Various biguanide derivatives are used as antihyperglycemic and antimalarial drugs (e.g., 1,1-dimethyl biguanide (metformin), phenylethyl biguanide (phenformin), N-(4-chlorophenyl)-N'-(isopropyl)-imidodicarbonimidic diamide (proguanil)); however, no common mechanism has been suggested in these controversial therapeutic actions. Biguanides bind endogenous metals that inhibit cysteine proteases i...

Sir—The multicenter randomized trial reported by Overbosch and colleagues [1] is important for 2 reasons. First, the study shows that when taken as malaria prophylaxis, mefloquine is not well tolerated by many travelers. Of the study participants randomized to receive mefloquine, 67.1% reported 1 adverse event, and, in 6% of mefloquine users, these events were severe (defined as requiring medic...

To the best of our knowledge, Stevens-Johnson syndrome (SJS) has not been reported previously as an adverse reaction to Malarone, which is a combination of atovaquone and proguanil hydrochloride used for antimalarial prophylaxis and therapy. We describe a 65-year-old patient who had SJS with typical clinical and histopathological findings associated with the use of Malarone prophylaxis for mala...

INTRODUCTION/OBJECTIVE Experimental and observational studies have linked mefloquine use to an increased risk of developing neuropsychiatric adverse effects such as depression or psychoses. Most of these reports relied on interview-based information from travellers. We conducted a population-based observational study using a database of medical records to quantify and compare the risk of psychi...

BACKGROUND Because malaria in endemic areas presents a serious threat to the health of aircrew, optimal prevention is important. An effective and safe prophylactic antimalarial drug is needed. The combination of 250 mg atovaquone with 100 mg proguanil HCl (atovaquone/proguanil, or A/P) has shown good prophylactic efficacy and tolerance for prevention of falciparum malaria. However, medication f...

WR99210 but does not affect the intrinsic activity of proguanil. Proc. Natl. Acad. Sci. U. S. A. 94, 10931–10936 30 Walter, R. etal. (1991) Pyrimethamine-resistantPlasmodiumfalciparum lack cross-resistance to methotrexate and 2,4-diamino-5-(substituted benzyl) pyrimidines. Parasitol. Res. 77, 346–350 31 Cunningham, R.F. et al. (1981) Clinical pharmacokinetics of probenecid. Clin. Pharmacokinet....

The rapid emergence of drug-resistant malaria parasites during the course of an infection remains a major challenge for providing accurate treatment guidelines. This is particularly important in cases of malaria treatment failure. Using a previously well-characterized case of malaria treatment failure, we show the utility of using next-generation sequencing for early detection of the rise and s...