Complex responses to movement-based disease control: when livestock trading helps

Livestock disease controls are often linked to movements between farms, for example, via quarantine and pre- or post-movement testing. Designing effective controls, therefore, benefits from accurate assessment of herd-to-herd transmission. Household models of human infections make use of R*, the number of groups infected by an initial infected group, which is a metapopulation level analogue of the basic reproduction number R0 that provides a better characterization of disease spread in a metapopulation. However, existing approaches to calculate R* do not account for individual movements between locations which means we lack suitable tools for livestock systems. We address this gap using next-generation matrix approaches to capture movements explicitly and introduce novel tools to calculate R* in any populations coupled by individual movements. We show that depletion of infectives in the source group, which hastens its recovery, is a phenomenon with important implications for design and efficacy of movement-based controls. Underpinning our results is the observation that R* peaks at intermediate livestock movement rates. Consequently, under movement-based controls, infection could be controlled at high movement rates but persist at intermediate rates. Thus, once control schemes are present in a livestock system, a reduction in movements can counterintuitively lead to increased disease prevalence. We illustrate our results using four important livestock diseases (bovine viral diarrhoea, bovine herpes virus, Johne's disease and Escherichia coli O157) that each persist across different movement rate ranges with the consequence that a change in livestock movements could help control one disease, but exacerbate another

Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy:Secondary analysis of data from a phase 3 randomised controlled trial

BACKGROUND: The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014. METHODS: Using data from 8922 African children aged 5-17 months and 6537 African infants aged 6-12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. FINDINGS: RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5-17 months than in those aged 6-12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6-12 weeks and higher immunogenicity in those aged 5-17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5-17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42-48) and that of the long-lived component was 591 days (557-632). After primary vaccination 12% (11-13) of the response was estimated to be long-lived, rising to 30% (28-32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98-153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity. INTERPRETATION: Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered. FUNDING: UK Medical Research Council

Greater male variability in daily energy expenditure develops through puberty

The authors also gratefully acknowledge funding from the Chinese Academy of Sciences (grant no. CAS153E11KYSB20190045) to J.R.S. and the US National Science Foundation (grant no. BCS-1824466) awarded to H.P. Acknowledgements Yvonne Schönbeck provided important information about morphometric measurements for Dutch children. A chat over dinner with Karsten Koehler, Eimear Dolan and Danny Longman brought up a number of thoughts that influenced this manuscript. The DLW database, which can be found at https://doublylabelled-waterdatabase.iaea.org/home, is hosted by the IAEA and generously supported by Taiyo Nippon Sanso and SERCON. We are grateful to the IAEA and these companies for their support and especially to Takashi Oono for his tremendous efforts at fundraising on our behalf.Peer reviewedPublisher PD

Variability in energy expenditure is much greater in males than females

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction. (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Total Daily Energy Expenditure Has Declined over the Past Three Decades Due to Declining Basal Expenditure, Not Reduced Activity Expenditure

Obesity is caused by prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes, is debated3,4. Here we used the IAEA DLW database on energy expenditure of adults in the USA and Europe (n = 4799) to explore patterns in total (TEE: n=4799), basal (BEE: n = 1432) and physical activity energy expenditure (AEE: n = 1432) over time. In both sexes total energy expenditure (TEE) adjusted for body composition and age declined with time, while adjusted AEE increased over time. In males adjusted BEE decreased significantly, but in females this didn’t reach significance. A larger dataset of basal metabolic rate (BMR equivalent to BEE) measurements of 9912 adults across 163 studies spanning 100 years replicated the decline in BEE in both sexes. Increasing obesity in the USA/Europe has probably not been fueled by reduced physical activity leading to lowered TEE. We identify here decline in adjusted BEE, as a previously unrecognized novel factor

Variation in human water turnover associated with environmental and lifestyle factors

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.acceptedVersio

Greater Male Variability in Daily Energy Expenditure Develops Through Puberty

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages

Energy compensation and adiposity in humans

Acknowledgments The DLW database, which can be found at https://doubly-labelled-water-database.iaea.org/home, is hosted by the IAEA and generously supported by Taiyo Nippon Sanso and SERCON. We are grateful to the IAEA and these companies for their support and especially to Takashi Oono for his tremendous efforts at fundraising on our behalf. The authors also gratefully acknowledge funding from the Chinese Academy of Sciences (CAS 153E11KYSB20190045) to J.R.S. and the US National Science Foundation (BCS-1824466) awarded to H.P. The funders played no role in the content of this manuscript. We are grateful for the data submission of David Ludwig and Cara Ebbeling, and for the analysis by Steve Heymsfield of his own data indicating no change in FFM hydration with age in adults.Peer reviewedPublisher PD