Recent advances in the molecular epidemiology of clinical malaria

This is the final version of the article. Available from the publisher via the DOI in this record.Human malaria is a complex disease that can show a wide array of clinical outcomes, from asymptomatic carriage and chronic infection to acute disease presenting various life-threatening pathologies. The specific outcome of an infection is believed to be determined by a multifactorial interplay between the host and the parasite but with a general trend toward disease attenuation with increasing prior exposure. Therefore, the main burden of malaria in a population can be understood as a function of transmission intensity, which itself is intricately linked to the prevalence of infected hosts and mosquito vectors, the distribution of infection outcomes, and the parasite population diversity. Predicting the long-term impact of malaria intervention measures therefore requires an in-depth understanding of how the parasite causes disease, how this relates to previous exposures, and how different infection pathologies contribute to parasite transmission. Here, we provide a brief overview of recent advances in the molecular epidemiology of clinical malaria and how these might prove to be influential in our fight against this important disease.MR is supported by the Medical Research Council (grant MR/M003906/1)

A Network Approach to Analyzing Highly Recombinant Malaria Parasite Genes

The var genes of the human malaria parasite Plasmodium falciparum present a challenge to population geneticists due to their extreme diversity, which is generated by high rates of recombination. These genes encode a primary antigen protein called PfEMP1, which is expressed on the surface of infected red blood cells and elicits protective immune responses. Var gene sequences are characterized by pronounced mosaicism, precluding the use of traditional phylogenetic tools that require bifurcating tree-like evolutionary relationships. We present a new method that identifies highly variable regions (HVRs), and then maps each HVR to a complex network in which each sequence is a node and two nodes are linked if they share an exact match of significant length. Here, networks of var genes that recombine freely are expected to have a uniformly random structure, but constraints on recombination will produce network communities that we identify using a stochastic block model. We validate this method on synthetic data, showing that it correctly recovers populations of constrained recombination, before applying it to the Duffy Binding Like-α (DBLα) domain of var genes. We find nine HVRs whose network communities map in distinctive ways to known DBLα classifications and clinical phenotypes. We show that the recombinational constraints of some HVRs are correlated, while others are independent. These findings suggest that this micromodular structuring facilitates independent evolutionary trajectories of neighboring mosaic regions, allowing the parasite to retain protein function while generating enormous sequence diversity. Our approach therefore offers a rigorous method for analyzing evolutionary constraints in var genes, and is also flexible enough to be easily applied more generally to any highly recombinant sequences

Genome-wide association studies in Plasmodium species

Genome-wide association studies (GWAS) look for correlations between traits of interest and genetic markers spread throughout the genome. A recent study in BMC Genetics has found that populations of the malaria parasite Plasmodium vivax should be amenable to GWAS searching for a genetic basis of parasite pathogenicity. Geographical substructure in populations may, however, prove a problem in interpreting the results

Mathematical Models for a New Era of Malaria Eradication

Maciej Boni and colleagues discuss a new model exploring how a switch in antimalarial drug use to artemisinin-based combination therapies will affect malaria prevalence and incidence in endemic regions

Inferring malaria parasite population structure from serological networks

The malaria parasite Plasmodium falciparum is characterized by high levels of genetic diversity at antigenic loci involved in virulence and immune evasion. Knowledge of the population structure and dynamics of these genes is important for designing control programmes and understanding the acquisition of immunity to malaria; however, high rates of homologous and non-homologous recombination as well as complex patterns of expression within hosts have hindered attempts to elucidate these structures experimentally. Here, we analyse serological data from Kenya using a novel network technique to deconstruct the relationships between patients' immune responses to different parasite isolates. We show that particular population structures and expression patterns produce distinctive signatures within serological networks of parasite recognition, which can be used to discriminate between competing hypotheses regarding the organization of these genes. Our analysis suggests that different levels of immune selection occur within different groups of the same multigene family leading to mixed population structures

Daily timing of low tide drives seasonality in intertidal emersion mortality risk

Sea level exerts a fundamental influence on the intertidal zone, where organisms are subject to immersion and emersion at varying timescales and frequencies. While emersed, intertidal organisms are exposed to atmospheric stressors which show marked diurnal and seasonal variability, therefore the daily and seasonal timing of low water is a key determinant of survival and growth in this zone. Using the example of shallow coral reefs, the coincidence of emersion with selected stressors was investigated for eight locations around the Australian coastline. Hourly water levels (1992 – 2016) from a high-resolution sea level hindcast (http://sealevelx.ems.uwa.edu.au), were linked to maximum surface solar radiation data from the Copernicus ERA5 atmospheric model and minimum atmospheric temperature observations from the Australian Bureau of Meteorology to identify seasonal patterns and historical occurrence of coral emersion mortality risk. Local tidal characteristics were found to dictate the time of day when low water, and therefore emersion mortality risk occurs, varying on a seasonal and regional basis. In general, risk was found to be greatest during the Austral spring when mean sea levels are lowest and a phase change in solar tidal constituents occurs. For all Great Barrier Reef sites, low tide occurs close to midday during winter and midnight in the summer, which may be fundamental factor supporting the historical bio-geographical development of the reef. Interannual variability in emersion mortality risk was mostly driven by non-tidal factors, particularly along the West Coast where El Niño events are associated with lower mean sea levels. This paper highlights the importance of considering emersion history when assessing intertidal environments, including shallow coral reef platform habitats, where critical low water events intrinsically influence coral health and cover. The study addresses a fundamental knowledge gap in both the field of water level science and intertidal biology in relation to the daily timing of low tide, which varies predictably on a seasonal and regional basis

Reconstructing a Latina temple spire : Temple 45, Sanchi

The initial aim of this thesis is to reconstruct, through drawings, the original design of the spire from Temple 45, a ruined Latina temple from the Buddhist, World Heritage Site of Sanchi in Madhya Pradesh. The hundreds of un-analysed architectural fragments from the temple that survive on site are the primary data for this project: a veritable three-dimensional jigsaw puzzle of pieces waiting to be studied and reassembled. In order to turn the mass of architectural data collected at Sanchi into a virtual reconstruction of the spire from Temple 45, an authentic and detailed method of Latina spire design must be used. Finding such a method, one ratified by the Vastusasastras, by the shape of surviving Latina superstructures, and by the proportions of Temple 45 and its spire courses, forms the second, broader research question of the thesis. Although Latina temples are a seminal feature of North Indian temple architecture, scholars' explanations of how they were designed are inconsistent, incomplete and often unconvincing. In pursuit of this design method, therefore, the thesis explores the origination and development of the Latina temple form across Central India. It interrogates contemporary scholars' theories of Latina spire design and investigates the role that the Vastusasdstras may have played in the practises of early temple architects. Vastusasastric descriptions of Latina spire design are turned into drawings of spire elevations in order to assess their credibility, and in doing so a particular method of spire design is ratified and additional design details are suggested in order to provide a working explanation. Using this method, four sets of spire proportions given in a West Indian text called the DiparUava are validated. These are shown to create convincing Latina elevations with proportions that are borne out by surviving Central Indian Latina temples, by an engraving of a half Latina spire carved into the hallway of the Harihara 2 Temple in Osian, and by the proportions of Temple 45 its fragmented remains. Drawing from these findings, and returning to the initial aim of the thesis, the thesis proposes a detailed and convincing elevation of the spire from Temple 45.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

SARS-CoV-2 transmission dynamics should inform policy

Funding: JM is supported in part by the U.S. National Institute of Allergy and Infectious Diseases [K01AI122853].It is generally agreed that striking a balance between resuming economic and social activities and keeping the effective reproductive number (R0) below 1 using non-pharmaceutical interventions is an important goal until and even after effective vaccines become available. Therefore, the need remains to understand how the virus is transmitted in order to identify high-risk environments and activities that disproportionately contribute to its spread so that effective preventative measures could be put in place. Contact tracing and household studies in particular provide robust evidence about the parameters of transmission. In this viewpoint, we discuss the available evidence from large-scale, well-conducted contact tracing studies from across the world and argue that SARS-CoV-2 transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities and socioeconomic factors associated with the highest risks of transmission.PostprintPeer reviewe

Reconstructing a Latina temple spire: Temple 45, Sanchi.

The initial aim of this thesis is to reconstruct, through drawings, the original design of the spire from Temple 45, a ruined Latina temple from the Buddhist, World Heritage Site of Sanchi in Madhya Pradesh. The hundreds of un-analysed architectural fragments from the temple that survive on site are the primary data for this project: a veritable three-dimensional jigsaw puzzle of pieces waiting to be studied and reassembled. In order to turn the mass of architectural data collected at Sanchi into a virtual reconstruction of the spire from Temple 45, an authentic and detailed method of Latina spire design must be used. Finding such a method, one ratified by the Vastusasastras, by the shape of surviving Latina superstructures, and by the proportions of Temple 45 and its spire courses, forms the second, broader research question of the thesis. Although Latina temples are a seminal feature of North Indian temple architecture, scholars' explanations of how they were designed are inconsistent, incomplete and often unconvincing. In pursuit of this design method, therefore, the thesis explores the origination and development of the Latina temple form across Central India. It interrogates contemporary scholars' theories of Latina spire design and investigates the role that the Vastusasdstras may have played in the practises of early temple architects. Vastusasastric descriptions of Latina spire design are turned into drawings of spire elevations in order to assess their credibility, and in doing so a particular method of spire design is ratified and additional design details are suggested in order to provide a working explanation. Using this method, four sets of spire proportions given in a West Indian text called the DiparUava are validated. These are shown to create convincing Latina elevations with proportions that are borne out by surviving Central Indian Latina temples, by an engraving of a half Latina spire carved into the hallway of the Harihara 2 Temple in Osian, and by the proportions of Temple 45 its fragmented remains. Drawing from these findings, and returning to the initial aim of the thesis, the thesis proposes a detailed and convincing elevation of the spire from Temple 45

Heterogeneous Mobile Phone Ownership and Usage Patterns in Kenya

The rapid adoption of mobile phone technologies in Africa is offering exciting opportunities for engaging with high-risk populations through mHealth programs, and the vast volumes of behavioral data being generated as people use their phones provide valuable data about human behavioral dynamics in these regions. Taking advantage of these opportunities requires an understanding of the penetration of mobile phones and phone usage patterns across the continent, but very little is known about the social and geographical heterogeneities in mobile phone ownership among African populations. Here, we analyze a survey of mobile phone ownership and usage across Kenya in 2009 and show that distinct regional, gender-related, and socioeconomic variations exist, with particularly low ownership among rural communities and poor people. We also examine patterns of phone sharing and highlight the contrasting relationships between ownership and sharing in different parts of the country. This heterogeneous penetration of mobile phones has important implications for the use of mobile technologies as a source of population data and as a public health tool in sub-Saharan Africa