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Background: A vaccine against Trypanosoma cruzi, the agent of Chagas disease, would be an excellent additional tool for disease control. A recombinant vaccine based on Tc24 and TSA1 parasite antigens was found to be safe and immunogenic in naïve macaques. Methods: We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the optimization of doses and formulation. We identified differentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires. Results: RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profile. Analysis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose. Conclusions: These data suggest that three vaccine doses may be needed for optimum immunogenicity and support the further evaluation of the protective efficacy of this vaccine. [ABSTRACT FROM AUTHOR]

Monte Carlo criticality simulations are widely used in nuclear safety demonstrations, as they offer an arbitrarily precise estimation of global and local tallies while making very few assumptions. However, since the inception of such numerical approaches, it is well known that bias might affect both the estimation of errors on these tallies and the tallies themselves. In particular, stochastic modeling approaches developed in the past decade have shed light on the prominent role played by spatial correlations through a phenomenon called neutron clustering. This effect is particularly of great significance when simulating loosely coupled systems (i.e., with a high dominance ratio). In order to tackle this problem, this paper proposes to recast the power iteration technique of Monte Carlo criticality codes into a variance reduction technique called Adaptive Multilevel Splitting. The central idea is that iterating over neutron generations can be seen as pushing a subpopulation of neutrons toward a generational detector (instead of a spatial detector as variance reduction techniques usually do). While both approaches allow for neutron population control, the former blindly removes or splits neutrons. In contrast, the latter optimizes the spatial, generational, and spectral attributes of neutrons when they are removed or split through an adjoint flux estimation, hence tempering both generational and spatial correlations. This is illustrated in the present paper with a simple case of a bare slab reactor in the one-speed theory on which the Adaptive Multilevel Splitting was applied and compared to variations of the Monte Carlo power iteration method used in neutron transport. Besides looking at the resulting efficiency of the methods, this work also aims to highlight the main mechanisms of the Adaptive Multilevel Splitting in criticality calculations. [ABSTRACT FROM AUTHOR]

Phylogenetic analysis of monkeypox virus genomes showed statistically significant divergence and nascent subclades during the 2022 mpox outbreak. Frequency of G>A/C>T transitions has increased in recent years, probably resulting from apolipoprotein B mRNA editing enzyme catalytic polypeptide 3G (APOBEC3) deaminase editing. This microevolutionary pattern most likely reflects community spread of the virus and adaptation to humans. [ABSTRACT FROM AUTHOR]

Stochastic fluctuations of the neutron population within a nuclear reactor are typically prevented by operating the core at a sufficient power, since a deterministic (i.e., exactly predictable) behavior of the neutron population is required by automatic safety systems to detect unwanted power excursions. In order to characterize the reactor operating conditions at which the fluctuations vanish, an experiment was designed and took place in 2017 at the Rensselaer Polytechnic Institute Reactor Critical Facility. This experiment however revealed persisting fluctuations and striking patchy spatial patterns in neutron spatial distributions. Here we report these experimental findings, interpret them by a stochastic modeling based on branching random walks, and extend them using a "numerical twin" of the reactor core. Consequences on nuclear safety will be discussed. Understanding and predicting fluctuations of the neutron population within a nuclear reactor is of fundamental importance for nuclear safety, especially in connection with reactor control at startup and shutdown. The study presents experiments and Monte Carlo simulations of persistent neutron fluctuations and correlations (stochastic noise and neutron clustering) in nuclear reactors which are interpreted by stochastic modelling based on branching random walks. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a neglected zoonosis of growing concern in the southern US, caused by the parasite Trypanosoma cruzi. We genotyped parasites in a large cohort of PCR positive dogs to shed light on parasite transmission cycles and assess potential relationships between parasite diversity and serological test performance. Methodology/principal findings: We used a metabarcoding approach based on deep sequencing of T. cruzi mini-exon marker to assess parasite diversity. Phylogenetic analysis of 178 sequences from 39 dogs confirmed the presence of T. cruzi discrete typing unit (DTU) TcI and TcIV, as well as TcII, TcV and TcVI for the first time in US dogs. Infections with multiple DTUs occurred in 38% of the dogs. These data indicate a greater genetic diversity of T. cruzi than previously detected in the US. Comparison of T. cruzi sequence diversity indicated that highly similar T. cruzi strains from these DTUs circulate in hosts and vectors in Louisiana, indicating that they are involved in a shared T. cruzi parasite transmission cycle. However, TcIV and TcV were sampled more frequently in vectors, while TcII and TcVI were sampled more frequently in dogs. Conclusions/significance: These observations point to ecological host-fitting being a dominant mechanism involved in the diversification of T. cruzi-host associations. Dogs with negative, discordant or confirmed positive T. cruzi serology harbored TcI parasites with different mini-exon sequences, which strongly supports the hypothesis that parasite genetic diversity is a key factor affecting serological test performance. Thus, the identification of conserved parasite antigens should be a high priority for the improvement of current serological tests. Author summary: Chagas disease is a neglected zoonosis of growing concern in the southern US, caused by the parasite Trypanosoma cruzi. Here we analyzed the parasite genetic diversity in a large cohort of infected dogs to better understand parasite transmission cycles and assess potential relationships between parasite diversity and serological test performance. We used DNA sequencing of a well characterized T. cruzi genetic marker to assess parasite diversity. We confirmed the presence of T. cruzi lineages TcI and TcIV, and report TcII, TcV and TcVI for the first time in US dogs. Parasite lineages TcIV TcII and TcVI appeared more frequent in dogs compared to insect vectors. Dogs with negative, discordant or confirmed positive T. cruzi serology harbored genetically different TcI parasites, which shows that parasite genetic diversity is a key factor affecting serological test performance. Thus, the identification of parasite antigens conserved across strains and lineages should be a high priority for the improvement of current serological tests. [ABSTRACT FROM AUTHOR]

