title: Atovaquone-Proguanil Remains a Potential Stopgap Therapy for Multidrug-Resistant Plasmodium falciparum in Areas along the Thai-Cambodian Border.
abstract: Our recent report of dihydroartemisinin-piperaquine failure to treat Plasmodium falciparum infections in Cambodia adds new urgency to the search for alternative treatments. Despite dihydroartemisinin-piperaquine failure, and higher piperaquine 50% inhibitory concentrations (IC50s) following reanalysis than those previously reported, P. falciparum remained sensitive to atovaquone (ATQ) in vitro. There were no point mutations in the P. falciparum cytochrome b ATQ resistance gene. Mefloquine, artemisinin, chloroquine, and quinine IC50s remained comparable to those from other recent reports. Atovaquone-proguanil may be a useful stopgap but remains susceptible to developing resistance when used as blood-stage therapy.
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand david.saunders.mil@afrims.org.
authors.forename: David L
authors.initials: DL
authors.lastname: Saunders
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Suwanna
authors.initials: S
authors.lastname: Chaorattanakawee
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Panita
authors.initials: P
authors.lastname: Gosi
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lanteri
authors.affiliation: Royal Cambodian Armed Forces, Phnom Penh, Cambodia.
authors.forename: Sok
authors.initials: S
authors.lastname: Somethy
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Worachet
authors.initials: W
authors.lastname: Kuntawunginn
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Mali
authors.initials: M
authors.lastname: Ittiverakul
authors.affiliation: USAMC-AFRIMS, Phnom Penh, Cambodia.
authors.forename: Soklyda
authors.initials: S
authors.lastname: Chann
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Carrie
authors.initials: C
authors.lastname: Gregory
authors.affiliation: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
authors.forename: Char Meng
authors.initials: CM
authors.lastname: Chuor
authors.affiliation: Royal Cambodian Armed Forces, Phnom Penh, Cambodia.
authors.forename: Satharath
authors.initials: S
authors.lastname: Prom
authors.affiliation: U.S. Army Medical Component-Armed Forces Research Institute for Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
authors.forename: Michele D
authors.initials: MD
authors.lastname: Spring
authors.affiliation: USAMC-AFRIMS, Phnom Penh, Cambodia.
authors.forename: Chanthap
authors.initials: C
authors.lastname: Lon
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D053626:Atovaquone / Q000627:therapeutic use*; D001483:Base Sequence; D002160:Cambodia; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002727:Proguanil / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D013785:Thailand; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D053626:Atovaquone; D016054:DNA, Protozoan; D004338:Drug Combinations; D002727:Proguanil; D011804:Quinolines; C109496:atovaquone, proguanil drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines