Intra-haplotypic recombination is unlikely to accompany meiotic crossover events in these areas of the genome Furthermore, we considered the extent to which our multiple-clone sampling strategy chosen to avoid underrepresentation of SNP linkage or diversity within infections might affect sample independence and variance-based statistical results.
Linkage decay plots and other diversity metrics above were therefore also repeated using only one clone per infection source. Following methods established to quantify complex microbial life cycles 73 , we inferred the frequency of sex and clonality in T.
These regression models were developed in Rogers et al. First, we created sequence alignment maps for ten non-recombinant individuals based on observed genotypes using BAMSurgeon v1. Maps were set up for each individual by inserting fixed polymorphisms from the true sample set into TcI-Sylvio sequence reads, then spiking in random mutations at rates corresponding to the average number of pairwise differences in the observed data.
In the second approach, we used fastsimcoal2 v5. We also visualized linkage patterns by measuring taxon topology weightings in windowed analysis. Taxon topology weightings provide a means to clarify phylogenetic structure by summarizing the extent to which tree topologies for a subset of samples contribute to the topology of the full tree These analyses prompted further sequence visualizations with Artemis v.
We then calculated the median of these windowed depth-means m , i. This procedure produced estimates of disomy for all chromosomes of the TcI—Sylvio guide-sample and outperformed techniques based on different window-sizes as well as those refined according to sequence annotation e.
We validated cases of chromosomal copy number variation by plotting kernel densities for m , as well as by assessing raw depth and alternate allele frequencies across variant sites. True, whole-chromosomal trisomy, for example, should translate to chromosome-wide elevations in read-depth and reductions in minor allele contributions to ca.
Intra-chromosomal amplification, in contrast, should create local shifts in read-depth and allelic composition within chromosomes. In follow-up assessment of temporal and sub-clonal ploidy variation, we re-sequenced three clones and derivative subclones on the Illumina NextSeq platform Supplementary Table 4.
Subclones were obtained using the limiting dilution method as described in Messenger et al. Further information on research design is available in the Nature Research Reporting Summary linked to this article.
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Derrien, T. Fast computation and applications of genome mappability. Cingolani, P. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w; iso -2; iso Austin 6 , 80—92 Clonal heterogeneity in T. More recently, molecular analysis methods showed that there is high diversity even within DTUs Roman et al. The already classic reference strains, such as the Y, Colombiana, Esmereldo, CL, and other strains, are highly passaged strains, kept for many years in laboratories, and are therefore subjected to the selective pressures inherent to these methods and hardly represent the diversity of T.
The selection of T. Clonal selection certainly also occurs in the natural environment and is directed by the host species mammal or triatomine infection route and other factors. Considering that each species and even individual interacts differently with the different subpopulations of T. Given that the true diversity of T. Finally, when faced with such a complex model, it is prudent not to dogmatize and to always be open to reviewing concepts.
Although Barretto has drawn attention to the correlation between environmental disruption and the onset of human disease, this knowledge has not been incorporated into the routine of preventive actions. Nor could it be incorporated because the transmission of T.
Therefore, the successful campaign to eliminate indoor T. Thus, it was possible to use the same vector combat methodology throughout. Despite the focus of the present study not being human disease or infection, the control of intradomicile T.
This was indeed a very important landmark. In fact, the Chagas Disease Control Program established in Brazil in achieved, in this continental-sized country, a highly successful campaign, starting from millions of infected people to zero in 25 years Schofield and Maudlin, In terms of public health, this was an enormous milestone.
Even though it was not technically complicated, it was necessary to train and supervise a large number of men who had to undergo hard work in some cases in very severe climatic conditions, working under standard protocols across the vast area, all without today's communication facilities.
An additional difficulty was the local peculiarities of several regions of the country. It was proposed that the control of T. Will there be intrahome transmission of T. It is hard to know. In addition to the improvements that have occurred in several housings, it was proposed that habitat change and adaptation to a new environment constitute a long evolutionary process in triatomines Schofield et al.
Currently, Chagas disease is of concern again but with an entirely new, challenging and very complex epidemiological profile. Trypanosomiasis by T.
This spillover to nonendemic areas, including other continents out of the Americas, is mainly due to uncontrolled migratory movements, blood transfusion and organ transplantation Franco-Paredes et al. Additionally, the enzootic nature of Chagas disease has been extending its limits, as has been observed in the southern United States, where an increase in the number of infected dogs as well as an increase in the areas of occurrence have been described Curtis-Robles et al. Dogs are the last barrier between the wild cycle of transmission and the human environment.
