Science.gov

Sample records for dimidiata chagas disease

  1. Antennal phenotype of Mexican haplogroups of the Triatoma dimidiata complex, vectors of Chagas disease.

    PubMed

    May-Concha, Irving; Guerenstein, Pablo G; Ramsey, Janine M; Rojas, Julio C; Catalá, Silvia

    2016-06-01

    Triatoma dimidiata (Latreille) is a species complex that spans North, Central, and South America and which is a key vector of all known discrete typing units (DTU) of Trypanosoma cruzi, the etiologic agent of Chagas disease. Morphological and genetic studies indicate that T. dimidiata is a species complex with three principal haplogroups (hg) in Mexico. Different markers and traits are still inconclusive regarding if other morphological differentiation may indicate probable behavioral and vectorial divergences within this complex. In this paper we compared the antennae of three Mexican haplogroups (previously verified by molecular markers ND4 and ITS-2) and discussed possible relationships with their capacity to disperse and colonized new habitats. The abundance of each type of sensillum (bristles, basiconics, thick- and thin-walled trichoids) on the antennae of the three haplogroups, were measured under light microscopy and compared using Kruskal-Wallis non-parametric and multivariate non-parametric analyses. Discriminant analyses indicate significant differences among the antennal phenotype of haplogroups either for adults and some nymphal stages, indicating consistency of the character to analyze intraspecific variability within the complex. The present study shows that the adult antennal pedicel of the T. dimidiata complex have abundant chemosensory sensilla, according with good capacity for dispersal and invasion of different habitats also related to their high capacity to adapt to conserved as well as modified habitats. However, the numerical differences among the haplogroups are suggesting variations in that capacity. The results here presented support the evidence of T. dimidiata as a species complex but show females and males in a different way. Given the close link between the bug's sensory system and its habitat and host-seeking behavior, AP characterization could be useful to complement genetic, neurological and ethological studies of the closely

  2. Public Street Lights Increase House Infestation by the Chagas Disease Vector Triatoma dimidiata

    PubMed Central

    Pacheco-Tucuch, Freddy Santiago; Ramirez-Sierra, Maria Jesus; Gourbière, Sébastien; Dumonteil, Eric

    2012-01-01

    Triatoma dimidiata is one of the primary vectors of Chagas disease. We previously documented the spatio-temporal infestation of houses by this species in the Yucatan peninsula, Mexico, and found that non-domiciliated triatomines were specifically attracted to houses. However, the factors mediating this attraction remained unclear. Artificial light has been known for a long time to attract many insect species, and therefore may contribute to the spread of different vector-borne diseases. Also, based on the collection of different species of triatomines with light traps, several authors have suggested that light might attract triatomines to houses, but the role of artificial light in house infestation has never been clearly demonstrated and quantified. Here we performed a spatial analysis of house infestation pattern by T. dimidiata in relation to the distribution of artificial light sources in three different villages from the Yucatan peninsula, Mexico. In all three villages, infested houses were significantly closer to public street light sources than non-infested houses (18.0±0.6 vs 22.6±0.4 m), and street lights rather than domestic lights were associated with house infestation. Accordingly, houses closer to a public street lights were 1.64 times more likely to be infested than houses further away (OR, CI95% 1.23–2.18). Behavioral experiments using a dual-choice chamber further confirmed that adult male and females were attracted to white light during their nocturnal activity. Attraction was also dependent on light color and decreased with increasing wavelength. While public lighting is usually associated with increased development, these data clearly show that it also directly contributes to house infestation by non-domiciliated T. dimidiata. PMID:22558384

  3. Invasion speeds of Triatoma dimidiata, vector of Chagas disease: An application of orthogonal polynomials method.

    PubMed

    Mesk, Mohammed; Mahdjoub, Tewfik; Gourbière, Sébastien; Rabinovich, Jorge E; Menu, Frédéric

    2016-04-21

    Demographic processes and spatial dispersal of Triatoma dimidiata, a triatomine species vector of Chagas disease, are modeled by integrodifference equations to estimate invasion capacity of this species under different ecological conditions. The application of the theory of orthogonal polynomials and the steepest descent method applied to these equations, allow a good approximation of the abundance of the adult female population and the invasion speed. We show that: (1) under the same mean conditions of demography and dispersal, periodic spatial dispersal results in an invasion speed 2.5 times larger than the invasion speed when spatial dispersal is continuous; (2) when the invasion speed of periodic spatial dispersal is correlated to adverse demographic conditions, it is 34.7% higher as compared to a periodic dispersal that is correlated to good demographic conditions. From our results we conclude, in terms of triatomine population control, that the invasive success of T. dimidiata may be most sensitive to the probability of transition from juvenile to adult stage. We discuss our main theoretical predictions in the light of observed data in different triatomines species found in the literature. PMID:26807809

  4. Eco-geographical differentiation among Colombian populations of the Chagas disease vector Triatoma dimidiata (Hemiptera: Reduviidae)

    PubMed Central

    Gómez-Palacio, Andrés; Triana, Omar; Jaramillo-O, Nicolás; Dotson, Ellen M.; Marcet, Paula L.

    2016-01-01

    Triatoma dimidiata is currently the main vector of Chagas disease in Mexico, most Central American countries and several zones of Ecuador and Colombia. Although this species has been the subject of several recent phylogeographic studies, the relationship among different populations within the species remains unclear. To elucidate the population genetic structure of T. dimidiata in Colombia, we analyzed individuals from distinct geographical locations using the cytochrome c oxidase subunit 1 gene and 7 microsatellite loci. A clear genetic differentiation was observed among specimens from three Colombian eco-geographical regions: Inter Andean Valleys, Caribbean Plains and Sierra Nevada de Santa Marta mountain (SNSM). Additionally, evidence of genetic subdivision was found within the Caribbean Plains region as well as moderate gene flow between the populations from the Caribbean Plains and SNSM regions. The genetic differentiation found among Colombian populations correlates, albeit weakly, with an isolation-by-distance model (IBD). The genetic heterogeneity among Colombian populations correlates with the eco-epidemiological and morphological traits observed in this species across regions within the country. Such genetic and epidemiological diversity should be taken into consideration for the development of vector control strategies and entomological surveillance. PMID:24035810

  5. Community-based sampling methods for surveillance of the Chagas disease vector, Triatoma dimidiata (Hemiptera: Reduviidae: Triatominae).

    PubMed

    Weeks, E N I; Davies, C; Rosales, C Cordón; Yeo, M; Gezan, S A; Parra-Henao, G; Cameron, M M

    2014-09-01

    In Guatemala, the most widespread vector of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae), the causative agent of Chagas disease, is Triatoma dimidiata (Latreille) (Hemiptera: Reduviidae: Triatominae). T. dimidiata is native to Guatemala and is present in both domestic and sylvatic habitats. Consequently, control of T. dimidiata is difficult because after successful elimination from homes, individual insects can recolonize homes from the surrounding environment. Therefore, intensive long-term surveillance of this species is essential to ensure adequate control is achieved. Manual inspection for signs of infestation, the current method used to monitor Triatominae throughout Central and South America, is labor and time-consuming, so cost-effective alternatives are needed. The current study compared the effectiveness of the current method of surveillance of T. dimidiata with community-based techniques of G6mez-Nuñez sensor boxes, collection and observation of bugs by householders, and presence of triatomine-like feces on walls. Although manual inspection was the most sensitive method when used alone, collection by householders also was sensitive and specific and involved less effort. Sensor boxes were not sensitive indicators of T. dimidiata infestation when used alone. Two recorded variables, visual inspection for feces and the sighting of bugs by householders, were sensitive and specific indicators of infestation, and in combination with collection by householders and sensor boxes these methods were significantly more likely to detect infestations than manual inspection alone. A surveillance program that combines multiple community-based techniques should have low cost and involve minimal effort from the government and at the same time promote sustainable community involvement in disease prevention.

  6. Phylogeographic Pattern and Extensive Mitochondrial DNA Divergence Disclose a Species Complex within the Chagas Disease Vector Triatoma dimidiata

    PubMed Central

    Monteiro, Fernando A.; Peretolchina, Tatiana; Lazoski, Cristiano; Harris, Kecia; Dotson, Ellen M.; Abad-Franch, Fernando; Tamayo, Elsa; Pennington, Pamela M.; Monroy, Carlota; Cordon-Rosales, Celia; Salazar-Schettino, Paz Maria; Gómez-Palacio, Andrés; Grijalva, Mario J.; Beard, Charles B.; Marcet, Paula L.

    2013-01-01

    Background Triatoma dimidiata is among the main vectors of Chagas disease in Latin America. However, and despite important advances, there is no consensus about the taxonomic status of phenotypically divergent T. dimidiata populations, which in most recent papers are regarded as subspecies. Methodology and Findings A total of 126 cyt b sequences (621 bp long) were produced for specimens from across the species range. Forty-seven selected specimens representing the main cyt b clades observed (after a preliminary phylogenetic analysis) were also sequenced for an ND4 fragment (554 bp long) and concatenated with their respective cyt b sequences to produce a combined data set totalling 1175 bp/individual. Bayesian and Maximum-Likelihood phylogenetic analyses of both data sets (cyt b, and cyt b+ND4) disclosed four strongly divergent (all pairwise Kimura 2-parameter distances >0.08), monophyletic groups: Group I occurs from Southern Mexico through Central America into Colombia, with Ecuadorian specimens resembling Nicaraguan material; Group II includes samples from Western-Southwestern Mexico; Group III comprises specimens from the Yucatán peninsula; and Group IV consists of sylvatic samples from Belize. The closely-related, yet formally recognized species T. hegneri from the island of Cozumel falls within the divergence range of the T. dimidiata populations studied. Conclusions We propose that Groups I–IV, as well as T. hegneri, should be regarded as separate species. In the Petén of Guatemala, representatives of Groups I, II, and III occur in sympatry; the absence of haplotypes with intermediate genetic distances, as shown by multimodal mismatch distribution plots, clearly indicates that reproductive barriers actively promote within-group cohesion. Some sylvatic specimens from Belize belong to a different species – likely the basal lineage of the T. dimidiata complex, originated ∼8.25 Mya. The evidence presented here strongly supports the proposition that T

  7. Evaluation of Spatially Targeted Strategies to Control Non-Domiciliated Triatoma dimidiata Vector of Chagas Disease

    PubMed Central

    Barbu, Corentin; Dumonteil, Eric; Gourbière, Sébastien

    2011-01-01

    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

  8. Phylogeography and Genetic Variation of Triatoma dimidiata, the Main Chagas Disease Vector in Central America, and Its Position within the Genus Triatoma

    PubMed Central

    Bargues, María Dolores; Klisiowicz, Debora R.; Gonzalez-Candelas, Fernando; Ramsey, Janine M.; Monroy, Carlota; Ponce, Carlos; Salazar-Schettino, Paz María; Panzera, Francisco; Abad-Franch, Fernando; Sousa, Octavio E.; Schofield, Christopher J.; Dujardin, Jean Pierre; Guhl, Felipe; Mas-Coma, Santiago

    2008-01-01

    Background Among Chagas disease triatomine vectors, the largest genus, Triatoma, includes species of high public health interest. Triatoma dimidiata, the main vector throughout Central America and up to Ecuador, presents extensive phenotypic, genotypic, and behavioral diversity in sylvatic, peridomestic and domestic habitats, and non-domiciliated populations acting as reinfestation sources. DNA sequence analyses, phylogenetic reconstruction methods, and genetic variation approaches are combined to investigate the haplotype profiling, genetic polymorphism, phylogeography, and evolutionary trends of T. dimidiata and its closest relatives within Triatoma. This is the largest interpopulational analysis performed on a triatomine species so far. Methodology and Findings Triatomines from Mexico, Guatemala, Honduras, Nicaragua, Panama, Cuba, Colombia, Ecuador, and Brazil were used. Triatoma dimidiata populations follow different evolutionary divergences in which geographical isolation appears to have had an important influence. A southern Mexican–northern Guatemalan ancestral form gave rise to two main clades. One clade remained confined to the Yucatan peninsula and northern parts of Chiapas State, Guatemala, and Honduras, with extant descendants deserving specific status. Within the second clade, extant subspecies diversity was shaped by adaptive radiation derived from Guatemalan ancestral populations. Central American populations correspond to subspecies T. d. dimidiata. A southern spread into Panama and Colombia gave the T. d. capitata forms, and a northwestern spread rising from Guatemala into Mexico gave the T. d. maculipennis forms. Triatoma hegneri appears as a subspecific insular form. Conclusions The comparison with very numerous Triatoma species allows us to reach highly supported conclusions not only about T. dimidiata, but also on different, important Triatoma species groupings and their evolution. The very large intraspecific genetic variability found in T

  9. Molecular Evidence of Demographic Expansion of the Chagas Disease Vector Triatoma dimidiata (Hemiptera, Reduviidae, Triatominae) in Colombia

    PubMed Central

    Gómez-Palacio, Andrés; Triana, Omar

    2014-01-01

    Background Triatoma dimidiata is one of the most significant vectors of Chagas disease in Central America and Colombia, and, as in most species, its pattern of genetic variation within and among populations is strongly affected by its phylogeographic history. A putative origin from Central America has been proposed for Colombian populations, and high genetic differentiation among three biographically different population groups has recently been evidenced. Analyses based on putatively neutral markers provide data from which past events, such as population expansions and colonization, can be inferred. We analyzed the genealogies of the nicotinamide adenine dinucleotide dehydrogenase 4 (ND4) and the cytochrome oxidase subunit 1-mitochondrial genes, as well as partial nuclear ITS-2 DNA sequences obtained across most of the eco-geographical range in Colombia, to assess the population structure and demographic factors that may explain the geographical distribution of T. dimidiata in this country. Results The population structure results support a significant association between genetic divergence and the eco-geographical location of population groups, suggesting that clear signals of demographic expansion can explain the geographical distribution of haplotypes of population groups. Additionally, empirical date estimation of the event suggests that the population's expansion can be placed after the emergence of the Panama Isthmus, and that it was possibly followed by a population fragmentation process, perhaps resulting from local adaptation accomplished by orographic factors such as geographical isolation. Conclusion Inferences about the historical population processes in Colombian T. dimidiata populations are generally in accordance with population expansions that may have been accomplished by two important biotic and orographic events such as the Great American Interchange and the uplift of the eastern range of the Andes mountains in central Colombia. PMID:24625572

  10. Effect of Hurricane Isidore on Triatoma dimidiata distribution and Chagas disease transmission risk in the Yucatán Peninsula of Mexico.

    PubMed

    Guzman-Tapia, Yadira; Ramirez-Sierra, Maria Jesus; Escobedo-Ortegon, Javier; Dumonteil, Eric

    2005-12-01

    Hurricanes can have devastating effects on health and may directly modulate vector-borne diseases. Chagas disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi and transmitted by triatomine bugs, and the effect of hurricanes on these bugs is largely unknown. We thus performed a detailed study of the changes in Triatoma dimidiata geographic distribution and infection rates after Hurricane Isidore devastated the Yucatán Peninsula in September 2002. Bugs were collected in 34 villages from the entire peninsula, during a year, starting 3 months after the hurricane. Pre- and posthurricane bug collections were compared to assess changes. The most notable effect was a large increase in domestic abundance of T. dimidiata during the 6 months after the hurricane. This increase was maximum along the path of the hurricane. These results suggest that vector control programs should be implemented along the path of hurricanes to prevent an increase in Chagas disease transmission risk in the ensuing months.

  11. Novel polymerase chain reaction-restriction fragment length polymorphism assay to determine internal transcribed spacer-2 group in the Chagas disease vector, Triatoma dimidiata (Latreille, 1811).

    PubMed

    Richards, Bethany; Rúa, Nicholas M de la; Monroy, Carlota; Stevens, Lori; Dorn, Patricia L

    2013-06-01

    Triatoma dimidiata is the most important Chagas disease insect vector in Central America as this species is primarily responsible for Trypanosoma cruzi transmission to humans, the protozoan parasite that causes Chagas disease. T. dimidiata sensu lato is a genetically diverse assemblage of taxa and effective vector control requires a clear understanding of the geographic distribution and epidemiological importance of its taxa. The nuclear ribosomal internal transcribed spacer 2 (ITS-2) is frequently used to infer the systematics of triatomines. However, oftentimes amplification and sequencing of ITS-2 fails, likely due to both the large polymerase chain reaction (PCR) product and polymerase slippage near the 5' end. To overcome these challenges we have designed new primers that amplify only the 3'-most 200 base pairs of ITS-2. This region distinguishes the ITS-2 group for 100% of known T. dimidiata haplotypes. Furthermore, we have developed a PCR-restriction fragment length polymorphism (RFLP) approach to determine the ITS-2 group, greatly reducing, but not eliminating, the number of amplified products that need to be sequenced. Although there are limitations with this new PCR-RFLP approach, its use will help with understanding the geographic distribution of T. dimidiata taxa and can facilitate other studies characterising the taxa, e.g. their ecology, evolution and epidemiological importance, thus improving vector control.

  12. Hypothesis testing clarifies the systematics of the main Central American Chagas disease vector, Triatoma dimidiata (Latreille, 1811), across its geographic range.

    PubMed

    Dorn, Patricia L; de la Rúa, Nicholas M; Axen, Heather; Smith, Nicholas; Richards, Bethany R; Charabati, Jirias; Suarez, Julianne; Woods, Adrienne; Pessoa, Rafaela; Monroy, Carlota; Kilpatrick, C William; Stevens, Lori

    2016-10-01

    The widespread and diverse Triatoma dimidiata is the kissing bug species most important for Chagas disease transmission in Central America and a secondary vector in Mexico and northern South America. Its diversity may contribute to different Chagas disease prevalence in different localities and has led to conflicting systematic hypotheses describing various populations as subspecies or cryptic species. To resolve these conflicting hypotheses, we sequenced a nuclear (internal transcribed spacer 2, ITS-2) and mitochondrial gene (cytochrome b) from an extensive sampling of T. dimidiata across its geographic range. We evaluated the congruence of ITS-2 and cyt b phylogenies and tested the support for the previously proposed subspecies (inferred from ITS-2) by: (1) overlaying the ITS-2 subspecies assignments on a cyt b tree and, (2) assessing the statistical support for a cyt b topology constrained by the subspecies hypothesis. Unconstrained phylogenies inferred from ITS-2 and cyt b are congruent and reveal three clades including two putative cryptic species in addition to T. dimidiata sensu stricto. Neither the cyt b phylogeny nor hypothesis testing support the proposed subspecies inferred from ITS-2. Additionally, the two cryptic species are supported by phylogenies inferred from mitochondrially-encoded genes cytochrome c oxidase I and NADH dehydrogenase 4. In summary, our results reveal two cryptic species. Phylogenetic relationships indicate T. dimidiata sensu stricto is not subdivided into monophyletic clades consistent with subspecies. Based on increased support by hypothesis testing, we propose an updated systematic hypothesis for T. dimidiata based on extensive taxon sampling and analysis of both mitochondrial and nuclear genes.

  13. Hypothesis testing clarifies the systematics of the main Central American Chagas disease vector, Triatoma dimidiata (Latreille, 1811), across its geographic range.

    PubMed

    Dorn, Patricia L; de la Rúa, Nicholas M; Axen, Heather; Smith, Nicholas; Richards, Bethany R; Charabati, Jirias; Suarez, Julianne; Woods, Adrienne; Pessoa, Rafaela; Monroy, Carlota; Kilpatrick, C William; Stevens, Lori

    2016-10-01

    The widespread and diverse Triatoma dimidiata is the kissing bug species most important for Chagas disease transmission in Central America and a secondary vector in Mexico and northern South America. Its diversity may contribute to different Chagas disease prevalence in different localities and has led to conflicting systematic hypotheses describing various populations as subspecies or cryptic species. To resolve these conflicting hypotheses, we sequenced a nuclear (internal transcribed spacer 2, ITS-2) and mitochondrial gene (cytochrome b) from an extensive sampling of T. dimidiata across its geographic range. We evaluated the congruence of ITS-2 and cyt b phylogenies and tested the support for the previously proposed subspecies (inferred from ITS-2) by: (1) overlaying the ITS-2 subspecies assignments on a cyt b tree and, (2) assessing the statistical support for a cyt b topology constrained by the subspecies hypothesis. Unconstrained phylogenies inferred from ITS-2 and cyt b are congruent and reveal three clades including two putative cryptic species in addition to T. dimidiata sensu stricto. Neither the cyt b phylogeny nor hypothesis testing support the proposed subspecies inferred from ITS-2. Additionally, the two cryptic species are supported by phylogenies inferred from mitochondrially-encoded genes cytochrome c oxidase I and NADH dehydrogenase 4. In summary, our results reveal two cryptic species. Phylogenetic relationships indicate T. dimidiata sensu stricto is not subdivided into monophyletic clades consistent with subspecies. Based on increased support by hypothesis testing, we propose an updated systematic hypothesis for T. dimidiata based on extensive taxon sampling and analysis of both mitochondrial and nuclear genes. PMID:27496718

  14. Environmental Determinants of the Distribution of Chagas Disease Vector Triatoma dimidiata in Colombia.

    PubMed

    Parra-Henao, Gabriel; Quirós-Gómez, Oscar; Jaramillo-O, Nicolas; Cardona, Ángela Segura

    2016-04-01

    Triatoma dimidiata (Hemiptera: Reduviidae) is a secondary vector of Trypanosoma cruzi in Colombia and represents an important epidemiological risk mainly in the central and oriental regions of the country where it occupies sylvatic, peridomestic, and intradomestic ecotopes, and because of this complex distribution, its distribution and abundance could be conditioned by environmental factors. In this work, we explored the relationship between T. dimidiata distribution and environmental factors in the northwest, northeast, and central zones of Colombia and developed predictive models of infestation in the country. The associations between the presence ofT. dimidiata and environmental variables were studied using logistic regression models and ecological niche modeling for a sample of villages in Colombia. The analysis was based on the information collected in field about the presence ofT. dimidiata and the environmental data for each village extracted from remote sensing images. The presence of Triatoma dimidiata(Latreille, 1811) was found to be significantly associated with the maximum vegetation index, minimum land surface temperature (LST), and the digital elevation for the statistical model. Temperature seasonality, annual precipitation, and vegetation index were the variables that most influenced the ecological niche model ofT. dimidiata distribution. The logistic regression model showed a good fit and predicted suitable habitats in the Andean and Caribbean regions, which agrees with the known distribution of the species, but predicted suitable habitats in the Pacific and Orinoco regions proposing new areas of research. Improved models to predict suitable habitats forT. dimidiata hold promise for spatial targeting of integrated vector management.

  15. Ecological niche and geographic distribution of the Chagas disease vector, Triatoma dimidiata (Reduviidae: Triatominae): Evidence for niche differentiation among cryptic species.

    PubMed

    Gómez-Palacio, Andrés; Arboleda, Sair; Dumonteil, Eric; Townsend Peterson, A

    2015-12-01

    The principal vector of Chagas disease in Central America, Triatoma dimidiata, shows considerable diversity of habitat, phenotype, and genotype across its geographic range (central Mexico to southern Ecuador), suggesting that it constitutes a complex of cryptic species. However, no consistent picture of the magnitude of ecological differentiation among populations of this complex has yet been developed. To assess ecological variation across the complex, we broadened the geographic coverage of phylogeographic data and analyses for the complex into Colombia and Mexico, with additional nuclear (ITS-2) and mitochondrial (ND4) DNA sequences. This information allowed us to describe distributions of previously documented clades in greater detail: Group I, from central Guatemala south to Ecuador; Group II, across Mexico south through the Yucatán Peninsula to Belize and northern Guatemala; and Group III, in northern Guatemala, Belize, and the Yucatán Peninsula. Using ecological niche modeling, we assessed ecological niche differentiation among the groups using four hypotheses of accessible areas (M) across the distribution of the complex. Results indicated clear niche divergence of Group I from Group II: the speciation process thus appears to have involved genetic and ecological changes, suggesting divergence in populations in response to environmental conditions.

  16. The Chagas disease domestic transmission cycle in Guatemala: Parasite-vector switches and lack of mitochondrial co-diversification between Triatoma dimidiata and Trypanosoma cruzi subpopulations suggest non-vectorial parasite dispersal across the Motagua valley.

    PubMed

    Pennington, Pamela M; Messenger, Louisa Alexandra; Reina, Jeffrey; Juárez, José G; Lawrence, Gena G; Dotson, Ellen M; Llewellyn, Martin S; Cordón-Rosales, Celia

    2015-11-01

    Parasites transmitted by insects must adapt to their vectors and reservoirs. Chagas disease, an American zoonosis caused by Trypanosoma cruzi, is transmitted by several species of triatomines. In Central America, Triatoma dimidiata is a widely dispersed vector found in sylvatic and domestic habitats, with distinct populations across the endemic region of Guatemala. Our aim was to test the strength of association between vector and parasite genetic divergence in domestic environments. Microsatellite (MS) loci were used to characterize parasites isolated from T. dimidiata (n=112) collected in domestic environments. Moderate genetic differentiation was observed between parasites north and south of the Motagua Valley, an ancient biogeographic barrier (FST 0.138, p=0.009). Slightly reduced genotypic diversity and increased heterozygosity in the north (Allelic richness (Ar)=1.00-6.05, FIS -0.03) compared to the south (Ar=1.47-6.30, FIS 0.022) suggest either a selective or demographic process during parasite dispersal. Based on parasite genotypes and geographic distribution, 15 vector specimens and their parasite isolates were selected for mitochondrial co-diversification analysis. Genetic variability and phylogenetic congruence were determined with mitochondrial DNA sequences (10 parasite maxicircle gene fragments and triatomine ND4+CYT b). A Mantel test as well as phylogenetic, network and principal coordinates analyses supported at least three T. dimidiata haplogroups separated by geographic distance across the Motagua Valley. Maxicircle sequences showed low T. cruzi genetic variability (π nucleotide diversity 0.00098) with no evidence of co-diversification with the vector, having multiple host switches across the valley. Sylvatic Didelphis marsupialis captured across the Motagua Valley were found to be infected with T. cruzi strains sharing MS genotypes with parasites isolated from domiciliated triatomines. The current parasite distribution in domestic environments

  17. Migration and Gene Flow Among Domestic Populations of the Chagas Insect Vector Triatoma dimidiata (Hemiptera: Reduviidae) Detected by Microsatellite Loci

    PubMed Central

    Stevens, Lori; Monroy, M. Carlota; Rodas, Antonieta Guadalupe; Hicks, Robin M.; Lucero, David E.; Lyons, Leslie A.; Dorn, Patricia L.

    2015-01-01

    Triatoma dimidiata (Latreille, 1811) is the most abundant and significant insect vector of the parasite Trypanosoma cruzi in Central America, and particularly in Guatemala. Tr. cruzi is the causative agent of Chagas disease, and successful disease control requires understanding the geographic distribution and degree of migration of vectors such as T. dimidiata that frequently re-infest houses within months following insecticide application. The population genetic structure of T. dimidiata collected from six villages in southern Guatemala was studied to gain insight into the migration patterns of the insects in this region where populations are largely domestic. This study provided insight into the likelihood of eliminating T. dimidiata by pesticide application as has been observed in some areas for other domestic triatomines such as Triatoma infestans. Genotypes of microsatellite loci for 178 insects from six villages were found to represent five genetic clusters using a Bayesian Markov Chain Monte Carlo method. Individual clusters were found in multiple villages, with multiple clusters in the same house. Although migration occurred, there was statistically significant genetic differentiation among villages (FRT = 0.05) and high genetic differentiation among houses within villages (FSR = 0.11). Relatedness of insects within houses varied from 0 to 0.25, i.e., from unrelated to half-sibs. The results suggest that T. dimidiata in southern Guatemala moves between houses and villages often enough that recolonization is likely, implying the use of insecticides alone is not sufficient for effective control of Chagas disease in this region and more sustainable solutions are required. PMID:26334816

  18. High Frequency of Human Blood in Triatoma dimidiata Captured Inside Dwellings in a Rural Community in the Yucatan Peninsula, Mexico, but Low Antibody Seroprevalence and Electrocardiographic Findings Compatible with Chagas Disease in Humans

    PubMed Central

    Monteon, Victor; Alducin, César; Hernández, Jorge; Ramos-Ligonio, Angel; Lopez, Ruth

    2013-01-01

    We studied a small rural community of 411 inhabitants localized in the state of Campeche in the Yucatan Peninsula, Mexico. In 44 collected triatomines captured inside the houses, human feeding source was revealed in 23 of 44 (52%) samples, and chicken feeding source was revealed in 16 of 44 (36%) samples. In a set of 29 triatomines, mouse was the feeding source in 13 (44%) samples, and dog was the feeding source in 7 (24%) samples. Infection index with Trypanosoma cruzi in collected triatomines was 38%, and all parasites belonged to discrete type unit I. Inhabitants referred high contact with triatomine's bite in 60 of 128 (47%) samples, but seroprevalence was 2.3% (3/128). Evidence of electrocardiographic alteration compatible with Chagas disease was observed only in one asymptomatic seropositive subject. In conclusion, Triatoma dimidiata in this region are preferentially infected with T. cruzi I and feed on human beings with relative high frequency, but seroprevalence and Chagas disease in humans is relatively low. PMID:23296447

  19. Chagas Disease

    MedlinePlus

    Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...