Integrating how biodiversity and infectious disease dynamics are linked at multiple levels and scales is highly challenging. Chagas disease is a vector‐borne disease, with specificities of the triatomine vectors and Trypanosoma cruzi parasite life histories resulting in a complex multihost and multistrain life cycle. Here, we tested the hypothesis that T. cruzi transmission cycles are shaped by triatomine host communities and gut microbiota composition by comparing the integrated interactions of Triatoma sanguisuga in southern Louisiana with feeding hosts, T. cruzi parasite and bacterial microbiota in two habitats. Bugs were collected from resident's houses and animal shelters and analysed for genetic structure, blood feeding sources, T. cruzi parasites, and bacterial diversity by PCR amplification of specific DNA markers followed by next‐generation sequencing, in an integrative metabarcoding approach. T. sanguisuga feeding host communities appeared opportunistic and defined by host abundance in each habitat, yielding distinct parasite transmission networks among hosts. The circulation of a large diversity of T. cruzi DTUs was also detected, with TcII and TcV detected for the first time in triatomines in the US. The bacterial microbiota was highly diverse and varied significantly according to the DTU infecting the bugs, indicating specific interactions among them in the gut. Expanding such studies to multiple habitats and additional triatomine species would be key to further refine our understanding of the complex life cycles of multihost, multistrain parasites such as T. cruzi, and may lead to improved disease control strategies. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi is one of the most important neglected parasitic diseases in the Americas. Vaccines represent an attractive complementary strategy for the control of T. cruzi infection and pre-clinical studies in mice demonstrated that trypomastigote surface antigen (TSA-1) and the flagellar calcium-binding (Tc24) parasite antigens are promising candidates for vaccine development. We performed here the first evaluation of the safety and immunogenicity of two recombinant vaccine antigens (named TSA1-C4 and Tc24-C4) in naïve non-human primates. Three rhesus macaques received 3 doses of each recombinant protein, formulated with E6020 (Eisai Co., Ltd.), a novel Toll-like receptor-4 agonist, in a stable emulsion. All parameters from blood chemistry and blood cell counts were stable over the course of the study and unaffected by the vaccine. A specific IgG response against both antigens was detectable after the first vaccine dose, and increased with the second dose. After three vaccine doses, stimulation of PBMCs with a peptide pool derived from TSA1-C4 resulted in the induction of TSA1-C4-specific TNFα-, IL-2- and IFNγ-producing CD4+ in one or two animals while stimulation with a peptide pool derived from Tc24-C4 only activated IFNγ-producing CD4+T cells in one animal. In two animals there was also activation of TSA1-C4-specific IL2-producing CD8+ T cells. This is the first report of the immunogenicity of T. cruzi- derived recombinant antigens formulated as an emulsion with a TLR4 agonist in a non-human primate model. Our results strongly support the need for further evaluation of the preventive efficacy of this type of vaccine in non-human primates and explore the effect of the vaccine in a therapeutic model of naturally-infected Chagasic non-human primates, which would strengthen the rationale for the clinical development as a human vaccine against Chagas disease. [ABSTRACT FROM AUTHOR]

The article offers information on the Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, and has limited treatment options with two drugs available Benznidazole and Nifurtimox. It states that therapeutic vaccination has been proposed for the control of T. cruzi infection. It mentions that preconceptional vaccine aimed at preventing future congenital transmission of the parasite would be good for control of the disease.

The article examines achievements and challenges in research related to Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected tropical disease (NTD) with a high disease burden in the Americas. It reports how estimates of Chagas disease burden and its epidemiological impact provide the basis for health interventions in both endemic and nonendemic countries.

Monte-Carlo burnup calculations are nowadays the reference method to obtain fuel inventories in reactor configurations. Their main drawback is the very long computing time associated with the calculation. A method is presented here which attempts to speed up the calculation by replacing full simulations by perturbation calculations based on correlated sampling. The method is tested in a PWR assembly configuration and numerical results are given for the figure of merit. These results show that a speed-up of up to a factor of 5 can be achieved. [ABSTRACT FROM AUTHOR]

Triatoma sanguisuga is one of the major vectors of Trypanosoma cruzi in the southeastern US, where it sustains a robust zoonotic parasite transmission cycle and occasional human infections. A better understanding of triatomine development may allow for alternative approaches to insecticide-based vector control. Indeed, the role of the gut microbiota and bacterial endosymbionts in triatomine development and in their vectorial capacity is emerging. We investigated here the differences in microbiota among nymph and adult T. sanguisuga, to shed light on the metabolomic interactions occurring during development. Microbiota composition was assessed by 16s gene amplification and deep sequencing from field-caught adult bugs and their laboratory-raised progeny. Significant differences in microbiota bacterial diversity and composition were observed between nymphs and adults. Laboratory-raised nymphs showed a higher taxonomic diversity, and at least seven families predominated. On the other hand, field-caught adults had a lower bacterial diversity and four families comprised most of the microbiota. These differences in compositions were associated with differences in predicted metabolism, with laboratory-raised nymphs microbiota metabolizing a limited diversity of carbon sources, with potential for resource competition between bacterial families, and the production of lactic acid as a predominant fermentation product. On the other hand, field-caught adult microbiota was predicted to metabolize a broader diversity of carbon sources, with complementarity rather than competition among taxa, and produced a diverse range of products in a more balanced manner. The restricted functionality of laboratory-raised nymph microbiota may be associated with their poor development in captivity, and further understanding of the metabolic interactions at play may lead to alternative vector control strategies targeting triatomine microbiota. [ABSTRACT FROM AUTHOR]

Highlights: [•] Particle clustering. [•] Monte Carlo criticality simulation. [•] Spatial correlations. [Copyright &y& Elsevier]

Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8×10−4 (95%CI: [2.6 ; 11.0]×10−4). This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900–4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known not to be proportional one to another. Author Summary: Chagas disease is a parasitic disease affecting about 10 million people, often living in poor conditions, and the disease contributes to impede their development. As several other infectious diseases (malaria, dengue or sleeping sickness), it is transmitted by blood-feeding insect vectors. While most other human pathogens are directly injected with the vector's saliva, Chagas disease parasite is transmitted through the insect's feces that are deposited on the skin during bloodmeals, which seems to be a very inefficient process. The probability of such transmission to human has thus been very hard to estimate, although it is crucial to predict where people are at risk and design effective control strategies. Using mathematical models integrating data on vectors and humans collected across Latin America, we estimated that for several vector species transmission occurs in 1 over 900–4000 contacts with infected insects. We further showed that our estimate allows prediction of human infection rates in various ecological conditions. These models will provide health policy makers with improved indexes to better prioritize/evaluate of the outcomes of vector control programs. [ABSTRACT FROM AUTHOR]

Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8×10−4 (95%CI: [2.6 ; 11.0]×10−4). This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900–4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known not to be proportional one to another. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that is prevalent in Latin America and is a leading cause of heart disease in the region. However, the disease is also present in North America, with Mexico and the United States having a significant number of cases. Poverty and lack of access to healthcare contribute to the transmission of the disease. There is a lack of awareness and surveillance of Chagas disease in North America, and efforts are needed to improve diagnosis, treatment, and research for the disease. [Extracted from the article]

The authors reflect on the occurrence of Chagas' disease in North America. They state that the first diagnosis of Chagas' disease in North America was the American trypanosomiasis caused by Trypanosoma cruzi in Mexico. They mention that connection between the disease transmission and poverty is caused by poor housing that lead for the invasion of triatomine bugs, lack of proper health and education. They say that poor people and specially pregnant women suffer from the burden of the disease.

Background: Chagas disease is a vector-borne disease of major importance in the Americas. Disease prevention is mostly limited to vector control. Integrated interventions targeting ecological, biological and social determinants of vector-borne diseases are increasingly used for improved control. Methodology/principal findings: We investigated key factors associated with transient house infestation by T. dimidiata in rural villages in Yucatan, Mexico, using a mixed modeling approach based on initial null-hypothesis testing followed by multimodel inference and averaging on data from 308 houses from three villages. We found that the presence of dogs, chickens and potential refuges, such as rock piles, in the peridomicile as well as the proximity of houses to vegetation at the periphery of the village and to public light sources are major risk factors for infestation. These factors explain most of the intra-village variations in infestation. Conclusions/significance: These results underline a process of infestation distinct from that of domiciliated triatomines and may be used for risk stratification of houses for both vector surveillance and control. Combined integrated vector interventions, informed by an Ecohealth perspective, should aim at targeting several of these factors to effectively reduce infestation and provide sustainable vector control. Author Summary: Chagas disease is a parasitic disease of major importance in the Americas, transmitted by triatomine insects. Integrated control interventions targeting a combination of factors associated with the presence of the insect vectors are increasingly investigated for improved control. Here we identified the factors associated with the seasonal intrusion of triatomine vectors in houses from the Yucatan peninsula, Mexico, by studying the characteristics of 308 houses from 3 villages. The presence of triatomine vectors was associated with the presence of dogs, chickens and potential bug refuges, such as rock piles, and the proximity of houses to vegetation at the periphery of the villages and to public light sources. Thus, factors favoring seasonal intrusion of triatomines appear different from those favoring their domiciliation. Integrated control interventions based on this Ecohealth perspective should focus on several of the factors identified in this study to achieve effective and sustainable vector control. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a vector-borne disease of major importance in the Americas. Disease prevention is mostly limited to vector control. Integrated interventions targeting ecological, biological and social determinants of vector-borne diseases are increasingly used for improved control. Methodology/principal findings: We investigated key factors associated with transient house infestation by T. dimidiata in rural villages in Yucatan, Mexico, using a mixed modeling approach based on initial null-hypothesis testing followed by multimodel inference and averaging on data from 308 houses from three villages. We found that the presence of dogs, chickens and potential refuges, such as rock piles, in the peridomicile as well as the proximity of houses to vegetation at the periphery of the village and to public light sources are major risk factors for infestation. These factors explain most of the intra-village variations in infestation. Conclusions/significance: These results underline a process of infestation distinct from that of domiciliated triatomines and may be used for risk stratification of houses for both vector surveillance and control. Combined integrated vector interventions, informed by an Ecohealth perspective, should aim at targeting several of these factors to effectively reduce infestation and provide sustainable vector control. [ABSTRACT FROM AUTHOR]

