Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis

Background: The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy. Findings: The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171–399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months. Conclusions: Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci

Plasticity in transmission strategies of the malaria parasite, Plasmodium chabaudi : environmental and genetic effects

Parasites may alter their behaviour to cope with changes in the within-host environment. In particular, investment in transmission may alter in response to the availability of parasite resources or host immune responses. However, experimental and theoretical studies have drawn conflicting conclusions regarding parasites' optimal (adaptive) responses to deterioration in habitat quality. We analyse data from acute infections with six genotypes of the rodent malaria species to quantify how investment in transmission (gametocytes) is influenced by the within-host environment. Using a minimum of modelling assumptions, we find that proportional investment in gametocytogenesis increases sharply with host anaemia and also increases at low parasite densities. Further, stronger dependence of investment on parasite density is associated with greater virulence of the parasite genotype. Our study provides a robust quantitative framework for studying parasites' responses to the host environment and whether these responses are adaptive, which is crucial for predicting the short-term and evolutionary impact of transmission-blocking treatments for parasitic diseases

The effects of subcurative praziquantel treatment on life-history traits and trade-offs in drug-resistant Schistosoma mansoni

Natural selection acts on all organisms, including parasites, to maximise reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian State-Space Models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma may be limited by life-history costs not present in susceptible counterparts. Schistosoma mansoni parasites from a praziquantel–susceptible (S), a praziquantel–resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by praziquantel treatment in the R line, could limit the spread of R parasites under praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond

A fundamental test for stellar feedback recipes in galaxy simulations

Direct comparisons between galaxy simulations and observations that both reach scales < 100 pc are strong tools to investigate the cloud-scale physics of star formation and feedback in nearby galaxies. Here we carry out such a comparison for hydrodynamical simulations of a Milky Way-like galaxy, including stochastic star formation, HII region and supernova feedback, and chemical post-processing at 8 pc resolution. Our simulation shows excellent agreement with almost all kpc-scale and larger observables, including total star formation rates, radial profiles of CO, HI, and star formation through the galactic disc, mass ratios of the ISM components, both whole-galaxy and resolved Kennicutt-Schmidt relations, and giant molecular cloud properties. However, we find that our simulation does not reproduce the observed de-correlation between tracers of gas and star formation on < 100 pc scales, known as the star formation 'uncertainty principle', which indicates that observed clouds undergo rapid evolutionary lifecycles. We conclude that the discrepancy is driven by insufficiently-strong pre-supernova feedback in our simulation, which does not disperse the surrounding gas completely, leaving star formation tracer emission too strongly associated with molecular gas tracer emission, inconsistent with observations. This result implies that the cloud-scale de-correlation of gas and star formation is a fundamental test for feedback prescriptions in galaxy simulations, one that can fail even in simulations that reproduce all other macroscopic properties of star-forming galaxies.Comment: 13 pages, 10 figures, accepted for publication in MNRA

Understanding functional benefits of Isoleucine and Arginine on poultry performance and health.

Poultry industry is rapidly moving towards utilizing the best ingredients to precisely feed the birds for better performance, welfare, health, and profitability. One of the practices that evolved over time with research is better optimization of amino acid utilization in the diets thus changing the crude protein landscape. Historically, if we compare the modern diets to diets from 1980, significant changes are visible in the use of unbound or crystalline amino acids leading to reduced levels of CP and reduced unutilized nitrogen in the diets. Multiple feed-grade amino acids are available in a cost-effective manner in poultry diets. Multiple research has been conducted over 80 years to better understand the optimal requirement of lower limiting amino acids in poultry, formulation with digestible amino acid values, and ideal amino acid formulation to achieve precision feeding of nutrients. Those findings enabled the nutritionist to incorporate crystalline amino acids, remove CP minimum, and crystalline amino acid maximum in the diets to lower the feed cost, reduce CP, reduce excess nitrogen in hindgut and improve the health of the birds and improve litter quality (Kidd 2000; Maia et al., 2021). A 1960 diet would only contain the Methionine as synthetic amino acid, whereas the 2023 diet would contain up to 5/6 limiting amino acids in USA-based broiler diets. The 4th, 5th and 6th limiting amino acids in USA-based poultry diets are usually Valine (Val), Isoleucine (Ile) and Arginine (Arg) depending on the ingredients used. With almost 90% of the industry using the 4th limiting amino acid, there is a need to understand the optimal requirement of 5th and 6th limiting amino acids for performance and other biological functionality. With Ile and Arg being the 5th and 6th limiting amino acid in most broiler, turkey, and layer diets, this article will discuss the importance of Ile and Arg in birds and the effect on performance and health

Understanding functional benefits of Isoleucine and Arginine on poultry performance and health.