A recent review on the subject estimated that there are , T. This number is likely underestimated. In Latin America, outbreaks and cases of oral Chagas disease have been increasing worryingly, especially because, in general, they result in severe clinical manifestations contrary to what is known of this infection in animals.
Opossums fed on infected triatomine or mice serologically convert much later than when infected subcutaneously and do not have patent parasitemia like humans. What makes the early diagnosis of Chagas disease fundamental is the increased chance of cure of the infected individuals who has early access to treatment and the increased chance of those infected and precociously treated individuals remaining asymptomatic and not progressing to the severe forms of disease.
What makes early detection of T. In fact, although T. Thus, the outbreak of Chagas disease that occurred in in southern Brazil, in Santa Catarina, related to the consumption of contaminated sugarcane juice, raised several tantalizing hypotheses that were being discarded as the real cause was brought to light as, for example, sugarcane plantations would favor the multiplication of triatomines. It was found that the contamination occurred at the sugarcane mill located near a window in which infected triatomines fell into from a neighboring palm tree probably attracted by light Roque et al.
Despite the presence of T. Humans in those areas did not expose themselves or their food to triatomine bugs. There was never a case or outbreak in these localities again. Several cases were reported in the riverside population, usually as a familial outbreak.
The difficulties in access to health professionals, the lack of information about the transmission and symptoms and, mainly, the complete absence of sanitary care likely resulted in the underestimation of such outbreaks. In fact, the distribution of bugs in Amazonian palm trees is neither homogeneous nor random but is much more intense in palm trees with higher accumulation of organic material Abad-Franch et al.
This feature may also occur when one beverage is produced and contaminated in one area but is consumed and responsible for infecting people in other areas.
This situation occurred in the largest Chagas disease oral outbreak ever reported in a school in the urban area of Caracas, Venezuela. In addition to beverages, T. In this case, the instrument used to cut vegetation probably came in contact with an infected bug probably cutting its body , and this same instrument was used to cut the palm heart before distributing it to the families.
On the other hand, bacaba juice is sporadically consumed and, due to its high output up to 10 liters , it is usually consumed with friends and for more than 1 day. The most recent outbreak in Brazil occurred in September , resulting in the infection of 16 individuals, and was associated with the consumption of the fruit of the patawa tree Oenocarpus bataua , a palm tree that reaches 25 m height.
This highly appreciated palm tree is found in the Amazon basin, and its fruits are used for several purposes, including juice preparation. Altogether, these cases demonstrate that, more than a specific food, human outbreak cases are the result of poor sanitary education and poor practices of food manipulation. Oral infection may occur directly by contact with infected triatomine feces, independent of comestibles, as was observed by fatal case of a 2-year-old boy from Guarapari, in the Brazilian Southeast Region.
The infection was associated with Triatoma vitticeps , a triatomine considered to be a secondary vector due to its delay of defecation after a blood meal but that demonstrated to be quite efficient in concomitantly hosting several T.
The boy was infected by handling this T. One of the largest Brazilian outbreaks of Chagas disease occurred in Ibimirim, in the Brazilian Northeast Region, and was tentatively associated with food.
Moreover, the real source of infection that resulted in 30 treated individuals was not yet identified 6 months later. These distinct epidemiological scenarios throughout Brazil show the necessity of distinct control measures. The definitive control of Chagas disease is possible and, more than that, is urgent. It should not be possible that this parasitosis is still a scourge more than one hundred years after its discovery and so much accumulated knowledge.
However, control will be possible only under an integrated multidisciplinary focus and not by the traditional control measures. Spraying in this new epidemiological scenario is the worst control method. The development of an understanding of all cultural, social and economic realities of the outbreak areas and, obviously, all epidemiological features, including fauna composition hosts and vectors, will be the only way to define and adopt the correct measures that must include economic, health and educational improvement.
Pioneers in epidemiology postulated that all infected organisms are equally capable of infecting other organisms; that is, they have similar infectious competence. Obviously, the emergence of a superspreader is also regulated by other variables, such as immunosuppression and concomitant infections. This phenomenon has already been described in numerous parasitic diseases, including Leishmania infantum Duthie et al. Trypanosoma cruzi is a mammalian hematozoan that depends on an insect vector for its passage to another mammalian host.
The chances of infecting a hematophagous insect are increased, among others, if the parasitic population in peripheral blood is high. Interestingly, parasites in fresh blood smears or other blood tests of infected mammals are extremely rare in Brazil, independent of the T.
Positive blood cultures or positive xenodiagnoses are parasitological enrichment methods that indicate high parasitemia and, therefore, the infectious potential of the animal. Working with hemocultures under field conditions is safer than working with xenodiagnoses, which includes a longer restraining time of the animal and is not free of accidents that result in the evasion of insects.
Figure 2A shows the distribution of T. TcV is the most rarely found DTU. Four aspects deserve to be highlighted: i the transmission strategies of the less frequent DTUs; ii the fact that these DTUs are detected at extremely distant points; iii the lack of association of DTUs with biomes; and iv the high diversity of DTUs in a relatively small area of the southeastern Atlantic Forest.
Increasing studies of habitats and areas will probably add information that may change this map. All of these questions show that the biological history of T.
Numerous chapters are still to be written about the biological history of T. Figure 2. Still considering the positive hemocultures, opossums, mainly Philander spp. This does not seem to be a superspreader maintenance strategy. The possible survival strategy of T.
Apparently, most mammalian species have high parasitemia periods for short times, i. Only some species have a long period of high parasitemia detectable by blood culture, which means a long period of infectious potential, as mentioned above. Most likely, infected animals with negative blood culture had already passed their early stages of infection and infectious potential.
To validate this hypothesis, it would be necessary to have representative samples of T. Another question refers to the permanence of the less frequent T. The two possible hypotheses are i that at some point in the infection, these genotypes had a high circulating blood population; or ii other unknown transmission mechanisms warrant transmission in low parasitemias, as is the case in Brazil of the DTUs TcV and TcVI that are rarely found in nature.
A plausible explanation can be drawn from a Santa Catarina outbreak in At that location, the wild mammal fauna was restricted to marsupials of the genus Didelphis whose blood cultures indicated in TcI in contrast to the human cases that were all by TcII. A clear demonstration of how biased associations can be established is provided by Guarapari's case of the child who became orally infected by T.
Reports of mixed human infections with such diversity of T. This is most likely due to the rarity of histopathological examinations followed by the molecular characterization of tissues of individuals in the acute phase, i. This individual would likely not maintain such diversity indefinitely. Infections by some DTUs could be self-solving. At least T. Additionally, even total blood PCR is not necessarily representative of the richness of trypanomatid genotypes and species that infect a particular individual, not to mention the selective pressures exerted on the parasites by the immune response.
The parasitological history of an individual is totally ignored when it is examined at later stages of infection. This results in at least two biases: i clinical manifestations are attributed only to that species or genotype that eventually is detected, and the possible effects of an initial multiple infection are totally ignored; and ii associations between the host and parasite species or genotypes are established based only on one single finding that is very probably not necessarily representative.
There are still many open questions on this topic, one of which specifically refers to the transmission of these genotypes and species that are so rarely found in nature. Are they becoming extinct, or are they beginning a process of expansion? Mixed infections by species or by subpopulations of the same species are common phenomena in nature.
They are difficult to follow because wildlife capture and recapture studies require very expensive infrastructure as well as specific diagnostic kits. Mixed infections by distinct T. Theoretical models predict an increase in virulence based on the competitive advantage of the most virulent subpopulations Cressler et al.
This would be the case with competition for nutrients. However, there are other variables that may alter this fate, such as the host immune response or the parasite's realized niche. Mixed infection is a topic that has been receiving increasing attention due to the possible impacts on the host. Concerning genotypes of T. The authors observed that unlike single infections, coinfections resulted in increased expression of IL10 and TNF, which led the authors to conclude that mixed infection has the potential to favor parasite control.
Other authors suggest that, in contrast, mixed infections tend to increase pathogenicity. Under natural conditions, the presence of T. It was not possible in this case to make any prediction on the course of this infection, but the acute course of the disease 3 weeks followed by death makes one think that in this case, perhaps the effect of the mixed infection would have had the opposite effect Dario et al. In fact, the evaluation of the resultant coinfection of distinct T.
The same methodological approach was used to test human T. Still concerning free-ranging wild mammals, small rodents were also able to harbor multiple T. Bats and marsupials have been proposed as bioaccumulators of Trypanosoma spp. The use of blood clots for the extraction of Trypanosoma spp. DNA and nested PCR using generalist primers followed by Sanger sequencing demonstrated to be a reliable parasitological method that is more accessible than next-generation sequencing, which is still costly, especially for developing countries.