  20. Chagas disease

    MedlinePlus

    ... will help control the spread of the disease. Blood banks in Central and South America screen donors for ... discarded if the donor has the parasite. Most blood banks in the United States began screening for Chagas ...

  1. Hunting, Swimming, and Worshiping: Human Cultural Practices Illuminate the Blood Meal Sources of Cave Dwelling Chagas Vectors (Triatoma dimidiata) in Guatemala and Belize

    PubMed Central

    Stevens, Lori; Monroy, M. Carlota; Rodas, Antonieta Guadalupe; Dorn, Patricia L.

    2014-01-01

    Background Triatoma dimidiata, currently the major Central American vector of Trypanosoma cruzi, the parasite that causes Chagas disease, inhabits caves throughout the region. This research investigates the possibility that cave dwelling T. dimidiata might transmit the parasite to humans and links the blood meal sources of cave vectors to cultural practices that differ among locations. Methodology/Principal Findings We determined the blood meal sources of twenty-four T. dimidiata collected from two locations in Guatemala and one in Belize where human interactions with the caves differ. Blood meal sources were determined by cloning and sequencing PCR products amplified from DNA extracted from the vector abdomen using primers specific for the vertebrate 12S mitochondrial gene. The blood meal sources were inferred by ≥99% identity with published sequences. We found 70% of cave-collected T. dimidiata positive for human DNA. The vectors had fed on 10 additional vertebrates with a variety of relationships to humans, including companion animal (dog), food animals (pig, sheep/goat), wild animals (duck, two bat, two opossum species) and commensal animals (mouse, rat). Vectors from all locations fed on humans and commensal animals. The blood meal sources differ among locations, as well as the likelihood of feeding on dog and food animals. Vectors from one location were tested for T. cruzi infection, and 30% (3/10) tested positive, including two positive for human blood meals. Conclusions/Significance Cave dwelling Chagas disease vectors feed on humans and commensal animals as well as dog, food animals and wild animals. Blood meal sources were related to human uses of the caves. We caution that just as T. dimidiata in caves may pose an epidemiological risk, there may be other situations where risk is thought to be minimal, but is not. PMID:25211347

  2. Information to act: household characteristics are predictors of domestic infestation with the Chagas vector Triatoma dimidiata in Central America.

    PubMed

    Bustamante Zamora, Dulce María; Hernández, Marianela Menes; Torres, Nuria; Zúniga, Concepción; Sosa, Wilfredo; de Abrego, Vianney; Monroy Escobar, María Carlota

    2015-07-01

    The interruption of vectorial transmission of Chagas disease by Triatoma dimidiata in central America is a public health challenge that cannot be resolved by insecticide application alone. In this study, we collected information on previously known household risk factors for infestation in 11 villages and more than 2,000 houses in Guatemala, Honduras, and El Salvador, and we constructed multivariate models and used multimodel inference to evaluate their importance as predictors of infestation in the region. The models had moderate ability to predict infested houses (sensitivity, 0.32-0.54) and excellent ability to predict noninfested houses (specificity higher than 0.90). Predictive ability was improved by including random village effects and presence of signs of infestation (insect feces, eggs, and exuviae) as fixed effects. Multimodel inference results varied depending on factors included, but house wall materials (adobe, bajareque, and palopique) and signs of infestation were among the most important predictive factors. Reduced models were not supported suggesting that all factors contributed to predictions. Previous knowledge and information from this study show that we have evidence to prioritize rural households for improvement to prevent house infestation with Triatoma dimidiata in Central America. House improvement will most likely have other health co-benefits. PMID:25870430

  3. Information to Act: Household Characteristics are Predictors of Domestic Infestation with the Chagas Vector Triatoma dimidiata in Central America

    PubMed Central

    Zamora, Dulce María Bustamante; Hernández, Marianela Menes; Torres, Nuria; Zúniga, Concepción; Sosa, Wilfredo; de Abrego, Vianney; Escobar, María Carlota Monroy

    2015-01-01

    The interruption of vectorial transmission of Chagas disease by Triatoma dimidiata in central America is a public health challenge that cannot be resolved by insecticide application alone. In this study, we collected information on previously known household risk factors for infestation in 11 villages and more than 2,000 houses in Guatemala, Honduras, and El Salvador, and we constructed multivariate models and used multimodel inference to evaluate their importance as predictors of infestation in the region. The models had moderate ability to predict infested houses (sensitivity, 0.32–0.54) and excellent ability to predict noninfested houses (specificity higher than 0.90). Predictive ability was improved by including random village effects and presence of signs of infestation (insect feces, eggs, and exuviae) as fixed effects. Multimodel inference results varied depending on factors included, but house wall materials (adobe, bajareque, and palopique) and signs of infestation were among the most important predictive factors. Reduced models were not supported suggesting that all factors contributed to predictions. Previous knowledge and information from this study show that we have evidence to prioritize rural households for improvement to prevent house infestation with Triatoma dimidiata in Central America. House improvement will most likely have other health co-benefits. PMID:25870430

  4. Chagas' disease.

    PubMed Central

    Tanowitz, H B; Kirchhoff, L V; Simon, D; Morris, S A; Weiss, L M; Wittner, M

    1992-01-01

    Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS. Images PMID:1423218

  5. Chagas Disease (American trypanosomiasis)

    MedlinePlus

    ... Features Commentaries 2014 Multimedia Contacts Chagas disease (American trypanosomiasis) Fact sheet Updated March 2016 Key facts About ... is essential. Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by ...

  6. Cuticular hydrocarbons of Chagas disease vectors in Mexico.

    PubMed

    Juarez, M Patricia; Carlson, David A; Salazar Schettino, Paz María; Mijailovsky, Sergio; Rojas, Gloria

    2002-09-01

    Capillary gas-liquid chromatography was used to analyse the cuticular hydrocarbons of three triatomine species, Triatoma dimidiata, T. barberi and Dipetalogaster maxima, domestic vectors of Chagas disease in Mexico. Mixtures of saturated hydrocarbons of straight and methyl-branched chains were characteristic of the three species, but quantitatively different. Major methylbranched components mostly corresponded to different saturated isomers of monomethyl, dimethyl and trimethyl branched hydrocarbons ranging from 29 to 39 carbon backbones. Sex-dependent, quantitative differences in certain hydrocarbons were apparent in T. dimidiata.

  7. [Update Chagas disease].

    PubMed

    Molina, Israel; Salvador, Fernando; Sánchez-Montalvá, Adrián

    2016-02-01

    The constant migration flows have favored the presence of people with Chagas disease in regions traditionally regarded as non-endemic, such as North America, Europe, Asia and Oceania. This has forced both health authorities and professionals to be updated in order to respond to such a demand for assistance. Recent years have led to significant progress in the field of diagnosis and treatment of Chagas disease, one of the most neglected tropical diseases. Recent clinical trials are providing new evidence that makes the management of these patients, a constant challenge for the professionals involved. Innovative diagnostic tools and therapeutic regimens, allow us to face the future of Chagas disease with optimism.

  8. Immunology of Chagas' disease*

    PubMed Central

    1974-01-01

    After reviewing present knowledge of the morphology, multiplication, and transmission of Trypanosoma cruzi, this Memorandum discusses the animal models that may be of value in understanding the immune mechanisms operating in Chagas' disease. The role of both circulating antibody and cell-mediated immunity in protection against the parasite is discussed, together with the possibility that immunopathological mechanisms may be responsible for some of the lesions found in patients with Chagas' disease. The immunodiagnostic methods at present available are also reviewed, and the possibility of producing a vaccine for human use is considered in the light of recent findings in experimental animals. A series of recommendations for further research is included. PMID:4218137

  9. Chagas disease, France.

    PubMed

    Lescure, François-Xavier; Canestri, Ana; Melliez, Hugues; Jauréguiberry, Stéphane; Develoux, Michel; Dorent, Richard; Guiard-Schmid, Jean-Baptiste; Bonnard, Philippe; Ajana, Faïza; Rolla, Valeria; Carlier, Yves; Gay, Frederick; Elghouzzi, Marie-Hélène; Danis, Martin; Pialoux, Gilles

    2008-04-01

    Chagas disease (CD) is endemic to Latin America; its prevalence is highest in Bolivia. CD is sometimes seen in the United States and Canada among migrants from Latin America, whereas it is rare in Europe. We report 9 cases of imported CD in France from 2004 to 2006.

  10. The history of Chagas disease.

    PubMed

    Steverding, Dietmar

    2014-01-01

    The ancestor of Trypanosome cruzi was probably introduced to South American via bats approximately 7-10 million years ago. When the first humans arrived in the New World, a sylvatic cycle of Chagas disease was then already well established. Paleoparasitological data suggests that human American trypanosomiasis originated in the Andean area when people founded the first settlements in the coastal region of the Atacama Desert. Identification of T. cruzi as the etiological agent and triatome bugs as the transmission vector of Chagas disease occurred within a few years at the beginning of the 20th century. History also teaches us that human activity leading to environmental changes, in particular deforestation, is the main cause for the spread of Chagas disease. Recently, migration of T. cruzi-infected patients has led to a distribution of Chagas disease from Latin America to non-endemic countries in Europe, North America and western Pacific region. PMID:25011546

  11. The history of Chagas disease

    PubMed Central

    2014-01-01

    The ancestor of Trypanosome cruzi was probably introduced to South American via bats approximately 7-10 million years ago. When the first humans arrived in the New World, a sylvatic cycle of Chagas disease was then already well established. Paleoparasitological data suggests that human American trypanosomiasis originated in the Andean area when people founded the first settlements in the coastal region of the Atacama Desert. Identification of T. cruzi as the etiological agent and triatome bugs as the transmission vector of Chagas disease occurred within a few years at the beginning of the 20th century. History also teaches us that human activity leading to environmental changes, in particular deforestation, is the main cause for the spread of Chagas disease. Recently, migration of T. cruzi-infected patients has led to a distribution of Chagas disease from Latin America to non-endemic countries in Europe, North America and western Pacific region. PMID:25011546

  12. Genetic Variation of North American Triatomines (Insecta: Hemiptera: Reduviidae): Initial Divergence between Species and Populations of Chagas Disease Vector

    PubMed Central

    Espinoza, Bertha; Martínez-Ibarra, Jose Alejandro; Villalobos, Guiehdani; De La Torre, Patricia; Laclette, Juan Pedro; Martínez-Hernández, Fernando

    2013-01-01

    The triatomines vectors of Trypanosoma cruzi are principal factors in acquiring Chagas disease. For this reason, increased knowledge of domestic transmission of T. cruzi and control of its insect vectors is necessary. To contribute to genetic knowledge of North America Triatominae species, we studied genetic variations and conducted phylogenetic analysis of different triatomines species of epidemiologic importance. Our analysis showed high genetic variations between different geographic populations of Triatoma mexicana, Meccus longipennis, M. mazzottii, M. picturatus, and T. dimidiata species, suggested initial divergence, hybridation, or classifications problems. In contrast, T. gerstaeckeri, T. bolivari, and M. pallidipennis populations showed few genetics variations. Analysis using cytochrome B and internal transcribed spacer 2 gene sequences indicated that T. bolivari is closely related to the Rubrofasciata complex and not to T. dimidiata. Triatoma brailovskyi and T. gerstaeckeri showed a close relationship with Dimidiata and Phyllosoma complexes. PMID:23249692

  13. Chagas Heart Disease: An Update.

    PubMed

    Malik, Lindsey H; Singh, Gagan D; Amsterdam, Ezra A

    2015-11-01

    Chagas disease, also known as American trypanosomiasis, results from infection by the protozoan Trypanosoma cruzi, and is a major cause of cardiac disease worldwide. Until recently, Chagas disease was confined to those areas of South and Central America where Trypanosoma cruzi is endemic. With the migration of infected individuals, however, the disease has spread, and it is estimated that 6-7 million people worldwide are infected. In the US alone, more than 7 million people from Trypanosoma cruzi-endemic countries became legal US residents by the turn of the century, resulting in a surge of Chagas disease in this country. According to preliminary estimates, the US now ranks seventh in the Western Hemisphere in number of individuals infected with Trypanosoma cruzi, and the disease has become a major public health concern due to limited awareness in the medical community.

  14. Acute Chagas Disease in a Returning Traveler

    PubMed Central

    Carter, Yvonne L.; Juliano, Jonathan J.; Montgomery, Susan P.; Qvarnstrom, Yvonne

    2012-01-01

    Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas. PMID:23091192

  15. House Infestation Dynamics and Feeding Sources of Triatoma dimidiata in Central Veracruz, Mexico

    PubMed Central

    Torres-Montero, Jesús; López-Monteon, Aracely; Dumonteil, Eric; Ramos-Ligonio, Angel

    2012-01-01

    Chagas disease is endemic in the state of Veracruz, Mexico, and we investigated here the dynamics of house infestation by Chagas disease vectors to understand disease transmission and design effective control interventions. Bug collections in 42 rural villages confirmed the widespread distribution of Triatoma dimidiata in central Veracruz. Unexpectedly, collection data further indicated a clear pattern of seasonal infestation by mostly adult bugs. Analysis of feeding sources with a polymerase chain reaction-heteroduplex assay indicated a frequent feeding on humans, in agreement with the high seroprevalence previously observed. Feeding sources also confirmed a significant dispersal of bugs between habitats. High dispersal capabilities and seasonal infestation may thus be a shared characteristic of several of the T. dimidiata sibling species from this complex. It would thus be critical to adapt vector control interventions to this behavior to improve their efficacy and sustainability, as the control of T. dimidiata has been notoriously challenging. PMID:22492153

  16. Heterologous Infection During Chagas' Disease

    NASA Astrophysics Data System (ADS)

    Sibona, G. J.; Condat, C. A.; Cossi Isasi, S.

    2007-05-01

    Human populations are often infected with more than one parasite strain. This is frequently the case with ChagasŠ disease, which is endemic to large regions of Latin America. In the present work we study the dynamics of the heterologous infection for this disease, using a model for the interaction between the trypanosoma cruzi parasite and the immune system. We find the dependence of the nature of the post-acute stage on the parameters characterizing the inoculated infectious strains.

  17. Duodenogastric reflux in Chagas' disease

    SciTech Connect

    Troncon, L.E.; Rezende Filho, J.; Iazigi, N.

    1988-10-01

    Increased duodenogastric reflux has been recognized as a cause of gastric mucosa damage. The frequent finding of bile-stained gastric juice and a suggested higher frequency of lesions of the gastric mucosa in patients with Chagas' disease, which is characterized by a marked reduction of myenteric neurons, suggest that impairment of intrinsic innervation of the gut might be associated with increased duodenogastric reflux. Duodenogastric bile reflux was quantified after intravenous injection of 99mtechnetium-HIDA, in 18 patients with chronic Chagas' disease, 12 controls, and 7 patients with Billroth II gastrectomy. All but one of the chagasic patients were submitted to upper digestive tract endoscopy. High reflux values (greater than or equal to 10%) were detected both in chagasic patients and in the controls, but the values for both groups were significantly lower (P less than 0.01) than those obtained for Billroth II patients (median: 55.79%; range: 12.58-87.22%). Reflux values tended to be higher in the Chagas' disease group (median: 8.20%; range: 0.0-29.40%) than in the control group (median: 3.20%; range: 0.0-30.64%), with no statistical difference between the two groups (P greater than 0.10). Chronic gastritis was detected by endoscopy in 12 chagasic patients, benign gastric ulcer in 2 patients, and a pool of bile in the stomach in 11 patients. However, neither the occurrence of gastric lesions nor the finding of bile-stained gastric juice was associated with high reflux values after (99mTc)HIDA injection. This study suggests that lesions of the intramural nervous system of the gut in Chagas' disease do not appear to be associated with abnormally increased duodenogastric reflux.

  18. Chagas Disease Risk in Texas

    PubMed Central

    Sarkar, Sahotra; Strutz, Stavana E.; Frank, David M.; Rivaldi, Chissa–Louise; Sissel, Blake; Sánchez–Cordero, Victor

    2010-01-01

    Background Chagas disease, caused by Trypanosoma cruzi, remains a serious public health concern in many areas of Latin America, including México. It is also endemic in Texas with an autochthonous canine cycle, abundant vectors (Triatoma species) in many counties, and established domestic and peridomestic cycles which make competent reservoirs available throughout the state. Yet, Chagas disease is not reportable in Texas, blood donor screening is not mandatory, and the serological profiles of human and canine populations remain unknown. The purpose of this analysis was to provide a formal risk assessment, including risk maps, which recommends the removal of these lacunae. Methods and Findings The spatial relative risk of the establishment of autochthonous Chagas disease cycles in Texas was assessed using a five–stage analysis. 1. Ecological risk for Chagas disease was established at a fine spatial resolution using a maximum entropy algorithm that takes as input occurrence points of vectors and environmental layers. The analysis was restricted to triatomine vector species for which new data were generated through field collection and through collation of post–1960 museum records in both México and the United States with sufficiently low georeferenced error to be admissible given the spatial resolution of the analysis (1 arc–minute). The new data extended the distribution of vector species to 10 new Texas counties. The models predicted that Triatoma gerstaeckeri has a large region of contiguous suitable habitat in the southern United States and México, T. lecticularia has a diffuse suitable habitat distribution along both coasts of the same region, and T. sanguisuga has a disjoint suitable habitat distribution along the coasts of the United States. The ecological risk is highest in south Texas. 2. Incidence–based relative risk was computed at the county level using the Bayesian Besag–York–Mollié model and post–1960 T. cruzi incidence data. This risk

  19. An innovative ecohealth intervention for Chagas disease vector control in Yucatan, Mexico

    PubMed Central

    Waleckx, Etienne; Camara-Mejia, Javier; Ramirez-Sierra, Maria Jesus; Cruz-Chan, Vladimir; Rosado-Vallado, Miguel; Vazquez-Narvaez, Santos; Najera-Vazquez, Rosario; Gourbière, Sébastien; Dumonteil, Eric

    2015-01-01

    Background Non-domiciliated (intrusive) triatomine vectors remain a challenge for the sustainability of Chagas disease vector control as these triatomines are able to transiently (re-)infest houses. One of the best-characterized examples is Triatoma dimidiata from the Yucatan peninsula, Mexico, where adult insects seasonally infest houses between March and July. Methods We focused our study on three rural villages in the state of Yucatan, Mexico, in which we performed a situation analysis as a first step before the implementation of an ecohealth (ecosystem approach to health) vector control intervention. Results The identification of the key determinants affecting the transient invasion of human dwellings by T. dimidiata was performed by exploring associations between bug presence and qualitative and quantitative variables describing the ecological, biological and social context of the communities. We then used a participatory action research approach for implementation and evaluation of a control strategy based on window insect screens to reduce house infestation by T. dimidiata. Conclusions This ecohealth approach may represent a valuable alternative to vertically-organized insecticide spraying. Further evaluation may confirm that it is sustainable and provides effective control (in the sense of limiting infestation of human dwellings and vector/human contacts) of intrusive triatomines in the region. PMID:25604765

  20. The Chronic Gastrointestinal Manifestations of Chagas Disease

    PubMed Central

    Matsuda, Nilce Mitiko; Miller, Steven M.; Evora, Paulo R. Barbosa

    2009-01-01

    Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi. The disease mainly affects the nervous system, digestive system and heart. The objective of this review is to revise the literature and summarize the main chronic gastrointestinal manifestations of Chagas disease. The chronic gastrointestinal manifestations of Chagas disease are mainly a result of enteric nervous system impairment caused by T. cruzi infection. The anatomical locations most commonly described to be affected by Chagas disease are salivary glands, esophagus, lower esophageal sphincter, stomach, small intestine, colon, gallbladder and biliary tree. Chagas disease has also been studied in association with Helicobacter pylori infection, interstitial cells of Cajal and the incidence of gastrointestinal cancer. PMID:20037711

  1. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors—autoimmunity—has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. PMID:25857229

  2. The Vasculature in Chagas Disease

    PubMed Central

    Prado, Cibele M.; Jelicks, Linda A.; Weiss, Louis M.; Factor, Stephen M.; Tanowitz, Herbert B.; Rossi, Marcos A.

    2013-01-01

    The cardiovascular manifestations of Chagas disease are well known. However, the contribution of the vasculature and specifically the microvasculature has received little attention. This chapter reviews the evidence supporting the notion that alterations in the microvasculature especially in the heart contribute to the pathogenesis of chagasic cardiomyopathy. These data may also be important in understanding the contributions of the microvasculature in the aetiologies of other cardiomyopathies. The role of endothelin-1 and of thromboxane A2 vascular spasm and platelet aggregation is also discussed. Further, these observations may provide target(s) for intervention. PMID:21884888

  3. Chagas Heart Disease: Report on Recent Developments

    PubMed Central

    Machado, Fabiana S.; Jelicks, Linda A.; Kirchhoff, Louis V.; Shirani, Jamshid; Nagajyothi, Fnu; Mukherjee, Shankar; Nelson, Randin; Coyle, Christina M.; Spray, David C.; Campos de Carvalho, Antonio C.; Guan, Fangxia; Prado, Cibele M.; Lisanti, Michael P.; Weiss, Louis M.; Montgomery, Susan P.; Tanowitz, Herbert B.

    2011-01-01

    Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. It is now being diagnosed in non-endemic areas due to immigration. Typical cardiac manifestations of Chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism and stroke. Clinical and laboratory-based research to define the pathology resulting from T. cruzi infection has shed light on many of the cellular and molecular mechanisms leading to these manifestations. Antiparasitic treatment may not be appropriate for patients with advanced cardiac disease. Clinical management of Chagas heart disease is similar to that used for cardiomyopathies due to other processes. Cardiac transplantation has been successfully performed in a small number of patients with Chagas heart disease. PMID:22293860

  4. Chagas Disease Cardiomyopathy: Immunopathology and Genetics

    PubMed Central

    Chevillard, Christophe

    2014-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30% of infected patients develop CCC suggest there might be a genetic component to disease susceptibility. Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper, we will review the immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC. PMID:25210230

  5. Chagas' disease as a foodborne illness.

    PubMed

    Pereira, Karen Signori; Schmidt, Flávio Luis; Guaraldo, Ana M A; Franco, Regina M B; Dias, Viviane L; Passos, Luiz A C

    2009-02-01

    Various researchers have studied the importance of the oral transmission of Chagas' disease since the mid-20th century. Only in recent years, due to an outbreak that occurred in the Brazilian State of Santa Catarina in 2005 and to various outbreaks occurring during the last 3 years in the Brazilian Amazon basin, mainly associated with the consumption of Amazonian palm berry or açaí (Euterpe oleracea Mart.) juice, has this transmission route aroused the attention of researchers. Nevertheless, reports published in the 1960s already indicated the possibility of Chagas' disease transmission via food in Brazil, mainly in the Amazonian region. Recently, in December 2007, an outbreak of Chagas' disease occurred in Caracas, Venezuela, related to ingestion of contaminated fruit juices. The objective of this article is to point out the importance of foodborne transmission in the etiology of Chagas' disease, on the basis of published research and Brazilian epidemiology data.

  6. The number of families of Triatoma dimidiata in a Guatemalan house.

    PubMed

    Melgar, Sergio; Chávez, Juan José; Landaverde, Patricia; Herrera, Franklin; Rodas, Antonieta; Enríquez, Eunice; Dorn, Patricia; Monroy, Carlota

    2007-05-01

    Triatoma dimidiata is an important vector of Chagas disease in Guatemala. To help understand the biology and population dynamics of the insect, we estimated the number of full sibling families living in one house. Forty one families with an average size of 2.17 individuals were detected using random amplification of polymorphic DNA-polymerase chain reaction genetic markers. This result suggests high levels of migration of the vector, polyandry, and a significant capability for spreading the disease.

  7. Geographic Distribution and Ecology of Triatoma dimidiata (Hemiptera: Reduviidae) in Colombia.

    PubMed

    Parra-Henao, Gabriel; Angulo, Víctor Manuel; Osorio, Lisardo; Jaramillo-O, Nicolás

    2016-01-01

    Triatoma dimidiata Latreille is the second most important vector of Chagas' disease in Colombia and is found in urban and periurban areas. From January 2007 to June 2008, we performed field work in 8 departments, 18 municipalities, and 44 rural villages, covering most of its known distribution and all of its ecological zones in the country. The goal was to determine the geographical distribution, the ecology, and house infestation indices of T. dimidiata over its range and hence the Chagas' disease transmission risk. In Colombia, T. dimidiata occupies a wide variety of ecosystems, from transformed ecosystems in the Andean biome with shrub and xerofitic vegetation to very dense forests in the humid tropical forests in the Sierra Nevada of Santa Marta. According to genetic and ecological criteria, at least two T. dimidiata forms of this species are present: populations from the northwest of the country (Caribbean plains) are restricted to palm tree habitats, and domestic involvement is limited to sporadic visits because of attraction by light; and populations of the east region (Andean mountains) presenting a complex distributional pattern including sylvatic, peridomestic, and domiciliated ecotopes, and occupying a great variety of life zones. The latter population is of epidemiological importance due to the demonstrated migration and genetical flow of individuals among the different habitats. Control, therefore, must take into account its diversity of habitats.

  8. Geographic Distribution and Ecology of Triatoma dimidiata (Hemiptera: Reduviidae) in Colombia.

    PubMed

    Parra-Henao, Gabriel; Angulo, Víctor Manuel; Osorio, Lisardo; Jaramillo-O, Nicolás

    2016-01-01

    Triatoma dimidiata Latreille is the second most important vector of Chagas' disease in Colombia and is found in urban and periurban areas. From January 2007 to June 2008, we performed field work in 8 departments, 18 municipalities, and 44 rural villages, covering most of its known distribution and all of its ecological zones in the country. The goal was to determine the geographical distribution, the ecology, and house infestation indices of T. dimidiata over its range and hence the Chagas' disease transmission risk. In Colombia, T. dimidiata occupies a wide variety of ecosystems, from transformed ecosystems in the Andean biome with shrub and xerofitic vegetation to very dense forests in the humid tropical forests in the Sierra Nevada of Santa Marta. According to genetic and ecological criteria, at least two T. dimidiata forms of this species are present: populations from the northwest of the country (Caribbean plains) are restricted to palm tree habitats, and domestic involvement is limited to sporadic visits because of attraction by light; and populations of the east region (Andean mountains) presenting a complex distributional pattern including sylvatic, peridomestic, and domiciliated ecotopes, and occupying a great variety of life zones. The latter population is of epidemiological importance due to the demonstrated migration and genetical flow of individuals among the different habitats. Control, therefore, must take into account its diversity of habitats. PMID:26487247

  9. The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions - A comprehensive review

    PubMed Central

    Coura, José Rodrigues

    2015-01-01

    This review deals with transmission of Trypanosoma cruzi by the most important domestic vectors, blood transfusion and oral intake. Among the vectors, Triatoma infestans, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidiata, Triatoma brasiliensis, Triatoma pseudomaculata, Triatoma sordida, Triatoma maculata, Panstrongylus geniculatus, Rhodnius ecuadoriensis and Rhodnius pallescens can be highlighted. Transmission of Chagas infection, which has been brought under control in some countries in South and Central America, remains a great challenge, particularly considering that many endemic countries do not have control over blood donors. Even more concerning is the case of non-endemic countries that receive thousands of migrants from endemic areas that carry Chagas disease, such as the United States of America, in North America, Spain, in Europe, Japan, in Asia, and Australia, in Oceania. In the Brazilian Amazon Region, since Shaw et al. (1969) described the first acute cases of the disease caused by oral transmission, hundreds of acute cases of the disease due to oral transmission have been described in that region, which is today considered to be endemic for oral transmission. Several other outbreaks of acute Chagas disease by oral transmission have been described in different states of Brazil and in other South American countries. PMID:25466622

  10. Immunosuppression and Chagas Disease: A Management Challenge

    PubMed Central

    Pinazo, María-Jesús; Espinosa, Gerard; Cortes-Lletget, Cristina; Posada, Elizabeth de Jesús; Aldasoro, Edelweiss; Oliveira, Inés; Muñoz, Jose; Gállego, Montserrat; Gascon, Joaquim

    2013-01-01

    Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally

  11. American Trypanosomiasis (Also Known as Chagas Disease) Blood Screening FAQs

    MedlinePlus

    ... concerned about getting Chagas disease? Why are blood banks now screening for Chagas disease? The transmission of ... have the disease after all. Will the blood bank let me know if my blood tests positive ...

