bArtemisinin derivatives are used in combination with other antimalarial drugs for treatment of multidrug-resistant malaria worldwide. Clinical resistance to artemisinin recently emerged in southeast Asia, yet in vitro phenotypes for discerning mechanism(s) of resistance remain elusive. Here, we describe novel phenotypic resistance traits expressed by artemisinin-resistant Plasmodium falciparum. The resistant parasites exhibit altered patterns of development that result in reduced exposure to drug at the most susceptible stage of development in erythrocytes (trophozoites) and increased exposure in the most resistant stage (rings). In addition, a novel in vitro delayed clearance assay (DCA) that assesses drug effects on asexual stages was found to correlate with parasite clearance half-life in vivo as well as with mutations in the Kelch domain gene associated with resistance (Pf3D7_1343700). Importantly, all of the resistance phenotypes were stable in cloned parasites for more than 2 years without drug pressure. The results demonstrate artemisinin-resistant P. falciparum has evolved a novel mechanism of phenotypic resistance to artemisinin drugs linked to abnormal cell cycle regulation. These results offer insights into a novel mechanism of drug resistance in P. falciparum and new tools for monitoring the spread of artemisinin resistance.A rtemisinin combination therapy (ACT) is the recommended treatment for multidrug-resistant malaria by the World Health Organization. These combinations rely on the fast-acting properties of the artemisinin derivative to rapidly clear parasites with the longer-acting partner drug clearing residual parasites, reducing the frequent observation of recrudescent infections when artemisinin drugs are used alone. Unfortunately, resistance to artemisinin derivatives has emerged in southeast Asia and now threatens the utility of the most important treatment options for Plasmodium falciparum malaria that is resistant to most antimalarial drugs. Clinical resistance to artemisinin is expressed as a reduced rate of parasite clearance from peripheral blood, resulting in a parasite clearance half-life of Ͼ5 h (1). Resistance to artemisinin is a heritable trait, linked to mutations in the Kelch propeller domains of Pf3D7_1343700, and it appears to be spreading in southeast Asia (1-3). Clearly, a public health disaster is looming if artemisinin resistance spreads globally, like the selective sweeps previously observed for chloroquine and pyrimethamine resistance (4-6).Despite the well-characterized phenotype of clinical resistance to artemisinin, resistance phenotypes in classical in vitro drug susceptibility assays, used successfully for other antimalarial drugs, have not been useful for detecting artemisinin resistance (7). Two modified in vitro assays have been used to assess resistance with some success (8, 9), with both assessing reduced susceptibility in the ring stage of development in erythrocytes; however, stable in vitro phenotypes in culture-adapted parasites remain elusive. Given the ...

Mpox was an emerging outbreak in California in 2022, primarily in major metropolitan areas, as part of the global mpox outbreak declared by World Health Organization in July 2022. Community hospitals outside of major metropolitan areas have seen fewer cases to date, so they may be less equipped to diagnose and treat patients with mpox. They may have limited public health resources commensurate with the area’s population density. Mpox may also be superimposed on ongoing local outbreaks of other sexually transmitted infections. We present a case of a person with HIV who contracted mpox and also developed secondary syphilis. Early detection can be beneficial for prompt treatment, decreased burden of disease for the individual, and prevention of further spread of the infection.