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Travel Medicine and Infectious Disease 2017
Topics: Antimalarials; Humans; Malaria; Mefloquine
PubMed: 29158041
DOI: 10.1016/j.tmaid.2017.11.006 -
Neurology India 2023Neuropsychiatric disorders, ranging from mild cognitive impairment to frank psychosis, have been associated with certain parasitic infections. The parasite may cause... (Review)
Review
Neuropsychiatric disorders, ranging from mild cognitive impairment to frank psychosis, have been associated with certain parasitic infections. The parasite may cause damage to the central nervous system in several ways: as a space-occupying lesion (neuro-cysticercosis), alteration of neurotransmitters (toxoplasmosis), generation of the inflammatory response (trypanosomiasis, schistosomiasis), hypovolemic neuronal injury (cerebral malaria), or a combination of these. Certain drugs like quinacrine (mepacrine), mefloquine, quinolone, and interferon alpha which are used to treat these parasitic infections can further cause neuropsychiatric adverse effects. This review summarizes the major parasitic infections that are associated with neuropsychiatric disorders and the pathogenesis involved in their processes. A high index of suspicion for parasitic diseases, especially in endemic areas, should be kept in patients presenting with neuropsychiatric symptoms. A multidimensional approach to identification of the offending parasite using serological, radiological, and molecular tests is required not only to ensure proper and prompt treatment of the primary parasitic infection but also to improve the prognosis of patients by complete resolution of neuropsychiatric symptoms.
Topics: Humans; Parasitic Diseases; Central Nervous System; Mental Disorders; Mefloquine; Cysticercosis
PubMed: 37148042
DOI: 10.4103/0028-3886.375424 -
Toxicology Dec 2021Mefloquine is a quinoline-based compound widely used as an antimalarial drug, particularly in chemoprophylaxis. Although decades of research have identified various... (Review)
Review
Mefloquine is a quinoline-based compound widely used as an antimalarial drug, particularly in chemoprophylaxis. Although decades of research have identified various aspects of mefloquine's anti-Plasmodium properties, toxic effects offset its robust use in humans. Mefloquine exerts harmful effects in several types of human cells by targeting many of the cellular lipids, proteins, and complexes, thereby blocking a number of downstream signaling cascades. In general, mefloquine modulates several cellular phenomena, such as alteration of membrane potential, induction of oxidative stress, imbalance of ion homeostasis, disruption of metabolism, failure of organelle function, etc., leading to cell cycle arrest and programmed cell death. This review aims to summarize the information on functional and mechanistic findings related to the cytotoxic effects of mefloquine.
Topics: Animals; Antimalarials; Apoptosis; Cell Cycle Checkpoints; Humans; Mefloquine; Membrane Potentials; Oxidative Stress
PubMed: 34678321
DOI: 10.1016/j.tox.2021.152995 -
Cold Spring Harbor Perspectives in... Jun 2017One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. e1000221 [2010]) and require protection from... (Review)
Review
One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. Chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout Africa, is rapidly losing its benefits for the same reason. No other drugs have yet been shown to be safe, tolerable, and effective as prevention for pregnant women, although monthly dihydroartemisinin-piperaquine has shown promise for reducing poor pregnancy outcomes. Insecticide-treated nets provide some benefits, such as reducing placental malaria and low birth weight. However, this leaves a heavy burden of maternal, fetal, and infant morbidity and mortality that could be avoided. Women naturally acquire resistance to over successive pregnancies as they acquire antibodies against parasitized red cells that bind chondroitin sulfate A in the placenta, suggesting that a vaccine is feasible. Pregnant women are an important reservoir of parasites in the community, and women of reproductive age must be included in any elimination effort, but several features of malaria during pregnancy will require special consideration during the implementation of elimination programs.
Topics: Africa; Antimalarials; Artemisinins; Drug Combinations; Drug Resistance; Female; Humans; Malaria; Malaria Vaccines; Mefloquine; Placenta; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Pregnancy Outcome; Pyrimethamine; Sulfadoxine
PubMed: 28213434
DOI: 10.1101/cshperspect.a025551 -
International Journal For Parasitology.... Dec 2021According to WHO, 2019 witnessed 229 million cases of malaria globally, of which Africa accounted for 94% of cases. Early diagnosis and treatment are the basis of... (Review)
Review
According to WHO, 2019 witnessed 229 million cases of malaria globally, of which Africa accounted for 94% of cases. Early diagnosis and treatment are the basis of malaria management, and the need for good chemoprophylaxis especially for people travelling to endemic areas is vital. There are a number of drug options available for the prophylaxis of malaria, mefloquine being one of the drugs used. Mefloquine has been around from the 1970s, and was developed in the United States keeping in mind the soldiers that were being deployed to areas where chloroquine resistant strains of Plasmodium were discovered. Mefloquine was preferred for its once a week dosage. Within a decade of its introduction, reports of the side effects associated with its long-term use surfaced. Mefloquine is now reported to cause a myriad of neuropsychiatric side effects including anxiety, sleep disturbance, depression, dizziness and frank psychosis, especially in patients with pre-existing psychiatric disorders. Many countries like the United States and the United Kingdom have updated their drug boxes to include the warning of these potential neuropsychiatric effects. This paper reviews the side effects of mefloquine and why there is a need to revisit its use in Indian drug policy.
Topics: Antimalarials; Chloroquine; Humans; Malaria; Mefloquine; Military Personnel
PubMed: 34339933
DOI: 10.1016/j.ijpddr.2021.06.003 -
Critical Reviews in Toxicology Mar 2021Mefloquine, a potent blood schizontocide, is effective against drug-resistant This property, along with its unique pharmacokinetic profile, makes mefloquine a widely... (Review)
Review
Mefloquine, a potent blood schizontocide, is effective against drug-resistant This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, several epidemiological studies have raised concerns on the safety of mefloquine as prophylaxis for malaria. Well-documented side-effects of mefloquine include abnormal dreams, insomnia, anxiety, and depressed mood, as well as nausea and dizziness (the last two most frequent effects). The mechanisms that underlie the neurological/psychiatric complications of mefloquine are poorly understood. The aim of this study was to review the literature on the neurotoxic mechanisms of action of mefloquine to better understand its potential toxicity in the central nervous system, highlighting the mechanisms that lead to its psychiatric disorders. Experimental studies on the neurotoxic effects of mefloquine discussed herein include brain transporters of mefloquine, alteration in neurotransmitters, disruption on calcium (Ca) homeostasis and neuroinflammation, generation of oxidative stress response in neurons (involving glutathione, increased F2-isoprostanes, accumulation of cytosolic lipid globules), and alteration of voltage-dependent channels, as well as gap junction intercellular communications. Although several hypotheses have been proposed for the mechanisms that mediate mefloquine-induced brain damage, they are not fully understood, necessitating additional studies in the future.
Topics: Antimalarials; Central Nervous System; Humans; Mefloquine; Nervous System
PubMed: 33905310
DOI: 10.1080/10408444.2021.1901258 -
Journal of Travel Medicine Jul 2020Pregnant travelers face numerous risks, notably increased susceptibility to or severity of multiple infections, including malaria. Because pregnant women residing in...
Pregnant travelers face numerous risks, notably increased susceptibility to or severity of multiple infections, including malaria. Because pregnant women residing in areas non-endemic for malaria are unlikely to have protective immunity, travel to endemic areas poses risk of severe illness and pregnancy complications, such as low birthweight and fetal loss. If travel to malaria-endemic areas cannot be avoided, preventive measures are critical. However, malaria chemoprophylaxis in pregnancy can be challenging, since commonly used regimens have varying levels of safety data and national guidelines differ. Furthermore, although chloroquine and mefloquine have wide acceptance for use in pregnancy, regional malaria resistance and non-pregnancy contraindications limit their use. Mosquito repellents, including N,N-diethyl-m-toluamide (DEET) and permethrin treatment of clothing, are considered safe in pregnancy and important to prevent malaria as well as other arthropod-borne infections such as Zika virus infection. Pregnant travelers at risk for malaria exposure should be advised to seek medical attention immediately if any symptoms of illness, particularly fever, develop.
Topics: Antimalarials; Chemoprevention; Chloroquine; Drug Resistance; Female; Humans; Malaria; Mefloquine; Pregnancy; Proguanil; Travel
PubMed: 32419013
DOI: 10.1093/jtm/taaa074 -
The Journal of Antimicrobial... Feb 2023In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites....
BACKGROUND
In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged. However, the lack of a viable alternative led Cambodia to adopt artesunate/mefloquine countrywide, raising concerns about a surge of triple-resistant P. falciparum strains.
OBJECTIVES
To assess the prevalence of triple-resistant parasites after artesunate/mefloquine implementation countrywide in Cambodia and to characterize their phenotype.
METHODS
For this multicentric study, 846 samples were collected from 2016 to 2019. Genotyping of molecular markers associated with artemisinin, piperaquine and mefloquine resistance was coupled with phenotypic analyses.
RESULTS
Only four triple-resistant P. falciparum isolates (0.47%) were identified during the study period. These parasites combined the pfk13 polymorphism with pfmdr1 amplification, pfpm2 amplification and/or pfcrt mutations. They showed significantly higher tolerance to artemisinin, piperaquine and mefloquine and also to the mefloquine and piperaquine combination.
CONCLUSIONS
The use of artesunate/mefloquine countrywide in Cambodia has not led to a massive increase of triple-resistant P. falciparum parasites. However, these parasites circulate in the population, and exhibit clear resistance to piperaquine, mefloquine and their combination in vitro. This study demonstrates that P. falciparum can adapt to more complex drug associations, which should be considered in future therapeutic designs.
Topics: Humans; Mefloquine; Plasmodium falciparum; Antimalarials; Artesunate; Cambodia; Prevalence; Artemisinins; Quinolines; Malaria, Falciparum; Drug Resistance
PubMed: 36508338
DOI: 10.1093/jac/dkac403