Mefloquine for preventing malaria in non-immune adult travellers

Croft, Ashley M.; Garner, Paul

doi:10.1002/14651858.cd000138

Cited by 23 publications

(6 citation statements)

References 86 publications

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“…If our results can be confirmed in proof-of-concept studies in humans, initially with current antimalarial dosages, it is conceivable that mefloquine can play a role in public health because the drug is widely and effectively used in malaria-endemic settings [28] , [29] , and because of the fact that malaria and schistosomiasis co-exist over large parts of sub-Saharan Africa and elsewhere [22] . The highest activities in S. mansoni- and S. japonicum -infected mice were observed when mefloquine was given at a single oral dose of 200–400 mg/kg, which correspond to 16–31 mg/kg in humans (dose calculator: http://www.fda.gov/cder/cancer/animalframe.htm ).…”

Section: Discussionmentioning

confidence: 67%

Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice

et al. 2009

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BackgroundThe treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice.Methodology/Principal FindingsA single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%–100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.Conclusions/SignificanceOur findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.

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Section: Discussionmentioning

confidence: 67%

Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice

et al. 2009

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“…In areas of intense malaria transmission, malaria chemoprophylaxis remains the most important strategy for preventing malaria in travellers [3], but its use may be associated with adverse outcomes and even death [4]. These potentially severe adverse effects may undermine compliant use of malaria chemoprophylaxis in travellers, in particular when considering that these travellers were usually healthy when commencing travel [5-9].…”

Section: Introductionmentioning

confidence: 99%

Severity of imported malaria: protective effect of taking malaria chemoprophylaxis

Vliegenthart-Jongbloed

Melo

Wolfswinkel

et al. 2013

Malar J

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BackgroundAlthough chemoprophylaxis remains an important strategy for preventing malaria in travellers, its effectiveness may be compromised by lack of adherence. Inappropriate use of chemoprophylaxis is likely to increase the risk of acquiring malaria, but may probably also worsen the severity of imported cases. The aim of this study was to assess the impact of use of malaria chemoprophylaxis on clinical features and outcome of imported malaria.MethodsDemographic, clinical and laboratory data of patients included in the Rotterdam Malaria Cohort between 1998 and 2011 were systematically collected and analysed. Patients were classified as self-reported compliant or non-compliant users or as non-users of chemoprophylaxis. Severe malaria was defined using the 2010 WHO criteria.ResultsDetails on chemoprophylaxis were available for 559 of the 604 patients, of which 64.6% were non-users, 17.9% were inadequate users and 17.5% reported to be adequate users. The group of non-users was predominated by patients with African ethnicity, partial immunity and people visiting friends and relatives. The majority contracted Plasmodium falciparum malaria. In contrast, compliant users acquired non-falciparum malaria more frequently, had significant lower P. falciparum loads on admission, shorter duration of hospitalization and significant lower odds for severe malaria as compared with non-users. Patients with P. falciparum malaria were more likely to have taken their chemoprophylaxis less compliantly than those infected with non-P. falciparum species. Multivariate analysis showed that self-reported adequate prophylaxis and being a partially immune traveller visiting friends and relatives was associated with significantly lower odds ratio of severe malaria. In contrast, age, acquisition of malaria in West-Africa and being a non-immune tourist increased their risk significantly.ConclusionsCompliant use of malaria chemoprophylaxis was associated with significantly lower odds ratios for severe malaria as compared with non-compliant users and non-users of chemoprophylaxis. After correction for age, gender and immunity, this protective effect of malaria chemoprophylaxis was present only in individuals who adhered compliantly to use of chemoprophylaxis. Patients with P. falciparum malaria were more likely to have used their chemoprophylaxis less compliantly than patients with non-P. falciparum malaria who were more likely to have contracted malaria in spite of compliant use of chemoprophylaxis.

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“…Mefloquine has been used for the chemoprophylaxis and treatment of malaria [1,2,3,4,5,6,7,8], schistosomes and other helminthes [9]. The use is limited by various side effects [4] including neuropsychiatric disorders [10,11,12,13,14], skin reactions [15] as well as risk of miscarriage and stillbirth [16].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Suicidal Erythrocyte Death by the Antimalarial Drug Mefloquine

Bissinger

Barking

Alzoubi

et al. 2015

Cell Physiol Biochem

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Background: The antimalarial drug mefloquine has previously been shown to stimulate apoptosis of nucleated cells. Similar to apoptosis, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), and ceramide. Methods: Phosphatidylserine abundance at the cell surface was estimated from annexin V binding, cell volume from forward scatter, reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca²⁺]_i from Fluo3-fluorescence, and ceramide abundance from specific antibody binding. Results: A 48 h treatment of human erythrocytes with mefloquine significantly increased the percentage of annexin-V-binding cells (≥5 µg/ml), significantly decreased forward scatter (≥5 µg/ml), significantly increased ROS abundance (5 µg/ml), significantly increased [Ca²⁺]_i (7.5 µg/ml) and significantly increased ceramide abundance (10 µg/ml). The up-regulation of annexin-V-binding following mefloquine treatment was significantly blunted but not abolished by removal of extracellular Ca²⁺. Even in the absence of extracellular Ca²⁺, mefloquine significantly increased annexin-V-binding. Conclusions: Mefloquine treatment leads to erythrocyte shrinkage and erythrocyte membrane scrambling, effects at least partially due to induction of oxidative stress, increase of [Ca²⁺]_i and up-regulation of ceramide abundance.

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Mefloquine for preventing malaria in non-immune adult travellers

Cited by 23 publications

References 86 publications

Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice

Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice

Severity of imported malaria: protective effect of taking malaria chemoprophylaxis

Stimulation of Suicidal Erythrocyte Death by the Antimalarial Drug Mefloquine

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