  12. Chagas Disease and Breast-feeding

    PubMed Central

    López-Vélez, Rogelio

    2013-01-01

    Chagas disease (infection by the protozoan Trypanosoma cruzi) is a major parasitic disease of the Americas and one of the main neglected tropical diseases. Although various routes of transmission sre recognized, the risk for transmission of the infection through breast-feeding has not clearly been established. We reviewed the literature on transmission of T. cruzi through breast-feeding to provide breast-feeding mothers with Chagas disease with medical guidance. Although data from animal studies and human studies are scarce, we do not recommend that mothers with Chagas disease discontinue breast-feeding, unless they are experiencing the acute phase of the disease, reactivated disease resulting from immunosuppression, or bleeding nipples. In these cases, thermal treatment of milk before feeding the infant may be considered. PMID:24050257

  13. Chagas disease and breast-feeding.

    PubMed

    Norman, Francesca F; López-Vélez, Rogelio

    2013-10-01

    Chagas disease (infection by the protozoan Trypanosoma cruzi) is a major parasitic disease of the Americas and one of the main neglected tropical diseases. Although various routes of transmission sre recognized, the risk for transmission of the infection through breast-feeding has not clearly been established. We reviewed the literature on transmission of T. cruzi through breast-feeding to provide breast-feeding mothers with Chagas disease with medical guidance. Although data from animal studies and human studies are scarce, we do not recommend that mothers with Chagas disease discontinue breast-feeding, unless they are experiencing the acute phase of the disease, reactivated disease resulting from immunosuppression, or bleeding nipples. In these cases, thermal treatment of milk before feeding the infant may be considered.

  14. American Trypanosomiasis (Also Known as Chagas Disease) Diagnosis

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Parasites - American Trypanosomiasis (also known as Chagas Disease) Note: Javascript is ... see the DPDx Web site: Chagas disease (American Trypanosomiasis) Diagnostic Procedures: Blood Specimens Get Email Updates To ...

  15. Two Distinct Triatoma dimidiata (Latreille, 1811) Taxa Are Found in Sympatry in Guatemala and Mexico

    PubMed Central

    Moguel, Barbara; Solorzano, Elizabeth; Dumonteil, Eric; Rodas, Antonieta; de la Rua, Nick; Garnica, Roberto; Monroy, Carlota

    2009-01-01

    Approximately 10 million people are infected with Trypanosoma cruzi, the causative agent of Chagas disease, which remains the most serious parasitic disease in the Americas. Most people are infected via triatomine vectors. Transmission has been largely halted in South America in areas with predominantly domestic vectors. However, one of the main Chagas vectors in Mesoamerica, Triatoma dimidiata, poses special challenges to control due to its diversity across its large geographic range (from Mexico into northern South America), and peridomestic and sylvatic populations that repopulate houses following pesticide treatment. Recent evidence suggests T. dimidiata may be a complex of species, perhaps including cryptic species; taxonomic ambiguity which confounds control. The nuclear sequence of the internal transcribed spacer 2 (ITS2) of the ribosomal DNA and the mitochondrial cytochrome b (mt cyt b) gene were used to analyze the taxonomy of T. dimidiata from southern Mexico throughout Central America. ITS2 sequence divides T. dimidiata into four taxa. The first three are found mostly localized to specific geographic regions with some overlap: (1) southern Mexico and Guatemala (Group 2); (2) Guatemala, Honduras, El Salvador, Nicaragua, and Costa Rica (Group 1A); (3) and Panama (Group 1B). We extend ITS2 Group 1A south into Costa Rica, Group 2 into southern Guatemala and show the first information on isolates in Belize, identifying Groups 2 and 3 in that country. The fourth group (Group 3), a potential cryptic species, is dispersed across parts of Mexico, Guatemala, and Belize. We show it exists in sympatry with other groups in Peten, Guatemala, and Yucatan, Mexico. Mitochondrial cyt b data supports this putative cryptic species in sympatry with others. However, unlike the clear distinction of the remaining groups by ITS2, the remaining groups are not separated by mt cyt b. This work contributes to an understanding of the taxonomy and population subdivision of T

  16. Natural Chagas Disease in Four Baboons

    PubMed Central

    Williams, Jeff T.; Dick, Edward J.; VandeBerg, John L.; Hubbard, Gene B.

    2010-01-01

    Background Chagas disease is common in Central and South America and the southern United States. The causative agent is Trypanosoma cruzi (T cruzi, Order Kinetoplastida, Family Trypanosomatidae), a kinetoplastid protozoan parasite of humans and other vertebrates. It is a serious public health issue and the leading cause of heart disease and cardiovascular death in Central and South America. In 1984 a colony baboon was discovered to be infected with T cruzi. Methods Since the initial diagnosis was made by microscopic observation of the amastigote forms of T. cruzi in myocardial fibers, T. cruzi amastigotes have been identified in three additional baboons. Results The primary findings were similar in all four baboons and were congestive heart failure with edema of dependent areas, hydrothorax, hydropericardium, and multifocal to diffuse lymphoplasmacytic myocarditis. Conclusions A baboon animal model of Chagas disease could contribute significantly to the development of therapies for the disease in humans. PMID:18671766

  17. The elimination of Chagas' disease from Brazil

    PubMed Central

    MASSAD, E.

    2008-01-01

    SUMMARY On 9 June 2006 the Pan American Health Organization (PAHO) presented the Minister of Health of Brazil with the International Elimination of Transmission of Chagas' Disease Certificate. This act was the culmination of an intensive process that began in 1991 with the Southern Cone Initiative, a joint agreement between the governments of Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay and Peru, to control Chagas' disease by the elimination of the main vector, Triatoma infestans. This initiative has been highly successful and the prevalence area of the vector diminished rapidly in the last years. As a consequence, the current seroprevalence in children aged between 0 and 5 years is of the order of 10−5, a clear indication that transmission, if it is occurring, is only accidental. In this review I calculate the basic reproduction number, R0, for Chagas' disease and demonstrate that its relatively low value (1·25) explains why vectorial transmission was interrupted relatively easily. In addition, I used a mathematical model to forecast how long the remaining cases of the disease, as well as the additional vertically transmitted cases will last. PMID:18053273

  18. House-Level Risk Factors for Triatoma dimidiata Infestation in Colombia

    PubMed Central

    Parra-Henao, Gabriel; Cardona, Ángela Segura; Quirós-Gómez, Oscar; Angulo, Víctor; Alexander, Neal

    2015-01-01

    In Colombia, the main vectors of Trypanosoma cruzi, the causative agent of Chagas disease, are Rhodnius prolixus and Triatoma dimidiata. T. dimidiata is present in the east region of Colombia as domestic, peridomestic, and sylvatic populations, resulting in difficulties for its control. A cost-effective way to prioritize houses for treatment is to stratify houses based on risk factors. In this study, risk factors were evaluated for potential associations with domicile infestation of T. dimidiata. There was an increased likelihood of domestic infestation associated with the presence of mixed roofs (odds ratio [OR] = 36.14, 95% confidence interval [95% CI] = 12.21–106.97), cats (OR = 3.94, 95% CI = 1.36–11.38), rock piles (OR = 5.28, 95% CI = 1.64–16.98), and bushes with height above 10 m (OR = 11.21, 95% CI = 2.08–60.45). These factors could be used to target surveillance and control of T. dimidiata to houses with an increased risk of being infested. PMID:25349372

  19. House-level risk factors for Triatoma dimidiata infestation in Colombia.

    PubMed

    Parra-Henao, Gabriel; Cardona, Ángela Segura; Quirós-Gómez, Oscar; Angulo, Víctor; Alexander, Neal

    2015-01-01

    In Colombia, the main vectors of Trypanosoma cruzi, the causative agent of Chagas disease, are Rhodnius prolixus and Triatoma dimidiata. T. dimidiata is present in the east region of Colombia as domestic, peridomestic, and sylvatic populations, resulting in difficulties for its control. A cost-effective way to prioritize houses for treatment is to stratify houses based on risk factors. In this study, risk factors were evaluated for potential associations with domicile infestation of T. dimidiata. There was an increased likelihood of domestic infestation associated with the presence of mixed roofs (odds ratio [OR] = 36.14, 95% confidence interval [95% CI] = 12.21-106.97), cats (OR = 3.94, 95% CI = 1.36-11.38), rock piles (OR = 5.28, 95% CI = 1.64-16.98), and bushes with height above 10 m (OR = 11.21, 95% CI = 2.08-60.45). These factors could be used to target surveillance and control of T. dimidiata to houses with an increased risk of being infested.

  20. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease.

    PubMed

    Bestetti, Reinaldo B; Restini, Carolina Baraldi A; Couto, Lucélio B

    2016-07-01

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas. PMID:27223644

  1. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease.

    PubMed

    Bestetti, Reinaldo B; Restini, Carolina Baraldi A; Couto, Lucélio B

    2016-07-01

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

  2. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease

    PubMed Central

    Bestetti, Reinaldo B.; Restini, Carolina Baraldi A.; Couto, Lucélio B.

    2016-01-01

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas. PMID:27223644

  3. A New Endemic Focus of Chagas Disease in the Northern Region of Veraguas Province, Western Half Panama, Central America

    PubMed Central

    Saldaña, Azael; Pineda, Vanessa; Martinez, Inri; Santamaria, Giovanna; Santamaria, Ana Maria; Miranda, Aracelis; Calzada, Jose E.

    2012-01-01

    Background Chagas disease was originally reported in Panama in 1931. Currently, the best knowledge of this zoonosis is restricted to studies done in historically endemic regions. However, little is known about the distribution and epidemiology of Chagas disease in other rural areas of the country. Methods and Findings A cross-sectional descriptive study was carried out between May 2005 – July 2008 in four rural communities of the Santa Fe District, Veraguas Province. The study included an entomologic search to collect triatomines, bloodmeal type identification and infection rate with trypanosomes in collected vectors using a dot- blot and PCR analysis, genotyping of circulating Trypanosoma cruzi (mini-exon gene PCR analysis) and the detection of chagasic antibodies among inhabitants. The vector Rhodnius pallescens was more frequently found in La Culaca and El Pantano communities (788 specimens), where it was a sporadic household visitor. These triatomines presented darker coloration and larger sizescompared with typical specimens collected in Central Panama. Triatoma dimidiata was more common in Sabaneta de El Macho (162 specimens). In one small sub-region (El Macho), 60% of the houses were colonized by this vector. Of the examined R. pallescens, 54.7.0% (88/161) had fed on Didelphis marsupialis, and 24.6% (34/138) of T. dimidiata specimens collected inside houses were positive for human blood. R. pallescens presented an infection index with T. cruzi of 17.7% (24/136), with T. rangeli of 12.5% (17/136) and 50.7% (69/136) were mixed infections. In 117 T. dimidiata domestic specimens the infection index with T. cruzi was 21.4%. Lineage I of T. cruzi was confirmed circulating in these vectors. A T. cruzi infection seroprevalence of 2.3% (24/1,056) was found in this population. Conclusions This is the first report of Chagas disease endemicity in Santa Fe District, and it should be considered a neglected public health problem in this area of Panama. PMID:22558095

  4. Chagas disease and globalization of the Amazon.

    PubMed

    Briceño-León, Roberto

    2007-01-01

    The increasing number of autochthonous cases of Chagas disease in the Amazon since the 1970s has led to fear that the disease may become a new public health problem in the region. This transformation in the disease's epidemiological pattern in the Amazon can be explained by environmental and social changes in the last 30 years. The current article draws on the sociological theory of perverse effects to explain these changes as the unwanted result of the shift from the "inward" development model prevailing until the 1970s to the "outward" model that we know as globalization, oriented by industrial forces and international trade. The current article highlights the implementation of five new patterns in agriculture, cattle-raising, mining, lumbering, and urban occupation that have generated changes in the environment and the traditional indigenous habitat and have led to migratory flows, deforestation, sedentary living, the presence of domestic animals, and changes in the habitat that facilitate colonization of human dwellings by vectors and the domestic and work-related transmission of the disease. The expansion of Chagas disease is thus a perverse effect of the globalization process in the Amazon.

  5. Chagas disease: changes in knowledge and management.

    PubMed

    Lescure, François-Xavier; Le Loup, Guillaume; Freilij, Hector; Develoux, Michel; Paris, Luc; Brutus, Laurent; Pialoux, Gilles

    2010-08-01

    More than 100 years after the discovery of human American trypanosomiasis by Carlos Chagas, our knowledge and management of the disease are profoundly changing. Substantial progress made by disease control programmes in most endemic areas contrasts with persisting difficulties in the Gran Chaco region in South America and the recent emergence of the disease in non-endemic areas because of population movements. In terms of pathogenesis, major discoveries have been made about the life cycle and genomics of Trypanosoma cruzi, and the role of the parasite itself in the chronic phase of the disease. From a clinical perspective, a growing number of arguments have challenged the notion of an indeterminate phase, and suggest new approaches to manage patients. New methods such as standardised PCR will be necessary to ensure follow-up of this chronic infection. Although drugs for treatment of Chagas disease are limited, poorly tolerated, and not very effective, treatment indications are expanding. The results of the Benznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT) trial in 2012 will also help to inform treatment. Mobilisation of financial resources to fund research on diagnosis and randomised controlled trials of treatment are international health priorities.

  6. Molecular Epidemiologic Source Tracking of Orally Transmitted Chagas Disease, Venezuela

    PubMed Central

    Segovia, Maikell; Martínez, Clara E.; Messenger, Louisa A.; Nessi, Anaibeth; Londoño, Juan C.; Espinosa, Raul; Martínez, Cinda; Alfredo, Mijares; Bonfante-Cabarcas, Rafael; Lewis, Michael D.; de Noya, Belkisyolé A.; Miles, Michael A.; Llewellyn, Martin S.

    2013-01-01

    Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing. PMID:23768982

  7. Immunoregulatory networks in human Chagas disease

    PubMed Central

    Dutra, Walderez O.; Menezes, Cristiane A.S.; Magalhães, Luisa M. D.; Gollob, Kenneth J.

    2014-01-01

    Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and, thus, influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies have led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks. PMID:24611805

  8. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead.

    PubMed

    Bonney, Kevin M; Engman, David M

    2015-06-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors-autoimmunity-has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease.

  9. Respiratory sinus arrhythmia in Chagas disease.

    PubMed

    Neves, Victor Ribeiro; Peltola, Mirja; Huikuri, Heikki; Rocha, Manoel Otávio da Costa; Ribeiro, Antonio Luiz

    2014-10-01

    We applied the respiratory sinus arrhythmia (RSA) quantification algorithm to 24-hour ECG recordings of Chagas disease (ChD) patients with (G1, n=148) and without left ventricular dysfunction (LVD) (G2, n=33), and in control subjects (G0, n=28). Both ChD groups displayed a reduced RSA index; G1=299 (144-812); G2=335 (162-667), p=0.011, which was correlated with vagal indexes of heart rate variability analysis. RSA index is a marker of vagal modulation in ChD patients.

  10. A global systematic review of Chagas disease prevalence among migrants.

    PubMed

    Conners, Erin E; Vinetz, Joseph M; Weeks, John R; Brouwer, Kimberly C

    2016-04-01

    Human migration has been identified as a potential factor for increased Chagas disease risk and has transformed the disease from a Latin American problem to a global one. We conducted a systematic review of the scientific literature between 2004-2014 in order to: summarize recent seroprevalence estimates of Chagas disease among Latin American migrants, in both endemic and non-endemic settings; compare seroprevalence estimates in migrants to countrywide prevalence estimates; and identify risk factors for Chagas disease among migrants. A total of 320 studies were screened and 23 studies were included. We found evidence that the prevalence of Chagas disease is higher than expected in some migrant groups and that reliance on blood donor screening prevalence estimates underestimates the burden of disease. Overall there is a dearth of high quality epidemiologic studies on the prevalence of Chagas disease in migrants, especially among intra-regional migrants within Latin America. Given that this zoonotic disease cannot likely be eradicated, improved surveillance and reporting is vital to continuing control efforts. More accurate health surveillance of both Latin American migrants and the Chagas disease burden will help countries appropriately scale up their response to this chronic disease. Overall, improved estimates of Chagas disease among migrants would likely serve to highlight the real need for better screening, diagnostics, and treatment of individuals living with the disease.

  11. Chagas' Disease: Pregnancy and Congenital Transmission

    PubMed Central

    Hernández, Roberto

    2014-01-01

    Chagas disease is a chronic infection that kills approximately 12,000 people a year. Mass migration of chronically infected and asymptomatic persons has caused globalization of Chagas disease and has made nonvectorial infection, including vertical and blood-borne transmission, more of a threat to human communities than vectorial infection. To control transmission, it is essential to test all pregnant women living in endemic countries and all pregnant women having migrated from, or having lived in, endemic countries. All children born to seropositive mothers should be tested not only within the first month of life but also at ~6 months and ~12 months of age. The diagnosis is made by identification of the parasite in blood before the age of 6 months and by identification of the parasite in blood and/or positive serology after 10 months of age. Follow up for a year is essential as a significant proportion of cases are initially negative and are only detected at a later stage. If the condition is diagnosed and treated early, the clinical response is excellent and the majority of cases are cured. PMID:24949443

  12. Infection Rate by Trypanosoma cruzi and Biased Vertebrate Host Selection in the Triatoma dimidiata (Hemiptera: Reduvidae) Species Complex.

    PubMed

    Ramirez-Sierra, M J; Dumonteil, E

    2016-01-01

    Chagas disease is a vector-borne disease, caused by the protozoan parasite Trypanosoma cruzi and transmitted by hematophagous insects. Triatoma dimidiata (Hemiptera: Reduvidae (Latreille 1811)) is one of the main vectors, and recent molecular studies indicate that it is a species complex, with potentially different vectorial competences. We investigated the differences in natural T. cruzi infection rate within T. dimidiata complex in Yucatan, Mexico. ITS-2 hybrid bugs had a twofold higher infection rate than ITS-2 Groups 2 and 3 bugs, and this pattern was consistent over time and in several villages. To test if T. dimidiata ITS-2 hybrid bugs could feed more frequently on T. cruzi-infected hosts, we evaluated their host-seeking behavior in a dual-choice chamber. Group 2 and 3 bugs were equally attracted to T. cruzi-infected or uninfected mice. On the contrary, ITS-2 hybrid bugs reached three times more frequently the T. cruzi-infected mouse, compared to the uninfected one, indicating a significant bias toward an infected host. This behavior may explain in part their higher natural infection rate. Further studies should explore the complex and unique interactions among T. cruzi, triatomines vectors, and mammalian hosts, as this may led to new strategies to interfere with transmission cycles and improve Chagas disease control.

  13. Demographic and dispersal constraints for domestic infestation by non-domicilated chagas disease vectors in the Yucatan Peninsula, Mexico.

    PubMed

    Gourbière, Sébastien; Dumonteil, Eric; Rabinovich, Jorge E; Minkoue, Raissa; Menu, Frédéric

    2008-01-01

    Chagas disease is one of the most important diseases in Latin America. Insecticides have been sprayed to control domiciliated vectors. However, some triatomine species are not strictly domiciliated, and the transmission risk posed by immigrants is identified as a major challenge. The design of new control strategies requires disentangling the importance of demography and immigration in vector occurrence inside houses. Using a population dynamics model, we confirmed that dispersal can explain satisfactorily the domestic abundance of Triatoma dimidiata in Yucatan, Mexico. A surprisingly low fecundity was also required (no more than one to two female offspring per female per trimester). A wide range of survival probabilities was possible, although the best fit was obtained for a very low immature survival (< or = 0.01/trimester). Our model predicted that domestic populations are not sustainable, and up to 90% of the individuals found in houses are immigrants. We discuss the potential of different strategies to control the transmission of Chagas disease by non-domiciliated vectors.

  14. Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

    PubMed

    Bestetti, Reinaldo B; Cardinalli-Neto, Augusto; Restini, Carolina B A; Couto, Lucelio B

    2016-01-01

    In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute.

  15. Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

    PubMed

    Bestetti, Reinaldo B; Cardinalli-Neto, Augusto; Restini, Carolina B A; Couto, Lucelio B

    2016-01-01

    In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute. PMID:26433162

  16. [The third and new face of Chagas disease].

    PubMed

    Pays, J-F

    2016-08-01

    After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease".

  17. [The third and new face of Chagas disease].

    PubMed

    Pays, J-F

    2016-08-01

    After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease". PMID:27376642

  18. American Trypanosomiasis (Also Known as Chagas Disease) Detailed FAQs

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Parasites - American Trypanosomiasis (also known as Chagas Disease) Note: Javascript is ... cruzi infection) is also referred to as American trypanosomiasis. It is estimated that as many as 8 ...

  19. Tc-99m pyrophosphate myocardial scanning in Chagas' disease

    SciTech Connect

    da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

    1981-04-01

    Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

  20. Tc-99m pyrophosphate myocardial scanning in Chagas' disease

    SciTech Connect

    Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

    1981-04-01

    Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

  1. Altered Cardiomyocyte Function and Trypanosoma cruzi Persistence in Chagas Disease.

    PubMed

    Cruz, Jader Santos; Santos-Miranda, Artur; Sales-Junior, Policarpo Ademar; Monti-Rocha, Renata; Campos, Paula Peixoto; Machado, Fabiana Simão; Roman-Campos, Danilo

    2016-05-01

    Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase chain reaction, we detected parasites at 90 dpi in right and left ventricles. In addition, we observed action potential prolongation and reduced transient outward K(+) current and L-type Ca(2+) current at 30 and 90 dpi. Taking together, our results demonstrate that T. cruzi infection leads to important modifications in electrical properties associated with inflammatory infiltrate and parasite persistence in mice right ventricle, suggesting a causal role between inflammation, parasite persistence, and altered cardiomyocyte function in Chagas disease. Thus, arrhythmias observed in Chagas disease may be partially related to altered electrical function in right ventricle.

  2. Chagas disease (American trypanosomiasis) in Mexico: an update.

    PubMed

    Carabarin-Lima, Alejandro; González-Vázquez, María Cristina; Rodríguez-Morales, Olivia; Baylón-Pacheco, Lidia; Rosales-Encina, José Luis; Reyes-López, Pedro Antonio; Arce-Fonseca, Minerva

    2013-08-01

    Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, a flagellated organism that is transmitted mainly to humans through the infected feces of triatomine kissing bugs (vector transmission in endemic areas) or by transfusion of infected blood, donations of infected organ, or transmission from an infected mother to her child at birth. Chagas disease was first described in 1909 by the Brazilian physician Carlos Chagas, and due to the parasite's distribution throughout North, Central and South America, the disease is commonly known as American trypanosomiasis. However, this disease is now present in non-endemic countries such as Canada, the United States of America, and several countries in Europe (principally Spain). Moreover, Chagas disease was recently designated by the World Health Organization as one of the main neglected tropical diseases. The aim of this review is to summarize the research efforts recently described in studies conducted in Mexico on Chagas disease. In this country, there are no existing vector control programs. In addition, there is no consensus on the diagnostic methods for acute and chronic Chagas disease in maternity wards and blood banks, and trypanocidal therapy is not administered to chronic patients. The actual prevalence of the disease is unknown because no official reporting of cases is performed. Therefore, the number of people infected by different routes of transmission (vector, congenital, blood transfusion, organ transplantation, or oral) is unknown. We believe that by promoting education about Chagas disease in schools starting at the basic elementary level and including reinforcement at higher education levels will ensure that the Mexican population would be aware of this health problem and that the control measures adopted will have more acceptance and success. We hope that this review sensitizes the relevant authorities and that the appropriate measures to reduce the risk of infection by T. cruzi

  3. Behavioural biology of Chagas disease vectors

    PubMed Central

    Lazzari, Claudio Ricardo; Pereira, Marcos Horácio; Lorenzo, Marcelo Gustavo

    2013-01-01

    Many arthropod species have adopted vertebrate blood as their main food source. Blood is rich in nutrients and, except for the presence of parasites, sterile. However, this food source is not freely available, nor is obtaining it devoid of risk. It circulates inside vessels hidden underneath the skin of mobile hosts that are able to defend themselves and even predate the insects that try to feed on them. Thus, the haematophagous lifestyle is associated with major morphological, physiological and behavioural adaptations that have accumulated throughout the evolutionary history of the various lineages of blood-sucking arthropods. These adaptations have significant consequences for the evolution of parasites as well as for the epidemiology of vector-transmitted diseases. In this review article, we analyse various aspects of the behaviour of triatomine bugs to illustrate how each behavioural trait represents a particular adaptation to their close association with their hosts, which may easily turn into predators. Our aim is to offer to the reader an up-to-date integrative perspective on the behaviour of Chagas disease vectors and to propose new research avenues to encourage both young and experienced colleagues to explore this aspect of triatomine biology. PMID:24473801

  4. Chronic Chagas disease: from basics to laboratory medicine.

    PubMed

    Haberland, Annekathrin; Saravia, Silvia Gilka Munoz; Wallukat, Gerd; Ziebig, Reinhard; Schimke, Ingolf

    2013-02-01

    Chagas disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10-30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemo therapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed.

  5. Reproductive isolation revealed in preliminary crossbreeding experiments using field collected Triatoma dimidiata (Hemiptera: Reduviidae) from three ITS–2 defined groups

    PubMed Central

    García, Mauricio; Menes, Marianela; Dorn, Patricia L.; Monroy, Carlota; Richards, Bethany; Panzera, Francisco; Bustamante, Dulce María

    2013-01-01

    Triatoma dimidiata, a Chagas disease vector distributed in Mexico, Central America, Colombia, Venezuela, Peru and Ecuador, has been studied using genetic markers and four groups have been defined by ITS–2 sequences: 1A, 1B, 2 and 3. To gather evidence on the divergence and reproductive isolation among T. dimidiata ITS–2 groups, we carried out 15 crossbreeding experiments with field–collected sylvan and domestic T. dimidiata from Guatemala where three groups are found: 1A, 2 and 3. Reciprocal crosses between individuals from groups 1A and 2, and a cross between group 2 individuals from different habitats, produced an average 129.78±42.29 eggs with hatching success ranging from 31.6% to 90.1%. The offspring of these crosses reached the adult stage, and crosses between F1 insects produced eggs. These results suggest that there are no pre– or post– zygotic reproductive barriers between groups 1A and 2, or within group 2. Crosses between group 3 females and males from groups 1A or 2 produced on average 85.67±30.26 eggs and none of them hatched. These results support the existence of pre– zygotic barriers between T. dimidiata group 3 and groups 1A and 2. The group 3 individuals were collected in sylvatic environments in Yaxha, Peten, Guatemala. Previously, distinct chromosomal characteristics (cytotype 3) were described in individuals from this population. Based on this evidence we suggest that this population is divergent at the species level from other T. dimidiata populations. PMID:24041592

  6. Benznidazole Shortage Makes Chagas Disease a Neglected Tropical Disease in Developed Countries: Data from Spain

    PubMed Central

    Navarro, Miriam; Norman, Francesca F.; Pérez-Molina, José Antonio; López-Vélez, Rogelio

    2012-01-01

    Chagas disease is a neglected tropical disease endemic in Latin America. The first-line treatment option is benznidazole, but stocks are expected to run out in the coming months. Spain would need around 5 million benznidazole tablets. This drug shortage could make Chagas disease a neglected tropical disease also in developed countries. PMID:22826485

  7. Use of a Novel Chagas Urine Nanoparticle Test (Chunap) for Diagnosis of Congenital Chagas Disease

    PubMed Central

    Castro-Sesquen, Yagahira E.; Gilman, Robert H.; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Sánchez, Gerardo; Valencia Ayala, Edward; Liotta, Lance; Bern, Caryn; Luchini, Alessandra

    2014-01-01

    Background Detection of congenital T. cruzi transmission is considered one of the pillars of control programs of Chagas disease. Congenital transmission accounts for 25% of new infections with an estimated 15,000 infected infants per year. Current programs to detect congenital Chagas disease in Latin America utilize microscopy early in life and serology after 6 months. These programs suffer from low sensitivity by microscopy and high loss to follow-up later in infancy. We developed a Chagas urine nanoparticle test (Chunap) to concentrate, preserve and detect T. cruzi antigens in urine for early, non-invasive diagnosis of congenital Chagas disease. Methodology/Principal Findings This is a proof-of-concept study of Chunap for the early diagnosis of congenital Chagas disease. Poly N-isopropylacrylamide nano-particles functionalized with trypan blue were synthesized by precipitation polymerization and characterized with photon correlation spectroscopy. We evaluated the ability of the nanoparticles to capture, concentrate and preserve T. cruzi antigens. Urine samples from congenitally infected and uninfected infants were then concentrated using these nanoparticles. The antigens were eluted and detected by Western Blot using a monoclonal antibody against T. cruzi lipophosphoglycan. The nanoparticles concentrate T. cruzi antigens by 100 fold (western blot detection limit decreased from 50 ng/ml to 0.5 ng/ml). The sensitivity of Chunap in a single specimen at one month of age was 91.3% (21/23, 95% CI: 71.92%–98.68%), comparable to PCR in two specimens at 0 and 1 month (91.3%) and significantly higher than microscopy in two specimens (34.8%, 95% CI: 16.42%–57.26%). Chunap specificity was 96.5% (71/74 endemic, 12/12 non-endemic specimens). Particle-sequestered T. cruzi antigens were protected from trypsin digestion. Conclusion/Significance Chunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease. PMID

  8. Interrupting Chagas disease transmission in Venezuela.

    PubMed

    Aché, A; Matos, A J

    2001-01-01

    The interruption of vectorial transmission of Chagas disease in Venezuela is attributed to the combined effects of ongoing entomoepidemiological surveillance, ongoing house spraying with residual insecticides and the concurrent building and modification of rural houses in endemic areas during almost five decades. The original endemic areas which totaled 750,000 km(2), have been reduced to 365,000 km(2). During 1958-1968, initial entomological evaluations carried out showed that the house infestation index ranged between 60-80%, the house infection index at 8-11% and a house density index of 30-50 triatomine bugs per house. By 1990-98, these indexes were further reduced to 1.6-4.0%, 0.01-0.6% and 3-4 bugs per house respectively. The overall rural population seroprevalence has declined from 44.5% (95% C.I.: 43.4-45.3%) to 9.2% (95% C.I.: 9.0-9.4%) for successive grouped periods from 1958 to 1998. The annual blood donor prevalence is firmly established below 1%. The population at risk of infection has been estimated to be less than four million. Given that prevalence rates are stable and appropriate for public health programmes, consideration has been given to potential biases that may distort results such as: a) geographical differences in illness or longevity of patients; b) variations in levels of ascertainment; c) variations in diagnostic criteria; and d) variations in population structure, mainly due to appreciable population migration. The endemic areas with continuous transmission are now mainly confined to piedmonts, as well as patchy foci in higher mountainous ranges, where the exclusive vector is Rhodnius prolixus. There is also an unstable area, of which landscapes are made up of grasslands with scattered broad-leaved evergreen trees and costal plains, where transmission is very low and occasional outbreaks are reported.

