Mepacrine hydrochloride

Despite their colonial experience with tropical medicine, Allied (United States, United Kingdom, Australia, and India) Armies in the Indo-Pacific region were surprised by the large number of Plasmodium vivax infections in their soldiers during the Second World War. Even after the institution of effective chemoprophylaxis with quinacrine, multiple cycles of clinical relapses often occurred when months of medication was discontinued. Nearly monthly symptomatic relapses (>10) were not unusual and resulted in important manpower losses after each campaign. Retrospective consideration suggests that small splenic size was associated with the risk of recurrent clinical episodes of vivax malaria. Potential non–mutually exclusive explanations for frequent relapses of vivax malaria in soldiers are reviewed. These include decreased retention of parasitized red blood cells by small spleens through greater filtration stringency preventing relapses from becoming clinically patent; small spleen size being a marker of lower innate and/or acquired immunity, modulating the risk of clinically patent recurrences; or small spleen size increasing the number of relapses through decreased removal of triggers of hypnozoite activation. Apparent splenic modulation of vivax malaria relapses suggests a complex interaction between the parasite and host that might be amenable to manipulation to facilitate malaria elimination.

Antimalarials (AMs) are old drugs with a wide range of beneficial effects in systemic lupus erythematosus (SLE) beyond the control of activity. The most recent debate is focused on defining the optimal doses to assure the best benefit/risk ratio.

We have reviewed the pharmacological basis underlying the various therapeutic effects of AMs and the beneficial and toxic effects of HCQ, also discussing the role of mepacrine not only as a substitute in cases of maculopathy, but also as a very effective therapy combined with HCQ. We searched PubMed and Embase for articles published in English at any time. We used the terms "hydroxychloroquine" or "mepacrine" or "chloroquine" or "antimalarials", "pharmacokinetics", "efficacy", "remission", "toxicity", "adherence". We reviewed original research articles, large observational studies, systematic reviews, and expert consensus statements. Additionally, studies were identified through the assessment of the reference lists of the evaluated manuscripts.

We advocate for the widespread use of HCQ at stable doses of 200 mg/d (≤4 mg/kg/d for most patients) and also for the early combination therapy with mepacrine to assure a good control of SLE activity, and also a durable and safe use of these essential drugs for the management of SLE.