Characterizing the spatial extent of epidemics at the outbreak stage is key to controlling the evolution of the disease. At the outbreak, the number of infected individuals is typically small, and therefore, fluctuations around their average are important: then, it is commonly assumed that the susceptible-infected-recovered mechanism can be described by a stochastic birth-death process of Galton-Watson type. The displacements of the infected individuals can be modeled by resorting to Brownian motion, which is applicable when long-range movements and complex network interactions can be safely neglected, like in the case of animal epidemics. In this context, the spatial extent of an epidemic can be assessed by computing the convex hull enclosing the infected individuals at a given time. We derive the exact evolution equations for the mean perimeter and the mean area of the convex hull, and we compare them with Monte Carlo simulations. [ABSTRACT FROM AUTHOR]

The evolution of several physical and biological systems, ranging from neutron transport in multiplying media to epidemics or population dynamics, can be described in terms of branching exponential flights, a stochastic process which couples a Galton-Watson birth-death mechanism with random spatial displacements. Within this context, one is often called to assess the length …V that the process travels in a given region V of the phase space, or the number of visits nV to this same region. In this paper, we address this issue by resorting to the Feynman-Kac formalism, which allows characterizing the full distribution of …V and nV and in particular deriving explicit moment formulas. Some other significant physical observables associated to … V and nV, such as the survival probability, are discussed as well, and results are illustrated by revisiting the classical example of the rod model in nuclear reactor physics. [ABSTRACT FROM AUTHOR]

Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease that disproportionately affects those living in poverty in the Americas. It is a leading cause of death and disability in the region, particularly due to chronic conditions like Chagasic cardiomyopathy. The disease is not only prevalent in Latin America but also in the US and Europe, with up to 1 million cases in the US alone. Access to treatment is limited and expensive, and the disease is highly stigmatized, hindering care. The text compares the challenges faced by individuals with Chagas disease to those with HIV/AIDS, highlighting the need for increased attention, resources, and global cooperation to address the epidemic and reduce health disparities. [Extracted from the article]

The article discusses issues related to emergence of Neglected tropical diseases (NTDs) in the U.S. According to an estimate all of the "bottom 100 million" in the nation suffer from at least one NTD including Chagas disease. It has been stated that there are many similarities between people living with Chagas disease and people living with HIV/AIDS that includes requirement for prolonged treatment courses in both diseases.