  9. The Costs of Preventing and Treating Chagas Disease in Colombia

    PubMed Central

    Castillo-Riquelme, Marianela; Guhl, Felipe; Turriago, Brenda; Pinto, Nestor; Rosas, Fernando; Martínez, Mónica Flórez; Fox-Rushby, Julia; Davies, Clive; Campbell-Lendrum, Diarmid

    2008-01-01

    Background The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare. PMID:19015725

  10. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  11. Acute Chagas disease in El Salvador 2000-2012 - Need for surveillance and control

    PubMed Central

    Sasagawa, Emi; de Aguilar, Ana Vilma Guevara; de Ramírez, Marta Alicia Hernández; Chévez, José Eduardo Romero; Nakagawa, Jun; Cedillos, Rafael Antonio; Kita, Kiyoshi

    2014-01-01

    Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole. PMID:24676660

  12. Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease.

    PubMed

    Sbaraglini, María L; Bellera, Carolina L; Fraccaroli, Laura; Larocca, Luciana; Carrillo, Carolina; Talevi, Alan; Alba Soto, Catalina D

    2016-07-01

    Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.

  13. Epidemiology of Chagas disease in Europe: many calculations, little knowledge.

    PubMed

    Strasen, Jörn; Williams, Tatjana; Ertl, Georg; Zoller, Thomas; Stich, August; Ritter, Oliver

    2014-01-01

    Chagas disease and its causative agent Trypanosoma cruzi are endemic in almost all countries in South and Middle America. Currently, there are more than 10 million affected people. It is the most common reason for heart failure and a frequent cause of intestinal problems in Latin America. The phenotype of the Chagas cardiomyopathy is varying. Dilative cardiomyopathy, often accompanied by an apical aneurysm is the most common finding in the end stage heart failure, but rhythm disorders like conduction blocks, ventricular or supraventricular forms of tachycardia or repolarization changes occur as well, mainly in the early stages. Migration of infected people leads to a distribution from the endemic countries to North America and Europe. Although more than 500,000 people of Latin American origin are currently living in Europe, Chagas disease is not considered as a public health problem, yet. Cases of transmission via blood donation, organ transplantation or from mother-to-child are reported for several European countries but there is no database for Germany. Current epidemiological data are mostly available from regional surveys from other countries or are extrapolated. Hence, there is a large variation in the estimated numbers on the incidence of Chagas. Robust and reliable data are lacking. This review gives an overview on the currently available data and calls for a German Chagas surveillance.

  14. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    PubMed Central

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  15. Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

    PubMed Central

    Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

    2014-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

  16. Experimental Vaccines against Chagas Disease: A Journey through History.

    PubMed

    Rodríguez-Morales, Olivia; Monteón-Padilla, Víctor; Carrillo-Sánchez, Silvia C; Rios-Castro, Martha; Martínez-Cruz, Mariana; Carabarin-Lima, Alejandro; Arce-Fonseca, Minerva

    2015-01-01

    Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms "Chagas disease" and "American trypanosomiasis" together with "vaccines" or "immunization". In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed.

  17. Chagas disease: control, elimination and eradication. Is it possible?

    PubMed

    Coura, José Rodrigues

    2013-12-01

    From an epidemiological point of view, Chagas disease and its reservoirs and vectors can present the following characteristics: (i) enzooty, maintained by wild animals and vectors, with broad occurrence from southern United States of America (USA) to southern Argentina and Chile (42ºN 49ºS), (ii) anthropozoonosis, when man invades the wild ecotope and becomes infected with Trypanosoma cruzi from wild animals or vectors or when the vectors and wild animals, especially marsupials, invade the human domicile and infect man, (iii) zoonosis-amphixenosis and exchanged infection between animals and humans by domestic vectors in endemic areas and (iv) zooanthroponosis, infection that is transmitted from man to animals, by means of domestic vectors, which is the rarest situation in areas endemic for Chagas disease. The characteristics of Chagas disease as an enzooty of wild animals and as an anthropozoonosis are seen most frequently in the Brazilian Amazon and in the Pan-Amazon region as a whole, where there are 33 species of six genera of wild animals: Marsupialia, Chiroptera, Rodentia, Edentata (Xenarthra), Carnivora and Primata and 27 species of triatomines, most of which infected with T. cruzi . These conditions place the resident populations of this area or its visitors - tourists, hunters, fishermen and especially the people whose livelihood involves plant extraction - at risk of being affected by Chagas disease. On the other hand, there has been an exponential increase in the acute cases of Chagas disease in that region through oral transmission of T. cruzi , causing outbreaks of the disease. In four seroepidemiological surveys that were carried out in areas of the microregion of the Negro River, state of Amazonas, in 1991, 1993, 1997 and 2010, we found large numbers of people who were serologically positive for T. cruzi infection. The majority of them and/or their relatives worked in piassava extraction and had come into contact with and were stung by wild

  18. Chagas disease: control, elimination and eradication. Is it possible?

    PubMed Central

    Coura, José Rodrigues

    2013-01-01

    From an epidemiological point of view, Chagas disease and its reservoirs and vectors can present the following characteristics: (i) enzooty, maintained by wild animals and vectors, with broad occurrence from southern United States of America (USA) to southern Argentina and Chile (42ºN 49ºS), (ii) anthropozoonosis, when man invades the wild ecotope and becomes infected with Trypanosoma cruzi from wild animals or vectors or when the vectors and wild animals, especially marsupials, invade the human domicile and infect man, (iii) zoonosis-amphixenosis and exchanged infection between animals and humans by domestic vectors in endemic areas and (iv) zooanthroponosis, infection that is transmitted from man to animals, by means of domestic vectors, which is the rarest situation in areas endemic for Chagas disease. The characteristics of Chagas disease as an enzooty of wild animals and as an anthropozoonosis are seen most frequently in the Brazilian Amazon and in the Pan-Amazon region as a whole, where there are 33 species of six genera of wild animals: Marsupialia, Chiroptera, Rodentia, Edentata (Xenarthra), Carnivora and Primata and 27 species of triatomines, most of which infected with T. cruzi . These conditions place the resident populations of this area or its visitors - tourists, hunters, fishermen and especially the people whose livelihood involves plant extraction - at risk of being affected by Chagas disease. On the other hand, there has been an exponential increase in the acute cases of Chagas disease in that region through oral transmission of T. cruzi , causing outbreaks of the disease. In four seroepidemiological surveys that were carried out in areas of the microregion of the Negro River, state of Amazonas, in 1991, 1993, 1997 and 2010, we found large numbers of people who were serologically positive for T. cruzi infection. The majority of them and/or their relatives worked in piassava extraction and had come into contact with and were stung by wild

  19. The burden of Chagas disease: estimates and challenges.

    PubMed

    Stanaway, Jeffrey D; Roth, Gregory

    2015-09-01

    Chagas disease, caused by infection with the protozoa Trypanosoma cruzi is transmitted most often by Triatominae insect vectors, but also through blood transfusion, organ transplant, and congenital transmission. Between 5 and 18 million people are currently infected and the infection is estimated to cause more than 10,000 deaths annually. The disease has 3 phases: acute, indeterminate, and chronic. The acute phase immediately follows infection. It is typically asymptomatic but produces fever and malaise in up to 5% of people. The indeterminate phase is asymptomatic. More than one-half of those infected will remain in this phase for life and never experience long-term sequelae. After a decade or more, 20% to 30% of people will experience chronic cardiovascular Chagas disease with sequelae including heart failure, arrhythmias, and thromboembolism. Another 15% to 20% will experience chronic digestive sequela including megaesophagus and megacolon. A complete accounting of the burden of Chagas disease requires estimating the prevalence of the infection, the prevalence of each of its sequelae among those with the infection, and the number of deaths attributable to the infection. Attempts to estimate Chagas disease prevalence are complicated by several challenges imposed by the disease's extreme spatial heterogeneity, quickly evolving temporal trends, the decades-long lag between infection and symptomatic disease, biased prevalence data, incomplete recognition of Chagas-attributable deaths, limited data on sequela, and a near total absence of data outside of endemic countries. Even though researchers have found methodological approaches to dealing with these challenges, there is a need for better data.

  20. Vector Blood Meals and Chagas Disease Transmission Potential, United States

    PubMed Central

    Dorn, Patricia L.; Hobson, Julia; de la Rua, Nicholas M.; Lucero, David E.; Klotz, John H.; Schmidt, Justin O.; Klotz, Stephen A.

    2012-01-01

    A high proportion of triatomine insects, vectors for Trypanosoma cruzi trypanosomes, collected in Arizona and California and examined using a novel assay had fed on humans. Other triatomine insects were positive for T. cruzi parasite infection, which indicates that the potential exists for vector transmission of Chagas disease in the United States. PMID:22469536

  1. Experimental Vaccines against Chagas Disease: A Journey through History

    PubMed Central

    Rodríguez-Morales, Olivia; Monteón-Padilla, Víctor; Carrillo-Sánchez, Silvia C.; Rios-Castro, Martha; Martínez-Cruz, Mariana; Carabarin-Lima, Alejandro; Arce-Fonseca, Minerva

    2015-01-01

    Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms “Chagas disease” and “American trypanosomiasis” together with “vaccines” or “immunization”. In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed. PMID:26090490

  2. American trypanosomiasis (Chagas' disease) in a Canadian immigrant infant.

    PubMed

    Montalvo-Hicks, L D; Trevenen, C L; Briggs, J N

    1980-08-01

    A case of American trypanosomiasis (Chagas' disease) is reported. A 13-month-old Mennonite girl who immigrated to Canada from Paraguay, died at the Children's Centre in Winnipeg from an acute myocarditis due to infection with Trypanosoma cruzi. This diagnosis should be considered when a patient from an endemic area presents with a clinical picture of myocarditis.

  3. Current drug therapy and pharmaceutical challenges for Chagas disease.

    PubMed

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection.

  4. Chagas disease in a Texan horse with neurologic deficits.

    PubMed

    Bryan, Laura K; Hamer, Sarah A; Shaw, Sarah; Curtis-Robles, Rachel; Auckland, Lisa D; Hodo, Carolyn L; Chaffin, Keith; Rech, Raquel R

    2016-01-30

    A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study.

  5. Current drug therapy and pharmaceutical challenges for Chagas disease.

    PubMed

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection

  6. Eco-bio-social research on community-based approaches for Chagas disease vector control in Latin America.

    PubMed

    Gürtler, Ricardo E; Yadon, Zaida E

    2015-02-01

    This article provides an overview of three research projects which designed and implemented innovative interventions for Chagas disease vector control in Bolivia, Guatemala and Mexico. The research initiative was based on sound principles of community-based ecosystem management (ecohealth), integrated vector management, and interdisciplinary analysis. The initial situational analysis achieved a better understanding of ecological, biological and social determinants of domestic infestation. The key factors identified included: housing quality; type of peridomestic habitats; presence and abundance of domestic dogs, chickens and synanthropic rodents; proximity to public lights; location in the periphery of the village. In Bolivia, plastering of mud walls with appropriate local materials and regular cleaning of beds and of clothes next to the walls, substantially decreased domestic infestation and abundance of the insect vector Triatoma infestans. The Guatemalan project revealed close links between house infestation by rodents and Triatoma dimidiata, and vector infection with Trypanosoma cruzi. A novel community-operated rodent control program significantly reduced rodent infestation and bug infection. In Mexico, large-scale implementation of window screens translated into promising reductions in domestic infestation. A multi-pronged approach including community mobilisation and empowerment, intersectoral cooperation and adhesion to integrated vector management principles may be the key to sustainable vector and disease control in the affected regions.

  7. Eco-bio-social research on community-based approaches for Chagas disease vector control in Latin America

    PubMed Central

    Gürtler, Ricardo E.; Yadon, Zaida E.

    2015-01-01

    This article provides an overview of three research projects which designed and implemented innovative interventions for Chagas disease vector control in Bolivia, Guatemala and Mexico. The research initiative was based on sound principles of community-based ecosystem management (ecohealth), integrated vector management, and interdisciplinary analysis. The initial situational analysis achieved a better understanding of ecological, biological and social determinants of domestic infestation. The key factors identified included: housing quality; type of peridomestic habitats; presence and abundance of domestic dogs, chickens and synanthropic rodents; proximity to public lights; location in the periphery of the village. In Bolivia, plastering of mud walls with appropriate local materials and regular cleaning of beds and of clothes next to the walls, substantially decreased domestic infestation and abundance of the insect vector Triatoma infestans. The Guatemalan project revealed close links between house infestation by rodents and Triatoma dimidiata, and vector infection with Trypanosoma cruzi. A novel community-operated rodent control program significantly reduced rodent infestation and bug infection. In Mexico, large-scale implementation of window screens translated into promising reductions in domestic infestation. A multi-pronged approach including community mobilisation and empowerment, intersectoral cooperation and adhesion to integrated vector management principles may be the key to sustainable vector and disease control in the affected regions. PMID:25604759

  8. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    PubMed

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease.

  9. Chagas disease: Present status of pathogenic mechanisms and chemotherapy.

    PubMed

    Maya, Juan Diego; Orellana, Myriam; Ferreira, Jorge; Kemmerling, Ulrike; López-Muñoz, Rodrigo; Morello, Antonio

    2010-01-01

    There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

  10. Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras

    PubMed Central

    Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H.

    2015-01-01

    Background Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. Methodology/Principal Findings We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Conclusions/Significance Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with

  11. Therapy of Chagas Disease: Implications for Levels of Prevention

    PubMed Central

    Sosa-Estani, Sergio; Colantonio, Lisandro; Segura, Elsa Leonor

    2012-01-01

    This paper reviews the evidence supporting the use of etiological treatment for Chagas disease that has changed the standard of care for patients with Trypanosoma cruzi infection in the last decades. Implications of this evidence on different levels of prevention as well as gaps in current knowledge are also discussed. In this regard, etiological treatment has shown to be beneficial as an intervention for secondary prevention to successfully cure the infection or to delay, reduce, or prevent the progression to disease, and as primary disease prevention by breaking the chain of transmission. Timely diagnosis during initial stages would allow for the prescription of appropriate therapies mainly in the primary health care system thus improving chances for a better quality of life. Based on current evidence, etiological treatment has to be considered as an essential public health strategy useful to reduce disease burden and to eliminate Chagas disease altogether. PMID:22523499

  12. Transmission of chagas disease (American trypanosomiasis) by food.

    PubMed

    Pereira, Karen Signori; Schmidt, Flávio Luis; Barbosa, Rodrigo L; Guaraldo, Ana M A; Franco, Regina M B; Dias, Viviane L; Passos, Luiz A C

    2010-01-01

    In April 2009, the centenary of the discovery of the American trypanosomiasis, or Chagas disease, was celebrated. A hundred years after the discovery, little has been invested in diagnostics and treatment because the disease affects mainly poor people in developing countries. However, some changes in the epidemiology of the disease are of great importance today. Chagas disease transmitted through food is a public health concern in all areas where there is a reservoir of Trypanosoma cruzi in wild animals (e.g., mammals and marsupials) and/or where infected triatomine bugs are in contact with human food source items (especially fruits and vegetables). Recently, several outbreaks of illness related to the ingestion of food contaminated with T. cruzi have been recorded in Brazil, Colombia, and Venezuela.

  13. The Epidemiology, Clinical Manifestations, and Management of Chagas Heart Disease.

    PubMed

    Malik, Lindsey H; Singh, Gagan D; Amsterdam, Ezra A

    2015-09-01

    Chagas disease results from infection by the protozoan parasite Trypanosoma cruzi and is endemic in Latin America. T cruzi is most commonly transmitted through the feces of an infected triatomine, but can also be congenital, via contaminated blood transfusion or through direct oral contact. In the acute phase, the disease can cause cardiac derangements such as myocarditis, conduction system abnormalities, and/or pericarditis. If left untreated, the disease advances to the chronic phase. Up to one-half of these patients will develop a cardiomyopathy, which can lead to cardiac failure and/or ventricular arrhythmias, both of which are major causes of mortality. Diagnosis is confirmed by serologic testing for specific immunoglobulin G antibodies. Initial treatment consists of the antiparasitic agents benznidazole and nifurtimox. The treatment of Chagas cardiac disease comprises standard medical therapy for heart failure and amiodarone for ventricular arrhythmias, with consideration for implantable cardioverter-defibrillator. Chagas disease causes the highest infectious burden of any parasitic disease in the Western Hemisphere, and increased awareness of this disease is essential to improve diagnosis, enhance management, and reduce spread.

  14. Challenges and perspectives of Chagas disease: a review

    PubMed Central

    2013-01-01

    Chagas disease (CD), also known as American trypanosomiasis, is caused by the flagellated protozoan Trypanosoma cruzi, and affects an estimated 8 to 10 million people worldwide. In Latin America, 25 million people live in risk areas, while in 2008 alone, 10,000 CD-related deaths were reported. This review aimed to evaluate the challenges of CD control, future perspectives, and actions performed worldwide to control expansion of the disease and its impact on public health in Latin America. PMID:24354455

  15. Chagas Disease, Migration and Community Settlement Patterns in Arequipa, Peru

    PubMed Central

    Gilman, Robert H.; Cornejo del Carpio, Juan G.; Naquira, Cesar; Bern, Caryn; Levy, Michael Z.

    2009-01-01

    Background Chagas disease is one of the most important neglected tropical diseases in the Americas. Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission. Methodology/Principal Findings This was a qualitative study that employed focus group discussions and in-depth interviews. Five focus groups and 50 in-depth interviews were carried out with 94 community members from three shantytowns and two traditional towns near Arequipa, Peru. Focus groups utilized participatory methodologies to explore the community's mobility patterns and the historical and current presence of triatomine vectors. In-depth interviews based on event history calendars explored participants' migration patterns and experience with Chagas disease and vectors. Focus group data were analyzed using participatory analysis methodologies, and interview data were coded and analyzed using a grounded theory approach. Entomologic data were provided by an ongoing vector control campaign. We found that migrants to shantytowns in Arequipa were unlikely to have brought triatomines to the city upon arrival. Frequent seasonal moves, however, took shantytown residents to valleys surrounding Arequipa where vectors are prevalent. In addition, the pattern of settlement of shantytowns and the practice of raising domestic animals by residents creates a favorable environment for vector proliferation and dispersal. Finally, we uncovered a phenomenon of population loss and replacement by low-income migrants in one traditional town, which created the human settlement pattern of a new shantytown within this traditional community. Conclusions/Significance The pattern of human migration is therefore an important underlying determinant of

  16. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

    PubMed Central

    Pinho, Rosa T.; Waghabi, Mariana C.; Cardillo, Fabíola; Mengel, José; Antas, Paulo R. Z.

    2016-01-01

    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials. PMID:27563302

  17. Development of a community-based intervention for the control of Chagas disease based on peridomestic animal management: an eco-bio-social perspective

    PubMed Central

    De Urioste-Stone, Sandra M.; Pennington, Pamela M.; Pellecer, Elizabeth; Aguilar, Teresa M.; Samayoa, Gabriela; Perdomo, Hugo D.; Enríquez, Hugo; Juárez, José G.

    2015-01-01

    Background Integrated vector management strategies depend on local eco-bio-social conditions, community participation, political will and inter-sectorial partnership. Previously identified risk factors for persistent Triatoma dimidiata infestation include the presence of rodents and chickens, tiled roofs, dirt floors, partial wall plastering and dog density. Methods A community-based intervention was developed and implemented based on cyclical stakeholder and situational analyses. Intervention implementation and evaluation combined participatory action research and cluster randomized pre-test post-test experimental designs. The intervention included modified insecticide application, education regarding Chagas disease and risk factors, and participatory rodent control. Results At final evaluation there was no significant difference in post-test triatomine infestation between intervention and control, keeping pre-test rodent and triatomine infestations constant. Knowledge levels regarding Chagas disease and prevention practices including rodent control, chicken management and health service access increased significantly only in intervention communities. The odds of nymph infection and rat infestation were 8.3 and 1.9-fold higher in control compared to intervention communities, respectively. Conclusion Vector control measures without reservoir control are insufficient to reduce transmission risk in areas with persistent triatomine infestation. This integrated vector management program can complement house improvement initiatives by prioritizing households with risk factors such as tiled roofs. Requirement for active participation and multi-sectorial coordination poses implementation challenges. PMID:25604767

  18. Prophylactic and therapeutic DNA vaccines against Chagas disease.

    PubMed

    Arce-Fonseca, Minerva; Rios-Castro, Martha; Carrillo-Sánchez, Silvia del Carmen; Martínez-Cruz, Mariana; Rodríguez-Morales, Olivia

    2015-01-01

    Chagas disease is a zoonosis caused by Trypanosoma cruzi in which the most affected organ is the heart. Conventional chemotherapy has a very low effectiveness; despite recent efforts, there is currently no better or more effective treatment available. DNA vaccines provide a new alternative for both prevention and treatment of a variety of infectious disorders, including Chagas disease. Recombinant DNA technology has allowed some vaccines to be developed using recombinant proteins or virus-like particles capable of inducing both a humoral and cellular specific immune response. This type of immunization has been successfully used in preclinical studies and there are diverse models for viral, bacterial and/or parasitic diseases, allergies, tumors and other diseases. Therefore, several research groups have been given the task of designing a DNA vaccine against experimental infection with T. cruzi. In this review we explain what DNA vaccines are and the most recent studies that have been done to develop them with prophylactic or therapeutic purposes against Chagas disease.

  19. Trypanosoma cruzi and Chagas' Disease in the United States

    PubMed Central

    Bern, Caryn; Kjos, Sonia; Yabsley, Michael J.; Montgomery, Susan P.

    2011-01-01

    Summary: Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century. PMID:21976603

  20. A case of Chagas' disease panniculitis after kidney transplantation.

    PubMed

    Campos, Fábio Prestes de; Pansard, Henry Mor; Arantes, Luiz Cláudio; Rodrigues, Arnaldo Teixeira; Daubermann, Melissa Falster; Azambuja, Marcos Felipe; Argenta, Laércio Cassol; Silva, Luiz Alberto Michet da

    2016-03-01

    Chagas' disease carries high morbidity and mortality due to acute parasitemia or cardiac, digestive, cutaneous or neurologic chronic lesions. Latin American countries have the majority of infected or at risk people. Transplanted patients using immunosuppressive agents may develop severe and even fatal forms of the disease. The available treatment causes frequent severe side-effects. A 59 years-old woman with end stage renal disease and positive serology for Chagas` disease, but without any clinical manifestation of this pathology, underwent kidney transplantation from a cadaveric donor and displayed three months later a thigh panniculitis from which a biopsy unveiled amastigote forms of Trypanosoma cruzi. The skin lesions disappeared following treatment with benzonidazole, but the drug was discontinued due to severe pancytopenia. Along with this, infection with E. faecalis and cytomegalovirus were treated with vancomicin and ganciclovir. The patient kept very well afterwards, with no new skin lesions and with good graft function. One year and three months after the transplant, she had an emergency surgery for an aortic dissecting aneurysm. Irreversible shock and death occurred in the immediate post-surgical period. It was not possible to establish or to rule out a relationship between the trypanosomiasis and the aortic lesions. Chagas` disease must be remembered in differential diagnosis of several clinical situations in transplant patients, mainly in endemic areas. The treatment can yeld good clinical response, but serious side-effects from the drugs may ensue. More effective and better tolerated options are in need for treatment or prophylaxis. PMID:27049374

  1. The Role of Haptoglobin Genotypes in Chagas Disease

    PubMed Central

    Mundaray Fernández, Ninomar; Fernández-Mestre, Mercedes

    2014-01-01

    Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection. PMID:25147423

  2. Triatoma dimidiata (Latreille, 1811): a review of its diversity across its geographic range and the relationship among populations.

    PubMed

    Dorn, Patricia L; Monroy, Carlota; Curtis, Andrew

    2007-03-01

    Due to its vast diversity the Chagas vector, Triatoma dimidiata, has been merged and split into species and subspecies since its first description in 1811. Across its geographic range from Southern Mexico to Northern Peru populations differ in their biology and ethology in many ways including those that directly affect vector capacity and competence. Recent phenetic and genetic data suggest that T. dimidiata can be divided into at least three clades and in fact may be a polytypic species or species complex. To effectively target this vector, it will be necessary to clearly understand how "T. dimidiata" is genetically partitioned both at the taxonomic and population level.

  3. Economic evaluation of Chagas disease screening in Spain.

    PubMed

    Imaz-Iglesia, Iñaki; Miguel, Lucía García-San; Ayala-Morillas, L Eduardo; García-Pérez, Lidia; González-Enríquez, Jesús; Blasco-Hernández, Teresa; Martín-Águeda, María Belén; Sarría-Santamera, Antonio

    2015-08-01

    Although Spain is the European country with the highest Chagas disease burden, the country does not have a national control program of the disease. The purpose of this study is to evaluate the efficiency of several strategies for Chagas disease screening among Latin American residents living in Spain. The following screening strategies were evaluated: (1) non-screening; (2) screening of the Latin American pregnant women and their newborns; (3) screening also the relatives of the positive pregnant women; (4) screening also the relatives of the negative pregnant women. A cost-utility analysis was carried out to compare the four strategies from two perspectives, the societal and the Spanish National Health System (SNHS). A decision tree representing the clinical evolution of Chagas disease throughout patient's life was built. The strategies were compared through the incremental cost-utility ratio, using euros as cost measurement and quality-adjusted life years as utility measurement. A sensitivity analysis was performed to test the model parameters and their influence on the results. We found the "Non-screening" as the most expensive and less effective of the evaluated strategies, from both the societal and the SNHS perspectives. Among the screening evaluated strategies the most efficient was, from both perspectives, to extent the antenatal screening of the Latin American pregnant women and their newborns up to the relatives of the positive women. Several parameters influenced significantly on the sensitivity analyses, particularly the chronic treatment efficacy or the prevalence of Chagas disease. In conclusion, for the general Latin American immigrants living in Spain the most efficient would be to screen the Latin American mothers, their newborns and the close relatives of the mothers with a positive serology. However for higher prevalence immigrant population the most efficient intervention would be to extend the program to the close relatives of the negative

  4. Methodological advances in drug discovery for Chagas disease

    PubMed Central

    Bustamante, Juan M.; Tarleton, Rick L.

    2011-01-01

    Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments. PMID:21712965

  5. Opportunity Cost for Early Treatment of Chagas Disease in Mexico

    PubMed Central

    Ramsey, Janine M.; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

    2014-01-01

    Background Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. Methodology/Principal Findings A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. Conclusions/Significance In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life. PMID:24743112

  6. [Representations, myths, and behaviors among Chagas disease patients with pacemakers].

