COVID-19 Vaccine Hesitancy among Healthcare Workers and Trainees in Freetown, Sierra Leone: A Cross-Sectional Study.

Despite having safe and efficacious vaccines against COVID-19, vaccine hesitancy is widespread. Although a trusted source of information, vaccine hesitancy has been reported among healthcare professionals, yet few studies have explored this phenomenon in sub-Saharan Africa. We conducted a cross-sectional survey of healthcare professionals in Sierra Leone from January to March 2022. Measures included sociodemographic/health-related information and COVID-19-related concerns. From the responses, we constructed a hesitancy (VAX) score, with higher scores implying negative attitudes or unwillingness to vaccinate. Multivariate linear regression was used to access factors associated with vaccine hesitancy. Overall, 592 participants submitted responses (67.2% female, mean age 29 years, 5.6% physicians/pharmacists, 44.3% medical students, 29.2% nurses, 20.9% nursing students). The mean VAX score was 43.27 ± 8.77, with 60.1% of respondents classified as vaccine hesitant (>50th percentile) and 13.8% as highly hesitant (>75th percentile). Worries about unforeseen future effects (76.3%), a preference for natural immunity (59.5%), and profiteering/mistrust of health authorities (53.1%) were the most common concerns. Being a medical student (β = 0.105, p = 0.011) and previously refusing a recommended vaccine (β = 0.177, p < 0.001) were predictors of COVID-19 vaccine hesitancy. Our findings call for addressing vaccine hesitancy among healthcare professionals as an essential component of strategies aimed at increasing COVID-19 vaccine uptake in this setting

Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess

The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jα18-/- mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using α-galactosylceramide (α-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d−/− mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-γ but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28∶0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-γ production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to α-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess

Entamoeba lysyl-tRNA Synthetase Contains a Cytokine-Like Domain with Chemokine Activity towards Human Endothelial Cells

Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity