Mefloquine Is Highly Efficacious against Chloroquine-Resistant Plasmodium vivax Malaria and Plasmodium falciparum Malaria in Papua, Indonesia

Abstract

Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chlo-roquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n 30), doxycycline (100 mg every 12 hours [7 days], n 20), or chloroquine with doxycycline (n 39); corresponding numbers for vivax malaria (n 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/ RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloro-quine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.

Neglect of Plasmodium vivax malaria

“…Survey work in Turkey [44,45] and in Vietnam [46] showed moderate levels of resistance (15% and 22% failure, respectively). A recent study in northeastern Indonesian New Guinea, where failure for CQ alone approaches 100%, showed only 18% failure when CQ was supplemented with PQ [47]. Surveys from South America show from no resistance to low levels of resistance [48,49].…”

“…Mefloquine (MQ) combined with PQ was effective in Papua, Indonesia (98% efficacy) [47], and CQ combined with PQ was much more effective than CQ alone [47,54]. Some work in primate models also showed good efficacy of both MQ and the experimental 8-aminoquinoline, tafenoquine [57][58][59].…”

Current therapies and future possibilities for drug development against liver-stage malaria

“…Unfortunately, resistance to sulfadoxine-pyrimethamine is now widespread, a widespread resistance to CQ, P. vivax remains sensitive to this treatment in most endemic regions. Mefloquine (MQ) is a quinine derivative agent that is active against the blood stages of P. falciparum and P. vivax infection (11). Its mechanism of action is still poorly understood; however, it is proposed to act through inhibition of hemoglobin endocytosis in Plasmodium parasites (12).…”

Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors

“…4 Mefloquine and QNX have been shown to be efficacious in CQ-resistant malaria. 7,11,28,33,41 Quinine, MFQ, and QNX have demonstrated the ability to penetrate the blood-brain barrier; therefore, QN and MFQ are effectively used to treat malaria-causing parasites that have entered the central nervous system. 3,5,21,22,32 In addition to targeting the AFVs of P. falciparum, CQ has recently received attention for its antitumor effects, where it was shown to accumulate in the lysosomes of tumor cells, blocking autophagy and preventing the degradation of autophagosomal content.…”