    PubMed

    Magnani, Claudia; Oliveira, Bruna Guimarães; Gontijo, Eliane Dias

    2007-07-01

    This anthropological study aimed to evaluate the incorporation of pacemakers into the lives of individuals with Chagas disease. An ethnographic methodology was used, based on an open interview focusing on the personal perceptions of 15 patients with chronic Chagas cardiopathy who had required pacemaker implants at the Federal University Hospital in Belo Horizonte, Minas Gerais State, Brazil. As part of a broader quality of life analysis, the study investigated the cultural, physical, and psychological resources used by patients to confront, explain, and accept the disease process, including mental representations on the cultural perception of the illness and definition of social relations. The study was intended to contribute to comprehensive patient care by health professionals, including psychosocial aspects. Decoded and integrated orientation in the cultural sphere assumes an important role in order to prevent disinformation from perpetuating the dissemination of popular myths as active elements in patient stigmatization. PMID:17572811

  7. Type 1 electrocardiographic Brugada pattern in a woman with Chagas disease: a case report.

    PubMed

    Brito, Mitermayer R; Miranda, Carlos Eduardo S; Rabelo, Walter; Marino, Roberto L

    2010-09-01

    A 56-year-old woman with well-documented Chagas disease was found to have a spontaneous type 1 electrocardiographic (ECG) pattern of Brugada syndrome. It is most likely that this characteristic ST-segment elevation is an unusual manifestation of the pathological changes in Chagas disease. This ECG pattern has been found with other cardiac pathology and has been reported to be induced in patients with Chagas disease.

  8. Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease.

    PubMed

    Sbaraglini, María L; Bellera, Carolina L; Fraccaroli, Laura; Larocca, Luciana; Carrillo, Carolina; Talevi, Alan; Alba Soto, Catalina D

    2016-07-01

    Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies. PMID:27216381

  9. Retracing Micro-Epidemics of Chagas Disease Using Epicenter Regression

    PubMed Central

    Levy, Michael Z.; Small, Dylan S.; Vilhena, Daril A.; Bowman, Natalie M.; Kawai, Vivian; Cornejo del Carpio, Juan G.; Cordova-Benzaquen, Eleazar; Gilman, Robert H.; Bern, Caryn; Plotkin, Joshua B.

    2011-01-01

    Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1 PMID:21935346

  10. Retracing micro-epidemics of Chagas disease using epicenter regression.

    PubMed

    Levy, Michael Z; Small, Dylan S; Vilhena, Daril A; Bowman, Natalie M; Kawai, Vivian; Cornejo del Carpio, Juan G; Cordova-Benzaquen, Eleazar; Gilman, Robert H; Bern, Caryn; Plotkin, Joshua B

    2011-09-01

    Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.

  11. Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

    PubMed Central

    Hidron, Alicia I.; Gilman, Robert H.; Justiniano, Juan; Blackstock, Anna J.; LaFuente, Carlos; Selum, Walter; Calderon, Martiza; Verastegui, Manuela; Ferrufino, Lisbeth; Valencia, Eduardo; Tornheim, Jeffrey A.; O'Neal, Seth; Comer, Robert; Galdos-Cardenas, Gerson; Bern, Caryn

    2010-01-01

    Background Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common. Methodology/Principal Findings The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz, Bolivia. Data included risk factors for T. cruzi infection, medical history, physical examination, electrocardiogram, echocardiogram, and contact 9 months after initial data collection to ascertain mortality. Serology and PCR for Trypanosoma cruzi were performed. Of 394 participants, 251 (64%) had confirmed T. cruzi infection by serology. Among seropositive participants, 109 (43%) had positive results by conventional PCR; of these, 89 (82%) also had positive results by real time PCR. There was a high prevalence of hypertension (64%) and overweight (body mass index [BMI] >25; 67%), with no difference by T. cruzi infection status. Nearly 60% of symptomatic congestive heart failure was attributed to Chagas cardiomyopathy; mortality was also higher for seropositive than seronegative patients (p = 0.05). In multivariable models, longer residence in an endemic province, residence in a rural area and poor housing conditions were associated with T. cruzi infection. Male sex, increasing age and poor housing were independent predictors of Chagas cardiomyopathy severity. Males and participants with BMI ≤25 had significantly higher likelihood of positive PCR results compared to females or overweight participants. Conclusions Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease. PMID:20502520

  12. A survey on Triatoma dimidiata in an urban area of the province of Heredia, Costa Rica.

    PubMed

    Zeledón, Rodrigo; Calvo, Nidia; Montenegro, Víctor M; Lorosa, Elias Seixas; Arévalo, Carolina

    2005-10-01

    Triatoma dimidiata has been found in several cities and towns of those countries where the insect is a domestic or peridomestic pest. In Central America, urban infestations occur in the capitals of at least five countries. During 2001 and 2002 a survey was carried out in the county of San Rafael, Heredia province, located 15 km northwest of San José, capital of Costa Rica, in order to determine the degree of infestation by T. dimidiata in an entire city block. Six peridomestic colonies of the insect were detected in the backyards of eight households. The ecotopes occupied by the insects consisted of store rooms with old objects, wood piles or firewood, and chicken coops. A total of 1917 insects were found in the six foci, during two sampling periods, and a mean infection rate by Trypanosoma cruzi of 28.4% was found in 1718 insects examined. The largest colony found in one of the households yielded 872 insects that were thriving mainly at the expenses of two dogs. Opossums and adult insects were common visitors of the houses and it became evident that this marsupial is closely related to the peridomestic cycle of the Chagas disease agent. Lack of colonization of the insect inside the human dwellings is explained by the type of construction and good sanitary conditions of the houses, in contrast to the situation in most peridomiciliary areas. Stomach blood samples from the insects showed that the main hosts were, in order of decreasing frequency: rodents, dogs, fowl, humans, opossums, and cats. The fact that no indication of infection with Chagas disease could be detected in the human occupants of the infested houses, vis a vis the high infection rate in dogs, is discussed.

  13. Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States.

    PubMed

    Edwards, James M; Gilner, Jennifer B; Hernandez, Jose; Kurtzberg, Joanne; Heine, R Phillips

    2016-08-01

    To assess patterns of Chagas disease, we reviewed results of screening umbilical cord blood from a US public cord blood bank during 2007-2014. Nineteen maternal donors tested positive for Trypanosoma cruzi parasites (0.04%). Because perinatal transmission of Chagas disease is associated with substantial illness, targeted prenatal programs should screen for this disease. PMID:27433974

  14. Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States

    PubMed Central

    Gilner, Jennifer B.; Hernandez, Jose; Kurtzberg, Joanne; Heine, R. Phillips

    2016-01-01

    To assess patterns of Chagas disease, we reviewed results of screening umbilical cord blood from a US public cord blood bank during 2007–2014. Nineteen maternal donors tested positive for Trypanosoma cruzi parasites (0.04%). Because perinatal transmission of Chagas disease is associated with substantial illness, targeted prenatal programs should screen for this disease. PMID:27433974

  15. Nuclear rDNA pseudogenes in Chagas disease vectors: evolutionary implications of a new 5.8S+ITS-2 paralogous sequence marker in triatomines of North, Central and northern South America.

    PubMed

    Bargues, M Dolores; Zuriaga, M Angeles; Mas-Coma, Santiago

    2014-01-01

    /taxonomic studies. It opens a new research field, Chagas disease epidemiology and control included, given its potential relationships with triatomine fitness, behaviour and adaptability. PMID:24239656

  16. Travelers' Health: Trypanosomiasis, American (Chagas Disease)

    MedlinePlus

    ... Global TravEpiNet Mobile Apps RSS Feeds Chapter 3 Infectious Diseases Related to Travel Recommend on Facebook Tweet Share ... and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Global Migration and Quarantine (DGMQ) ...

  17. IL18 Gene Variants Influence the Susceptibility to Chagas Disease.

    PubMed

    Leon Rodriguez, Daniel A; Carmona, F David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-03-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

  18. Resveratrol Reverses Functional Chagas Heart Disease in Mice

    PubMed Central

    Mata-Santos, Hilton; Vicentino, Amanda R. R.; Feijó, Daniel F.; Meyer-Fernandes, José R.; Paula-Neto, Heitor A.; Medei, Emiliano; Bozza, Marcelo T.; Lannes-Vieira, Joseli; Paiva, Claudia N.

    2016-01-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC. PMID:27788262

  19. [Chagas disease. American trypanosomiasis. Recommendation for non-endemic zones].

    PubMed

    2010-04-01

    The following recommendations were made at the end of the consensus workshop organized by the Société de Pathologie Exotique (Exotic Pathology Society) (Paris, 26 June 2009). They apply to people of Latin American origin (immigrants, children born in France to a Latin-American mother, French people originating in Guyana) and expatriates and travellers who have stayed in areas where Chagas disease is endemic. These recommendations concern screening for people who are infected but asymptomatic, diagnosis of acute forms, diagnosis of chronic forms with clinical manifestations and therapeutic procedure.

  20. Reactivation of Chagas Disease: Implications for Global Health.

    PubMed

    Perez, Catherine J; Lymbery, Alan J; Thompson, R C Andrew

    2015-11-01

    Reactivation of Chagas Disease (CD) is a global public health issue. Reactivation of disease can affect the management of CD and its clinical outcome, adding pressure to global health systems because it exacerbates symptoms, leading to misdiagnosis and delays in the administration of correct treatments. Concurrent infections complicate the issue of reactivation, because there are various parasites and disease treatment regimens that are able to influence or suppress the immune system of the host, reactivating disease within infected individuals. The effect of delayed symptoms of chronic CD and the potential for disease reactivation are of great importance to nonendemic regions of the world, where knowledge about CD is lacking and the potential for vectorial transmission is not known.

  1. Squalene Synthase As a Target for Chagas Disease Therapeutics

    PubMed Central

    Chan, Hsiu-Chien; Li, Jikun; Zheng, Yingying; Huang, Chun-Hsiang; Ren, Feifei; Chen, Chun-Chi; Zhu, Zhen; Galizzi, Melina; Li, Zhu-Hong; Rodrigues-Poveda, Carlos A.; Gonzalez-Pacanowska, Dolores; Veiga-Santos, Phercyles; de Carvalho, Tecia Maria Ulisses; de Souza, Wanderley; Urbina, Julio A.; Wang, Andrew H.-J.; Docampo, Roberto; Li, Kai; Liu, Yi-Liang; Oldfield, Eric; Guo, Rey-Ting

    2014-01-01

    Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS) from a trypanosomatid parasite, Trypanosoma cruzi, the causative agent of Chagas disease. We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. We also show that the lipophilic bisphosphonates have low nM activity against T. cruzi and inhibit endogenous sterol biosynthesis and that E5700 acts synergistically with the azole drug, posaconazole. The determination of the structures of trypanosomatid and human SQS enzymes with a diverse set of inhibitors active in cells provides insights into SQS inhibition, of interest in the context of the development of drugs against Chagas disease. PMID:24789335

  2. Squalene synthase as a target for Chagas disease therapeutics.

    PubMed

    Shang, Na; Li, Qian; Ko, Tzu-Ping; Chan, Hsiu-Chien; Li, Jikun; Zheng, Yingying; Huang, Chun-Hsiang; Ren, Feifei; Chen, Chun-Chi; Zhu, Zhen; Galizzi, Melina; Li, Zhu-Hong; Rodrigues-Poveda, Carlos A; Gonzalez-Pacanowska, Dolores; Veiga-Santos, Phercyles; de Carvalho, Tecia Maria Ulisses; de Souza, Wanderley; Urbina, Julio A; Wang, Andrew H-J; Docampo, Roberto; Li, Kai; Liu, Yi-Liang; Oldfield, Eric; Guo, Rey-Ting

    2014-05-01

    Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS) from a trypanosomatid parasite, Trypanosoma cruzi, the causative agent of Chagas disease. We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. We also show that the lipophilic bisphosphonates have low nM activity against T. cruzi and inhibit endogenous sterol biosynthesis and that E5700 acts synergistically with the azole drug, posaconazole. The determination of the structures of trypanosomatid and human SQS enzymes with a diverse set of inhibitors active in cells provides insights into SQS inhibition, of interest in the context of the development of drugs against Chagas disease. PMID:24789335

  3. Identifying spatial data availability and spatial data needs for Chagas disease mitigation in South America.

    PubMed

    Morris, Emily; Bone, Christopher

    2016-05-01

    The objective of this paper on Chagas disease is to determine the availability and spatial resolution of existing data that can be used to address Chagas disease transmission risk in South America. A literature review was conducted to determine prominent variables that models utilize to assist with efforts to mitigate Chagas disease. Next, a Web search was performed to collect publicly available spatial data pertaining to these variables for the countries in South America. The data were classified based on type and spatial extent, which were then used to create maps of data availability of variables related to Chagas disease transmission. Governments can use this information to better direct their resources to collect data and control the spread of triatomines and Chagas more effectively, and potentially identify more cost-effective strategies for eliminating triatomine vectors.

  4. Agrochemicals against Malaria, Sleeping Sickness, Leishmaniasis and Chagas Disease

    PubMed Central

    Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

    2012-01-01

    In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively. PMID:23145187

  5. Historical Perspectives on the Epidemiology of Human Chagas Disease in Texas and Recommendations for Enhanced Understanding of Clinical Chagas Disease in the Southern United States

    PubMed Central

    Garcia, Melissa N.; Woc-Colburn, Laila; Aguilar, David; Hotez, Peter J.; Murray, Kristy O.

    2015-01-01

    Chagas disease (Trypanosoma cruzi infection) has recently been identified as an important neglected tropical disease in the United States. Anecdotally referred to as a “silent killer,” it leads to the development of potentially fatal cardiac disease in approximately 30% of those infected. In an attempt to better understand the potential of Chagas disease as a significant underlying cause of morbidity in Texas, we performed a historical literature review to assess disease burden. Human reports of triatomine bites and disease exposure were found to be prevalent in Texas. Despite current beliefs that Chagas disease is a recently emerging disease, we report historical references dating as far back as 1935. Both imported cases and autochthonous transmission contribute to the historical disease burden in Texas. We end by discussing the current knowledge gaps, and recommend priorities for advancing further epidemiologic studies and their policy implications. PMID:26540273

  6. Historical Perspectives on the Epidemiology of Human Chagas Disease in Texas and Recommendations for Enhanced Understanding of Clinical Chagas Disease in the Southern United States.

    PubMed

    Garcia, Melissa N; Woc-Colburn, Laila; Aguilar, David; Hotez, Peter J; Murray, Kristy O

    2015-11-01

    Chagas disease (Trypanosoma cruzi infection) has recently been identified as an important neglected tropical disease in the United States. Anecdotally referred to as a "silent killer," it leads to the development of potentially fatal cardiac disease in approximately 30% of those infected. In an attempt to better understand the potential of Chagas disease as a significant underlying cause of morbidity in Texas, we performed a historical literature review to assess disease burden. Human reports of triatomine bites and disease exposure were found to be prevalent in Texas. Despite current beliefs that Chagas disease is a recently emerging disease, we report historical references dating as far back as 1935. Both imported cases and autochthonous transmission contribute to the historical disease burden in Texas. We end by discussing the current knowledge gaps, and recommend priorities for advancing further epidemiologic studies and their policy implications.

  7. Risks of endemicity, morbidity and perspectives regarding the control of Chagas disease in the Amazon Region.

    PubMed

    Coura, José Rodrigues; Junqueira, Angela Cv

    2012-03-01

    Chagas disease, in the Amazon Region as elsewhere, can be considered an enzootic disease of wild animals or an anthropozoonosis, an accidental disease of humans that is acquired when humans penetrate a wild ecosystem or when wild triatomines invade human dwellings attracted by light or searching for human blood. The risk of endemic Chagas disease in the Amazon Region is associated with the following phenomena: (i) extensive deforestation associated with the displacement of wild mammals, which are the normal sources of blood for triatomines, (ii) adaptation of wild triatomines to human dwellings due to the need for a new source of blood for feeding and (iii) uncontrolled migration of human populations and domestic animals that are already infected with Trypanosoma cruzi from areas endemic for Chagas disease to the Amazon Region. Several outbreaks of severe acute cases of Chagas disease, as well as chronic cases, have been described in the Amazon Region. Control measures targeted to avoiding endemic Chagas disease in the Amazon Region should be the following: improving health education in communities, training public health officials and communities for vector and Chagas disease surveillance and training local physicians to recognise and treat acute and chronic cases of Chagas diseases as soon as possible.

  8. Chagas Disease Awareness among Latin American Immigrants Living in Los Angeles, California

    PubMed Central

    Sanchez, Daniel R.; Traina, Mahmoud I.; Hernandez, Salvador; Smer, Aiman M.; Khamag, Haneen; Meymandi, Sheba K.

    2014-01-01

    Approximately 300,000 persons have Chagas disease in the United States, although almost all persons acquired the disease in Latin America. We examined awareness of Chagas disease among Latin American immigrants living in Los Angeles, California. We surveyed 2,677 persons (age range = 18–60 years) in Los Angeles who resided in Latin America for at least six months. A total of 62% of the participants recalled seeing triatomines in Latin America, and 27% of the participants reported triatomine bites at least once per year while living abroad. A total of 86% of the participants had never heard of Chagas disease. Of persons who had heard of Chagas disease, 81% believed that it was not serious. More than 95% of those who had heard of Chagas disease would want to be tested and treated. Most Latin American immigrants living in Los Angeles recalled exposure to vectors of Chagas disease. However, they have little knowledge of this disease. Increasing awareness of Chagas disease is needed in this high-risk population. PMID:25200261

  9. IL18 Gene Variants Influence the Susceptibility to Chagas Disease.

    PubMed

    Leon Rodriguez, Daniel A; Carmona, F David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-03-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control. PMID:27027876

  10. IL18 Gene Variants Influence the Susceptibility to Chagas Disease

    PubMed Central

    Leon Rodriguez, Daniel A; Carmona, F. David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-01-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control. PMID:27027876

  11. Membranous nephropathy PLA2R+ associated with Chagas disease

    PubMed Central

    Silva, Vanessa dos Santos; Viero, Rosa Marlene

    2015-01-01

    Chagas disease (CD) — a tropical parasitic disease caused by the protozoan Trypanosoma cruzi — is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure. PMID:26558244

  12. Membranous nephropathy PLA2R+ associated with Chagas disease.

    PubMed

    Xavier-Júnior, José Cândido Caldeira; Silva, Vanessa Dos Santos; Viero, Rosa Marlene

    2015-01-01

    Chagas disease (CD) - a tropical parasitic disease caused by the protozoan Trypanosoma cruzi - is a major health problem in Latin America. The immune response against the parasite is responsible for chronic CD lesions. Currently, there are no reports of an association between CD and membranous nephropathy (MN). The detection of the phospholipase A2 receptor (PLA2R) as a target antigen in idiopathic MN can improve the differential diagnosis of primary and secondary forms of MN. The authors report the case of a male patient with positive serology for CD who presented sudden death and underwent autopsy. Histological sections of the heart showed multifocal inflammatory infiltrate composed mainly of mononuclear cells, leading to myocardiocytes necrosis and interstitial fibrosis. The kidneys showed a MN with positive expression for PLA2R. As far as we know, this is the first report of a case of primary MN in a patient with CD, with severe chronic cardiomyopathy and heart failure.

  13. Chagas disease in Texas: recognizing the significance and implications of evidence in the literature.

    PubMed

    Hanford, Elaine Jennifer; Zhan, F Benjamin; Lu, Yongmei; Giordano, Alberto

    2007-07-01

    Chagas disease is endemic and is recognized as a major health problem in many Latin American countries. Despite the parallels between socio-economic and environmental conditions in Texas and much of Latin America, Chagas disease is not a notifiable human disease in Texas. Based on extensive review of related literature, this paper seeks to recognize the evidence that Chagas Disease is endemic to Texas but the epidemiological, parasitological and entomological patterns of Chagas disease in Texas are both different from and parallel to other endemic regions. We find that with a growing immigrant human reservoir, the epidemiological differences may be reduced and result in increasing incidence of the disease. Chagas disease should be recognized as an emerging disease among both immigrant and indigenous populations. Without proper actions, Chagas disease will place increasing burden on the health care system. Current medical treatments consist of chemotherapies that carry the risk of serious side effects; curing the potentially fatal disease remains equivocal. Therefore, as shown in South America, prevention is paramount and can be successfully achieved through intervention and education. We conclude that biogeographical research is needed to (1) distinguish the dynamic evolution of the agent-vector-host system, (2) document locations with greater risk and identify mechanisms responsible for observed changes in risk, and (3) assist in developing a model for Triatomid vector-borne disease in states like Texas where the disease is both endemic and may be carried by a sizeable immigrant population. Tracking of Chagas disease and planning for appropriate health care services would also be aided by including Chagas disease on the list of reportable diseases for humans.

  14. On palms, bugs, and Chagas disease in the Americas.

    PubMed

    Abad-Franch, Fernando; Lima, Marli M; Sarquis, Otília; Gurgel-Gonçalves, Rodrigo; Sánchez-Martín, María; Calzada, José; Saldaña, Azael; Monteiro, Fernando A; Palomeque, Francisco S; Santos, Walter S; Angulo, Victor M; Esteban, Lyda; Dias, Fernando B S; Diotaiuti, Liléia; Bar, María Esther; Gottdenker, Nicole L

    2015-11-01

    Palms are ubiquitous across Neotropical landscapes, from pristine forests or savannahs to large cities. Although palms provide useful ecosystem services, they also offer suitable habitat for triatomines and for Trypanosoma cruzi mammalian hosts. Wild triatomines often invade houses by flying from nearby palms, potentially leading to new cases of human Chagas disease. Understanding and predicting triatomine-palm associations and palm infestation probabilities is important for enhancing Chagas disease prevention in areas where palm-associated vectors transmit T. cruzi. We present a comprehensive overview of palm infestation by triatomines in the Americas, combining a thorough reanalysis of our published and unpublished records with an in-depth review of the literature. We use site-occupancy modeling (SOM) to examine infestation in 3590 palms sampled with non-destructive methods, and standard statistics to describe and compare infestation in 2940 palms sampled by felling-and-dissection. Thirty-eight palm species (18 genera) have been reported to be infested by ∼39 triatomine species (10 genera) from the USA to Argentina. Overall infestation varied from 49.1-55.3% (SOM) to 62.6-66.1% (dissection), with important heterogeneities among sub-regions and particularly among palm species. Large palms with complex crowns (e.g., Attalea butyracea, Acrocomia aculeata) and some medium-crowned palms (e.g., Copernicia, Butia) are often infested; in slender, small-crowned palms (e.g., Euterpe) triatomines associate with vertebrate nests. Palm infestation tends to be higher in rural settings, but urban palms can also be infested. Most Rhodnius species are probably true palm specialists, whereas Psammolestes, Eratyrus, Cavernicola, Panstrongylus, Triatoma, Alberprosenia, and some Bolboderini seem to use palms opportunistically. Palms provide extensive habitat for enzootic T. cruzi cycles and a critical link between wild cycles and transmission to humans. Unless effective means to

  15. On palms, bugs, and Chagas disease in the Americas.

    PubMed

    Abad-Franch, Fernando; Lima, Marli M; Sarquis, Otília; Gurgel-Gonçalves, Rodrigo; Sánchez-Martín, María; Calzada, José; Saldaña, Azael; Monteiro, Fernando A; Palomeque, Francisco S; Santos, Walter S; Angulo, Victor M; Esteban, Lyda; Dias, Fernando B S; Diotaiuti, Liléia; Bar, María Esther; Gottdenker, Nicole L

    2015-11-01

    Palms are ubiquitous across Neotropical landscapes, from pristine forests or savannahs to large cities. Although palms provide useful ecosystem services, they also offer suitable habitat for triatomines and for Trypanosoma cruzi mammalian hosts. Wild triatomines often invade houses by flying from nearby palms, potentially leading to new cases of human Chagas disease. Understanding and predicting triatomine-palm associations and palm infestation probabilities is important for enhancing Chagas disease prevention in areas where palm-associated vectors transmit T. cruzi. We present a comprehensive overview of palm infestation by triatomines in the Americas, combining a thorough reanalysis of our published and unpublished records with an in-depth review of the literature. We use site-occupancy modeling (SOM) to examine infestation in 3590 palms sampled with non-destructive methods, and standard statistics to describe and compare infestation in 2940 palms sampled by felling-and-dissection. Thirty-eight palm species (18 genera) have been reported to be infested by ∼39 triatomine species (10 genera) from the USA to Argentina. Overall infestation varied from 49.1-55.3% (SOM) to 62.6-66.1% (dissection), with important heterogeneities among sub-regions and particularly among palm species. Large palms with complex crowns (e.g., Attalea butyracea, Acrocomia aculeata) and some medium-crowned palms (e.g., Copernicia, Butia) are often infested; in slender, small-crowned palms (e.g., Euterpe) triatomines associate with vertebrate nests. Palm infestation tends to be higher in rural settings, but urban palms can also be infested. Most Rhodnius species are probably true palm specialists, whereas Psammolestes, Eratyrus, Cavernicola, Panstrongylus, Triatoma, Alberprosenia, and some Bolboderini seem to use palms opportunistically. Palms provide extensive habitat for enzootic T. cruzi cycles and a critical link between wild cycles and transmission to humans. Unless effective means to

  16. Short report: Increasing access to treatment for Chagas disease: the case of Morelos, Mexico.

    PubMed

    Manne-Goehler, Jennifer; Ramsey, Janine M; Salgado, Marco Ocampo; Wirtz, Veronika J; Reich, Michael R

    2014-12-01

    Chagas disease is a neglected vector-borne disease with an estimated prevalence of 1.1 million cases in Mexico. Recent research showed that access to treatment of Chagas disease is limited in Mexico, with < 0.5% of infected cases treated. This brief report used quantitative data from the Morelos Program on Chagas disease and qualitative analysis of key informant interviews to examine strategies to increase treatment access for infected patients in Morelos, Mexico. From 2007 to 2011, 263 (9.2%) of the registered cases of Chagas disease in Mexico occurred in Morelos. Among these, 152 (57.8%) were treated and 97.3% of those treated received benznidazole. The assessment finds that state officials decided to directly purchase benznidazole from the distributor to increase access and improve clinical quality of treatment of patients in their state. They also faced significant barriers, especially in regulation and health system organization, which limited efforts to make high quality treatment available.

  17. Gene-deleted live-attenuated Trypanosoma cruzi parasites as vaccines to protect against Chagas disease.

    PubMed

    Sánchez-Valdéz, Fernando J; Pérez Brandán, Cecilia; Ferreira, Arturo; Basombrío, Miguel Ángel

    2015-05-01

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. This illness is now becoming global, mainly due to congenital transmission, and so far, there are no prophylactic or therapeutic vaccines available to either prevent or treat Chagas disease. Therefore, different approaches aimed at identifying new protective immunogens are urgently needed. Live vaccines are likely to be more efficient in inducing protection, but safety issues linked with their use have been raised. The development of improved protozoan genetic manipulation tools and genomic and biological information has helped to increase the safety of live vaccines. These advances have generated a renewed interest in the use of genetically attenuated parasites as vaccines against Chagas disease. This review discusses the protective capacity of genetically attenuated parasite vaccines and the challenges and perspectives for the development of an effective whole-parasite Chagas disease vaccine.

  18. Epicuticular lipids induce aggregation in Chagas disease vectors

    PubMed Central

    Figueiras, Alicia N Lorenzo; Girotti, Juan R; Mijailovsky, Sergio J; Juárez, M Patricia

    2009-01-01

    Background The triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Aggregation behavior plays an important role in their survival by facilitating the location of refuges and cohesion of aggregates, helping to keep them safely assembled into shelters during daylight time, when they are vulnerable to predators. There are evidences that aggregation is mediated by thigmotaxis, by volatile cues from their faeces, and by hexane-extractable contact chemoreceptive signals from their cuticle surface. The epicuticular lipids of Triatoma infestans include a complex mixture of hydrocarbons, free and esterified fatty acids, alcohols, and sterols. Results We analyzed the response of T. infestans fifth instar nymphs after exposure to different amounts either of total epicuticular lipid extracts or individual lipid fractions. Assays were performed in a circular arena, employing a binary choice test with filter papers acting as aggregation attractive sites; papers were either impregnated with a hexane-extract of the total lipids, or lipid fraction; or with the solvent. Insects were significantly aggregated around papers impregnated with the epicuticular lipid extracts. Among the lipid fractions separately tested, only the free fatty acid fraction promoted significant bug aggregation. We also investigated the response to different amounts of selected fatty acid components of this fraction; receptiveness varied with the fatty acid chain length. No response was elicited by hexadecanoic acid (C16:0), the major fatty acid component. Octadecanoic acid (C18:0) showed a significant assembling effect in the concentration range tested (0.1 to 2 insect equivalents). The very long chain hexacosanoic acid (C26:0) was significantly attractant at low doses (≤ 1 equivalent), although a repellent effect was observed at higher doses. Conclusion The detection of contact aggregation pheromones has practical application in Chagas disease

  19. Heart transplant recipient with history of Chagas disease and elevated panel-reactive antibodies.

    PubMed

    Davalos-Krebs, Gleidys

    2015-12-01

    Chagas disease is caused by a protozoan named Trypanosoma cruzi transmitted to humans by reduviid bugs. Severe dilated cardiomyopathy from chronic T cruzi infection is the most common finding, leading to end-stage heart failure. Heart transplant is an effective treatment for Chagas heart disease. However, T cruzi reactivation is of great concern, predisposing patients to episodes of myocarditis and rejection. A 56-year-old woman with a history of Chagas disease and elevated calculated panel reactive antibodies (CPRAs) underwent induction therapy and desensitization strategies aimed at lowering CPRAs, as elevated CPRAs have been implicated in the development of antibody-mediated rejection and reduced allograft survival. Clinical phases and signs and symptoms of Chagas disease are briefly described in an attempt to promote awareness of the disease among clinicians. In addition, serology assays approved in the United States as well as recommendations of experts on Chagas disease to assess tissues and blood specimens from endemic areas are outlined. Ultimately, the importance of ongoing surveillance is emphasized, as the future of heart transplant recipients with Chagas disease is unpredictable and the presence or reactivation of the disease requires prompt attention in an effort to prevent graft failure and death.

