine regimen to body weight. It is worth considering this factor, though, also taking into account the lipophilic behaviour of this drug, which has an apparent volume of distribution between 13 to 40 1 kg-1 with a mean of 20 1 kg-1. Both apparent volume of distribution and individual systemic clearance are probably influenced by body fat, thus causing different pharmacokinetic profiles [7, 25, 26].
In conclusion, although in this case the failure of mefloquine prophylaxis was most probably due to drug resistance, the indication given by some scientific societies that mefloquine dosage should be modulated by body weight seems reasonable and should probably be considered in new guidelines.
Written informed consent was obtained from the patient for the publication of this report.
- Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Bansod S, Rhein HG: Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data. MalarJ. 2011, 10: 292-10.1186/1475-2875-10-292.View ArticleGoogle Scholar
- CDC: Health Information for International Travel. 2012, The yellow book,http://www.cdc.gov/yellowbook,Google Scholar
- WHO: International travel and health. 2012, Geneva: World Health Organization,http://www.who.int/ith,Google Scholar
- Lalloo DG, Shingadia D, Pasvol G, Chiodini PL, Whitty CJ, Beeching NJ, Hill DR, Warrell DA, Bannister BA: UK malaria treatment guidelines. J Infection. 2007, 54: 111-121. 10.1016/j.jinf.2006.12.003.View ArticleGoogle Scholar
- DTG: Empfehlungen zur Malaravorbeugung. 2011,http://www.dtg.org,Google Scholar
- Hatz C, Nothdurft H: Malaria protection for short-term travelers. Internist. 2006, 47 (8): 810-812. 10.1007/s00108-006-1653-4. 814–817View ArticlePubMedGoogle Scholar
- van Riemsdijk MM, Sturkenboom MC, Ditters JM, Tulen JH, Ligthelm RJ, Overbosch D, Stricker BH: Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine. Br J Clin Pharmacol. 2004, 57: 506-512. 10.1046/j.1365-2125.2003.02035.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, Herold M, Krebs B, Veit O, Allwinn R, Steffen R: Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ. 2003, 327: 1078-10.1136/bmj.327.7423.1078.PubMed CentralView ArticlePubMedGoogle Scholar
- 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. Ann Trop Med Parasitol. 2004, 98: 639-641. 10.1179/000349804225021262.View ArticlePubMedGoogle Scholar
- Green MD, Bergqvist Y, Mount DL, Corbett S, D'Souza MJ: Improved validated assay for the determination of mefloquine and its carboxy metabolite in plasma, serum and whole blood using solid-phase extraction and high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1999, 727: 159-165. 10.1016/S0378-4347(99)00080-8.View ArticlePubMedGoogle Scholar
- Gutman J, Green M, Durand S, Rojas OV, Ganguly B, Quezada WM, Utz GC, Slutsker L, Ruebush TK, Bacon DJ: Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria. Malar J. 2009, 8: 58-10.1186/1475-2875-8-58.PubMed CentralView ArticlePubMedGoogle Scholar
- Callen EC, Church CO: Plasmodium falciparum malaria associated with mefloquine failure in Gambia. Pharmacotherapy. 2006, 26: 1526-1528. 10.1592/phco.26.10.1526.View ArticlePubMedGoogle Scholar
- Wichmann O, Betschart B, Loscher T, Nothdurft HD, Sonnenburg FV, Jelinek T: Prophylaxis failure due to probable mefloquine resistant P. falciparum from Tanzania. Acta Trop. 2003, 86: 63-65. 10.1016/S0001-706X(03)00003-2.View ArticlePubMedGoogle Scholar
- Gari-Toussaint M, Pradines B, Mondain V, Keundjian A, Dellamonica P, Le Fichoux Y: [Senegal and malaria. True prophylactic failure of mefloquine] (in French). Presse Med. 2002, 31: 1136-PubMedGoogle Scholar
- Gizolme D, Receveur MC, Bouzidi P, Theron P: [Relative failure of mefloquine chemoprophylaxis on the occasion of a trip to Togo. 3 cases within the same family] (in French). Presse Med. 1998, 27: 1575-1576.PubMedGoogle Scholar
- Lobel HO, Varma JK, Miani M, Green M, Todd GD, Grady K, Barber AM: Monitoring for mefloquine-resistant Plasmodium falciparum in Africa: implications for travelers’ health. Am J Trop Med Hyg. 1998, 59: 129-132.PubMedGoogle Scholar
- Matteelli A, Chiodera A, Castelli F, Caligaris S, Minardi C, Carosi G: Failure of mefloquine chemoprophylaxis for malaria in Mozambique. J Travel Med. 1995, 2: 260-261. 10.1111/j.1708-8305.1995.tb00673.x.View ArticlePubMedGoogle Scholar
- Magill AJ, Smoak BL: Failure of mefloquine chemoprophylaxis for malaria in Somalia. N Engl J Med. 1993, 329: 1206-View ArticlePubMedGoogle Scholar
- Raccurt CP, Dumestre-Toulet V, Abraham E, Le Bras M, Brachet-Liermain A, Ripert C: Failure of falciparum malaria prophylaxis by mefloquine in travelers from West Africa. Am J Trop Med Hyg. 1991, 45: 319-324.PubMedGoogle Scholar
- Ooi WW: Failure of mefloquine prophylaxis in east Africa. N Engl J Med. 1991, 324 (2): 130-PubMedGoogle Scholar
- Durieux I, Boibieux A, Biron F, Ringwald P, Piens MA, Peyramond D: [Failure of chemoprevention with mefloquine in western Africa] (in French). Presse Med. 1990, 19 (33): 1548-1549.PubMedGoogle Scholar
- Ringwald P, Bartczak S, Le Bras J, Bricaire F, Matheron S, Bauchet J, Coulaud JP: Failure of anti-malarial prophylaxis with mefloquine in Africa. Trans R Soc Trop Med Hyg. 1990, 84: 348-349. 10.1016/0035-9203(90)90311-2.View ArticlePubMedGoogle Scholar
- Gay F, Binet MH, Bustos MD, Rouveix B, Danis M, Roy C, Gentilini M: Mefloquine failure in child contracting falciparum malaria in West Africa. Lancet. 1990, 335: 120-121. 10.1016/0140-6736(90)90597-X.View ArticlePubMedGoogle Scholar
- Bricaire F, Gay F, Caumes E, Datry A, Bustos D, Felix H, Paris L, Danis M, Gentilini M: [Failure of prevention of malaria by mefloquine in West Africa] (in French). Ann Med Onterne. 1990, 141 (6): 512-514.Google Scholar
- Karbwang J, White NJ: Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet. 1990, 19: 264-279. 10.2165/00003088-199019040-00002.View ArticlePubMedGoogle Scholar
- Palmer KJ, Holliday SM, Brogden RN: Mefloquine: a review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1993, 45: 430-475.View ArticlePubMedGoogle Scholar
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