Comparing Methods to Genetically Engineer Bacteriophage and Increase Host Range.

INTRODUCTION: Antibacterial resistance is an emerging problem in military medicine. Disruptions to the health care systems in war-torn countries that result from ongoing conflict can potentially exacerbate this problem and increase the risk to U.S. forces in the deployed environment. Therefore, novel therapies are needed to mitigate the impact of these potentially devastating infections on military operations. Bacteriophages are viruses that infect and kill bacteria. They can be delivered as therapeutic agents and offer a promising alternative to traditional antibiotic chemotherapy. There are several potential benefits to their use, including high specificity and comparative ease of use in the field setting. However, the process of engineering phages for military medical applications can be a laborious and time-consuming endeavor. This review examines available techniques and compares their efficacy. MATERIALS AND METHODS: This review evaluates the scientific literature on the development and application of four methods of bacteriophage genome engineering and their consideration in the context of military applications. Preffered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for a systematic review of available literature that met criteria for analysis and inclusion. The research completed for this review article originated from the United States Military Academy's library "Scout" search engine, which compiles results from 254 available databases (including PubMed, Google Scholar, and SciFinder). Particular attention was focused on identifying useful mechanistic insight into the nature of the engineering technique, the ease of use, and the applicability of the technique to countering the problem of antimicrobial resistance in the military setting. RESULTS: A total of 52 studies were identified that met inclusion criteria following PRISMA guidelines. The bioengineering techniques analyzed included homologous recombination (12 articles), in vivo recombineering (9 articles), bacteriophage recombineering of electroporated DNA (7 articles), and the CRISPR-Cas system (10 articles). Rates of success and fidelity varied across each platform, and comparative benefits and drawbacks are considered. CONCLUSIONS: Each of the phage engineering techniques addressed herein varies in amount of effort and overall success rate. CRISPR-Cas-facilitated modification of phage genomes presents a highly efficient method that does not require a lengthy purification and screening process. It therefore appears to be the method best suited for military medical applications.

HPV Vaccine Usage Among the U.S. Military Academy Corps of Cadets (2018-2025).

INTRODUCTION: Human papillomavirus (HPV) is a common sexually transmitted virus that infects over 13 million people every year. Over 80% of sexually active adults will acquire HPV at some point in their lives, which is concerning since certain high-risk strains of HPV can cause six types of cancer. Vaccination against HPV is safe and effective, but despite high vaccine efficacy, vaccination rates are low among both service members and civilians. MATERIALS AND METHODS: We conducted a retrospective, cross-sectional study to identify the percentage of United States Military Academy (USMA) Cadets who had received at least one HPV vaccine and those who completed the vaccine series. Deidentified vaccination and demographic data were retrieved from the Defense Health Agency Military Health System Data Repository (MDR) for all Cadets who were enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025). To identify the population of Cadets for our study and confirm presence of "any" vaccine in the MDR, Tdap vaccination information was also retrieved. The study population was defined as any Cadet who was enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025) and had record of an HPV and/or Tdap vaccine in the MDR. We compared demographic information between the identified population and known demographics of the USMA population to confirm that the retrieved data were consistent with population demographics. Descriptive statistics were performed to identify demographic differences based on vaccinated and unvaccinated Cadets and to determine the percentage of Cadets who received at least one HPV vaccine. Vaccine series completion was defined as the receipt of three HPV vaccine doses among those who reported receiving at least one dose of HPV vaccine or two doses if vaccinated before the age 15. RESULTS: A total of 9,567 Cadets were assessed for eligibility with 9,433 having Tdap and/or HPV vaccine on record. Of these Cadets, 5,738/9,433 (60.8%) had received at least one HPV vaccine. Of those starting the series, 4,492 completed the two- or three-dose series for a completion rate of 47.6%. We found HPV vaccine completion rate among female Cadets (55.6%) is higher than that of male Cadets (45.2%). More Cadets from minority groups received one vaccine; however, full completion rates were similar for both the groups (48.1%). In contrast, the percentage of Cadets vaccinated against Tdap was 97.2%. Most of those vaccinated received their first vaccine between the ages of 11 and 15 (53.0%) and their final vaccine after they turned 16 (68.9%). CONCLUSION: Though the vaccination rate among the Corps of Cadets is comparable to the public, it is still less than the 80.0% goal set by the Healthy People 2030 objective. Based on these results, we recommend that the USMA modify its policy on HPV vaccine administration to encourage more vaccine uptake. We also conclude that further studies on the rationale for avoiding the vaccine are necessary to better inform educational campaigns and mitigate stigma.