  20. Heart transplant recipient with history of Chagas disease and elevated panel-reactive antibodies.

    PubMed

    Davalos-Krebs, Gleidys

    2015-12-01

    Chagas disease is caused by a protozoan named Trypanosoma cruzi transmitted to humans by reduviid bugs. Severe dilated cardiomyopathy from chronic T cruzi infection is the most common finding, leading to end-stage heart failure. Heart transplant is an effective treatment for Chagas heart disease. However, T cruzi reactivation is of great concern, predisposing patients to episodes of myocarditis and rejection. A 56-year-old woman with a history of Chagas disease and elevated calculated panel reactive antibodies (CPRAs) underwent induction therapy and desensitization strategies aimed at lowering CPRAs, as elevated CPRAs have been implicated in the development of antibody-mediated rejection and reduced allograft survival. Clinical phases and signs and symptoms of Chagas disease are briefly described in an attempt to promote awareness of the disease among clinicians. In addition, serology assays approved in the United States as well as recommendations of experts on Chagas disease to assess tissues and blood specimens from endemic areas are outlined. Ultimately, the importance of ongoing surveillance is emphasized, as the future of heart transplant recipients with Chagas disease is unpredictable and the presence or reactivation of the disease requires prompt attention in an effort to prevent graft failure and death. PMID:26645921

  1. Ecological, Social and Biological Risk Factors for Continued Trypanosoma cruzi Transmission by Triatoma dimidiata in Guatemala

    PubMed Central

    Bustamante, Dulce M.; De Urioste-Stone, Sandra M.; Juárez, José G.; Pennington, Pamela M.

    2014-01-01

    Background Chagas disease transmission by Triatoma dimidiata persists in Guatemala and elsewhere in Central America under undefined ecological, biological and social (eco-bio-social) conditions. Methodology Eco-bio-social risk factors associated with persistent domiciliary infestation were identified by a cross-sectional survey and qualitative participatory methods. Quantitative and qualitative data were generated regarding Trypanosoma cruzi reservoirs and triatomine hosts. Blood meal analysis and infection of insects, dogs and rodents were determined. Based on these data, multimodel inference was used to identify risk factors for domestic infestation with the greatest relative importance (>0.75). Principal Findings Blood meal analysis showed that 64% of 36 bugs fed on chickens, 50% on humans, 17% on dogs; 24% of 34 bugs fed on Rattus rattus and 21% on Mus musculus. Seroprevalence among 80 dogs was 37%. Eight (17%) of 46 M. musculus and three (43%) of seven R. rattus from households with infected triatomines were infected with T. cruzi Distinct Typing Unit I. Results from interviews and participatory meetings indicated that vector control personnel and some householders perceived chickens roosting and laying eggs in the house as bug infestation risk factors. House construction practices were seen as a risk factor for bug and rodent infestation, with rodents being perceived as a pest by study participants. Multimodel inference showed that house infestation risk factors of high relative importance are dog density, mouse presence, interior wall plaster condition, dirt floor, tile roofing and coffee tree presence. Conclusions/Significance Persistent house infestation is closely related to eco-bio-social factors that maintain productive T. dimidiata habitats associated with dogs, chickens and rodents. Triatomine, dog and rodent infections indicate active T. cruzi transmission. Integrated vector control methods should include actions that consider the role of

  2. Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina.

    PubMed

    Moscatelli, Guillermo; Berenstein, Ada; Tarlovsky, Ana; Siniawski, Susana; Biancardi, Miguel; Ballering, Griselda; Moroni, Samanta; Schwarcz, Marta; Hernández, Susana; García-Bournissen, Facundo; Cozzi, Andrés Espejo; Freilij, Héctor; Altcheh, Jaime

    2015-08-01

    The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate.

  3. Chagas disease and transfusion medicine: a perspective from non-endemic countries.

    PubMed

    Angheben, Andrea; Boix, Lucia; Buonfrate, Dora; Gobbi, Federico; Bisoffi, Zeno; Pupella, Simonetta; Gandini, Giorgio; Aprili, Giuseppe

    2015-10-01

    In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their "historical" boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas.

  4. Chagas disease and transfusion medicine: a perspective from non-endemic countries

    PubMed Central

    Angheben, Andrea; Boix, Lucia; Buonfrate, Dora; Gobbi, Federico; Bisoffi, Zeno; Pupella, Simonetta; Gandini, Giorgio; Aprili, Giuseppe

    2015-01-01

    In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their “historical” boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas. PMID:26513769

  5. Chagas disease and transfusion medicine: a perspective from non-endemic countries.

    PubMed

    Angheben, Andrea; Boix, Lucia; Buonfrate, Dora; Gobbi, Federico; Bisoffi, Zeno; Pupella, Simonetta; Gandini, Giorgio; Aprili, Giuseppe

    2015-10-01

    In the last decades, increasing international migration and travel from Latin America to Europe have favoured the emergence of tropical diseases outside their "historical" boundaries. Chagas disease, a zoonosis endemic in rural areas of Central and South America represents a clear example of this phenomenon. In the absence of the vector, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products. As most patients with Chagas disease are asymptomatic and unaware of their condition, in case of blood donation they can inadvertently represent a serious threat to the safety of the blood supply in non-endemic areas. Since the first cases of transfusion-transmitted Chagas disease were described in the last years, non-endemic countries began to develop ad hoc strategies to prevent and control the spread of the infection. United States, Spain, United Kingdom and France first recognised the need for Trypanosoma cruzi screening in at-risk blood donors. In this review, we trace an up-to-date perspective on Chagas disease, describing its peculiar features, from epidemiological, pathological, clinical and diagnostic points of view. Moreover, we describe the possible transmission of Chagas disease through blood or blood products and the current strategies for its control, focusing on non-endemic areas. PMID:26513769

  6. Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina

    PubMed Central

    Moscatelli, Guillermo; Berenstein, Ada; Tarlovsky, Ana; Siniawski, Susana; Biancardi, Miguel; Ballering, Griselda; Moroni, Samanta; Schwarcz, Marta; Hernández, Susana; García-Bournissen, Facundo; Cozzi, Andrés Espejo; Freilij, Héctor; Altcheh, Jaime

    2015-01-01

    The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate. PMID:26222020

  7. Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina.

    PubMed

    Moscatelli, Guillermo; Berenstein, Ada; Tarlovsky, Ana; Siniawski, Susana; Biancardi, Miguel; Ballering, Griselda; Moroni, Samanta; Schwarcz, Marta; Hernández, Susana; García-Bournissen, Facundo; Cozzi, Andrés Espejo; Freilij, Héctor; Altcheh, Jaime

    2015-08-01

    The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate. PMID:26222020

  8. Chagas disease in the United States: a cause for concern in Louisiana?

    PubMed

    Diaz, James H

    2007-01-01

    Chagas disease, or American trypanosomiasis, is an arthropod-borne protozoan infectious disease, hyperendemic throughout Latin America, caused by Trypanosoma cruzi, and transmitted to man by reduviid or kissing bugs. Throughout the Americas, Chagas disease shares many life cycle features with malaria, including transmission of infectious stages by local arthropods, exacerbation or reactivation of subclinical infections by immunosuppression (particularly HIV/AIDS) and pregnancy, and both transplacental and transfusion-related transmission. Although most cases of Chagas disease in the United States (US) are imported, significant numbers of Latin American immigrants contribute to the US blood supply and donate cadaveric tissues and organs for human transplantation, thus increasing the risks of both transfusion and transplantation-transmitted Chagas disease from unscreened blood products and transplantable tissues and organs. In addition, the risks of local reduviid bug-transmitted autochthonous or indigenous Chagas disease are also increasing as more immigrant workers enter the displaced populations of the Gulf South, including Louisiana, to assist in rebuilding efforts after Hurricanes Katrina and Rita. Although screening donated blood products for malaria remains impractical, consideration should now be given to serologically screening all donated blood and organs for Chagas disease in the US, as in most countries of Latin America, especially in high risk areas of California and the southern US, including Louisiana.

  9. Clinical aspects of Chagas disease and implications for novel therapies.

    PubMed

    Menezes, Cristiane; Costa, Germano Carneiro; Gollob, Kenneth J; Dutra, Walderez O

    2011-09-01

    The interaction between the protozoan parasite Trypanosoma cruzi and the human host dates back 9000 years, as demonstrated by molecular analysis of material obtained from Andean mummies indicating the presence of the parasite's kinetoplast DNA in populations from Chile and Peru. This long-established interaction, which persists today, demonstrates that T. cruzi has established a very well adapted relationship with the human host. From a host-parasite relationship point-of-view this is desirable, however, such a high degree of adaptation is perhaps the foundation for many of the unknowns that surround this disease. Unveiling of the immunological mechanisms that underlie the establishment of pathology, identification of parasite-associated factors that determine strain-differential tissue tropism, discovery of host genetic elements that influence the development of different clinical forms of the disease, and understanding environmental factors that may influence the host-parasite interactions, are some of the key questions remaining to be answered. The response to these questions will aid in addressing some of the current challenges in Chagas disease: fulfilling the need for efficient diagnosis, developing effective prophylactic measures, discovering effective therapeutics, and finding methods to control disease progression.

  10. Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

    PubMed

    Abras, Alba; Gállego, Montserrat; Llovet, Teresa; Tebar, Silvia; Herrero, Mercedes; Berenguer, Pere; Ballart, Cristina; Martí, Carmen; Muñoz, Carmen

    2016-06-01

    Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity with Leishmania spp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity with Leishmania species. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.

  11. Assessment of rectocolonic morphology and function in patients with Chagas disease in Barcelona (Spain).

    PubMed

    Salvador, Fernando; Mego, Marianela; Sánchez-Montalvá, Adrián; Morís, María; Ramírez, Kathleen; Accarino, Ana; Malagelada, Juan-Ramon; Azpiroz, Fernando; Molina, Israel

    2015-05-01

    The aim of this study was to determine the relationship between colonic symptoms, radiological abnormalities, and anorectal dysfunction in patients with Chagas disease. We performed a cross-sectional study of untreated patients diagnosed with Chagas disease. All patients were evaluated clinically (by a questionnaire for colonic symptoms based on Rome III criteria) and underwent a barium enema and anorectal manometry. A control group of patients with functional constipation and without Chagas disease was included in the study. Overall, 69 patients were included in the study: 42 patients were asymptomatic and 27 patients had abdominal symptoms according to Rome III criteria. Anorectal manometry showed a higher proportion of abnormalities in symptomatic patients than in asymptomatic ones (73% versus 21%, respectively; P < 0.0001). Megarectum was detected in a similar proportion in the different subgroups regardless of the presence of symptoms or abnormalities in anorectal functions. Among non-Chagas disease patients with functional constipation, 90% had an abnormal anorectal manometry study. Patients with Chagas disease present a high proportion of constipation with dyssynergic defecation in anorectal manometry but a low prevalence of impaired rectoanal inhibitory reflex, although these abnormalities may be nonspecific for Chagas disease. The presence of megarectum is a nonspecific finding.

  12. Chronic Chagas disease with advanced cardiac complications in Japan: Case report and literature review.

    PubMed

    Imai, Kazuo; Maeda, Takuya; Sayama, Yusuke; Osa, Morichika; Mikita, Kei; Kurane, Ichiro; Miyahira, Yasushi; Kawana, Akihiko; Miura, Sachio

    2015-10-01

    Due to the unprecedented recent increases in global migration, Chagas disease has become a global health threat and its epidemiology has drastically changed. Here we describe the first case in Japan of benznidazole treatment for chronic Chagas disease characterized by advanced cardiac complications. A 55-year-old Japanese-Brazilian woman who had previously presented with chronic heart failure was diagnosed as having Chagas disease and treated with benznidazole to prevent aggravation of her cardiac complications. However, benznidazole administration was stopped on day 56 due to severe drug-induced peripheral neuritis. Sixteen months later, her serologic test for Trypanosoma cruzi is still positive and she is being followed regularly by cardiology. Despite an estimated prevalence of over 4000 cases in Japan, only a few cases of Chagas disease have been reported. A Medline search revealed only 7 cases identified between 1995 and 2014 in Japan: in 6 cases, complications of chronic Chagas disease were apparent at the time of presentation, and sudden death occurred in 2 of these cases due to cardiac complications. This clinical case and literature review re-emphasize the urgent need to establish a surveillance network and improve the diagnostic methods and treatment framework for Chagas disease in Japan.

  13. Urbanization, land tenure security and vector-borne Chagas disease.

    PubMed

    Levy, Michael Z; Barbu, Corentin M; Castillo-Neyra, Ricardo; Quispe-Machaca, Victor R; Ancca-Juarez, Jenny; Escalante-Mejia, Patricia; Borrini-Mayori, Katty; Niemierko, Malwina; Mabud, Tarub S; Behrman, Jere R; Naquira-Velarde, Cesar

    2014-08-22

    Modern cities represent one of the fastest growing ecosystems on the planet. Urbanization occurs in stages; each stage characterized by a distinct habitat that may be more or less susceptible to the establishment of disease vector populations and the transmission of vector-borne pathogens. We performed longitudinal entomological and epidemiological surveys in households along a 1900 × 125 m transect of Arequipa, Peru, a major city of nearly one million inhabitants, in which the transmission of Trypanosoma cruzi, the aetiological agent of Chagas disease, by the insect vector Triatoma infestans, is an ongoing problem. The transect spans a cline of urban development from established communities to land invasions. We find that the vector is tracking the development of the city, and the parasite, in turn, is tracking the dispersal of the vector. New urbanizations are free of vector infestation for decades. T. cruzi transmission is very recent and concentrated in more established communities. The increase in land tenure security during the course of urbanization, if not accompanied by reasonable and enforceable zoning codes, initiates an influx of construction materials, people and animals that creates fertile conditions for epidemics of some vector-borne diseases.

  14. Urbanization, land tenure security and vector-borne Chagas disease

    PubMed Central

    Levy, Michael Z.; Barbu, Corentin M.; Castillo-Neyra, Ricardo; Quispe-Machaca, Victor R.; Ancca-Juarez, Jenny; Escalante-Mejia, Patricia; Borrini-Mayori, Katty; Niemierko, Malwina; Mabud, Tarub S.; Behrman, Jere R.; Naquira-Velarde, Cesar

    2014-01-01

    Modern cities represent one of the fastest growing ecosystems on the planet. Urbanization occurs in stages; each stage characterized by a distinct habitat that may be more or less susceptible to the establishment of disease vector populations and the transmission of vector-borne pathogens. We performed longitudinal entomological and epidemiological surveys in households along a 1900 × 125 m transect of Arequipa, Peru, a major city of nearly one million inhabitants, in which the transmission of Trypanosoma cruzi, the aetiological agent of Chagas disease, by the insect vector Triatoma infestans, is an ongoing problem. The transect spans a cline of urban development from established communities to land invasions. We find that the vector is tracking the development of the city, and the parasite, in turn, is tracking the dispersal of the vector. New urbanizations are free of vector infestation for decades. T. cruzi transmission is very recent and concentrated in more established communities. The increase in land tenure security during the course of urbanization, if not accompanied by reasonable and enforceable zoning codes, initiates an influx of construction materials, people and animals that creates fertile conditions for epidemics of some vector-borne diseases. PMID:24990681

  15. SQ109, a new drug lead for Chagas disease.

    PubMed

    Veiga-Santos, Phercyles; Li, Kai; Lameira, Lilianne; de Carvalho, Tecia Maria Ulisses; Huang, Guozhong; Galizzi, Melina; Shang, Na; Li, Qian; Gonzalez-Pacanowska, Dolores; Hernandez-Rodriguez, Vanessa; Benaim, Gustavo; Guo, Rey-Ting; Urbina, Julio A; Docampo, Roberto; de Souza, Wanderley; Oldfield, Eric

    2015-04-01

    We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug

  16. SQ109, a New Drug Lead for Chagas Disease

    PubMed Central

    Veiga-Santos, Phercyles; Li, Kai; Lameira, Lilianne; de Carvalho, Tecia Maria Ulisses; Huang, Guozhong; Galizzi, Melina; Shang, Na; Li, Qian; Gonzalez-Pacanowska, Dolores; Hernandez-Rodriguez, Vanessa; Benaim, Gustavo; Guo, Rey-Ting; Urbina, Julio A.; Docampo, Roberto; de Souza, Wanderley

    2015-01-01

    We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug

  17. Population Pharmacokinetics of Benznidazole in Adult Patients with Chagas Disease

    PubMed Central

    Aldasoro, E.; Guerrero, L.; Posada, E.; Serret, N.; Mejía, T.; Urbina, J. A.; Gascón, J.

    2015-01-01

    The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h; V/F, 89.6 liters; and Ka, 1.15 h−1). No covariates were found to be significant for CL/F and V/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011

  18. Evolution of Chagas disease screening programs and control programs: historical perspective.

    PubMed

    Dias, João Carlos Pinto

    2015-09-01

    Chagas disease remains an important health problem in Latin America, affecting approximately 8 million to 10 million individuals. This disease originated from an ancient enzootic cycle, and human infection has been detected in 4,000- to 9,000-year-old mummies and has expanded with European colonization, reaching its peak prevalence in the 20th century. Discovered in 1909, the disease remained obscure and uncontrolled until the 1950s, when the generalization of serology, the characterization of chronic cardiomyopathy, and effective insecticides began. By the 1960s, national control programs were launched and incidence began to decrease as a result. During this time, scientific improvements became increasingly available to address disease management. Presently, challenges in managing Chagas disease include maintaining sustainable epidemiological surveillance, the spread of the disease to nonendemic countries, the apparent spread of oral transmission, and new symptoms and manifestations. This review discusses the possibilities and challenges in facing Chagas disease in the coming decades.

  19. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  20. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  1. Progress towards the elimination of transmission of Chagas disease in Latin America.

    PubMed

    Moncayo, A

    1997-01-01

    From a global perspective, Chagas disease represents the third largest tropical disease burden after malaria and schistosomiasis. The estimated average annual per-capita gross domestic product in Latin America is US$2,966. The economic loss for the continent due to early mortality and disability by this disease in economically most productive young adults currently amounts to US$8,156 million which is equivalent to 2.5% of the external debt of the whole continent in 1995. In 1991, the Ministers of Health of Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay, launched the Southern Cone Initiative for elimination of transmission of Chagas disease. The progress towards elimination of vectorial and transfusional transmission of Chagas disease in Uruguay, Chile, Argentina and Brazil has been documented by reports from the national control programmes of the above countries. Current data on disinfestation of houses, coverage of screening in blood banks and serology in children and young adults indicate that the interruption of the vectorial and transfusional transmission of Chagas disease will be achieved in these countries as follows: Uruguay and Chile in 1999, Brazil and Argentina in 2003. By eliminating the transmission of Chagas disease in the above countries, the incidence of the disease in the whole of Latin America will be reduced by more than 70%. PMID:9477549

  2. Translational challenges of animal models in Chagas disease drug development: a review

    PubMed Central

    Chatelain, Eric; Konar, Nandini

    2015-01-01

    Chagas disease, or American trypanosomiasis, caused by Trypanosoma cruzi parasite infection is endemic in Latin America and presents an increasing clinical challenge due to migrating populations. Despite being first identified over a century ago, only two drugs are available for its treatment, and recent outcomes from the first clinical trials in 40 years were lackluster. There is a critical need to develop new drugs to treat Chagas disease. This requires a better understanding of the progression of parasite infection, and standardization of animal models designed for Chagas disease drug discovery. Such measures would improve comparison of generated data and the predictability of test hypotheses and models designed for translation to human disease. Existing animal models address both disease pathology and treatment efficacy. Available models have limited predictive value for the preclinical evaluation of novel therapies and need to more confidently predict the efficacy of new drug candidates in clinical trials. This review highlights the overall lack of standardized methodology and assessment tools, which has hampered the development of efficacious compounds to treat Chagas disease. We provide an overview of animal models for Chagas disease, and propose steps that could be undertaken to reduce variability and improve predictability of drug candidate efficacy. New technological developments and tools may contribute to a much needed boost in the drug discovery process. PMID:26316715

  3. Translational challenges of animal models in Chagas disease drug development: a review.

    PubMed

    Chatelain, Eric; Konar, Nandini

    2015-01-01

    Chagas disease, or American trypanosomiasis, caused by Trypanosoma cruzi parasite infection is endemic in Latin America and presents an increasing clinical challenge due to migrating populations. Despite being first identified over a century ago, only two drugs are available for its treatment, and recent outcomes from the first clinical trials in 40 years were lackluster. There is a critical need to develop new drugs to treat Chagas disease. This requires a better understanding of the progression of parasite infection, and standardization of animal models designed for Chagas disease drug discovery. Such measures would improve comparison of generated data and the predictability of test hypotheses and models designed for translation to human disease. Existing animal models address both disease pathology and treatment efficacy. Available models have limited predictive value for the preclinical evaluation of novel therapies and need to more confidently predict the efficacy of new drug candidates in clinical trials. This review highlights the overall lack of standardized methodology and assessment tools, which has hampered the development of efficacious compounds to treat Chagas disease. We provide an overview of animal models for Chagas disease, and propose steps that could be undertaken to reduce variability and improve predictability of drug candidate efficacy. New technological developments and tools may contribute to a much needed boost in the drug discovery process.

  4. Lack of Segregation between Two Species of Chagas Disease Vectors

    PubMed Central

    Mota, Theo; Lorenzo, Marcelo Gustavo

    2012-01-01

    Triatoma infestans and Panstrongylus megistus are relevant Chagas disease vectors. An apparent segregation among these triatomine species inside human households was suggested to rely on mutual repellence between them. However, P. megistus and T. infestans show aggregation responses to chemical signals emitted by the other species. These findings do not rule out the possibility that stimuli other than chemical signals could mediate repellence when these species exploit shelters simultaneously. In the present study, we investigated how P. megistus and T. infestans exploit shelters in controlled laboratory conditions and how insect density and environmental illumination modulate this behavior. We evaluated whether these species aggregate inside shelters or mutually repel each other. Panstrongylus megistus and T. infestans show specific patterns of shelter exploitation, which are differentially affected by insect density and environment illumination. In particular, P. megistus is more sensitive to insect density than T. infestans, whereas T. infestans shows higher sensitivity to illumination than P. megistus. Nevertheless, these species exploit shelters randomly without any apparent repellence. PMID:22764300

  5. Genomic Changes of Chagas Disease Vector, South America

    PubMed Central

    Dujardin, Jean Pierre; Nicolini, Paula; Caraccio, María Noel; Rose, Virginia; Tellez, Tatiana; Bermúdez, Hernán; Bargues, María Dolores; Mas-Coma, Santiago; O’Connor, José Enrique; Pérez, Ruben

    2004-01-01

    We analyzed the main karyologic changes that have occurred during the dispersion of Triatoma infestans, the main vector of Chagas disease. We identified two allopatric groups, named Andean and non-Andean. The Andean specimens present C-heterochromatic blocks in most of their 22 chromosomes, whereas non-Andean specimens have only 4–7 autosomes with C-banding. These heterochromatin differences are the likely cause of a striking DNA content variation (approximately 30%) between Andean and non-Andean insects. Our study, together with previous historical and genetic data, suggests that T. infestans was originally a sylvatic species, with large quantities of DNA and heterochromatin, inhabiting the Andean region of Bolivia. However, the spread of domestic T. infestans throughout the non-Andean regions only involved insects with an important reduction of heterochromatin and DNA amounts. We propose that heterochromatin and DNA variation mainly reflected adaptive genomic changes that contribute to the ability of T. infestans to survive, reproduce, and disperse in different environments. PMID:15109410

  6. Direct micromethod for diagnosis of acute and congenital Chagas' disease.

    PubMed Central

    Feilij, H; Muller, L; Gonzalez Cappa, S M

    1983-01-01

    A microhematocrit concentration method (MH) for immediate diagnosis of Chagas' disease during the acute stage or in congenital cases was standardized. Parasitemia as low as 1,000 parasites per ml was detected, after centrifugation of six 50-microliters capillary tubes, by 10-min microscopic observation of each buffy coat spread between slide and cover glass. Operator's time was reduced by at least one-third when compared with a fresh blood observation (FB). In 12 of the 15 patients studied, diagnosis was performed in 4.9 +/- 3.08 min with MH, whereas 27.0 +/- 12.1 min were necessary when FB was used. In the three remaining patients whose FB results were negative, MH became positive after 13, 16, and 40 min. In our experience, FB proved to be more sensitive than previously reported. Suckling mouse inoculation also proved to be sensitive but, as in xenodiagnosis and in hemoculture, the delay in getting the final result was a limiting factor. PMID:6413530

  7. Controlled but not cured: Structural processes and explanatory models of Chagas disease in tropical Bolivia.

    PubMed

    Forsyth, Colin

    2015-11-01

    Dressler (2001:456) characterizes medical anthropology as divided between two poles: the constructivist, which focuses on the "meaning and significance that events have for people," and the structuralist, which emphasizes socioeconomic processes and relationships. This study synthesizes structuralist and constructivist perspectives by investigating how structural processes impact explanatory models of Chagas disease in a highly endemic area. The research took place from March-June 2013 through the Centro Medico Humberto Parra, a non-profit clinic servicing low income populations in Palacios, Bolivia and surrounding communities. Semistructured interviews (n = 68) and consensus analysis questionnaires (n = 48) were administered to people dealing with Chagas disease. In the interview narratives, respondents link Chagas disease with experiences of marginalization and rural poverty, and describe multilayered impediments to accessing treatment. They often view the disease as incurable, but this reflects inconsistent messages from the biomedical system. The consensus analysis results show strong agreement on knowledge of the vector, ethnomedical treatment, and structural factors related to Chagas disease. In interpreting Chagas disease, respondents account for the structural factors which place them at risk and impede access to care. PMID:26432176

  8. Immunosuppression and Chagas disease; experience from a non-endemic country.

    PubMed

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality.

  9. Controlled but not cured: Structural processes and explanatory models of Chagas disease in tropical Bolivia.

    PubMed

    Forsyth, Colin

    2015-11-01

    Dressler (2001:456) characterizes medical anthropology as divided between two poles: the constructivist, which focuses on the "meaning and significance that events have for people," and the structuralist, which emphasizes socioeconomic processes and relationships. This study synthesizes structuralist and constructivist perspectives by investigating how structural processes impact explanatory models of Chagas disease in a highly endemic area. The research took place from March-June 2013 through the Centro Medico Humberto Parra, a non-profit clinic servicing low income populations in Palacios, Bolivia and surrounding communities. Semistructured interviews (n = 68) and consensus analysis questionnaires (n = 48) were administered to people dealing with Chagas disease. In the interview narratives, respondents link Chagas disease with experiences of marginalization and rural poverty, and describe multilayered impediments to accessing treatment. They often view the disease as incurable, but this reflects inconsistent messages from the biomedical system. The consensus analysis results show strong agreement on knowledge of the vector, ethnomedical treatment, and structural factors related to Chagas disease. In interpreting Chagas disease, respondents account for the structural factors which place them at risk and impede access to care.

  10. [What is not searched, it is difficult to find: Chagas' disease].

    PubMed

    Briceno, Luis; Mosca, Walter

    2016-05-01

    A conservative estimation indicates that more than 400 000 Latin American immigrants are living in Italy. Several studies have shown that among these, the prevalence of Chagas disease is between 3.9% and 17%, so it is not unlikely to find a patient with this disease during a cardiology visit. How many patients from Latin America are diagnosed with heart failure in Italy and no one has ever thought about a possible Chagas disease? This brief review describes the situation of the disease in Italy, its characteristics, the etiology of this disease and its treatment. The latter aspect will be discussed considering the recent published results of the BENEFIT study, where it was found that treatment with benznidazole in patients with Chagas' cardiomyopathy is able to reduce significantly the detection of parasites in the blood, but it is not able to prevent clinical deterioration during 5 years of follow-up. The possible implications of these results will be discussed.

  11. [José Lima Pedreira de Freitas and the redefinition and control of Chagas disease].