Background: Chagas disease is a major neglected tropical disease with deep socio-economical effects throughout Central and South America. Vector control programs have consistently reduced domestic populations of triatomine vectors, but non-domiciliated vectors still have to be controlled efficiently. Designing control strategies targeting these vectors is challenging, as it requires a quantitative description of the spatio-temporal dynamics of village infestation, which can only be gained from combinations of extensive field studies and spatial population dynamic modelling. Methodology/Principal Findings: A spatially explicit population dynamic model was combined with a two-year field study of T. dimidiata infestation dynamics in the village of Teya, Mexico. The parameterized model fitted and predicted accurately both intra-annual variation and the spatial gradient in vector abundance. Five different control strategies were then applied in concentric rings to mimic spatial design targeting the periphery of the village, where vectors were most abundant. Indoor insecticide spraying and insect screens reduced vector abundance by up to 80% (when applied to the whole village), and half of this effect was obtained when control was applied only to the 33% of households closest to the village periphery. Peri-domicile cleaning was able to eliminate up to 60% of the vectors, but at the periphery of the village it has a low effect, as it is ineffective against sylvatic insects. The use of lethal traps and the management of house attractiveness provided similar levels of control. However this required either house attractiveness to be null, or ≥5 lethal traps, at least as attractive as houses, to be installed in each household. Conclusion/Significance: Insecticide and insect screens used in houses at the periphery of the village can contribute to reduce house infestation in more central untreated zones. However, this beneficial effect remains insufficient to allow for a unique spatially targeted strategy to offer protection to all households. Most efficiently, control should combine the use of insect screens in outer zones to reduce infestation by both sylvatic and peri-domiciliated vectors, and cleaning of peri-domicile in the centre of the village where sylvatic vectors are absent. The design of such spatially mixed strategies of control offers a promising avenue to reduce the economic cost associated with the control of non-domiciliated vectors. Author Summary: Chagas disease is one of the most important parasitic diseases in Latin America. Since the 1980's, many national and international initiatives have contributed to eliminate vectors developing inside human domiciles. Today's challenge is to control vectors that are non-adapted to the human domicile, but still able to transmit the parasite through regular short stay in the houses. Here, we assess the potential of different control strategies applied in specific spatial patterns using a mathematical model that reproduces the dynamic of dispersion of such 'non-domiciliated' vectors within a village of the Yucatan Peninsula, Mexico. We show that no single strategy applied in the periphery of the village, where the insects are more abundant, provides satisfying protection to the whole village. However, combining the use of insect screens in houses at the periphery of the village (to simultaneously fight insects dispersing from the garden and the forest), and the cleaning of the peri-domicile areas of the centre of the village (where sylvatic insects are absent), would provide a cost-effective control. This type of spatially mixed strategy offers a promising way to reduce the cost associated with the repeated interventions required to control non-domiciliated vectors that permanently attempt to infest houses. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a major neglected tropical disease with deep socio-economical effects throughout Central and South America. Vector control programs have consistently reduced domestic populations of triatomine vectors, but non-domiciliated vectors still have to be controlled efficiently. Designing control strategies targeting these vectors is challenging, as it requires a quantitative description of the spatio-temporal dynamics of village infestation, which can only be gained from combinations of extensive field studies and spatial population dynamic modelling. Methodology/Principal Findings: A spatially explicit population dynamic model was combined with a two-year field study of T. dimidiata infestation dynamics in the village of Teya, Mexico. The parameterized model fitted and predicted accurately both intra-annual variation and the spatial gradient in vector abundance. Five different control strategies were then applied in concentric rings to mimic spatial design targeting the periphery of the village, where vectors were most abundant. Indoor insecticide spraying and insect screens reduced vector abundance by up to 80% (when applied to the whole village), and half of this effect was obtained when control was applied only to the 33% of households closest to the village periphery. Peri-domicile cleaning was able to eliminate up to 60% of the vectors, but at the periphery of the village it has a low effect, as it is ineffective against sylvatic insects. The use of lethal traps and the management of house attractiveness provided similar levels of control. However this required either house attractiveness to be null, or $5 lethal traps, at least as attractive as houses, to be installed in each household. Conclusion/Significance: Insecticide and insect screens used in houses at the periphery of the village can contribute to reduce house infestation in more central untreated zones. However, this beneficial effect remains insufficient to allow for a unique spatially targeted strategy to offer protection to all households. Most efficiently, control should combine the use of insect screens in outer zones to reduce infestation by both sylvatic and peri-domiciliated vectors, and cleaning of peridomicile in the centre of the village where sylvatic vectors are absent. The design of such spatially mixed strategies of control offers a promising avenue to reduce the economic cost associated with the control of non-domiciliated vectors. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a major parasitic disease in Latin America, prevented in part by vector control programs that reduce domestic populations of triatomines. However, the design of control strategies adapted to non-domiciliated vectors, such as Triatoma dimidiata, remains a challenge because it requires an accurate description of their spatio-temporal distributions, and a proper understanding of the underlying dispersal processes. Methodology/Principal Findings: We combined extensive spatio-temporal data sets describing house infestation dynamics by T. dimidiata within a village, and spatially explicit population dynamics models in a selection model approach. Several models were implemented to provide theoretical predictions under different hypotheses on the origin of the dispersers and their dispersal characteristics, which we compared with the spatio-temporal pattern of infestation observed in the field. The best models fitted the dynamic of infestation described by a one year time-series, and also predicted with a very good accuracy the infestation process observed during a second replicate one year time-series. The parameterized models gave key insights into the dispersal of these vectors. i) About 55% of the triatomines infesting houses came from the peridomestic habitat, the rest corresponding to immigration from the sylvatic habitat, ii) dispersing triatomines were 5–15 times more attracted by houses than by peridomestic area, and iii) the moving individuals spread on average over rather small distances, typically 40–60 m/15 days. Conclusion/Significance: Since these dispersal characteristics are associated with much higher abundance of insects in the periphery of the village, we discuss the possibility that spatially targeted interventions allow for optimizing the efficacy of vector control activities within villages. Such optimization could prove very useful in the context of limited resources devoted to vector control. Author Summary: Chagas disease is one of the most important neglected diseases in Latin America. Although insecticides have been successfully sprayed to control domiciliated vector populations, this strategy has proven to be ineffective in areas where non-domiciliated vectors immigrating from peridomestic or sylvatic ecotopes can (re-)infest houses. The development of strategies for the control of non-domiciliated vectors has thus been identified by the World Health Organization as a major challenge. Such development primarily requires a description of the spatio-temporal dynamics of infestation by these vectors, and a good understanding of their dispersal. We combined for the first time extensive spatio-temporal data sets describing house infestation dynamics by Triatoma dimidiata inside one village, and spatially explicit population dynamics models. The models fitted and predicted remarkably the observed infestation dynamics. They thus provided both key insights into the dispersal of T. dimidiata in this area, and a suitable mathematical background to evaluate the efficacy of various control strategies. Interestingly, the observed and modelled patterns of infestation suggest that interventions could focus on the periphery of the village, where there is the highest risk of transmission. Such spatial optimization may allow for reducing the cost of control, compensating for repeated interventions necessary for non-domiciliated vectors. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a major parasitic disease in Latin America, prevented in part by vector control programs that reduce domestic populations of triatomines. However, the design of control strategies adapted to non-domiciliated vectors, such as Triatoma dimidiata, remains a challenge because it requires an accurate description of their spatio-temporal distributions, and a proper understanding of the underlying dispersal processes. Methodology/Principal Findings: We combined extensive spatio-temporal data sets describing house infestation dynamics by T. dimidiata within a village, and spatially explicit population dynamics models in a selection model approach. Several models were implemented to provide theoretical predictions under different hypotheses on the origin of the dispersers and their dispersal characteristics, which we compared with the spatio-temporal pattern of infestation observed in the field. The best models fitted the dynamic of infestation described by a one year time-series, and also predicted with a very good accuracy the infestation process observed during a second replicate one year time-series. The parameterized models gave key insights into the dispersal of these vectors. i) About 55% of the triatomines infesting houses came from the peridomestic habitat, the rest corresponding to immigration from the sylvatic habitat, ii) dispersing triatomines were 5-15 times more attracted by houses than by peridomestic area, and iii) the moving individuals spread on average over rather small distances, typically 40-60 m/15 days. Conclusion/Significance: Since these dispersal characteristics are associated with much higher abundance of insects in the periphery of the village, we discuss the possibility that spatially targeted interventions allow for optimizing the efficacy of vector control activities within villages. Such optimization could prove very useful in the context of limited resources devoted to vector control. [ABSTRACT FROM AUTHOR]

Abstract: Trypanosoma cruzi and the genus Leishmania are protozoan parasites causing diseases of major public health importance, and the recent completion of the sequencing of their genomes has opened new opportunities to further our understanding of the mechanisms required for protection and the development of vaccines. For example, trans-sialidases, one of the largest protein families from T. cruzi, contain dominant CD8+ T cell epitopes, and their use as preventive or therapeutic vaccines in different animal models has provided encouraging results. A much wider range of antigens and vaccine formulations have been tested against Leishmania, and new correlates for protection are being defined, such as the induction of multifunctional Th1 effector cells capable of producing a complex set of cytokines. Also, while a large number of these vaccine candidates have been rather successful in mouse models, their usefulness in more relevant animal models is still poor, in spite of significant immunogenicity. Novel proteomics and genomics approaches are being used for antigen discovery and the identification of new vaccine candidates, some of which have shown promise for the control of infection. These studies cast little doubt that T. cruzi and Leishmania genomes represent major resources for understanding key aspects of the mechanisms of immune protection against these parasites, and the increasing use of these tools will greatly impact vaccine development. [Copyright &y& Elsevier]

Various variance-reduction techniques are used in Monte Carlo particle transport. Most of them rely either on a hypothesis made by the user (parameters of the exponential biasing, mesh and weight bounds for weight windows, etc.) or on a previous calculation of the system with, for example, a deterministic solver. This paper deals with a new acceleration technique, namely, autoadaptative neural network biasing. Indeed, instead of using any a priori knowledge of the system, it is possible, at a given point in a simulation, to use the Monte Carlo histories previously simulated to train a neural network, which, in return, should be able to provide an estimation of the adjoint flux, used then for biasing the simulation. We will describe this method, detail its implementation in the Monte Carlo code Tripoli4, and discuss its results on two test cases. [ABSTRACT FROM AUTHOR]

