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Mueller, I.

Publications and source records attributed to Mueller, I..

7 recordsLinked to original sources

Taking sharper pictures of malaria with CAMERAs: Combined Antibodies to Measure Exposure Recency Assays

Antibodies directed against malaria parasites are easy and inexpensive to measure but remain an underutilized surveillance tool due to a lack of consensus on what to measure and how to interpret results. High throughput screening of antibodies from well-characterized cohorts offers a means to substantially improve existing assays by rationally choosing the most informative sets of responses and analytical methods. Recent data suggest that high-resolution data on malaria exposure can be obtained from a small number of samples by measuring a handful of properly chosen antibody responses. In this review, we will discuss how standardized multi-antibody assays can be developed and efficiently integrated into existing surveillance activities, with great potential to greatly augment the breadth and quality of information available to direct and monitor malaria control and elimination efforts.

epidemiology

An automated barcode tracking system for behavioural studies in birds

O_LIRecent advances in technology allow researchers to automate the measurement of animal behaviour. These methods have multiple advantages over direct observations and manual data input as they reduce bias related to human perception and fatigue, and deliver more extensive and complete data sets that enhance statistical power. One major challenge that automation can overcome is the observation of many individuals at once, enabling whole-group or whole-population tracking.\nC_LIO_LIWe provide a detailed description for implementing an automated system for tracking birds. Our system uses printed, machine-readable codes mounted on backpacks. This simple, yet robust, tagging system can be used simultaneously on multiple individuals to provide data on bird identity, position and directionality. Further, because our codes and backpacks are printed on paper, they are very lightweight.\nC_LIO_LIWe describe the implementation of this automated system on two flocks of zebra finches. We test different camera options, and describe their advantages and disadvantages. We show that our method is reliable, relatively easy to implement and monitor, and with proper handling, has proved to be safe for the birds over long periods of time. Further, we highlight how using single-board computers to control the frequency and duration of image capture makes this system affordable, flexible, and adaptable to a range of study systems.\nC_LIO_LIThe ability to automate the measurement of individual positions has the potential to significantly increase the power of both observational and experimental studies. The system can capture both detailed interactions (using video recordings) and repeated observations (e.g. once per second for the entire day) of individuals over long timescales (months or potentially years). This approach opens the door to tracking life-long relationships among individuals, while also capturing fine-scale differences in behaviour.\nC_LI

animal behavior and cognition

Integrated transcriptomic, proteomic and epigenomic analysis of Plasmodium vivax salivary-gland sporozoites

Plasmodium vivax is the key obstacle to malaria elimination in Asia and Latin America, largely attributed to its ability to form resilient hypnozoites (sleeper-cells) in the host liver that escape treatment and cause relapsing infections. The decision to form hypnozoites is made early in the liver infection and may already be set in sporozoites prior to invasion. To better understand these early stages of infection, we undertook a comprehensive transcriptomic and histone epigenetic characterization of P. vivax sporozoites. The salivary-gland sporozoite transcriptome is heavily composed of transcripts associated with functions needed for early infection of the vertebrate host and development within hepatocytes. Through comparisons to recently published proteome data for the P. vivax sporozoite, our study finds that although highly transcribed, these transcripts are not detectable as proteins and may be regulated through translational repression; a finding we test for a small subset of transcripts and proteins through immunofluorescent microscopy of sporozoites and liver stages in humanized mice. We identify differential transcription between the sporozoite and published transcriptomes of asexual blood-stages and mixed versus hypnozoite-enriched liver stages. These comparisons point to multiple layers of transcriptional, post-transcriptional and post-translational control that appear active in sporozoites and to a lesser extent hypnozoites, but largely absent in replicating liver schizonts or mixed blood-stages. Common transcripts up-regulated in sporozoites and hypnozoites compared to mixed (i.e., schizont) liver-stages identify genes linked to dormancy/persistence in bacteria, amoebae and plants. We also characterise histone epigenetic modifications in the P. vivax sporozoite and explore their role in regulating transcription. Collectively, these data support the hypothesis that the sporozoite as a tightly programmed stage primed to infect the human host and identifies potential mechanisms for hypnozoite-formation that may be further explored in liver stage models.

microbiology

Human Migration And The Spread Of Malaria Parasites To The New World

BackgroundThe Americas were the last continent to be settled by modern humans, but how and when human malaria parasites arrived in the New World is uncertain. Here, we apply phylogenetic analysis and coalescent-based gene flow modeling to a global collection of Plasmodium falciparum and P. vivax mitogenomes to infer the demographic history and geographic origins of malaria parasites circulating in the Americas. Importantly, we examine P. vivax mitogenomes from previously unsampled forest-covered sites along the Atlantic Coast of Brazil, including the vivax-like species P. simium that locally infects platyrrhini monkeys.\n\nResultsThe best-supported gene flow models are consistent with migration of both malaria parasites from Africa and South Asia to the New World, with no genetic signature of a population bottleneck upon parasite's arrival in the Americas. We found evidence of additional gene flow from Melanesia in P. vivax (but not P. falciparum) mitogenomes from the Americas and speculate that some P. vivax lineages might have arrived with the Australasian peoples who contributed genes to Native Americans in pre-Columbian times. Mitochondrial haplotypes characterized in P. simium from monkeys from the Atlantic Forest are shared by local humans. These vivax-like lineages have not spread to the Amazon Basin, are much less diverse than P. vivax circulating elsewhere in Brazil, and show no close genetic relatedness with P. vivax populations from other continents.\n\nConclusionsEnslaved peoples brought from a wide variety of African locations were major carriers of P. falciparum mitochondrial lineages into the Americas, but additional human migration waves are likely to have contributed to the extensive genetic diversity of present-day New World populations of P. vivax. The reduced genetic diversity of vivax-like monkey parasites, compared with human P. vivax from across this country, argues for a recent human-to-monkey transfer of these lineages in the Atlantic Forest of Brazil.\n\nAuthor summaryMalaria is currently endemic to the Americas, with over 400,000 laboratory-confirmed infections reported annually, but how and when human malaria parasites entered this continent remains largely unknown. To determine the geographic origins of malaria parasites currently circulating in the Americas, we examined a global collection of Plasmodium falciparum and P. vivax mitochondrial genomes, including those from understudied isolates of P. vivax and P. simium, a vivax-like species that infect platyrrhini monkeys, from the Atlantic Forest of Brazil. We found evidence of significant historical migration to the New World of malaria parasites from Africa and, to a lesser extent, South Asia, with further genetic contribution of Melanesian lineages to South American P. vivax populations. Importantly, mitochondrial haplotypes of P. simium are shared by monkeys and humans from the Atlantic Forest, most likely as a result of a recent human-to-monkey transfer. Interestingly, these potentially zoonotic lineages are not found in the Amazon Basin, the main malaria-endemic area in the Americas. We conclude that enslaved Africans were the main carriers of P. falciparum mitochondrial lineages into the Americas, whereas additional migration waves of Australasian peoples and parasites may have contributed to the genetic makeup of present-day New World populations of P. vivax.

microbiology

Development Of Amplicon Deep Sequencing Markers And Data Analysis Pipeline For Genotyping Multi-Clonal Malaria Infections

Amplicon deep sequencing permits sensitive detection of minority clones and improves discriminatory power for genotyping multi-clone Plasmodium falciparum infections. Such high resolution is needed for molecular monitoring of drug efficacy trials. Targeted sequencing of molecular marker csp and novel marker cpmp was conducted in duplicate on mixtures of parasite culture strains and 37 field samples. A protocol to multiplex up to 384 samples in a single sequencing run was applied. Software \"HaplotypR\" was developed for data analysis. Cpmp was highly diverse (He=0.96) in contrast to csp (He=0.57). Minority clones were robustly detected if their frequency was >1%. False haplotype calls owing to sequencing errors were observed below that threshold. To reliably detect haplotypes at very low frequencies, experiments are best performed in duplicate and should aim for coverage of >10000 reads/amplicon. When compared to length polymorphic marker msp2, highly multiplexed amplicon sequencing displayed greater sensitivity in detecting minority clones.

microbiology

Long-term sustained malaria control leads to inbreeding and fragmentation of Plasmodium vivax populations

The human malaria parasite Plasmodium vivax is resistant to malaria control strategies maintaining high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing P. vivax population structure that would facilitate elimination, we genotyped samples from a wide range of transmission intensities and spatial scales in the Southwest Pacific, including two time points at one site (Tetere, Solomon Islands) during intensified control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n= 420), and hypoendemic Vanuatu (n=24) revealed increasing population structure and multilocus linkage disequilibrium and a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination.

epidemiology

Detecting Selection Signals In Plasmodium falciparum Using Identity-By-Descent Analysis

Identification of genomic regions that are identical by descent (IBD) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions. Unfortunately however, IBD analyses have been underutilized inanalysis of other organisms, including human pathogens. This is in part due to the lack of statistical methodologies for non-diploid genomes in addition to the added complexity of multiclonal infections. As such, we have developed an IBD methodology, called isoRelate, for analysis of haploid recombining microorganisms in the presence of multiclonal infections. Using the inferred IBD status at genomic locations, we have also developed a novel statistic for identifying loci under positive selection and propose relatedness networks as a means of exploring shared haplotypes within populations. We evaluate the performance of our methodologies for detecting IBD and selection, including comparisons with existing tools, then perform an exploratory analysis of whole genome sequencing data from a global Plasmodium falciparum dataset of more than 2500 genomes. This analysis identifies Southeast Asia as havingmany highly related isolates, possibly as a result of both reduced transmission from intensified control efforts and population bottlenecks following the emergence of antimalarial drug resistance. Many signals of selection are also identified, most of which overlap genes that are known to be associated with drug resistance, in addition to two novel signals observed in multiple countries that have yet to be explored in detail. Additionally, we investigate relatedness networks over the selected loci and determine that one of these sweeps has spread between continents while the other has arisen independently in different countries. IBD analysis of microorganisms using isoRelate can be used for exploring population structure, positive selection and haplotype distributions, and will be a valuable tool for monitoring disease control and elimination efforts of many diseases.

bioinformatics