Atovaquone and Proguanil for the Treatment of Malaria in Brazil

Abstract

The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000 -100,000 ring forms/mL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil. . Written informed consent was obtained from all subjects, and the ethical ferent regimens raises the cost and the chance of side effects guidelines for Universidade de São Paulo and Walter Reed Army Institute of and leads to poor compliance. The development of new Research were followed. drugs is costly and slow (relative to the development of para-

Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group.

“…[1][2][3][4][5][6][7][8][9][10] These studies enrolled 1,395 patients with Plasmodium falciparum malaria and 32 patients with non-falciparum malaria, including 278 females and 200 children Յ 12 years of age. Four uncontrolled studies evaluated 397 patients.…”

No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate–Mefloquine in Northwestern Brazil

“…Between 2001 and 2007, uncomplicated falciparum malaria in Brazil was treated with quinine plus doxycycline (formerly tetracycline) for 7 days or a single MQ dose (15 mg/kg). 3 Clinical surveillance in the late 1990s revealed cure rates of 98.9% for MQ 4 and between 77.3% and 100% for quinine plus tetracycline 5,6 in northern Mato Grosso, central Brazil, despite emerging evidence for quinine 7 and MQ 8 resistance in vitro. The main P. falciparum transmission hotspot in the Amazon basin of Brazil is Juruá Valley, close to the border with Peru.…”

Prophylactic activity of atovaquone against Plasmodium falciparum in humans.

“…Instead it is now formulated in fixed combination with proguanil, with which it is synergistic (Malarone; Glaxo Wellcome, Inc., Research Triangle Park, NC). 11,12 Ample clinical evidence indicates that atovaquone and proguanil, individually or in combination, act against erythrocytic falciparum parasites, 11,[13][14][15][16] and that proguanil alone has activity against exoerythrocytic stages. 17 Although atovaquone affects P. berghei in cultured hepatocytes 18 and in rats, 19 no study has addressed the question of whether atovaquone itself has causal activity against P. falciparum.…”