Quantifying the impacts of variation in entomological and epidemiological determinants of malaria transmission

Malaria epidemiology is characterised by extensive heterogeneity that manifests across a range of spatial and temporal scales. This heterogeneity is driven by a diversity of factors spanning the human host, the parasite, the mosquito vector and the environment. Together, variation in these factors lead to marked differences in the epidemiology of malaria across different settings; in where malaria is concentrated, how malaria is transmitted and who is most at-risk. These differences have material consequences for the impact of control interventions aimed at combatting the disease, underscoring the crucial need to better understand and quantify the factors underlying heterogeneity in malaria epidemiology and transmission dynamics. In this thesis, I use a combination of statistical and mathematical modelling to further our understanding of how variation in the epidemiological and entomological determinants of malaria transmission drives heterogeneity in dynamics across settings and explore the implications of this variation for control efforts. Accurate ascertainment of malaria infections represents a crucial component of malaria surveillance and control. Previous work has revealed the often-substantial prevalence of infections with parasite densities lower than the threshold of detection by microscopy (so called “submicroscopic” infections). The drivers of these infections remain uncertain, despite their established relevance to onwards transmission. In Chapter 2, I carry out a systematic literature review and meta-analysis exploring the prevalence of submicroscopic malaria infections and how this varies between settings. My results highlight extensive variation between settings, with much of this driven by a combination of both historical and current levels of transmission. Crucially, these results highlight significant variation in the prevalence of submicroscopic infections even across settings characterised by similar current levels of transmission, with implications for the utility of control efforts specifically targeting this infected sub-group depending on the context. Within communities, the distribution of malaria infections is frequently characterised by extensive spatial heterogeneity, which can make identification and treatment of infections challenging. In Chapter 3, using a regression-based approach, I characterise the fine-scale spatial clustering of malaria infections at the household level across a diverse range of sub-Saharan African settings through systematic analysis of 57 Demographic and Health Surveys spanning 23 countries. My results highlight that malaria infections cluster within households, and that the extent of this clustering becomes significantly more pronounced as transmission declines – a factor which will affect the comparative impact of household-targeting or whole-community based control strategies and result in their appropriateness depending closely on the levels of transmission characterising a setting. In addition to this spatial heterogeneity, malaria transmission dynamics are also frequently characterised by extensive temporal heterogeneity, a phenomenon underpinned by the (often annual) temporal fluctuations in the size of the mosquito populations responsible for transmission. Many questions remain surrounding the drivers of these dynamics however, questions that are rarely answerable from individual entomological studies (focussed on only a single location or species). In Chapter 4 I carry out a systematic literature review to collate anopheline mosquito time-series data from across India and develop a statistical framework capable of characterising the dominant temporal patterns in this dataset. The results demonstrate extensive diversity in the timing and extent of seasonality across mosquito species, but also show that this diversity can be clustered into a small number of “dynamical archetypes”, each shaped and driven by a largely unique set of environmental factors including rainfall, temperature, proximity to water bodies and patterns of land use. In Chapter 5, I apply this framework to time-series data from across South Asia and the Middle East for the highly efficient vector Anopheles stephensi, to better understand the factors shaping its seasonal dynamics and the likely impact of its recent establishment in the Horn of Africa. My results reveal significant differences in the extent of seasonality across Anopheles stephensi populations, with dynamics frequently differing between rural and urban settings, suggesting structural differences in how these environments shape patterns of vector abundance and potentially warranting different vector control strategies depending on predominant patterns of land-use. Integrating these seasonal profiles into a mathematical model of malaria transmission highlights the crucial need for an understanding of the timing of seasonal peaks in vector density if control interventions like IRS are to be most effectively deployed. Overall, the results presented here highlight some of the drivers influencing spatial and temporal heterogeneity in malaria epidemiology, quantifies how they contribute to the diverse malaria dynamics observed across different settings, and explores the implication of this variation for effective control of the disease.Open Acces

The Adoption of Socio-Technological Environments to Drive Classroom Change

Comprend des références bibliographique

The algal pyrenoid: key unanswered questions.

The confinement of Rubisco in a chloroplast microcompartment, or pyrenoid, is a distinctive feature of most microalgae, and contributes to perhaps ~30 Pg of carbon fixed each year, yet our understanding of pyrenoid composition, regulation, and function remains fragmentary. Recently, significant progress in understanding the pyrenoid has arisen from studies using mutant lines, mass spectrometric analysis of isolated pyrenoids, and advanced ultrastructural imaging of the microcompartment in the model alga Chlamydomonas. The emergence of molecular details in other lineages provides a comparative framework for this review, and evidence that most pyrenoids function similarly, even in the absence of a common ancestry. The objective of this review is to explore pyrenoid diversity throughout key algal lineages and discuss whether common ultrastructural and cellular features are indicative of common functional processes. By characterizing pyrenoid origins in terms of mechanistic and structural parallels, we hope to provide key unanswered questions which will inform future research directions

How plants feel the cold: dissecting distinct vernalisation responses across arabidopsis thaliana accessions.

The winter annual Arabidopsis thaliana requires a prolonged period of cold in order to establish competency to flower, in a process known as vernalisation. Accessions of Arabidopsis worldwide show distinct and highly variable vernalisation responses and a significant amount of this variation has been mapped to a single locus- FLOWERING LOCUS C (FLC). Whilst the source of the variation is known, the particular polymorphisms, and the exact nature by which they influence different aspects of the vernalisation process remains comparatively unexplored. This thesis addresses two questions: firstly, what genetic features of FLC across different accessions contribute to their distinct vernalisation responses? And secondly, how does the process of vernalisation in different accessions differ to produce these distinct vernalisation requirements? The work presented here addresses these questions from a number of different perspectives. Chromatin immunoprecipitation (ChIP) experiments point to the role of altered chromatin dynamics as the driver of different vernalisation requirements in two different Arabidopsis thaliana accessions. Expression analysis of transgenic chimeric FLC loci containing domains from both rapidly and slowly vernalising accessions highlights the importance of particular single nucleotide polymorphisms (SNPs) in affecting FLC’s propensity to reactivate upon return to warmth after a short period of cold. Finally, analysis of FLC suppression dynamics during cold exposure across a range of accessions illustrates mechanistic differences in vernalisation as the driver of distinct vernalisation requirements. The work presented in this thesis examines the natural diversity in vernalisation requirements across Arabidopsis thaliana accessions in order to better resolve the nature of such variation, both in terms of its causative features as well as the underpinning mechanism. In doing so, it highlights that a small number of polymorphisms are able to alter the process of vernalisation in significant ways, and that, additionally, the way in which the vernalisation mechanism has been altered varies across accessions

Harmonic Maa{\ss}-Jacobi forms of degree 1 with higher rank indices

We define and investigate real analytic weak Jacobi forms of degree 1 and arbitrary rank. En route we calculate the Casimir operator associated to the maximal central extension of the real Jacobi group, which for rank exceeding 1 is of order 4. In ranks exceeding 1, the notions of H-harmonicity and semi-holomorphicity are the same.Comment: 28 page

Technology supported collaborative learning.

"This research is supported by le ministère de l'Éducation, du Loisir et du Sport dans le cadre du Programme d'aide à la recherche sur l'enseignement et l'apprentissage (PAREA)"Titre de la couv.: Technology supported collaborative learning.Titre de l'écran-titre (visionné le 10 sept. 2009).Également disponible en format papier.Bibliogr