    PubMed

    Rocha, Juan Stuardo Yazlle

    2016-08-01

    A brief overview of the evolution of knowledge about Chagas disease since its discovery by Carlos Chagas in 1909 until the mid-1940s is presented. The trajectory of physician Pedreira de Freitas and his growing involvement in research in the area led to his contributions to laboratory diagnosis - which lent consistency and security to epidemiological surveys of Chagas disease - and the redefinition of the scale of the disease in Brazil and the Americas with its terrible social and economic impact. His proposal for the disease prevention model - based on selective purging in the application of insecticide - was adopted nationally and internationally and made it possible to bring the disease under control in Brazil and other countries. He devoted himself with equal intensity to enhancing the teaching of medical practices in the community and was a pioneer in the implementation of preventive medicine in medical education in Brazil. PMID:27557035

  12. [What is not searched, it is difficult to find: Chagas' disease].

    PubMed

    Briceno, Luis; Mosca, Walter

    2016-05-01

    A conservative estimation indicates that more than 400 000 Latin American immigrants are living in Italy. Several studies have shown that among these, the prevalence of Chagas disease is between 3.9% and 17%, so it is not unlikely to find a patient with this disease during a cardiology visit. How many patients from Latin America are diagnosed with heart failure in Italy and no one has ever thought about a possible Chagas disease? This brief review describes the situation of the disease in Italy, its characteristics, the etiology of this disease and its treatment. The latter aspect will be discussed considering the recent published results of the BENEFIT study, where it was found that treatment with benznidazole in patients with Chagas' cardiomyopathy is able to reduce significantly the detection of parasites in the blood, but it is not able to prevent clinical deterioration during 5 years of follow-up. The possible implications of these results will be discussed. PMID:27310907

  13. [Postpartum treatment without interrupting breastfeeding in a patient with Chagas disease].

    PubMed

    Vela-Bahena, Luz Elena; Vergara, Raymundo; Vite, Ludmila; Ramos, Celso

    2015-08-01

    Chagas disease is a problem of global public health. It is caused by the protozoan Trypanosoma cruzi, which is acquired through exposure to infected triatomine feces, blood transfusion, organ transplantation, orally, by laboratory accidents and congenitally (mother-child); the latter is a public health problem in endemic countries and is the most common form in non-endemic countries. In Mexico, there are few studies on congenital transmission of Chagas disease. The majority of pregnant women with Chagas disease are chronic and asymptomatic, and there is a risk of products with low birth weight and abortions, yet most infants are asymptomatic and treatment in pregnancy is contraindicated. Here, we report a case of a 24-year-old who was diagnosed with Chagas disease by donating blood and confirmed by the State Laboratory of Public Health. Before starting treatment, 13 weeks pregnancy was detected and followed up until the birth; mother was seropositive for Chagas disease and child was negative by parasitological studies. Breastfeeding was initiated at birth and one month, after consulting with experts, treating the mother began with benznidazole for 45 days; in general, the treatment was well tolerated, but the patient remained seropositive. PMID:26591033

  14. Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

    PubMed

    Halperin, Anthony; Pajuelo, Monica; Tornheim, Jeffrey A; Vu, Nancy; Carnero, Andrés M; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Camacho, Marilyn; Justiniano, Juan; Colanzi, Rony; Bowman, Natalie M; Morris, Tiffany; MacDougall, Hamish; Bern, Caryn; Moore, Steven T; Gilman, Robert H

    2016-06-01

    Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients. PMID:27044564

  15. Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

    PubMed

    Halperin, Anthony; Pajuelo, Monica; Tornheim, Jeffrey A; Vu, Nancy; Carnero, Andrés M; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Camacho, Marilyn; Justiniano, Juan; Colanzi, Rony; Bowman, Natalie M; Morris, Tiffany; MacDougall, Hamish; Bern, Caryn; Moore, Steven T; Gilman, Robert H

    2016-06-01

    Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients.

  16. Socio-Cultural Aspects of Chagas Disease: A Systematic Review of Qualitative Research

    PubMed Central

    Ventura-Garcia, Laia; Roura, Maria; Pell, Christopher; Posada, Elisabeth; Gascón, Joaquim; Aldasoro, Edelweis; Muñoz, Jose; Pool, Robert

    2013-01-01

    Background Globally, more than 10 million people are infected with Trypanosoma cruzi, which causes about 20 000 annual deaths. Although Chagas disease is endemic to certain regions of Latin America, migratory flows have enabled its expansion into areas where it was previously unknown. Economic, social and cultural factors play a significant role in its presence and perpetuation. This systematic review aims to provide a comprehensive overview of qualitative research on Chagas disease, both in endemic and non-endemic countries. Methodology/Principal Findings Searches were carried out in ten databases, and the bibliographies of retrieved studies were examined. Data from thirty-three identified studies were extracted, and findings were analyzed and synthesized along key themes. Themes identified for endemic countries included: socio-structural determinants of Chagas disease; health practices; biomedical conceptions of Chagas disease; patient's experience; and institutional strategies adopted. Concerning non-endemic countries, identified issues related to access to health services and health seeking. Conclusions The emergence and perpetuation of Chagas disease depends largely on socio-cultural aspects influencing health. As most interventions do not address the clinical, environmental, social and cultural aspects jointly, an explicitly multidimensional approach, incorporating the experiences of those affected is a potential tool for the development of long-term successful programs. Further research is needed to evaluate this approach. PMID:24069473

  17. Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

    PubMed Central

    Ramírez, Juan David; Montilla, Marleny; Cucunubá, Zulma M.; Floréz, Astrid Carolina; Zambrano, Pilar; Guhl, Felipe

    2013-01-01

    Background Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. Methodology and Principal Findings High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. Conclusions These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed. PMID:23437405

  18. Barriers to Treatment Access for Chagas Disease in Mexico

    PubMed Central

    Manne, Jennifer M.; Snively, Callae S.; Ramsey, Janine M.; Salgado, Marco Ocampo; Bärnighausen, Till; Reich, Michael R.

    2013-01-01

    Background According to World Health Organization (WHO) prevalence estimates, 1.1 million people in Mexico are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease (CD). However, limited information is available about access to antitrypanosomal treatment. This study assesses the extent of access in Mexico, analyzes the barriers to access, and suggests strategies to overcome them. Methods and Findings Semi-structured in-depth interviews were conducted with 18 key informants and policymakers at the national level in Mexico. Data on CD cases, relevant policy documents and interview data were analyzed using the Flagship Framework for Pharmaceutical Policy Reform policy interventions: regulation, financing, payment, organization, and persuasion. Data showed that 3,013 cases were registered nationally from 2007–2011, representing 0.41% of total expected cases based on Mexico's national prevalence estimate. In four of five years, new registered cases were below national targets by 11–36%. Of 1,329 cases registered nationally in 2010–2011, 834 received treatment, 120 were pending treatment as of January 2012, and the treatment status of 375 was unknown. The analysis revealed that the national program mainly coordinated donation of nifurtimox and that important obstacles to access include the exclusion of antitrypanosomal medicines from the national formulary (regulation), historical exclusion of CD from the social insurance package (organization), absence of national clinical guidelines (organization), and limited provider awareness (persuasion). Conclusions Efforts to treat CD in Mexico indicate an increased commitment to addressing this disease. Access to treatment could be advanced by improving the importation process for antitrypanosomal medicines and adding them to the national formulary, increasing education for healthcare providers, and strengthening clinical guidelines. These recommendations have important implications for other countries in

  19. Cost-effectiveness of Chagas disease interventions in latin america and the Caribbean: Markov models.

    PubMed

    Wilson, Leslie S; Strosberg, Arthur M; Barrio, Kimberly

    2005-11-01

    Chagas disease is a parasitic disease in Latin America. Despite vector control programs that have reduced incidence by 70%, there are at least 12-14 million prevalent cases. We used a Markov model to examine strategies for control and treatment of Chagas disease that compared annual costs, life expectancies, and cost-effectiveness of three vector control and drug treatment strategies. Vector control programs alone and vector control plus drug treatment are dominant over no vector control (i.e., less costly and save more lives), and vector control plus drug is highly cost-effective compared with vector control alone. We demonstrated expected changes in deaths over time resulting from various prevention approaches. Vector control affects primarily incidence, not decreasing deaths and prevalence for 30 years, while drug treatment affects prevalence and deaths immediately. The best strategy to combat Chagas disease is combinations of vector control and a potential new drug.

  20. Should trypanocidal therapy be used to treat patients in the chronic phase of Chagas disease?

    PubMed

    Popoff, Federico; Izcovich, Ariel

    2015-10-26

    Antiparasitic treatment of patients with Chagas’ disease in chronic stage could prevent the complications related to the disease. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials and 11 observational studies. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether antiparasitic treatment improves survival or reduces complications related to chronic Chagas’ disease because the certainty of the evidence is very low.

  1. [Congenital Chagas disease in the city of Salta, Argentina].

    PubMed

    Zaidenberg, M; Segovia, A

    1993-01-01

    The immune response to Trypanosoma cruzi was studied in our hospital in 937 pregnant women(PW) and their 929 newborns(NB), group I; 4 NB from this center not included in the first group, group II and 35 NB derived from other centers, group III. Two positive results among indirect hemagglutination (IHA), complement fixation(CF) and indirect hemagglutination(IHA), complement fixation(CF) and indirect immunofluorescence(IIF) tests were considered as the criterion of previous infection with T. cruzi in PW. The presence of T. cruzi in blood, explored in fresh smears by serial micro-hematocrite and/or by xenodiagnosis, was the only criterion to define infection in NB. All NB were followed up by direct agglutination (DA) with or without 2 mercaptoethanol (DA-w2ME, DA-wo2ME) and IIF in order to establish the specific antibody kinetics. Clinical studies on NB with T. cruzi infection include routine laboratory tests. Benznidazole (3 to 7 mg/kg/day) and, in 1 case, nifurtimox (15 mg/kg/day) were employed as therapeutic agents. T. cruzi infection was confirmed in 149 PW(15.9%), table I. These chagasic mothers delivered 6 chagasic NB (CCHD-NB), (4%). Diagnosis of congenital Chagas' disease accounted for a total of 12 NB out of the 968 studied. 4 out of them were positive by both microhematocrite and blood smears and 7 by microhematocrite alone. Xenodiagnosis was performed in 2 NB resulting positive in both cases, table II. The most usual clinical findings included hepatomegaly (present in all cases), splenomegaly 8/12, jaundice 10/12 and prematurity 5/12, table 3. Laboratory findings showed anemia to be of hypochromic microcytic type in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Community Participation in Chagas Disease Vector Surveillance: Systematic Review

    PubMed Central

    Abad-Franch, Fernando; Vega, M. Celeste; Rolón, Miriam S.; Santos, Walter S.; Rojas de Arias, Antonieta

    2011-01-01

    Background Vector control has substantially reduced Chagas disease (ChD) incidence. However, transmission by household-reinfesting triatomines persists, suggesting that entomological surveillance should play a crucial role in the long-term interruption of transmission. Yet, infestation foci become smaller and harder to detect as vector control proceeds, and highly sensitive surveillance methods are needed. Community participation (CP) and vector-detection devices (VDDs) are both thought to enhance surveillance, but this remains to be thoroughly assessed. Methodology/Principal Findings We searched Medline, Web of Knowledge, Scopus, LILACS, SciELO, the bibliographies of retrieved studies, and our own records. Data from studies describing vector control and/or surveillance interventions were extracted by two reviewers. Outcomes of primary interest included changes in infestation rates and the detection of infestation/reinfestation foci. Most results likely depended on study- and site-specific conditions, precluding meta-analysis, but we re-analysed data from studies comparing vector control and detection methods whenever possible. Results confirm that professional, insecticide-based vector control is highly effective, but also show that reinfestation by native triatomines is common and widespread across Latin America. Bug notification by householders (the simplest CP-based strategy) significantly boosts vector detection probabilities; in comparison, both active searches and VDDs perform poorly, although they might in some cases complement each other. Conclusions/Significance CP should become a strategic component of ChD surveillance, but only professional insecticide spraying seems consistently effective at eliminating infestation foci. Involvement of stakeholders at all process stages, from planning to evaluation, would probably enhance such CP-based strategies. PMID:21713022

  3. Modulation of immune response in experimental Chagas disease

    PubMed Central

    Basso, Beatriz

    2013-01-01

    Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage’s role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response (modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi

  4. High specificity of Trypanosoma cruzi epimastigote ribonucleoprotein as antigen in serodiagnosis of Chagas' disease.

    PubMed Central

    Solana, M E; Katzin, A M; Umezawa, E S; Miatello, C S

    1995-01-01

    We assessed the performance of an enzyme-linked immunosorbent assay (ELISA) with the Trypanosoma cruzi epimastigote ribosomal fraction (Tulahuen and Y strains) in order to improve the diagnostic specificity of the test. A total of 100 serum samples from patients with chronic Chagas' disease from Brazil and Argentina were studied. Sera from 116 patients, without Chagas' disease, including 10 with active mucocutaneous leishmaniasis and 20 with visceral leishmaniasis, were used as controls. Immunoglobulin G (IgG) antibodies against the ribosomal fraction (ribonucleoproteins [RNPs]) in the ELISA were found in 97% of samples from patients with Chagas' disease. A total of 99% of the sera from patients without the disease were negative, including sera from patients with mucocutaneous and visceral leishmaniases. The distribution of IgG isotypes in randomly chosen serum samples was determined by ELISA; IgG1 and IgG3 were predominant (100% exhibited IgG1 and 85% exhibited IgG3, and 50% also presented the IgG2 isotype. The distribution of the IgG subclasses was confirmed by the Western blot (immunoblot) technique. When total IgG was assayed by Western blot assay, no correlation was found between the pattern of serum reactivity and the clinical features of the patients with Chagas' disease. Therefore, no typical profile of polypeptide recognition could be associated with any clinical form of Chagas' disease (cardiomyopathy or megaviscera). Our results showed that sera from patients with Chagas' disease react with ribosomal antigens and display a typical profile of IgG isotypes (IgG1 plus IgG3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7650167

  5. Chagas disease (Trypanosoma cruzi) and HIV co-infection in Colombia.

    PubMed

    Hernández, Carolina; Cucunubá, Zulma; Parra, Edgar; Toro, German; Zambrano, Pilar; Ramírez, Juan David

    2014-09-01

    Chagas disease is a complex zoonotic pathology caused by the kinetoplastid Trypanosoma cruzi. This parasite presents remarkable genetic variability and has been grouped into six discrete typing units (DTUs). The association between the DTUs and clinical outcome remains unknown. Chagas disease and co-infection with HIV/AIDS has been reported widely in Brazil and Argentina. Herein, we present the molecular analyses from a Chagas disease patient with HIV/AIDS co-infection in Colombia who presented severe cardiomyopathy, pleural effusion, and central nervous system involvement. A mixed infection by T. cruzi genotypes was detected. We suggest including T. cruzi in the list of opportunistic pathogens for the management of HIV patients in Colombia. The epidemiological implications of this finding are discussed.

  6. The Sphingolipid Biosynthetic Pathway Is a Potential Target for Chemotherapy against Chagas Disease

    PubMed Central

    Koeller, Carolina Macedo; Heise, Norton

    2011-01-01

    The protozoan parasite Trypanosoma cruzi is the causative agent of human Chagas disease, for which there currently is no cure. The life cycle of T. cruzi is complex, including an extracellular phase in the triatomine insect vector and an obligatory intracellular stage inside the vertebrate host. These phases depend on a variety of surface glycosylphosphatidylinositol-(GPI-) anchored glycoconjugates that are synthesized by the parasite. Therefore, the surface expression of GPI-anchored components and the biosynthetic pathways of GPI anchors are attractive targets for new therapies for Chagas disease. We identified new drug targets for chemotherapy by taking the available genome sequence information and searching for differences in the sphingolipid biosynthetic pathways (SBPs) of mammals and T. cruzi. In this paper, we discuss the major steps of the SBP in mammals, yeast and T. cruzi, focusing on the IPC synthase and ceramide remodeling of T. cruzi as potential therapeutic targets for Chagas disease. PMID:21603271

  7. [Control of Chagas disease in pregnant Latin-American women and her children].

    PubMed

    Merino, Francisco J; Martínez-Ruiz, Rocío; Olabarrieta, Iciar; Merino, Paloma; García-Bujalance, Silvia; Gastañaga, Teresa; Flores-Chavez, María

    2013-09-01

    Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area.

  8. [Control of Chagas disease in pregnant Latin-American women and her children].

    PubMed

    Merino, Francisco J; Martínez-Ruiz, Rocío; Olabarrieta, Iciar; Merino, Paloma; García-Bujalance, Silvia; Gastañaga, Teresa; Flores-Chavez, María

    2013-09-01

    Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area. PMID:24080893

  9. Integrated control of Chagas disease for its elimination as public health problem--a review.

    PubMed

    Sosa-Estani, Sergio; Segura, Elsa Leonor

    2015-05-01

    Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease. PMID:25993503

  10. Integrated control of Chagas disease for its elimination as public health problem - A Review

    PubMed Central

    Sosa-Estani, Sergio; Segura, Elsa Leonor

    2015-01-01

    Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease. PMID:25993503

  11. Integrated control of Chagas disease for its elimination as public health problem--a review.

    PubMed

    Sosa-Estani, Sergio; Segura, Elsa Leonor

    2015-05-01

    Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease.

  12. Anti-triatomine saliva immunoassays for the evaluation of impregnated netting trials against Chagas disease transmission

    PubMed Central

    Schwarz, Alexandra; Juarez, Jenny Ancca; Richards, Jean; Rath, Bruno; Machaca, Victor Quispe; Castro, Yagahira E.; Málaga, Edith S.; Levy, Katelyn; Gilman, Robert H.; Bern, Caryn; Verastegui, Manuela; Levy, Michael Z.

    2011-01-01

    Insecticide-impregnated nets can kill triatomine bugs, but it remains unclear whether they can protect against Chagas disease transmission. In a field trial in Quequeña, Peru, sentinel guinea pigs placed in intervention enclosures covered by deltamethrin-treated nets showed significantly lower antibody responses to saliva of Triatoma infestans compared with animals placed in pre-existing control enclosures. Our results strongly suggest that insecticide-treated nets prevent triatomine bites and can thereby protect against infection with Trypanosoma cruzi. Anti-salivary immunoassays are powerful new tools to evaluate intervention strategies against Chagas disease. PMID:21426907

  13. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

    PubMed Central

    Zingales, Bianca; Miles, Michael A; Moraes, Carolina B; Luquetti, Alejandro; Guhl, Felipe; Schijman, Alejandro G; Ribeiro, Isabela

    2014-01-01

    This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape. PMID:25317712

  14. Anti-triatomine saliva immunoassays for the evaluation of impregnated netting trials against Chagas disease transmission.

    PubMed

    Schwarz, Alexandra; Juarez, Jenny Ancca; Richards, Jean; Rath, Bruno; Machaca, Victor Quispe; Castro, Yagahira E; Málaga, Edith S; Levy, Katelyn; Gilman, Robert H; Bern, Caryn; Verastegui, Manuela; Levy, Michael Z

    2011-05-01

    Insecticide-impregnated nets can kill triatomine bugs, but it remains unclear whether they can protect against Chagas disease transmission. In a field trial in Quequeña, Peru, sentinel guinea pigs placed in intervention enclosures covered by deltamethrin-treated nets showed significantly lower antibody responses to saliva of Triatoma infestans compared with animals placed in pre-existing control enclosures. Our results strongly suggest that insecticide-treated nets prevent triatomine bites and can thereby protect against infection with Trypanosoma cruzi. Anti-salivary immunoassays are powerful new tools to evaluate intervention strategies against Chagas disease.

  15. Science, health and development: Chagas disease in Brazil, 1943-1962.

    PubMed

    Kropf, S Petraglia

    2005-12-01

    The present paper discusses the historical construction and legitimacy of Chagas disease as a distinct nosological entity and as a public health issue in Brazil. It focuses on the activities of a group of researchers from Oswaldo Cruz Institute who worked at the Centre for the Study and Prevention of Chagas disease, located in Bambuí, Minas Gerais. Led in the 1940s and 50s by Emmanuel Dias, disciple of Carlos Chagas, the group made important contributions to the clinical characterization of Chagas disease as a cardiac illness, established the fact that it was technically possible to control the disease by using residual insecticides, and engaged in intense political mobilization to have the disease included as part of the Health Ministry sanitation campaigns. My hypothesis is that the group's work was a determining factor in the overcoming of certain unresolved controversies that had surrounded the medical and social identity of the disease since the 1920s. I examine to what extent this process was directly linked both to post-war optimism over new possibilities of combating infectious diseases and to the national and international debate on the relation between health and economic and social development.

  16. A 4-year follow-up study of a rural community with endemic Chagas' disease*

    PubMed Central

    Puigbó, J. J.; Rhode, J. R. Nava; Barrios, H. García; Yépez, C. Gil

    1968-01-01

    The paper reports on a 4-year follow-up study that represents the continuation of a previous cross-sectional study on Chagas' disease carried out in a rural community (Belén) in Venezuela. The earlier study included 1210 persons all over 5 years of age out of a total of 1656 inhabitants and demonstrated a high prevalence of Chagas' infection (47.3%) and a high rate of Chagas' disease seropositivity among those with chronic myocardial heart disease (84.8%); heart disease was found in 17.3% of persons studied. The follow-up study was based on 812 persons and established that in the sample the frequency of Chagas' infection was 16.3% and that of heart disease 2.2%. Clinical, electrocardiographic and radiological analyses were made on patients with previous heart disease as well as on new patients. Different evolutive electrocardiographic patterns have been found, including variations ranging from normal to definitively abnormal. ImagesFIG. 1FIG. 2 PMID:4974002

  17. Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

    PubMed

    Vasconcelos, R H T; Azevedo, E de A N; Diniz, G T N; Cavalcanti, M da G A de M; de Oliveira, W; de Morais, C N L; Gomes, Y de M

    2015-07-01

    In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.

  18. The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease.

    PubMed

    Junqueira, Caroline; Caetano, Braulia; Bartholomeu, Daniella C; Melo, Mariane B; Ropert, Catherine; Rodrigues, Maurício M; Gazzinelli, Ricardo T

    2010-09-15

    Infection with the protozoan parasite Trypanosoma cruzi, the agent of Chagas disease, is characterised by a variable clinical course - from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. The variability in disease outcome has been attributed to host responses as well as parasite heterogeneity. In this article, we review studies indicating the importance of immune responses as key determinants of host resistance to T. cruzi infection and the pathogenesis of Chagas disease. Particular attention is given to recent studies defining the role of cognate innate immune receptors and immunodominant CD8+ T cells that recognise parasite components - both crucial for host-parasite interaction and disease outcome. In light of these studies we speculate about parasite strategies that induce a strong and long-lasting T-cell-mediated immunity but at the same time allow persistence of the parasite in the vertebrate host. We also discuss what we have learned from these studies for increasing our understanding of Chagas pathogenesis and for the design of new strategies to prevent the development of Chagas disease. Finally, we highlight recent studies employing a genetically engineered attenuated T. cruzi strain as a vaccine shuttle that elicits potent T cell responses specific to a tumour antigen and protective immunity against a syngeneic melanoma cell line.

  19. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches.

    PubMed

    Noya, Belkisyolé Alarcón de; Díaz-Bello, Zoraida; Colmenares, Cecilia; Ruiz-Guevara, Raiza; Mauriello, Luciano; Muñoz-Calderón, Arturo; Noya, Oscar

    2015-05-01

    Orally transmitted Chagas disease has become a matter of concern due to outbreaks reported in four Latin American countries. Although several mechanisms for orally transmitted Chagas disease transmission have been proposed, food and beverages contaminated with whole infected triatomines or their faeces, which contain metacyclic trypomastigotes of Trypanosoma cruzi, seems to be the primary vehicle. In 2007, the first recognised outbreak of orally transmitted Chagas disease occurred in Venezuela and largest recorded outbreak at that time. Since then, 10 outbreaks (four in Caracas) with 249 cases (73.5% children) and 4% mortality have occurred. The absence of contact with the vector and of traditional cutaneous and Romana's signs, together with a florid spectrum of clinical manifestations during the acute phase, confuse the diagnosis of orally transmitted Chagas disease with other infectious diseases. The simultaneous detection of IgG and IgM by ELISA and the search for parasites in all individuals at risk have been valuable diagnostic tools for detecting acute cases. Follow-up studies regarding the microepidemics primarily affecting children has resulted in 70% infection persistence six years after anti-parasitic treatment. Panstrongylus geniculatus has been the incriminating vector in most cases. As a food-borne disease, this entity requires epidemiological, clinical, diagnostic and therapeutic approaches that differ from those approaches used for traditional direct or cutaneous vector transmission.

  20. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches

    PubMed Central

    de Noya, Belkisyolé Alarcón; Díaz-Bello, Zoraida; Colmenares, Cecilia; Ruiz-Guevara, Raiza; Mauriello, Luciano; Muñoz-Calderón, Arturo; Noya, Oscar

    2015-01-01

    Orally transmitted Chagas disease has become a matter of concern due to outbreaks reported in four Latin American countries. Although several mechanisms for orally transmitted Chagas disease transmission have been proposed, food and beverages contaminated with whole infected triatomines or their faeces, which contain metacyclic trypomastigotes of Trypanosoma cruzi, seems to be the primary vehicle. In 2007, the first recognised outbreak of orally transmitted Chagas disease occurred in Venezuela and largest recorded outbreak at that time. Since then, 10 outbreaks (four in Caracas) with 249 cases (73.5% children) and 4% mortality have occurred. The absence of contact with the vector and of traditional cutaneous and Romana’s signs, together with a florid spectrum of clinical manifestations during the acute phase, confuse the diagnosis of orally transmitted Chagas disease with other infectious diseases. The simultaneous detection of IgG and IgM by ELISA and the search for parasites in all individuals at risk have been valuable diagnostic tools for detecting acute cases. Follow-up studies regarding the microepidemics primarily affecting children has resulted in 70% infection persistence six years after anti-parasitic treatment. Panstrongylus geniculatus has been the incriminating vector in most cases. As a food-borne disease, this entity requires epidemiological, clinical, diagnostic and therapeutic approaches that differ from those approaches used for traditional direct or cutaneous vector transmission. PMID:25946155

  1. Characterization of the Dispersal of Non-Domiciliated Triatoma dimidiata through the Selection of Spatially Explicit Models

    PubMed Central

    Barbu, Corentin; Dumonteil, Eric; Gourbière, Sébastien

    2010-01-01

    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. PMID:20689823

  2. Triatominae Biochemistry Goes to School: Evaluation of a Novel Tool for Teaching Basic Biochemical Concepts of Chagas Disease Vectors

    ERIC Educational Resources Information Center

    Cunha, Leonardo Rodrigues; de Oliveria Cudischevitch, Cecília; Carneiro, Alan Brito; Macedo, Gustavo Bartholomeu; Lannes, Denise; da Silva-Neto, Mário Alberto Cardoso

    2014-01-01

    We evaluate a new approach to teaching the basic biochemistry mechanisms that regulate the biology of Triatominae, major vectors of "Trypanosoma cruzi," the causative agent of Chagas disease. We have designed and used a comic book, "Carlos Chagas: 100 years after a hero's discovery" containing scientific information…

  3. Chagas Disease in 2 Geriatric Rhesus Macaques (Macaca mulatta) Housed in the Pacific Northwest

    PubMed Central

    Dickerson, Mary F; Astorga, Nestor Gerardo; Astorga, Nestor Rodrigo; Lewis, Anne D

    2014-01-01

    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission. PMID:25296019

  4. On the possibility of autochthonous Chagas disease in Roraima, Amazon region, Brazil, 2000-2001.

    PubMed

    Luitgards-Moura, José Francisco; Borges-Pereira, José; Costa, Jane; Zauza, Patrícia Lago; Rosa-Freitas, Maria Goreti

    2005-01-01

    Chagas disease has been almost entirely eradicated from the arid zones in Central and Northeastern Brazil where rare or no autochthonous cases have been reported. However, in the last 10 years the disease has increasingly been registered in the Amazon Region. Aiming to investigate the possibility of the occurrence of autochthonous cycle of Chagas disease in Roraima, triatomine collections, vectorial susceptibility studies (this one to be shown elsewhere), parasitological and serological analyses were conducted in three agricultural settlement areas (Rorainópolis, Passarão Project and Ilha Community). Blood-donor candidates were also investigated. This is the first epidemiological survey on Chagas disease conducted in agricultural settlements in Roraima. Triatomine species found were Triatoma maculata, Rhodnius pictipes, Rhodnius robustus and Panstrongylus geniculatus. Trypanosoma cruzi detection analyses included xenodiagnosis, indirect immunofluorescence, indirect hemaglutination, ELISA and kinetoplast PCR amplification. Natural triatomine infection was not found in intestinal contents. Twenty-five adult settlers (1.4% out of 1821, all > 15 year-old, 20 migrants) presented anti-T. cruzi antibodies. Two migrant settlers (from Minas Gerais and Maranhão) tested positive for more than two serological tests, besides either being positive for xenodiagnosis or PCR. Results show that Chagas disease is not endemic in the areas studied. However, all elements of the transmission cycle are present, demanding for an adequate and continuous vigilance.

