Projecting vaccine demand and impact for emerging zoonotic pathogens.

BACKGROUND: Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response. METHODS: We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies to assess sustainable vaccine manufacturing needs, vaccine stockpile requirements, and the potential impact of the outbreak response. This framework incorporates geographically variable zoonotic spillover rates, human-to-human transmission, and the implementation of reactive vaccination campaigns in response to disease outbreaks. As proof of concept, we applied the framework to four priority pathogens: Lassa virus, Nipah virus, MERS coronavirus, and Rift Valley virus. RESULTS: Annual vaccine regimen requirements for a population-wide strategy ranged from > 670,000 (95% prediction interval 0-3,630,000) regimens for Lassa virus to 1,190,000 (95% PrI 0-8,480,000) regimens for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower (between 1/25 and 1/700) than those required by a population-wide strategy. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R0 values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination. CONCLUSIONS: Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios. Uncertainties in our model estimates highlight several knowledge gaps that need to be addressed to target vulnerable populations more accurately. These include surveillance gaps that mask the true geographic distribution of each pathogen, details of key routes of spillover from animal reservoirs to humans, and the role of human-to-human transmission outside of healthcare settings. In addition, our estimates are based on the current epidemiology of each pathogen, but pathogen evolution could alter vaccine stockpile requirements.

The association between fluoride in water and blood pressure in children and adolescents.

BACKGROUND: The objective of this study was to determine the association between water and plasma fluoride and blood pressure (BP) among children and adolescents. METHODS: Our study population was individuals of 8-18 years in the 2013-2016 National Health and Nutrition Examination Survey. We performed a multivariable linear and logistic regression analysis to examine the relationship between fluoride and BP. RESULTS: In a linear regression analysis for systolic BP (SBP) (mm Hg) adjusting for age, sex, race, and poverty, fluoride in water (mg/L) was significant with a coefficient of -0.44 (p = 0.046) among adolescents (12-18 years). Additional adjustments for race, poverty, serum levels of cotinine, and BMI remained significant. While an inverse relationship was found in children (8-11 years), none were significant. Fluoride in plasma was not significant across all ages. The odds ratio of high BP for an increase in water fluoride also was not significant. CONCLUSIONS: Higher concentrations of fluoride in water were associated with low SBP only among adolescents. Fluoride alone cannot be responsible for BP as several biological metabolic processes may influence its physiological effects. Fluoride consumption should be considered in conjunction with these processes. IMPACT: The high fluoride in drinking water was statistically significantly associated with low systolic BP in children and adolescents. The odds ratio of high BP for an increase in fluoride in drinking water was not significant. Our study contributes to the existing literature by providing individualized data and results on an individual level.