Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.
ABSTRACT Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii . We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
Abstract Background Novel strategies in medical education including the flipped classroom, test-enhanced learning, and gaming have proven to be effective for preclinical learners but little is known about their efficacy in post-graduate education. We implemented an educational tool in our Infectious Diseases (ID) Fellowship Training program called TACO (To Assess Cognitive Operations) Tuesday that utilizes aspects of the flipped classroom, test-enhanced learning, and gaming to improve ID fellow engagement, satisfaction, knowledge retention, and board examination preparation in association with a weekly ID core didactic curriculum. Methods One to three multiple choice clinical vignettes were emailed to ID fellows the day prior to their weekly didactic lecture. The first fellow to answer all questions correctly was the winner for the week. The correct answer choices along with detailed rationales were distributed to all fellows at the end of the week. After one year of using this educational tool, we surveyed fellows to evaluate its impact on their engagement with the weekly didactic sessions, self-perception of content retention, and sense of preparation for the ID board examination. Results We had a response rate of 82% with 9 of 11 fellows polled participating. Of those, two-thirds attempted to answer the multiple-choice questions prior to lecture and most (77%) reviewed the correct answer choices and rationales weekly. All participants felt the educational tool helped improve their engagement with the lectures and half felt it increased overall satisfaction with their educational experience. The majority felt the tool increased content retention and their level of preparation for the ID board examination. Implementation of this tool was associated with a higher mean IDSA in-training examination score compared with scores from the previous year (518 vs 469). Conclusion ID fellows found that an educational tool utilizing a flipped classroom, test-enhanced learning, and gaming in association with a weekly core didactic curriculum increased their engagement, satisfaction, knowledge retention, and board examination preparation. Future studies will investigate the impact of this tool on knowledge retention and ID board examination scores within our institution as well as across institutions. Disclosures All authors: No reported disclosures.
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus linked to devastating neurologic diseases. Immune responses to flaviviruses may be pathogenic or protective. Our understanding of human immune responses to ZIKV in vivo remains limited. Therefore, we performed a longitudinal molecular and phenotypic characterization of innate and adaptive immune responses during an acute ZIKV infection. We found that innate immune transcriptional and genomic responses were both cell type- and time-dependent. While interferon stimulated gene induction was common to all innate immune cells, the upregulation of important inflammatory cytokine genes was primarily limited to monocyte subsets. Additionally, genomic analysis revealed substantial chromatin remodeling at sites containing cell-type specific transcription factor binding motifs that may explain the observed changes in gene expression. In this dengue virus-experienced individual, adaptive immune responses were rapidly mobilized with T cell transcriptional activity and ZIKV neutralizing antibody responses peaking 6 days after the onset of symptoms. Collectively this study characterizes the development and resolution of an in vivo human immune response to acute ZIKV infection in an individual with pre-existing flavivirus immunity.