Trypanosomiasis is one of the most important parasitic diseases worldwide. The undesirable side effects and low efficacy of classical trypanocidal drugs underline the necessity of the development of new drugs from natural products. Although marine algae have been recognized as attractive sources of known and novel bioactive compounds, very little research has been focused on antiprotozoal activity. Aqueous and organic extracts of 29 species of marine algae (14 species of Rhodophyta, seven species of Phaeophyta, and eight species of Chlorophyta) collected from the Gulf of Mexico and Caribbean coast of the Yucatan Peninsula (Mexico) were evaluated for their antiprotozoal activity in vitro against Trypanosoma cruzi trypomastigotes. The toxicity of these extracts was evaluated using brine shrimp ( Artemia salina). The cytotoxicity on mammalian cells was also assessed by the MTT viability assay. The organic extracts from Dictyota caribea Horning & Schnetter, Lobophora variegata (J.V. Lamouroux) Womersley, Turbinaria turbinata Linnaeus, and Laurencia microcladia Kützing possess promising in vitro activity against T. cruzi trypomastigotes. The toxicity displayed by Laurencia microcladia against Artemia salina and the high cytotoxicity exhibited by T. turbinata must be taken into account in further studies. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is the most important vector-borne disease in Latin America. Regional initiatives based on residual insecticide spraying have successfully controlled domiciliated vectors in many regions. Non-domiciliated vectors remain responsible for a significant transmission risk, and their control is now a key challenge for disease control. Methodology/Principal Findings: A mathematical model was developed to predict the temporal variations in abundance of non-domiciliated vectors inside houses. Demographic parameters were estimated by fitting the model to two years of field data from the Yucatan peninsula, Mexico. The predictive value of the model was tested on an independent data set before simulations examined the efficacy of control strategies based on residual insecticide spraying, insect screens, and bednets. The model accurately fitted and predicted field data in the absence and presence of insecticide spraying. Pyrethroid spraying was found effective when 50 mg/m2 were applied yearly within a two-month period matching the immigration season. The >80% reduction in bug abundance was not improved by larger doses or more frequent interventions, and it decreased drastically for different timing and lower frequencies of intervention. Alternatively, the use of insect screens consistently reduced bug abundance proportionally to the reduction of the vector immigration rate. Conclusion/Significance: Control of non-domiciliated vectors can hardly be achieved by insecticide spraying, because it would require yearly application and an accurate understanding of the temporal pattern of immigration. Insect screens appear to offer an effective and sustainable alternative, which may be part of multi-disease interventions for the integrated control of neglected vector-borne diseases. Author Summary: Chagas disease is the most important vector-borne disease in Latin America. Residual insecticide spraying has been used successfully for the elimination of domestic vectors in many regions. However, some vectors of non-domestic origin are able to invade houses, and they are now a key challenge for further disease control. We developed a mathematical model to predict the temporal variations in abundance of non-domiciliated vectors inside houses, based on triatomine demographic parameters. The reliability of the predictions was demonstrated by comparing these with different sets of insect collection data from the Yucatan peninsula, Mexico. We then simulated vector control strategies based on insecticide spraying, insect, screens and bednets to evaluate their efficacy at reducing triatomine abundance in the houses. An optimum reduction in bug abundance by at least 80% could be obtained by insecticide application only when doses of at least 50 mg/m2 were applied every year within a two-month period matching the house invasion season by bugs. Alternatively, the use of insect screens consistently reduced bug abundance in the houses and offers a sustainable alternative. Such screens may be part of novel interventions for the integrated control of various vector-borne diseases. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is the most important vector-borne disease in Latin America. Regional initiatives based on residual insecticide spraying have successfully controlled domiciliated vectors in many regions. Non-domiciliated vectors remain responsible for a significant transmission risk, and their control is now a key challenge for disease control. Methodology/Principal Findings: A mathematical model was developed to predict the temporal variations in abundance of non-domiciliated vectors inside houses. Demographic parameters were estimated by fitting the model to two years of field data from the Yucatan peninsula, Mexico. The predictive value of the model was tested on an independent data set before simulations examined the efficacy of control strategies based on residual insecticide spraying, insect screens, and bednets. The model accurately fitted and predicted field data in the absence and presence of insecticide spraying. Pyrethroid spraying was found effective when 50 mg/m2 were applied yearly within a two-month period matching the immigration season. The >80% reduction in bug abundance was not improved by larger doses or more frequent interventions, and it decreased drastically for different timing and lower frequencies of intervention. Alternatively, the use of insect screens consistently reduced bug abundance proportionally to the reduction of the vector immigration rate. Conclusion/Significance: Control of non-domiciliated vectors can hardly be achieved by insecticide spraying, because it would require yearly application and an accurate understanding of the temporal pattern of immigration. Insect screens appear to offer an effective and sustainable alternative, which may be part of multi-disease interventions for the integrated control of neglected vector-borne diseases. [ABSTRACT FROM AUTHOR]

As part of an ongoing effort to develop a vaccine against Leishmania mexicana, we tested DNA vaccines encoding L. mexicana GP63, CPb, and LACK, and L. amazonensis GP46, to evaluate this strategy and define the best antigen candidates. Immune responses and vaccine efficacy were evaluated in BALB/c mice immunized with plasmid DNA encoding the different antigens. All four DNA vaccines induced Leishmania-specific humoral and lympho-proliferative immune responses. However, only mice immunized with VR1012-GP46, VR1012-GP63 and VR1012-CPb were partially protected against infection, as evidenced by reduced lesion size and parasite burden. Interestingly, immunization of mice with a mixture of these three plasmids further increased protection. Thus, plasmids encoding CPb, GP63 and GP46 represent good candidates for further development of DNA vaccines against L. mexicana. [Copyright &y& Elsevier]

Infections with SARS-CoV-2 can progress toward multiple clinical outcomes, and the identification of factors associated with disease severity would represent a major advance to guide care and improve prognosis. We tested for associations between SARS-CoV-2 genomic variants from an international cohort of 2508 patients and mortality rates. Findings were validated in a second cohort. Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality. Three SNPs remained associated with mortality in a generalized linear model (GLM) that also included patient age, sex, geographic region, and month of sample collection. Multiple SNPs were confirmed in the validation cohort. These SNPs represent targets to assess the mechanisms underlying COVID-19 disease severity and warrant straightforward validation in functional studies. [ABSTRACT FROM AUTHOR]

Investigates the relationship between the cold-induced increase in sarcoplasmic reticulum CA2+ transport proteins and the development of muscular nonshivering thermogenesis. Time course of expression of the sarcoplasmic or endoplasmic reticulum Ca2+-ATPASE; Calcium uptake; Polyacrylamide gel electrophoresis and immunoblot analysis.

Compares the body and peripheral skin temperatures, metabolic rate and thermal insulation in juvenile and adult Gentoo penguins. Metabolic and insulative responses in air and water; Metabolic rate; Thermal insulation; Peripheral skin temperature.

Studies the effects of prolonged cold exposure on the functioning of the sarcoplasmic reticulum (SR) in ducklings. Contents of SR Ca2+ -ATPase and Ca2+ release channel in the gastrocnemius muscle; Increase in SR Ca2+ -ATPase activity; Relationship with nonshivering thermogenesis of muscular origin.

