Evaluation in Our New Normal Environment: Navigating the Challenges with Data Collection

Background: Data collection is a critical component of all evaluations. However, it often presents a number of challenges under the best of circumstances. For instance, the evaluation budget and time frame both have implications for the quality and type of data that is collected. Additionally, adherence to high quality international ethical best practices is necessary when collecting data for any purpose, methodological rigor is important for ensuring the credibility of the evaluation, improving access to important documents and stakeholders, as well as decreasing excessive evaluation anxiety on the part of critical stakeholders, when possible, is vital. These challenges have now been considerably exacerbated by the COVID-19 global health pandemic which has changed our world in fundamental ways. In what is now considered as our new normal environment, evaluators will need to make profound changes to the manner in which they plan and undertake data collection. Objectives: This paper examines the many and varied challenges that will be encountered with data collection in our new normal environment. This new normal has had an impact on evaluation practices in all countries, developed and developing, and has significantly amplified existing challenges in countries with limited evaluation culture, budgets, technological coverage, access, and connectivity. It makes an important contribution to the literature since data collection has historically and traditionally been conducted using primarily face-to-face field work and through the freedom of movement of people to undertake this task. Setting: Not applicable. Intervention: Not applicable. Research Design: Desk review was utilized for the preparation of this paper. Findings: Evaluators need to be extremely flexible, innovative, and amendable to different approaches to data collections as our new normal environment will likely be with us for a while. This pandemic has thrown everyone a very painful curveball and introduced significant new work-related challenges for a myriad of work types and work environments. Innovation and the willingness to learn new methods have become an important necessity to help with learning, accountability, transparency. The COVID-19 pandemic has highlighted the plight of the most vulnerable and evidence-based data is the only means to assist this group. Evaluators must rise to the challenge, devise new ways to collect data that is credible and useful, and continue to promote the importance and benefits of the field of evaluation. As such, evaluators have an important role to play in the global economic recovery efforts. Keywords: budgets, challenges; COVID-19; data collection; evaluation; evaluators; new normal environment; time fram

Mimicking native display of cd0873 on liposomes augments its potency as an oral vaccine against clostridioides difficile

Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally to hamsters induces neutralising antibodies locally as well as systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was to determine whether displaying CD0873 on liposomes, mimicking native presentation, would drive a stronger antibody response. The recombinant form we previously tested resembles the naturally cleaved lipoprotein commencing with a cysteine but lacking lipid modification. A synthetic lipid (DHPPA-Mal) was designed for conjugation of this protein via its N-terminal cysteine to the maleimide headgroup. DHPPA-Mal was first formulated with liposomes to produce MalLipo; then, CD0873 was conjugated to headgroups protruding from the outer envelope to generate CD0873-MalLipo. The immunogenicity of CD0873-MalLipo was compared to CD0873 in hamsters. Intestinal sIgA and CD0873-specific serum IgG were induced in all vaccinated animals; however, neutralising activity was greatest for the CD0873-MalLipo group. Our data hold great promise for development of a novel oral vaccine platform driving intestinal and systemic immune responses

Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses

IntroductionVaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood.Methods and resultsHere, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV.DiscussionTherefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.</p

Mice Deficient in T-bet Form Inducible NO Synthase-Positive Granulomas That Fail to Constrain Salmonella.

Clearance of intracellular infections caused by Salmonella Typhimurium (STm) requires IFN-γ and the Th1-associated transcription factor T-bet. Nevertheless, whereas IFN-γ-/- mice succumb rapidly to STm infections, T-bet-/- mice do not. In this study, we assess the anatomy of immune responses and the relationship with bacterial localization in the spleens and livers of STm-infected IFN-γ-/- and T-bet-/- mice. In IFN-γ-/- mice, there is deficient granuloma formation and inducible NO synthase (iNOS) induction, increased dissemination of bacteria throughout the organs, and rapid death. The provision of a source of IFN-γ reverses this, coincident with subsequent granuloma formation and substantially extends survival when compared with mice deficient in all sources of IFN-γ. T-bet-/- mice induce significant levels of IFN-γ- after challenge. Moreover, T-bet-/- mice have augmented IL-17 and neutrophil numbers, and neutralizing IL-17 reduces the neutrophilia but does not affect numbers of bacteria detected. Surprisingly, T-bet-/- mice exhibit surprisingly wild-type-like immune cell organization postinfection, including extensive iNOS+ granuloma formation. In wild-type mice, most bacteria are within iNOS+ granulomas, but in T-bet-/- mice, most bacteria are outside these sites. Therefore, Th1 cells act to restrict bacteria within IFN-γ-dependent iNOS+ granulomas and prevent dissemination

