Parents' and caregivers' role toward childhood vaccination in Albania: assessment of predictors of vaccine hesitancy.

Background: Vaccination has saved millions of lives through the protection of individuals and populations from communicable diseases. Vaccine hesitancy, defined as the delay in acceptance or refusal of vaccines despite the availability of vaccination services, has become a growing global concern. The objective of this study was to investigate parents'/caregivers' hesitancy toward childhood vaccination and its predictors in Albania. Study design: A cross-sectional survey was conducted. Methods: The data comes from a survey conducted on a sample of parents/caregivers (89.6% mothers) of children aged 6 months to 8 years at health care vaccination centers in seven Albanian cities from December 2020 to February 2021. Parents/caregivers (one per child) were interviewed by trained healthcare staff using a standardized questionnaire on six main content domains, including immunization behavior, beliefs about vaccine safety and efficacy, attitudes about vaccines, vaccination confidence, estimation of vaccine delay, and the intention to immunize children against SARS-CoV-2, and a self-reported hesitancy. The Albanian Ministry of Health approved the questionnaire, after it was translated, validated and adapted to the local setting. Statistical analyses included independent sample t-tests (p<0.05) and a logistic regression (OR; 95% C.I.). Results: A total of 475 parents/caregivers of children aged from 6 months to 8 years, attending childhood vaccination in public health services, were interviewed. To the question "how hesitant you are about childhood vaccination", a high number of parents/caregivers (46%) responded that they do not feel hesitant at all, and 32% were not hesitant, a small number of parents/caregivers said they are very hesitant (5%) or somewhat hesitant (12%). A binary logistic model was fitted to the data to test the hypothesis regarding the relationship between parental vaccine hesitancy and possible predictors. A lower parental attitude toward childhood vaccines (OR = 3.7; 95% C.I. 1.102-12.421), a health center with a high vaccine delay (OR = 2.878; C.I. 95% 1.735-4.773), and low confidence in health staff information (OR = 2.042; 95% C.I. 1.156-3.605) were all independent predictors of parental vaccine hesitancy. Regarding intention to vaccinate children against COVID-19, when available, nearly 75% of parents/caregivers showed hesitancy. Conclusions: Our results highlighted the role of positive parents'/caregivers' attitudes toward childhood vaccines followed by high staff confidence and good health center organization in order to deal with vaccine hesitancy, particularly for traditional and well-known childhood vaccines. Nevertheless, the hesitancy can be a critical barrier for childhood vaccination when we have to introduce a new vaccine, as is demonstrated in the recent vaccination campaign against the ongoing pandemic of SARS-CoV2.

The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis.

Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development. DLST is the E2 transferase of the α-ketoglutarate (α-KG) dehydrogenase complex (KGDHC), which converts α-KG to succinyl-CoA in the TCA cycle. RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of α-KG and a decrease of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy.

Critical interplay between parasite differentiation, host immunity, and antigenic variation in trypanosome infections.

Increasing availability of pathogen genomic data offers new opportunities to understand the fundamental mechanisms of immune evasion and pathogen population dynamics during chronic infection. Motivated by the growing knowledge on the antigenic variation system of the sleeping sickness parasite, the African trypanosome, we introduce a mechanistic framework for modeling within-host infection dynamics. Our analysis focuses first on a single parasitemia peak and then on the dynamics of multiple peaks that rely on stochastic switching between groups of parasite variants. A major feature of trypanosome infections is the interaction between variant-specific host immunity and density-dependent parasite differentiation to transmission life stages. In this study, we investigate how the interplay between these two types of control depends on the modular structure of the parasite antigenic archive. Our model shows that the degree of synchronization in stochastic variant emergence determines the relative dominance of general over specific control within a single peak. A requirement for multiple-peak dynamics is a critical switch rate between blocks of antigenic variants, which implies constraints on variant surface glycoprotein (VSG) archive genetic diversification. Our study illustrates the importance of quantifying the links between parasite genetics and within-host dynamics and provides insights into the evolution of trypanosomes.