Poultry industry is rapidly moving towards utilizing the best ingredients to precisely feed the birds for better performance, welfare, health, and profitability. One of the practices that evolved over time with research is better optimization of amino acid utilization in the diets thus changing the crude protein landscape. Historically, if we compare the modern diets to diets from 1980, significant changes are visible in the use of unbound or crystalline amino acids leading to reduced levels of CP and reduced unutilized nitrogen in the diets. Multiple feed-grade amino acids are available in a cost-effective manner in poultry diets. Multiple research has been conducted over 80 years to better understand the optimal requirement of lower limiting amino acids in poultry, formulation with digestible amino acid values, and ideal amino acid formulation to achieve precision feeding of nutrients. Those findings enabled the nutritionist to incorporate crystalline amino acids, remove CP minimum, and crystalline amino acid maximum in the diets to lower the feed cost, reduce CP, reduce excess nitrogen in hindgut and improve the health of the birds and improve litter quality (Kidd 2000; Maia et al., 2021). A 1960 diet would only contain the Methionine as synthetic amino acid, whereas the 2023 diet would contain up to 5/6 limiting amino acids in USA-based broiler diets. The 4th, 5th and 6th limiting amino acids in USA-based poultry diets are usually Valine (Val), Isoleucine (Ile) and Arginine (Arg) depending on the ingredients used. With almost 90% of the industry using the 4th limiting amino acid, there is a need to understand the optimal requirement of 5th and 6th limiting amino acids for performance and other biological functionality. With Ile and Arg being the 5th and 6th limiting amino acid in most broiler, turkey, and layer diets, this article will discuss the importance of Ile and Arg in birds and the effect on performance and health

A Bayesian approach for inferring the dynamics of partially observed endemic infectious diseases from space-time-genetic data

We describe a statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information. Previous approaches to reconstructing transmission trees have assumed all infections in the study area originated from a single introduction and that a large fraction of cases were observed. There are as yet no approaches appropriate for endemic situations in which a disease is already well established in a host population and in which there may be multiple origins of infection, or that can enumerate unobserved infections missing from the sample. Our proposed framework addresses these shortcomings, enabling reconstruction of partially observed transmission trees and estimating the number of cases missing from the sample. Analyses of simulated datasets show the method to be accurate in identifying direct transmissions, while introductions and transmissions via one or more unsampled intermediate cases could be identified at high to moderate levels of case detection. When applied to partial genome sequences of rabies virus sampled from an endemic region of South Africa, our method reveals several distinct transmission cycles with little contact between them, and direct transmission over long distances suggesting significant anthropogenic influence in the movement of infected dogs

Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus

Due to the poor-fidelity of the enzymes involved in RNA genome replication, foot-and-mouth disease (FMD) virus samples comprise of unique polymorphic populations. In this study, deep sequencing was utilised to characterise the diversity of FMD virus (FMDV) populations in 6 infected cattle present on a single farm during the series of outbreaks in the UK in 2007. A novel RT–PCR method was developed to amplify a 7.6 kb nucleotide fragment encompassing the polyprotein coding region of the FMDV genome. Illumina sequencing of each sample identified the fine polymorphic structures at each nucleotide position, from consensus level changes to variants present at a 0.24% frequency. These data were used to investigate population dynamics of FMDV at both herd and host levels, evaluate the impact of host on the viral swarm structure and to identify transmission links with viruses recovered from other farms in the same series of outbreaks. In 7 samples, from 6 different animals, a total of 5 consensus level variants were identified, in addition to 104 sub-consensus variants of which 22 were shared between 2 or more animals. Further analysis revealed differences in swarm structures from samples derived from the same animal suggesting the presence of distinct viral populations evolving independently at different lesion sites within the same infected animal