Atovaquone-Proguanil: Report From the CDC Expert Meeting on Malaria Chemoprophylaxis (Ii)

Abstract

The fixed dose combination of atovaquone and proguanil hydrochloride, marketed under the trade name Malarone, is the most recently approved agent in North America for the prevention and treatment of chloroquine- and multi-drug resistant Plasmodium falciparum malaria. In both adult and pediatric populations, atovaquone-proguanil demonstrates consistently high protective efficacy against P. falciparum, and in treatment trials, cure rates exceed 93%. Only a handful of genetically confirmed treatment failures have been reported to date. Atovaquone-proguanil has an excellent safety profile during both prophylaxis and treatment courses, with severe adverse events rarely reported. This topical review will examine the evidence behind the current indications for use of atovaquone-proguanil, and will summarize the current body of literature surrounding safety and tolerability.

Family Compliance With Counseling for Children Traveling to the Tropics

“…11 The 66% malaria chemoprophylaxis compliance is consistent with other studies. [12][13][14] Reasons previously reported for poor compliance are destination 15,16 and young age 14,17,18 (as in our patients), as well as purpose of the trip (VFR or tourism) and malaria prophylaxis tolerance 19 (neither significant in this study). In fact, VFR people are an extremely varied group.…”

Incidence of Malaria among Mosquito Collectors Conducting Human Landing Catches in Western Kenya

“…Chemoprophylaxis has been shown to be very effective in preventing malaria in non-immune travelers as well as in semi-immune populations living in malaria endemic areas. [9][10][11] Despite many attempts to find a suitable replacement for the HLC, [12][13][14] none have consistently proven to be as sensitive and as versatile as the HLC, and given the risks of malaria infection and illness, the use of the HLC remains controversial. Increasingly, ethical review committees are reluctant to approve studies that include the use of HLCs given the concern about increased risk of disease among collectors.…”

Antimalarial quinolones: Synthesis, potency, and mechanistic studies

“…The usefulness of these drugs has greatly diminished due to the spread of drug-resistant strains of both P. falciparum and P. vivax (White, 2004, White, et al, 1999 throughout malarious regions of the world. Consequently, therapeutic options for treatment of malaria are dwindling and replacement drugs, the endoperoxide artesunate (Ashley and White, 2005, Edwards and Biagini, 2006, Meshnick, 2002 [including its formulation with other drugs, i.e., "artemisinin combination therapies"] and the atovaquone -proguanil combination known as Malarone® (Boggild, et al, 2007), offer a rather thin wall of protection against a total collapse in malaria chemotherapy. As a result there is an urgent need for developing new and safe drugs for treating or preventing malaria.…”

“…A unique and defining feature of acridones optimized for antimalarial potency is the presence of an extended alkyl or alkoxy side chain that is terminated by one or more trifluoromethyl (CF 3 ) groups. While it may be assumed that such modification would enhance in vivo efficacy by blocking or hindering catabolism of the side chain by host P450 enzymes, the striking enhancement of in vitro potency suggests that the CF 3 groups are important in the antiplasmodial mode of action of the acridone constructs.…”