The "Dr. Hideyo Noguchi" Regional Research Center, located at the Autonomous University of Yucatan in Mexico, is a leading facility for scientific medical research. The center was established in 1975 and has since grown to include departments in tropical pathology, reproductive health, physiology, and social sciences. It has become a major research facility in southern Mexico, with a focus on infectious and tropical diseases. The center has made significant contributions to the understanding and control of diseases such as dengue, West Nile virus, rickettsiosis, leishmaniasis, and Chagas disease. It also plays a role in training health professionals and contributes to the formal teaching programs of the university. The center's research has had a significant impact on regional and national health policies. [Extracted from the article]

The article focuses on the history and achievements of the Autonomous University of Yucatan in Southern Mexico. It states that the public university was founded on October 12, 1975 and was named in honor of Hideyo Noguchi, a famous Japanese scientist who worked on yellow fever in the region. Moreover, the Center has established itself with 66 researchers and 44 research technicians by which its mission is to improve research in health, disease, social sciences.

Chagas disease is a zoonotic, parasitic, vector-borne neglected tropical disease that affects the lives of over 6 million people throughout the Americas. Trypanosoma cruzi, the causative agent, presents extensive genetic diversity. Here we report the genome sequence of reference strain SC43cl1, a hybrid strain belonging to the TcV discrete typing unit (DTU). The assembled diploid genome was 79 Mbp in size, divided into 1236 contigs with an average coverage reaching 180×. There was extensive synteny of SC43cl1 genome with closely related TcV and TcVI genomes, with limited sequence rearrangements. TcVI genomes included several expansions not present in TcV strains. Comparative analysis of both nuclear and kinetoplast sequences clearly separated TcV from TcVI strains, which strongly supports the current DTU classification. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi is a protozoan parasite causing Chagas disease, with a complex life cycle involving different stages in insect vectors and mammalian hosts. Amastigotes are an intracellular form that replicates in the cytoplasm of host cells, and recent studies suggested that dormant forms may be contributing to parasite persistence, suggesting cellular heterogeneity among amastigotes. We investigated here if a transcriptomic approach could identify some heterogeneity in intracellular amastigotes and identify a dormant population. We used gene expression data derived from bulk RNA-sequencing of T. cruzi infection of human fibroblasts for deconvolution using CDSeq, which allows to simultaneously estimate amastigote cell-type proportions and cell-type-specific expression profiles. Six amastigote subpopulations were identified, confirming intracellular amastigotes heterogeneity, and one population presented characteristics of non-replicative dormant parasites, based on replication markers and TcRAD51 expression. Transcriptomic approaches appear to be powerful to understand T. cruzi cell differentiation and expansion of these studies could provide further insight on the role different cell types in parasite persistence and Chagas disease pathogenesis. [ABSTRACT FROM AUTHOR]

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient's home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel species of Triatoma in Belize indicates an increased risk of transmission to humans in the region and warrants expanded surveillance and further investigation. [ABSTRACT FROM AUTHOR]

Chagas disease by Trypanosoma cruzi (T. cruzi) infection is a leading cause of myocarditis worldwide. Chagas cardiomyopathy is presented with a wide variety of conduction abnormalities including arrhythmias, first- and second-degree atrioventricular blockade, left ventricular systolic dysfunction and some cases heart failure leading to the death. Currently, there are no effective treatments available against advanced Chagas disease. With the advance in the development of novel therapies, it is important to utilize an animal model that can effectively replicate the diverse stages of Chagas disease, including chronic asymptomatic and symptomatic infection, that are akin to those observed in humans. Therefore, to characterize the cardiac alterations during the evolution of the infection, we evaluated the progression of cardiomyopathy caused by T. cruzi H1 infection in both BALB/c and ICR mouse models by performing electrocardiogram (ECG) studies in unanesthetized mice every month until 210 days post-infection (dpi). In the late chronic phase of infection, we also performed echocardiogram (ECHO) studies to further assess cardiac function. In conclusion, we demonstrated that ICR mice were more susceptible to cardiac alterations compared to BALB/c mice and both mouse strains are suitable experimental models to study chronic T. cruzi infection and novel treatments. [ABSTRACT FROM AUTHOR]

The behavior of Monte Carlo criticality simulations is often assessed by examining the convergence of the so-called entropy function. In this work, we shall show that the entropy function may lead to a misleading interpretation, and that potential issues occur when spatial correlations induced by fission events are important. We will support our analysis by examining the higher-order moments of the entropy function and the center of mass of the neutron population. Within the framework of a simplified model based on branching processes, we will relate the behavior of the spatial fluctuations of the fission chains to the key parameters of the simulated system, namely, the number of particles per generation, the reactor size and the migration area. Numerical simulations of a fuel rod and of a whole core suggest that the obtained results are quite general and hold true also for real-world applications. [ABSTRACT FROM AUTHOR]

A multifaceted intervention to improve syphilis screening and treatment in pregnant women in Kinshasa, Democratic Republic of the Congo and in Lusaka, Zambia: a cluster randomised controlled trial. I cruzi i infection into preventing mother-to-child transmission of HIV and syphilis should encourage us to also simplify our screening approaches for Chagas disease [[2], [12]]. We are proposing a new screening algorithm (Fig 1) that would decrease the number of false negatives, simplify the follow-up, and accelerate access to treatment for children. [Extracted from the article]