Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era

Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/ or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples fromboth human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control. This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'

Is 8:30 a.m. Still Too Early to Start School? A 10:00 a.m. School Start Time Improves Health and Performance of Students Aged 13-16.

While many studies have shown the benefits of later school starts, including better student attendance, higher test scores, and improved sleep duration, few have used starting times later than 9:00 a.m. Here we report on the implementation and impact of a 10 a.m. school start time for 13 to 16-year-old students. A 4-year observational study using a before-after-before (A-B-A) design was carried out in an English state-funded high school. School start times were changed from 8:50 a.m. in study year 0, to 10 a.m. in years 1-2, and then back to 8:50 a.m. in year 3. Measures of student health (absence due to illness) and academic performance (national examination results) were used for all students. Implementing a 10 a.m. start saw a decrease in student illness after 2 years of over 50% (p < 0.0005 and effect size: Cohen's d = 1.07), and reverting to an 8:50 a.m. start reversed this improvement, leading to an increase of 30% in student illness (p < 0.0005 and Cohen's d = 0.47). The 10:00 a.m. start was associated with a 12% increase in the value-added number of students making good academic progress (in standard national examinations) that was significant (<0.0005) and equivalent to 20% of the national benchmark. These results show that changing to a 10:00 a.m. high school start time can greatly reduce illness and improve academic performance. Implementing school start times later than 8:30 a.m., which may address the circadian delay in adolescents' sleep rhythms more effectively for evening chronotypes, appears to have few costs and substantial benefits

'Magic coins' and 'magic squares': the discovery of astrological sigils in the Oldenburg Letters

Enclosed in a 1673 letter to Henry Oldenburg were two drawings of a series of astrological sigils, coins and amulets from the collection of Strasbourg mathematician Julius Reichelt (1637–1719). As portrayals of particular medieval and early modern sigils are relatively rare, this paper will analyse the role of these medals in medieval and early modern medicine, the logic behind their perceived efficacy, and their significance in early modern astrological and cabalistic practice. I shall also demonstrate their change in status in the late seventeenth century from potent magical healing amulets tied to the mysteries of the heavens to objects kept in a cabinet for curiosos. The evolving perception of the purpose of sigils mirrored changing early modern beliefs in the occult influences of the heavens upon the body and the natural world, as well as the growing interests among virtuosi in collecting, numismatics and antiquities

Spillover, hybridization, and persistence in schistosome transmission dynamics at the human-animal interface.

Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the Schistosoma genus, and the Schistosoma spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids. Combining model-based approaches and analyses of parasitological, molecular, and epidemiological data from northern Senegal, a region with a high prevalence of schistosome hybrids, we aimed to unravel the transmission dynamics of this complex multihost, multiparasite system. Using Bayesian methods and by estimating the basic reproduction number (R0 ), we evaluate the frequency of zoonotic spillover of Schistosoma bovis from livestock and the potential for onward transmission of hybrid S. bovis × S. haematobium offspring within human populations. We estimate R0 of hybrid schistosomes to be greater than the critical threshold of one (1.76; 95% CI 1.59 to 1.99), demonstrating the potential for hybridization to facilitate spread and establishment of schistosomiasis beyond its original geographical boundaries. We estimate R0 for S. bovis to be greater than one in cattle (1.43; 95% CI 1.24 to 1.85) but not in other ruminants, confirming cattle as the primary zoonotic reservoir. Through longitudinal simulations, we also show that where S. bovis and S. haematobium are coendemic (in livestock and humans respectively), the relative importance of zoonotic transmission is predicted to increase as the disease in humans nears elimination

Contact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence

Abstract: Emerging evidence suggests that contact tracing has had limited success in the UK in reducing the R number across the COVID-19 pandemic. We investigate potential pitfalls and areas for improvement by extending an existing branching process contact tracing model, adding diagnostic testing and refining parameter estimates. Our results demonstrate that reporting and adherence are the most important predictors of programme impact but tracing coverage and speed plus diagnostic sensitivity also play an important role. We conclude that well-implemented contact tracing could bring small but potentially important benefits to controlling and preventing outbreaks, providing up to a 15% reduction in R. We reaffirm that contact tracing is not currently appropriate as the sole control measure

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets

Failure of human rhombic lip differentiation underlies medulloblastoma formation

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB

Extract from Two Letters, Dated December 7th and 12th, 1765, from the Rev. Mr. William Borlase, of Ludgvan, in Cornwall, F. R. S. to Emanuel Mendes da Costa, Librarian, &c. to the Royal Society

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Impact of a Lisbon-type tsunami on the U.K. coastline and the implications for tsunami propagation over broad continental shelves

We investigate the propagation of tsunamis toward the European shelf break, using six different initial conditions (based on the 1755 Lisbon earthquake), in order to assess the hazard to this region. Only one of our source models, an assumed earthquake magnitude of 8.7 Mw with a zonal fault orientation, resulted in significant wave heights at the U.K. coastline. Because of wave spreading, only a fraction of the tsunami energy from such an event reaches the northwest European shelf, which itself provides a further buffer through reflection and frictional dissipation. However, we found significant local reamplification due to wave interactions and resonance on the continental shelf. The maximum elevations obtained were comparable to severe winter storm conditions, but with extreme local variability in the tsunami amplitude. Our results suggest that the impact of any repeat of this event would be very sensitive to the precise location and orientation of the source deformation, as well as by complex topographic interactions on the shelf. The uncertainties arising from the combination of source orientation and bathymetric interaction suggest that any assessment of risk, for places where tsunamis are likely, should consider a large ensemble of initial condition