Evaluation in Our New Normal Environment: Navigating the Challenges with Data Collection

Background: Data collection is a critical component of all evaluations. However, it often presents a number of challenges under the best of circumstances. For instance, the evaluation budget and time frame both have implications for the quality and type of data that is collected. Additionally, adherence to high quality international ethical best practices is necessary when collecting data for any purpose, methodological rigor is important for ensuring the credibility of the evaluation, improving access to important documents and stakeholders, as well as decreasing excessive evaluation anxiety on the part of critical stakeholders, when possible, is vital. These challenges have now been considerably exacerbated by the COVID-19 global health pandemic which has changed our world in fundamental ways. In what is now considered as our new normal environment, evaluators will need to make profound changes to the manner in which they plan and undertake data collection. Objectives: This paper examines the many and varied challenges that will be encountered with data collection in our new normal environment. This new normal has had an impact on evaluation practices in all countries, developed and developing, and has significantly amplified existing challenges in countries with limited evaluation culture, budgets, technological coverage, access, and connectivity. It makes an important contribution to the literature since data collection has historically and traditionally been conducted using primarily face-to-face field work and through the freedom of movement of people to undertake this task. Setting: Not applicable. Intervention: Not applicable. Research Design: Desk review was utilized for the preparation of this paper. Findings: Evaluators need to be extremely flexible, innovative, and amendable to different approaches to data collections as our new normal environment will likely be with us for a while. This pandemic has thrown everyone a very painful curveball and introduced significant new work-related challenges for a myriad of work types and work environments. Innovation and the willingness to learn new methods have become an important necessity to help with learning, accountability, transparency. The COVID-19 pandemic has highlighted the plight of the most vulnerable and evidence-based data is the only means to assist this group. Evaluators must rise to the challenge, devise new ways to collect data that is credible and useful, and continue to promote the importance and benefits of the field of evaluation. As such, evaluators have an important role to play in the global economic recovery efforts. Keywords: budgets, challenges; COVID-19; data collection; evaluation; evaluators; new normal environment; time fram

Bordetella pertussis isolates vary in their interactions with human complement components

Contains fulltext : 191888.pdf (publisher's version ) (Open Access

Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains.

Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn

Mice deficient in T-bet form inducible NO synthase-positive granulomas that fail to constrain Salmonella

Clearance of intracellular infections caused by Salmonella Typhimurium (STm) requires IFN-γ and the Th1-associated transcription factor T-bet. Nevertheless, whereas IFN-γ-/- mice succumb rapidly to STm infections, T-bet-/- mice do not. In this study, we assess the anatomy of immune responses and the relationship with bacterial localization in the spleens and livers of STm-infected IFN-γ-/- and T-bet-/- mice. In IFN-γ-/- mice, there is deficient granuloma formation and inducible NO synthase (iNOS) induction, increased dissemination of bacteria throughout the organs, and rapid death. The provision of a source of IFN-γ reverses this, coincident with subsequent granuloma formation and substantially extends survival when compared with mice deficient in all sources of IFN-γ. T-bet-/- mice induce significant levels of IFN-γ- after challenge. Moreover, T-bet-/- mice have augmented IL-17 and neutrophil numbers, and neutralizing IL-17 reduces the neutrophilia but does not affect numbers of bacteria detected. Surprisingly, T-bet-/- mice exhibit surprisingly wild-type-like immune cell organization postinfection, including extensive iNOS+ granuloma formation. In wild-type mice, most bacteria are within iNOS+ granulomas, but in T-bet-/- mice, most bacteria are outside these sites. Therefore, Th1 cells act to restrict bacteria within IFN-γ-dependent iNOS+ granulomas and prevent dissemination