Malaria parasites within red blood cells digest host hemoglobin into a hydrophobic heme polymer, known as hemozoin (HZ), which is subsequently released into the blood stream and then captured by and concentrated in the reticulo-endothelial system. Accumulating evidence suggests that HZ is immunologically active, but the molecular mechanism(s) through which HZ modulates the innate immune system has not been elucidated. This work demonstrates that HZ purified from Plasmodium falciparum is a novel non-DNA ligand for Toll-like receptor (TLR)9. HZ activated innate immune responses in vivo and in vitro, resulting in the production of cytokines, chemokines, and up-regulation of costimulatory molecules. Such responses were severely impaired in TLR9−/− and myeloid differentiation factor 88 (MyD88)−/−, but not in TLR2, TLR4, TLR7, or Toll/interleukin 1 receptor domain–containing adaptor-inducing interferon β−/− mice. Synthetic HZ, which is free of the other contaminants, also activated innate immune responses in vivo in a TLR9-dependent manner. Chloroquine (CQ), an antimalarial drug, abrogated HZ-induced cytokine production. These data suggest that TLR9-mediated, MyD88-dependent, and CQ-sensitive innate immune activation by HZ may play an important role in malaria parasite–host interactions.

Parental vaccine hesitancy is becoming an increasingly important public health concern in the United States. In March 2020, an assessment of the latest CDC National Immunization Survey data found that more than one-third of U.S. children between the ages of 19 and 35 months were not following the recommended early childhood immunization schedule. Furthermore, a 2019 national survey found that approximately 1 in 4 parents reported serious concerns towards vaccinating their children. Vaccine hesitancy is now associated with a decrease in vaccine coverage and an increase in vaccine-preventable disease outbreaks and epidemics in the United States. Many studies have focused on understanding and defining the new socio-medical term, vaccine hesitancy; few have attempted to summarize past and current health communication interventions and strategies that have been successful or unsuccessful in tackling this growing phenomenon. This systematic literature review will attempt to aid public health professionals with a catalogue of health communication interventions and strategies to ultimately address and prevent parental vaccine hesitancy in the long term. Out of 1239 search results, a total of 75 articles were included for analysis, ranging from systematic reviews, quantitative surveys, and experimental designs to ethnographic and qualitative studies. For the presentation of results, a taxonomy was used to organize communication interventions according to their intended purpose. The catalogue of interventions was further broken down into specific components and themes that were identified in the literature as essential to either the success or failure in preventing and addressing parental vaccine hesitancy towards childhood vaccines.

Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for Plasmodium falciparum malaria. It has been suggested that the cytotoxic effect of artemisinin is mediated by free radicals followed by the alkylation of P. falciparum proteins. The endoperoxide bridge, the active moiety of artemisinin derivatives, is cleaved in the presence of ferrous iron, generating reactive oxygen species (ROS) and other free radicals. However, the emergence of resistance to artemisinin in P. falciparum underscores the need for new insights into the molecular mechanisms of antimalarial activity of artemisinin. Here we show that artesunate (ART) induces DNA double-strand breaks in P. falciparum in a physiologically relevant dose-and time-dependent manner. DNA damage induced by ART was accompanied by an increase in the intracellular ROS level in the parasites. Mannitol, a ROS scavenger, reversed the cytotoxic effect of ART and reduced DNA damage, and modulation of glutathione (GSH) levels was found to impact ROS and DNA damage induced by ART. Accumulation of ROS, increased DNA damage, and the resulting antiparasite effect suggest a causal relationship between ROS, DNA damage, and parasite death. Finally, we also show that ARTinduced ROS production involves a potential role for NADPH oxidase, an enzyme involved in the production of superoxide anions. Our results with P. falciparum provide novel insights into previously unknown molecular mechanisms underlying the antimalarial activity of artemisinin derivatives and may help in the design of next-generation antimalarial drugs against the most virulent Plasmodium species.