Emerging infectious diseases (EIDs) constitute an important global health security problem. During EID outbreaks, patient centred research can play a significant role in informing evidence-based care for patients, in calibrating public health responses, and in directing effective policy and research. However, to date, this type of research has been limited in impact. This thesis sets out to improve the value of patient centred research in combating EID outbreaks. It provides a structured analysis of what has previously constrained efforts to rapidly accumulate high-quality evidence. It provides primary data from research conducted during an outbreak, and conducted in an outbreak vulnerable setting. And it provides recommendations that aim to facilitate high-quality data collection in future events. This thesis contains four results chapters. Chapter 2 systematically reviews elements of the research response to two EID outbreaks of public health importance. Chapter 3 provides findings of a phase II clinical trial of an investigational therapy for Ebola virus disease (EVD), contextualises the utility of this and comparable work in improving patient care, and discusses the operational feasibility of such work during an epidemic. Chapter 4 focuses specifically on improving one element - disease characterisation - during EID outbreaks. It achieves this through presenting a systematic analysis of bias in the characterisation of EVD and recommends how to prioritise data gathering for high-risk pathogens. Chapter 5 exemplifies how clinical data collection practices can progress between outbreaks. It is the first stage of work undertaken to improve the clinical characterisation of communicable diseases in the vulnerable environment of refugee camps. This thesis demonstrates progress towards having higher quality clinical research conducted during the time frame of an epidemic. Future work can focus on the most important barriers to accelerating research, now that these have been more clearly defined.

Emerging infectious diseases continue to represent serious threats to global human health. Novel zoonotic pathogens are continually being recognised, and some ultimately cause significant disease burdens and extensive epidemics. Research and public health initiatives often face emerging pathogens with limited knowledge and resources. Inferences from empirical modelling have begun to uncover the factors determining cross-species transmission and emergence in humans, and subsequently guide risk assessments. However, the dynamics of virulence and transmissibility during the process of emergence are not well understood. Here, I focus on RNA viruses, a priority pathogen type because of their potential for rapid evolution. I use comparative trait-based analyses to investigate how aspects of both host and virus ecology contribute to the risk of virulence and transmissibility within human RNA viruses. To explore these questions, data were collected via systematic literature search protocols. In the first half of this thesis, I focus on viral determinants of virulence and transmissibility. I ask whether virulence can be predicted by viral traits of tissue tropism, transmission route, transmissibility and taxonomic classification. Using a machine learning approach, the most prominent predictors of severe virulence were breadth of tissue tropism, and nonvector-borne transmission routes. When applied to newly reported viruses as test set, the final model predicted disease severity with 87% accuracy. Next, I assess support for hypothesised routes of adaptation during emergence using phylogenetic state-switching models. Propensity for adaptation in small ‘stepwise’ movements versus large ‘off-the-shelf’ jumps differed between virus taxa, though no single route dominated, suggesting multiple independent trajectories of adaptation to human hosts. In addition, phylogenetic regressions showed vector and respiratory-transmitted viruses to be more likely to progress through early stages of emergence. In the second half of this thesis, I focus on how dynamics of virulence and transmissibility differ with respect to nonhuman host diversity, identity, and ecology. Using a regression framework, I observe that viruses with a broader mammalian host range exhibited higher risk of severe virulence, but lower risk of transmissibility, which may reflect potential trade-offs of host specificity. Furthermore, viruses with artiodactyl hosts exhibited lower risk of severe virulence and viruses with bat or nonhuman primate hosts exhibited higher risk of transmissibility. Next, I test hypotheses that mammal species with faster-paced life history may be predisposed to host viruses with greater virulence and transmissibility. Mammal body mass was used as an established proxy for pace of life history. In regression analyses, mammals with faster-paced life history hosted more viruses with severe virulence, though evidence for a relationship with transmissibility was limited. The broad-scale associations presented in this thesis suggest the evolution of virulence and human-to-human transmissibility during zoonotic emergence is a multifactorial, highly dynamic process influenced by both virus and host ecology. Despite this, general characteristics of high-risk emerging viruses are evident. For example, severe virulence was associated with broad niche diversity of both tissue tropisms at the within-host scale, and host species at the macroecological scale. However, risk factors for virulence and human-to-human transmissibility often did not coincide, which may imply an overarching trade-off between these traits. These analyses can contribute to preparedness and direction within public health strategies by identifying likely candidates for high-impact emergence events among previously known and newly discovered human viruses. The inherent connectivity between RNA viruses, their nonhuman hosts and the resulting implications for human health emphasise the holistic nature of emerging diseases and supports the One Health perspective for infectious disease research.

Le chikungunya, la dengue et la bilharziose urogénitale sont des maladies vectorielles émergentes qui ont récemment trouvé des conditions favorables à leur transmission en France métropolitaine.Santé publique France, l’Agence en charge de la surveillance de l’état de santé de la population française est en première ligne pour détecter et investiguer ces émergences afin d’orienter les mesures de leur prévention et de leur contrôle. Postulant que chaque épidémie constitue une situation d’« expérimentation naturelle », l’objectif de cette thèse était de montrer comment chaque investigation d’épidémie apporte l’opportunité d’acquérir des connaissances scientifiques sur la contribution des cas asymptomatiques à l’introduction, la dissémination et l’endémisation des maladies vectorielles de façon réactive.Notre méta-analyse d’études de séroprévalence per- et post-épidémiques suggère que, contrairement à nos attentes, la lignée de virus chikungunya qui a émergé en 2004 dans l’Océan Indien qui était associée moins d’infections asymptomatiques que les autres. Dans une étude de la séroprévalence de la dengue à Nîmes en 2015, nous avons montré que le potentiel de diffusion de la dengue en France restait actuellement limité. Les données du dépistage des personnes exposées au risque de bilharziose urogénitale en Corse montrant une fréquence élevée d'infections pré-symptomatiques, nous avons évoqué un risque d’endémisation de la maladie qui a justifié son inscription sur la liste des maladies à déclaration obligatoire.Ce travail de thèse démontre qu’une approche pragmatique basée sur une veille sanitaire sensible associée à des investigations épidémiologiques de terrain précoces peut contribuer à aussi bien à la lutte contre les émergences qu’à l’évolution des connaissances. / Conditions recently proved favourable to transmission of emerging vector-borne diseases, chikungunya, dengue and urogenital schistosomiasis in mainland France.Santé publique France, the Agency in charge of public health surveillance in France is at the forefront of detecting and investigating emerging infectious disease in order to guide prevention and control measures. Assuming that each outbreak constitutes a situation of "natural experimentation", the aim of this thesis was to show how outbreak investigations give the opportunity to acquire rapidly scientific knowledge on the contribution of asymptomatic cases to the introduction, dissemination and endemisation of vector-borne diseases.Through a meta-analysis of per and post-epidemic seroprevalence studies,we have shown that the chikungunya virus lineage that emerged in the Indian Ocean in 2004 is associated with a lower frequency of asymptomatic infections. In a dengue serosurvey in Nîmes in 2015, we showed that the diffusion potential of dengue in France is currently limited. Screening data of urogenital bilharziasis in persons exposed in Corsica showed a high frequency of pre-symptomatic infections suggestive of a risk of endemisation of the disease that justified its inclusion on the list of notifiable diseases.This thesis work shows that a pragmatic approach based on sensitive surveillance associated with early field outbreak investigations can significantly contribute to both emerging infections control and the advancement of knowledge.