Studying biological phenomena without considering the scenario in which they occur results in the loss of precious and potentially enlightening information.
The determination of the spatial distribution of the elements that compose the epidemiological chain of a parasitic disease is of pivotal importance for the determination of trends and risk evaluation. Moreover, it is worth mentioning that the attempts to control a given multihost parasite that displays a huge intraspecific heterogeneity and a complex transmission cycle as expressed by different epidemiological and enzootiological scenarios employing one single measure will be insufficient.
The sustainability of successful control of Chagas in multiple current epidemiological scenarios requires multidisciplinary studies. All of the host species select subpopulations of T. The study of landscape by the classic methodology of mapping by means of discrete typing units and sharp boundaries does not consider transition areas.
Nevertheless, environmental and biological phenomena are typically continuous and exhibit a gradual transition from one to another. The fuzzy logic developed by Zadeh in the s is able to solve the strongly non-linear nature of uncertainty and subjectivity inherent in biological data.
Furthermore, the spatial analysis by the fuzzy inference method is a cartographic approach that makes it possible to model the spatial distribution of continuous biological phenomena, representing these distribution levels. Modeling by fuzzy logic allows the incorporation of multidisciplinary expert knowledge into the evaluation process. Despite posing as a paradigm break in comparison to the valuation methodologies based on classic logic, fuzzy theory facilitates dialog between the professionals of exact sciences, responsible for computational implementation, and experts from different biological areas because it allows the use of linguistic variables and simplistic logical rules.
Such logic has been vastly used in biological modeling due to its peculiar features, especially the capacity to model complex and non-linear problems in a simple way.
Fuzzy logic is a novel approach for Chagas disease risk prediction. This model already demonstrated the possibility of identifying areas with different degrees of risk, thus allowing a continuous and integrated representation of the variables involved in T. The output data obtained can be used to support decision-making in epidemiological surveillance of Chagas disease and are certainly an example that can be applied to several other parasite infections in distinct areas Xavier et al.
Fuzzy models are highly promising for evaluating T. Spatial analysis by the interpolation method, followed by map algebra, is able to model the spatial distribution of biological phenomena and their distribution and eventual association with other parameters or variables, enhancing the decision power of responsible authorities. Acute Chagas disease outbreaks are increasing in the Amazon basin as a result of oral transmission. This scenario requires a new approach to identify hotspot transmission areas and implement control measures.
A geospatial approach using interpolation and map algebra methods to evaluate mammalian fauna was demonstrated to be a reliable strategy to detect hotspot transmission areas in the wild. The construction of maps with mammalian fauna variables, including the infection rates by T. Consequently, it was shown that monitoring T. The results obtained by visual examination of the maps were validated by statistical analysis Xavier et al.
Here, we briefly described some features that have been landmarks in the course of knowledge building on Trypanosoma cruzi. Because it is such a complex parasite, T.
While the main attributes of T. Undoubtedly, the huge technological advance and the consequent stronger analytical power allowed the resolution of many of these issues. However, the current epidemiological profile of Chagas disease, due to the oral route, constitutes a challenge and a scourge, especially for people with less access to adequate sanitary conditions and medical care. This kind of attitude is paralyzing, just as paralyzing as the lack of self-confidence and the hesitation to publish their findings.
Science also includes intuition beyond assumptions built on solid foundations. It was a boarding school where several young people became ill and Chagas disease was diagnosed. At the time, all searches for triatomines resulted in vain. The outbreak remained unexplained. It was not far from the truth.
In , almost 20 years later, Deane and coauthors described the extracellular cycle of T. So also did Carlos Chagas: he made the discoveries that made him famous while in charge of studying malaria in the region where a railway was built.
As soon as he was informed by a construction engineer of the blood-sucking insects, he did not hesitate to collect and examine them. He also examined domestic and wild animals as well as humans. Accordingly, he closed the main contours of this new zoonosis. Technological advancement has resulted in new insights into the parasitism phenomenon and consequently in the reformulation of concepts. An example is the definition of what constitutes a reservoir.
The very concepts of reservoir and of what is a parasite have been changing since the days of Carlos Chagas. In this sense, the most didactic and clear definition of what is a reservoir does not refer to the number of species or the ability to cause or not to damage but defines reservoir as one animal species or a set of animal species responsible for maintaining the parasite in the wild.
This set of animals will be different for each location and time scale Jansen et al. Parasitic specificity has also been revisited as a consequence of technological innovation, and the awareness of the importance of including wild animals and their parasites in parasitology studies has increased.
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