Exploring perspectives on antimicrobial stewardship: a qualitative study of health managers in Kenya.

BACKGROUND: Antimicrobial resistance is a significant public health concern with the establishment of antimicrobial stewardship in hospitals being increasingly obligatory. Perspectives and insights of health managers on antimicrobial stewardship (AMS), complementary health services and building blocks are imperative towards implementation of robust AMS programs. This study aimed to understand perspectives of hospital managers on AMS and identify areas of management engagement while addressing potential blockades to change. METHODS: A cross-sectional, qualitative, multicenter study was conducted in three hospitals in Kenya. Key-informant interviews on perspectives on AMS were administered to hospital managers. Qualitative data was captured using audio tapes and field notes, transcribed and managed using NVivo 12 software. An iterative process was used to develop the thematic framework and updated in two rounds of iteration analysis. Analysis charts for each emergent theme were developed and categorized across all participants. RESULTS: Perspectives on AMS are described in five thematic categories; Importance of antimicrobial stewardship and the role of medicines and therapeutics committee, availability of antimicrobial formulary and usage surveillance systems, laboratory competency and recommendations for infection prevention and management, educational resources and communications channels available, building blocks and low-lying fruits for Antimicrobial Stewardship Committees. The role of stewardship collaboration in diagnosis and antimicrobial prescription was alluded to with managers indicating a growing rise in occurrence of antimicrobial resistance. There lacked contextualized, hospital specific antimicrobial formulary and adequate laboratory competency. Staff training and communication channels were available in varying capacity across the three hospitals. Building blocks identified include medicines and therapeutics committee, education, and training platforms (Continuous Medical Education and Continuous Professional Development activities) and hospital leadership commitment. CONCLUSIONS: The practice of antimicrobial stewardship is not implemented and well developed as demonstrated by lack of core AMS complementary health services. However, the health managers are aware of the fundamental importance of antimicrobial stewardship programs and the vast benefits of implementation and institutionalization of AMS to hospitals and their clients. The findings underpin the importance of understanding and incorporating perspectives of health managers on existing contextual mechanisms that can be leveraged on to establish robust AMS programs in the fight against antimicrobial resistance.

Modulation of immune responses by Plasmodium falciparum infection in asymptomatic children living in the endemic region of Mbita, western Kenya.

Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear why a long period is required to gain clinical immunity to malaria, and how such immunity is maintained. Although malaria infection is reported to induce inhibition of immune responses, studies on asymptomatic individuals living in endemic regions of malaria are relatively scarce. We conducted a cross-sectional study of immune responses in asymptomatic school children aged 4-16years living in an area where Plasmodium falciparum and Schistosoma mansoni infections are co-endemic in Kenya. Peripheral blood mononuclear cells were subjected to flow cytometric analysis and cultured to determine proliferative responses and cytokine production. The proportions of cellular subsets in children positive for P. falciparum infection at the level of microscopy were comparable to the negative children, except for a reduction in central memory-phenotype CD8+ T cells and natural killer cells. In functional studies, the production of cytokines by peripheral blood mononuclear cells in response to P. falciparum crude antigens exhibited strong heterogeneity among children. In addition, production of IL-2 in response to anti-CD3 and anti-CD28 monoclonal antibodies was significantly reduced in P. falciparum-positive children as compared to -negative children, suggesting a state of unresponsiveness. These data suggest that the quality of T cell immune responses is heterogeneous among asymptomatic children living in the endemic region of P. falciparum, and that the responses are generally suppressed by active infection with Plasmodium parasites.

Subcellular dissemination of prothymosin alpha at normal physiology: immunohistochemical vis-a-vis western blotting perspective.

BACKGROUND: The cell type, cell status and specific localization of Prothymosin α (PTMA) within cells seemingly determine its function. PTMA undergoes 2 types of protease proteolytic modifications that are useful in elucidating its interactions with other molecules; a factor that typifies its roles. Preferably a nuclear protein, PTMA has been shown to function in the cytoplasm and extracellularly with much evidence leaning on pathognomonic status. As such, determination of its cellular distribution under normal physiological context while utilizing varied techniques is key to illuminating prospective validation of its distinct functions in different tissues. Differential distribution insights at normal physiology would also portent better basis for further clarification of its interactions and proteolytic modifications under pathological conditions like numerous cancer, ischemic stroke and immunomodulation. We therefore raised an antibody against the C terminal of PTMA to use in tandem with available antibody against the N terminal in a murine model to explicate the differences in its distribution in brain cell types and major peripheral organs through western blotting and immunohistochemical approaches. RESULTS: The newly generated antibody was applied against the N-terminal antibody to distinguish truncated versions of PTMA or deduce possible masking of the protein by other interacting molecules. Western blot analysis indicated presence of a truncated form of the protein only in the thymus, while immunohistochemical analysis showed that in brain hippocampus the full-length PTMA was stained prominently in the nucleus whereas in the stomach full-length PTMA staining was not observed in the nucleus but in the cytoplasm. CONCLUSION: Truncated PTMA could not be detected by western blotting when both antibodies were applied in all tissues examined except the thymus. However, immunohistochemistry revealed differential staining by these antibodies suggesting possible masking of epitopes by interacting molecules. The differential localization patterns observed in the context of nucleic versus cytoplasmic presence as well as punctate versus diffuse pattern in tissues and cell types, warrant further investigations as to the forms of PTMA interacting partners.