Enhancing Mission Wellness: Iterative Optimization and Stakeholder Engagement to Promote Sexual and Reproductive Health in the United States Military.

INTRODUCTION: Sexual and reproductive health is critical for the readiness of the warfighter, as costs of sexually transmitted infections and unintended pregnancy result in added health care costs, lost mission time, and impact on morale. The Multiphase Optimization Strategy (MOST) is an engineering-inspired framework used to optimize biobehavioral interventions. The Military Active-Duty Reproductive and Sexual Health (MARSH) research team applied the MOST framework to develop "Mission Wellness"-an electronic health intervention to promote sexual and reproductive health within the U.S. Military. MATERIALS AND METHODS: From 2017 to 2022, the MARSH team implemented the first and second phases of MOST to develop and optimize "Mission Wellness." All phases received institutional review board approval. The first phase consisted of expert and literature review, qualitative interviews, and beta testing to identify intervention components and the optimization objective and to inform study design. The second phase consisted of a factorial trial. RESULTS: Figures 1-4 outline the research program approach, demographics of the sample, and format of the app. Service members who used the application found it to be acceptable and, overall, reported that it would be easier to talk to a sexual partner about risk behaviors and history at the post-intervention assessment compared to baseline. This iterative optimization approach using both local and strategic engagement enhanced program development and set the stage for dissemination and implementation efforts. CONCLUSIONS: In line with the iterative nature of MOST, the lessons learned during the optimization trial led the MARSH team to return "Mission Wellness" to the preparation phase. The utilization of mixed (i.e., qualitative and quantitative) research methods and engagement with stakeholders at multiple levels of the military enterprise provided the information necessary to further optimize "Mission Wellness." This programmatic approach also provides a blueprint for the development of research design and testing in military health care balancing rigor and agility.

Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human Malaria Infection.

BACKGROUND: A live-attenuated Plasmodium falciparum sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same P. falciparum strain as in the vaccine). Using a more stringent CHMI, with heterologous parasites (different P. falciparum strain), we assessed the impact of higher PfSPZ doses, a novel multi-dose prime regimen, and a delayed vaccine boost upon vaccine efficacy (VE). METHODS: We immunized 4 groups that each contained 15 healthy, malaria-naive adults. Group 1 received 5 doses of 4.5 x 105 PfSPZ (Days 1, 3, 5, and 7; Week 16). Groups 2, 3, and 4 received 3 doses (Weeks 0, 8, and 16), with Group 2 receiving 9.0 × 105/doses; Group 3 receiving 18.0 × 105/doses; and Group 4 receiving 27.0 × 105 for dose 1 and 9.0 × 105 for doses 2 and 3. VE was assessed by heterologous CHMI after 12 or 24 weeks. Volunteers not protected at 12 weeks were boosted prior to repeat CHMI at 24 weeks. RESULTS: At 12-week CHMI, 6/15 (40%) participants in Group 1 (P = .04) and 3/15 (20%) participants in Group 2 remained aparasitemic, as compared to 0/8 controls. At 24-week CHMI, 3/13 (23%) participants in Group 3 and 3/14 (21%) participants in Group 4 remained aparasitemic, versus 0/8 controls (Groups 2-4, VE not significant). Postboost, 9/14 (64%) participants versus 0/8 controls remained aparasitemic (3/6 in Group 1, P = .025; 6/8 in Group 2, P = .002). CONCLUSIONS: Administering 4 stacked priming injections (multi-dose priming) resulted in 40% VE against heterologous CHMI, while dose escalation of PfSPZ using single-dose priming was not significantly protective. Boosting unprotected subjects improved VE at 24 weeks, to 64%. CLINICAL TRIALS REGISTRATION: NCT02601716.