A G358S mutation in the Plasmodium falciparum Na⁺ pump PfATP4 confers clinically-relevant resistance to cipargamin

Diverse compounds target the Plasmodium falciparum Na(+) pump PfATP4, with cipargamin and (+)-SJ733 the most clinically-advanced. In a recent clinical trial for cipargamin, recrudescent parasites emerged, with most having a G358S mutation in PfATP4. Here, we show that PfATP4(G358S) parasites can withstand micromolar concentrations of cipargamin and (+)-SJ733, while remaining susceptible to antimalarials that do not target PfATP4. The G358S mutation in PfATP4, and the equivalent mutation in Toxoplasma gondii ATP4, decrease the sensitivity of ATP4 to inhibition by cipargamin and (+)-SJ733, thereby protecting parasites from disruption of Na(+) regulation. The G358S mutation reduces the affinity of PfATP4 for Na(+) and is associated with an increase in the parasite’s resting cytosolic [Na(+)]. However, no defect in parasite growth or transmissibility is observed. Our findings suggest that PfATP4 inhibitors in clinical development should be tested against PfATP4(G358S) parasites, and that their combination with unrelated antimalarials may mitigate against resistance development

Utilization of Traditional Chinese Medicine Practitioners in Later Life in Mainland China

Mainland China is one of the world’s most rapidly aging countries, and yet there is very limited literature on traditional Chinese medicine (TCM) use in older individuals. This study aimed to determine the national and provincial prevalence of TCM practitioner utilization in later life and associated factors. We used World Health Organization China Study on Global Aging and Adult Health Wave 1 data to determine descriptive statistics of the study population of participants aged 50 years and over. Multivariate logistic regression was conducted controlling for sociodemographic and health factors. A total of 14% of participants utilized a TCM practitioner, and the prevalence of utilization varied significantly by locality. Utilization was more likely in participants living in rural areas [adjusted odds ratio (OR) = 12.96; p < 0.001], Hubei (OR = 7.17; p < 0.001), or Shandong provinces (OR = 4.21; p < 0.001) and being diagnosed with chronic lung disease (OR = 1.97; p = 0.005). Hence, rurality, provincial influence, and chronic lung diseases are significant factors associated with TCM practitioner utilization among older individuals in China. These findings may inform policy for preservation and development of TCM nationally as well as its sustainability in an increasingly aging society