  5. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY.

    PubMed

    Bravo-Tobar, Iván Darío; Nello-Pérez, Carlota; Fernández, Alí; Mogollón, Nora; Pérez, Mary Carmen; Verde, Juan; Concepción, Juan Luis; Rodriguez-Bonfante, Claudina; Bonfante-Cabarcas, Rafael

    2015-01-01

    Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

  6. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

    PubMed Central

    BRAVO-TOBAR, Iván Darío; NELLO-PÉREZ, Carlota; FERNÁNDEZ, Alí; MOGOLLÓN, Nora; PÉREZ, Mary Carmen; VERDE, Juan; CONCEPCIÓN, Juan Luis; RODRIGUEZ-BONFANTE, Claudina; BONFANTE-CABARCAS, Rafael

    2015-01-01

    SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease. PMID:26603224

  7. Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects

    PubMed Central

    Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, BT; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto

    2013-01-01

    Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children’s Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA. PMID:23151163

  8. Genotyping of Trypanosoma cruzi in a hyper-endemic area of Colombia reveals an overlap among domestic and sylvatic cycles of Chagas disease

    PubMed Central

    2014-01-01

    Background Chagas disease is a neglected illness caused by the Trypanosoma cruzi parasite, which widely affects American communities. This study attempted to identify T. cruzi genotypes circulating in four indigenous communities of the Sierra Nevada of Santa Marta, Colombia, to investigate parasite transmission dynamics in these communities. In addition, some epidemiological variables to determine the risk factors for infection with this parasite, such as the prevalence of T. cruzi infection, the triatomine species, and the domestic and sylvatic mammals that act as vectors and reservoirs of the parasite in the domestic, peridomestic and sylvatic cycles, were examined. Methods We developed a prospective study to identify the main risk factors associated with T. cruzi infection in the region. The T. cruzi prevalence was determined by ELISA, IFA and PCR. Triatomines species and both domestic and sylvatic mammals from all communities were captured and sampled. To analyze parasite transmission dynamics in these four communities, eight DNA parasite probes were generated from insect and reservoir samples, and a DNA blot analysis were carried out. Results Serological studies revealed 37% prevalence in the four communities, and Kasakumake was the most endemic region, containing approximately 70% seropositives. Moreover, the molecular diagnosis showed a high correlation between the serological data and the T. cruzi circulating in the patients’ blood. A total of 464 triatomine insects were collected in domestic, peridomestic and sylvatic environments, and these insects belonged to five different species; Rhodnius prolixus and Triatoma dimidiata were the two more important species transmitting the parasite. After studying the eco-epidemiological factors in these four communities, the most important risk factors for infection with the parasite were determined. These risk factors are a high infection rate of people and domestic animals, the construction materials of the houses

  9. The molluscicidal properties of Apodytes dimidiata subsp. dimidiata (Icacinaceae).

    PubMed

    Pretorius, S J; Joubert, P H; Scott, A H; Fourie, T G

    1991-06-01

    The molluscicidal and piscicidal activity of extracts from the leaves, berries and bark of the tree Apodytes dimidiata were evaluated experimentally. The leaves were highly toxic to both Bulinus africanus and Biomphalaria pfeifferi, the intermediate host snails of Schistosoma spp. B. pfeifferi profusely exuded mucus which appeared to render some protection against the toxic substance(s) of the plant but did not prevent their eventual demise. The LC10 after one-hour exposures of fish (Oreochromis mossambicus) was within molluscicidal levels. PMID:2051521

  10. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    PubMed Central

    Gonzalez-Mejia, Martha Elba; Torres-Rasgado, Enrique; Porchia, Leonardo M; Salgado, Hilda Rosas; Totolhua, José-Luis; Ortega, Arturo; Hernández-Kelly, Luisa Clara Regina; Ruiz-Vivanco, Guadalupe; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels. PMID:24676665

  11. Oral transmission of Chagas disease by consumption of açaí palm fruit, Brazil.

    PubMed

    Nóbrega, Aglaêr A; Garcia, Marcio H; Tatto, Erica; Obara, Marcos T; Costa, Elenild; Sobel, Jeremy; Araujo, Wildo N

    2009-04-01

    In 2006, a total of 178 cases of acute Chagas disease were reported from the Amazonian state of Pará, Brazil. Eleven occurred in Barcarena and were confirmed by visualization of parasites on blood smears. Using cohort and case-control studies, we implicated oral transmission by consumption of açaí palm fruit.

  12. PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL.

    PubMed

    Lopes, Patrícia da Silva; Ramos, Eliezer Lucas Pires; Gómez-Hernández, César; Ferreira, Gabriela Lícia Santos; Rezende-Oliveira, Karine

    2015-12-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results.

  13. Investigation of the role of IL17A gene variants in Chagas disease.

    PubMed

    Leon Rodriguez, D A; Echeverría, L E; González, C I; Martin, J

    2015-12-01

    Human host genetic factors have been suggested to be determinants of the prevalence and clinical forms of Chagas disease. In this regard, IL-17A is believed to control parasitemia and protect against heart disease. In this work, we assessed whether IL17A gene polymorphisms are related to infection and/or development of the cardiac form of Chagas disease by genotyping for five IL17A SNPs (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) in 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n=595), seropositive asymptomatic (n=175) and chronic Chagas cardiomyopathy (n=401). Our results showed that SNP rs8193036, which is located upstream of the coding region of the gene, was slightly associated with protection against T. cruzi infection (P=0.0170, P(FDR)=0.0851, odds ratio (OR)=0.80, confidence interval (CI)=0.66-0.96) and associated with protection against the development of cardiomyopathy (P=0.0065, P(FDR)=0.0324, OR=0.75, CI=0.60-0.92). This finding suggests that this IL17A polymorphism could be associated with Trypanosoma cruzi infection and the development of chronic cardiomyopathy due to differential expression of cytokine IL-17A.

  14. PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL.

    PubMed

    Lopes, Patrícia da Silva; Ramos, Eliezer Lucas Pires; Gómez-Hernández, César; Ferreira, Gabriela Lícia Santos; Rezende-Oliveira, Karine

    2015-12-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results. PMID:27049698

  15. PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL

    PubMed Central

    LOPES, Patrícia da Silva; RAMOS, Eliezer Lucas Pires; GÓMEZ-HERNÁNDEZ, César; FERREIRA, Gabriela Lícia Santos; REZENDE-OLIVEIRA, Karine

    2015-01-01

    Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results. PMID:27049698

  16. Modeling Chagas Disease at Population Level to Explain Venezuela's Real Data

    PubMed Central

    González-Parra, Gilberto; Chen-Charpentier, Benito M.; Bermúdez, Moises

    2015-01-01

    Objectives In this paper we present an age-structured epidemiological model for Chagas disease. This model includes the interactions between human and vector populations that transmit Chagas disease. Methods The human population is divided into age groups since the proportion of infected individuals in this population changes with age as shown by real prevalence data. Moreover, the age-structured model allows more accurate information regarding the prevalence, which can help to design more specific control programs. We apply this proposed model to data from the country of Venezuela for two periods, 1961–1971, and 1961–1991 taking into account real demographic data for these periods. Results Numerical computer simulations are presented to show the suitability of the age-structured model to explain the real data regarding prevalence of Chagas disease in each of the age groups. In addition, a numerical simulation varying the death rate of the vector is done to illustrate prevention and control strategies against Chagas disease. Conclusion The proposed model can be used to determine the effect of control strategies in different age groups. PMID:26929912

  17. Chagas' disease and the use of implantable cardioverter-defibrillators in Brazil.

    PubMed

    Rosa, Ronaldo F; Neto, Argemiro S; Franken, Roberto A

    2006-01-01

    The authors discuss the epidemiology and pathogenesis of Chagas' disease in Brazil, including the use of treatment with a cardioverter-defibrillator in patients with low ejection fraction. Select patients may benefit from resynchronization therapy associated with cardioverter-defibrillator treatment. Electrophysiologic study is indicated in the assessment of the potential utility of an implantable cardioverter-defibrillator. PMID:17086031

  18. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease.

    PubMed

    Gonzalez-Mejia, Martha Elba; Torres-Rasgado, Enrique; Porchia, Leonardo M; Salgado, Hilda Rosas; Totolhua, José-Luis; Ortega, Arturo; Hernández-Kelly, Luisa Clara Regina; Ruiz-Vivanco, Guadalupe; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

    2014-04-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

  19. Triatoma sanguisuga Blood Meals and Potential for Chagas Disease, Louisiana, USA

    PubMed Central

    Suarez, Julianne; Richards, Bethany; Dorn, Patricia L.

    2014-01-01

    To evaluate human risk for Chagas disease, we molecularly identified blood meal sources and prevalence of Trypanosoma cruzi infection among 49 Triatoma sanguisuga kissing bugs in Louisiana, USA. Humans accounted for the second most frequent blood source. Of the bugs that fed on humans, ≈40% were infected with T. cruzi, revealing transmission potential. PMID:25418456

  20. Protection of vascular endothelium by aspirin in a murine model of chronic Chagas' disease.

    PubMed

    Molina-Berríos, Alfredo; Campos-Estrada, Carolina; Lapier, Michel; Duaso, Juan; Kemmerling, Ulrike; Galanti, Norbel; Ferreira, Jorge; Morello, Antonio; López-Muñoz, Rodrigo; Maya, Juan Diego

    2013-07-01

    Chronic Chagas' disease affects 10-30 % of patients infected with Trypanosoma cruzi, and it mainly manifests as cardiomyopathy. Important pathophysiological mechanisms involved in the cardiac lesions include activation of the endothelium and induced microvascular alterations. These processes involve the production of endothelial adhesion molecules and thromboxane A2, which are involved in inflammatory cell recruitment and platelet aggregation, respectively. Cyclooxygenase inhibitors such as aspirin decrease thromboxane production and alter the course of Chagas' disease, both in the acute and chronic phases. We studied the effects of the administration of low and high doses of aspirin during the early phase of T. cruzi infection, following microvascular damage in the context of a chronic murine model of Chagas' disease. The effects of both schedules were assessed at 24 and 90 days postinfection by evaluating parasitemia, mortality, and cardiac histopathological changes as well as the expression of ICAM, VCAM, and E-selectin in cardiac tissue. Thromboxane A2, soluble ICAM, and E-selectin blood levels were also measured. While aspirin did not affect parasitemia or mortality in the infected mice, it decreased both cardiac inflammatory infiltrates and thromboxane levels. Additionally, at 90 days postinfection, aspirin normalized sICAM and sE-selectin levels. Considering the improved endothelial function induced by aspirin, we propose the possibility of including this drug in clinical therapy to treat chronic Chagas' disease.

  1. Association of the Functional MICA-129 Polymorphism With the Severity of Chronic Chagas Heart Disease.

    PubMed

    Ayo, Christiane Maria; Oliveira, Amanda Priscila de; Camargo, Ana Vitória da Silveira; Mattos, Cinara Cássia Brandão de; Bestetti, Reinaldo Bulgarelli; Mattos, Luiz Carlos de

    2015-10-15

    MICA-129 polymorphism affects the binding affinity of MICA molecules with the NKG2D receptor and influences effector cell function. The genotype met/met was associated with the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease, while the val/val genotype was associated with the absence of LVSD.

  2. Congenital Chagas' disease transmission in the United States: Diagnosis in adulthood.

    PubMed

    Murillo, Jorge; Bofill, Lina M; Bolivar, Hector; Torres-Viera, Carlos; Urbina, Julio A; Benhayon, Daniel; Torres, Jaime R

    2016-01-01

    Two brothers with congenitally-acquired Chagas' disease (CD) diagnosed during adulthood are reported. The patients were born in the USA to a mother from Bolivia who on subsequent assessment was found to be serologically positive for Trypanosoma cruzi. Serologic screening of all pregnant women who migrated from countries with endemic CD is strongly recommended. PMID:27516969

  3. Effects of aspirin-triggered resolvin D1 on peripheral blood mononuclear cells from patients with Chagas' heart disease.

    PubMed

    Ogata, Haline; Teixeira, Maxelle Martins; Sousa, Rodrigo Cunha de; Silva, Marcos Vinícius da; Correia, Dalmo; Rodrigues Junior, Virmondes; Levy, Bruce David; Rogério, Alexandre de Paula

    2016-04-15

    Chagas disease is caused by Trypanosoma cruzi (T. cruzi). In some patients with Chagas disease, symptoms progress to chronic chagasic cardiomyopathy. Endogenously, inflammation is resolved in the presence of lipid mediators such as aspirin-triggered RvD1 (AT-RvD1) which has anti-inflammatory and pro-resolution effects. Here, we demonstrated, for the first time, the effects of AT-RvD1 on T. cruzi antigen-stimulated peripheral blood mononuclear cells (PBMCs) from patients with Chagas heart disease. The levels of IFN-γ, TNF-α, IL-10, and IL-13 increased in PBMCs from cardiac-form Chagas patients in stage B1 (patients with fewer heart abnormalities) stimulated with T. cruzi antigen compared to those in non-stimulated PBMCs. AT-RvD1 reduced the IFN-γ concentrations in PBMCs from patients with Chagas disease stimulated with T. cruzi antigen compared to stimulated with T. cruzi antigen cells. AT-RvD1 treatment resulted in no observable changes in TNF-α, IL-10, and IL-13 levels. AT-RvD1 significantly decreased the percentage of necrotic cells and caused a significant reduction in the proliferation rate of T. cruzi antigen-stimulated PBMCs from patients with Chagas disease. These findings demonstrate that AT-RvD1 modulates the immune response in Chagas disease patients and might have potential to be used as an alternative approach for slowing the development of further heart damage.

  4. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

    PubMed Central

    Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

    2015-01-01

    The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario. PMID:26676323

  5. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease.

    PubMed

    Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

    2015-12-01

    The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario. PMID:26676323

  6. A scientometric evaluation of the Chagas disease implementation research programme of the PAHO and TDR.

    PubMed

    Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E

    2013-11-01

    The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997-2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

  7. A Scientometric Evaluation of the Chagas Disease Implementation Research Programme of the PAHO and TDR

    PubMed Central

    Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E.

    2013-01-01

    The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

  8. Human Chagas Disease and Migration in the Context of Globalization: Some Particular Aspects

    PubMed Central

    Pinto Dias, João Carlos

    2013-01-01

    Human Chagas disease originated in Latin America, being spread around the world in relation with multiple bioecological, sociocultural, and political factors. The process of the disease production and dispersion is discussed, emphasizing the human migration and correlated aspects, in the context of globalization. Positive and negative consequences concern the future of this trypanosomiasis, mainly in terms of the ecologic and sociopolitical characteristics of the endemic and nonendemic countries. PMID:23606862

  9. Current Understanding of Immunity to Trypanosoma cruzi Infection and Pathogenesis of Chagas Disease

    PubMed Central

    Machado, Fabiana S.; Dutra, Walderez O.; Esper, Lisia; Gollob, Kenneth; Teixeira, Mauro M.; Factor, Stephen M.; Weiss, Louis M.; Nagajyothi, Fnu; Tanowitz, Herbert B.; Garg, Nisha J.

    2012-01-01

    Chagas disease caused by Trypanosoma cruzi remains an important neglected tropical disease and a cause of significant morbidity and mortality. No longer confined to endemic areas of Latin America, it is now found in non-endemic areas due to immigration. The parasite may persist in any tissue, but in recent years there has been increased recognition of adipose tissue both as an early target of infection and a reservoir of chronic infection. The major complications of this disease are cardiomyopathy and megasyndromes involving the gastrointestinal tract. The pathogenesis of Chagas disease is complex and multifactorial involving many interactive pathways. The significance of innate immunity, including the contributions of cytokines, chemokines, reactive oxygen species, and oxidative stress, has been emphasized. The role of the components of the eicosanoid pathway such as thromboxane A2 and the lipoxins has been demonstrated to have profound effects as both pro-and anti-inflammatory factors. Additionally, we discuss the vasoconstrictive actions of thromboxane A2 and endothelin-1n Chagas disease. Human immunity to T. cruzi infection and its role in pathogen control and disease progression have not been fully investigated. However, recently, it was demonstrated that a reduction in the anti-inflammatory cytokine IL-10 was associated with clinically significant chronic chagasic cardiomyopathy. PMID:23076807

  10. Sperm Morphological Features Associated with Chronic Chagas Disease in the Semen of Experimentally Infected Dogs

    PubMed Central

    Rodríguez-Morales, Olivia; Pedro-Martínez, Elvia; Hernández-Pichardo, José Ernesto; Alejandre-Aguilar, Ricardo; Aranda-Fraustro, Alberto; Graullera-Rivera, Verónica; Arce-Fonseca, Minerva

    2014-01-01

    The presence of trypanosomatids in the reproductive systems of different mammals (causing genital lesions in the acute stage of the disease) may predispose the animals to low semen quality. However, there are no studies examining the alterations in the sperm morphological features in the chronic stage of Trypanosoma cruzi infection. Knowledge of these aspects is important to understand the other ways of transmission of the Chagas disease. Progressive motility, mass motility, concentration, and sperm morphology of 84 ejaculates of dogs that were chronically infected with T. cruzi were evaluated. Most of the findings were consistent with the reference values and with those obtained from healthy control dogs. The scrotal circumference was not correlated with spermatozoa concentration in the infected animals. In conclusion, the T. cruzi Ninoa (MHOM/MX/1994/Ninoa) strain does not cause significant alterations in the semen quality of dogs experiencing chronic Chagas disease (at concentrations of 5 × 104 to 1 × 106 parasites per animal). PMID:25114010

  11. Chagas Disease in a Non-endemic Country: A Multidisciplinary Research, Bologna, Italy.

    PubMed

    Di Girolamo, Chiara; Martelli, Giulia; Ciannameo, Anna; Vocale, Caterina; Fini, Marco; Stefanini, Angelo; Landini, Maria Paola; Viale, Pierluigi; Verucchi, Gabriella

    2016-06-01

    Global processes have brought about a substantial change in the epidemiological landscape of Chagas disease, spreading it to non-endemic areas. Italy is the second country in Europe in terms of Latin American migrants and expected infection rate. Given that scenario, the Bologna University Teaching Hospital undertaken a study aimed at providing preliminary data on the prevalence and investigating the knowledge and the subjective perceptions of Chagas disease, migration pathways and other relevant ill-health experiences. A cross-sectional study was undertaken in association with an ethnographic research. Between November 2010 and May 2013 Chagas disease testing was offered to people who attended the hospital and data were collected to investigate the broader socio-demographic and cultural factors. 151 individuals were screened for anti T. cruzi antibodies; 12 of them, 10 Bolivians and 2 Argentinians, were seroreactive, resulting in an overall prevalence of 7.94 %. Both the quantitative and the qualitative analysis revealed a degree of heterogeneity in terms of knowledge and perceptions of the disease as well as of migration pathways. The results are comparable with those reported by previous studies with similar characteristics and highlight the relevance of such public health issue in a non-endemic context. Moreover, the interdisciplinary approach has greatly helped to unveil the complex social and cultural implications of Chagas disease, to explain the subjective ill-health experiences, and to understand the ways in which the broader socio-economic and cultural context affects an intervention and its potential for success or failure.

  12. The Prevalence of Chagas Heart Disease in a Central Bolivian Community Endemic for Trypanosoma Cruzi

    PubMed Central

    Yager, Jessica E.; Lozano Beltran, Daniel F.; Torrico, Faustino; Gilman, Robert H.; Bern, Caryn

    2015-01-01

    Background Though the incidence of new Trypanosoma cruzi infections has decreased significantly in endemic regions in the Americas, medical professionals continue to encounter a high burden of resulting Chagas disease among infected adults. The current prevalence of Chagas heart disease in a community setting is not known; nor is it known how recent insecticide vector control measures may have impacted the progression of cardiac disease in an infected population. Objectives and Methods Nested within a community serosurvey in rural and periurban communities in central Bolivia, we performed a cross-sectional cardiac substudy to evaluate adults for historical, clinical, and electrocardiographic evidence of cardiac disease. All adults between the ages of 20 and 60 years old with T. cruzi infection and those with a clinical history, physical exam, or ECG consistent with cardiac abnormalities were also scheduled for echocardiography. Results and conclusions Of the 604 cardiac substudy participants with definitive serology results, 183 were seropositive for infection with T. cruzi (30.3%). Participants who were seropositive for T. cruzi infection were more likely to have conduction system defects (1.6% versus 0 for complete right bundle branch block and 10.4% versus 1.9% for any bundle branch block; p=0.008 and p<0.001, respectively). However, there was no statistically significant difference in the prevalence of bradycardia among seropositive versus seronegative participants. Echocardiogram findings were not consistent with a high burden of Chagas cardiomyopathy: valvulopathies were the most common abnormality, and few participants were found to have low ejection fraction or left ventricular dilatation. No participants had significant heart failure. Though almost one third of adults in the community were seropositive for T. cruzi infection, few had evidence of Chagas heart disease. PMID:26407509

  13. Access to care for Chagas disease in the United States: a health systems analysis.

    PubMed

    Manne-Goehler, Jennifer; Reich, Michael R; Wirtz, Veronika J

    2015-07-01

    There are 300,000 estimated cases of Chagas disease in the United States but limited data on access to care. This study analyzed trends in access to care for Chagas disease in the United States and assessed the national and state barriers to access. Data on cases in blood donors and drug releases were obtained from the AABB (formerly American Association of Blood Banks) and U.S. Centers for Disease Control and Prevention (CDC), respectively. Semi-structured in-depth interviews were conducted with 30 key informants at the national level and in five states where treatment had been released. Interview responses were analyzed according to the health systems dimensions of regulation, financing, payment, organization, and persuasion. Data indicate that 1,908 cases were identified in the blood donation system from 2007 to 2013 and that CDC released 422 courses of benznidazole or nifurtimox during this period. The barriers to access at the national level include limited diagnostic and institutionalized referral and care processes, lack of financing for patient-care activities, and limited awareness and training among providers. This study demonstrates that access to treatment of Chagas disease in the United States is limited. The lack of licensing is only one of several barriers to access, highlighting the need for a health systems perspective when scaling up access to these essential medicines.

  14. Chagas disease in the 21st Century: a public health success or an emerging threat?

    PubMed Central

    Bonney, Kevin M.

    2014-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health burden in Latin America and a potentially serious emerging threat to a number of countries throughout the world. Although public health programs have significantly reduced the prevalence of Chagas disease in Latin America in recent decades, the number of infections in the United States and non-endemic countries in Europe and the Western Pacific Region continues to rise. Moreover, there is still no vaccine or highly effective cure available for the approximately 10 million people currently infected with T. cruzi, a third of which will develop potentially fatal cardiomyopathy and/or severe digestive tract disorders. As Chagas disease becomes an increasingly globalized public health issue in the twenty-first century, continued attentiveness from governmental and health organizations as well as improved diagnostic tools, expanded surveillance and increased research funding will be required to maintain existing public health successes and stymie the spread of the disease to new areas and populations. PMID:24626257

  15. Modelling inter-human transmission dynamics of Chagas disease: analysis and application.

    PubMed

    Fabrizio, M C; Schweigmann, N J; Bartoloni, N J

    2014-05-01

    Transmission of Trypanosoma cruzi, the causal agent of Chagas disease, has expanded from rural endemic to urban areas due to migration. This so-called urban Chagas is an emerging health problem in American, European, Australian and Japanese cities. We present a mathematical model to analyse the dynamics of urban Chagas to better understand its epidemiology. The model considers the three clinical stages of the disease and the main routes of inter-human transmission. To overcome the complexities of the infection dynamics, the next-generation matrix method was developed. We deduced expressions which allowed estimating the number of new infections generated by an infected individual through each transmission route at each disease stage, the basic reproduction number and the number of individuals at each disease stage at the outbreak of the infection. The analysis was applied to Buenos Aires city (Argentina). We estimated that 94% of the new infections are generated by individuals in the chronic indeterminate stage. When migration was not considered, the infection disappeared slowly and R0 = 0.079, whereas when migration was considered, the number of individuals in each stage of the infection tended to stabilize. The expressions can be used to estimate different numbers of infected individuals in any place where only inter-human transmission is possible. PMID:24533945

  16. From ancient to contemporary molecular eco-epidemiology of Chagas disease in the Americas.

    PubMed

    Guhl, Felipe; Auderheide, Arthur; Ramírez, Juan David

    2014-08-01

    One of the best-studied populations with regard to Chagas disease is from the coastal area of northern Chile at the foot of the western Andean slopes. The extremely arid climate here generates rapid, spontaneous desiccation of buried bodies, arresting the decay process. The absence of rainfall then preserves these dried bodies (mummies) for millennia. The aim of the present study was to perform the first molecular paleoepidemiological study on a set of 43 mummified human remains from the Atacama Desert in Northern Chile in order to elucidate the transmission dynamics and determinants of ancient genotypes, to try to unravel the natural history of the Trypanosoma cruzi taxon and Chagas disease. Interestingly, TcBat, a recently described Discrete Taxonomic Unit, emerges as the plausible ancestor of T. cruzi. The findings herein presented allow us to present a plausible model of T. cruzi transmission in pre-Columbian civilisations. PMID:24675555

  17. Population genetic structure of Meccus longipennis (Hemiptera, Reduviidae, Triatominae), vector of Chagas disease in West Mexico.

    PubMed

    Brenière, Simone Frédérique; Waleckx, Etienne; Magallón-Gastélum, Ezequiel; Bosseno, Marie-France; Hardy, Xavier; Ndo, Cyrille; Lozano-Kasten, Felipe; Barnabé, Christian; Kengne, Pierre

    2012-03-01

    The originally wild species of the Meccus complex are important vectors of Chagas disease in Mexico. In West Mexico, Meccus longipennis plays an important epidemiological role. To understand the genetic structure of the domestic and wild populations of this species, a preliminary study with five polymorphic microsatellite loci was conducted. The population genetics analysis showed high structuring between peridomestic biotopes, with breeding subunits detected in a single peridomestic structure. In the wild environment, two genetic patterns were observed according to the biotope, possible breeding subunits in large rocky formations and a larger panmictic unit in agropastoral areas, suggesting considerable dispersal of bugs in this biotope. Moreover, the discovery of two foci of wild populations at the edge of Guadalajara city raises the question of new urban areas where the phenomenon of bug incursions into households could constitute a risk of transmission of Chagas disease.

  18. Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

    PubMed Central

    Ferreira, Ludmila Rodrigues Pinto; Frade, Amanda Farage; Baron, Monique Andrade; Navarro, Isabela Cunha; Kalil, Jorge; Chevillard, Christophe; Cunha-Neto, Edecio

    2014-01-01

    Chagas disease cardiomyopathy (CCC), the main consequence of Trypanosoma cruzi (T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon (IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease. PMID:25228957

  19. Diversity-Oriented Synthesis Yields a New Drug Lead for Treatment of Chagas Disease

    PubMed Central

    2013-01-01

    A phenotypic high-throughput screen using ∼100,000 compounds prepared using Diversity-Oriented Synthesis yielded stereoisomeric compounds with nanomolar growth-inhibition activity against the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. After evaluating stereochemical dependence on solubility, plasma protein binding and microsomal stability, the SSS analogue (5) was chosen for structure–activity relationship studies. The p-phenoxy benzyl group appended to the secondary amine could be replaced with halobenzyl groups without loss in potency. The exocyclic primary alcohol is not needed for activity but the isonicotinamide substructure is required for activity. Most importantly, these compounds are trypanocidal and hence are attractive as drug leads for both acute and chronic stages of Chagas disease. Analogue (5) was nominated as the molecular libraries probe ML341 and is available through the Molecular Libraries Probe Production Centers Network. PMID:24900788

  20. High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross-Sectional Evaluation

    PubMed Central

    Sánchez-Montalvá, Adrián; Moris, María; Mego, Marianela; Salvador, Fernando; Accarino, Anna; Ramírez, Kathleen; Azpiroz, Fernando; Ruiz-de-Leon, Antonio; Molina, Israel

    2016-01-01

    Introduction Gastrointestinal involvement affects 30–40% of the patients with chronic Chagas disease. Esophageal symptoms appear once the structural damage is established. Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement. Method We performed a cross-sectional study at the Vall d’Hebron University Hospital (Barcelona, Spain) between May 2011 and April 2012. Consecutive patients diagnosed with Chagas disease in the chronic phase were offered to participate. All patients underwent a structured questionnaire about digestive symptoms, a barium esophagogram (Rezende classification) and an esophageal high resolution manometry (HRM). A control group of patients with heartburn who underwent an esophageal HRM in our hospital was selected. Results 62 out of 73 patients that were included in the study fulfilled the study protocol. The median age of the Chagas disease group (CG) was 37 (IQR 32–45) years, and 42 (67.7%) patients were female. Twenty-seven (43.5%) patients had esophageal symptoms, heartburn being the most frequent. Esophagogram was abnormal in 5 (8.77%). The esophageal HRM in the CG showed a pathological motility pattern in 14 patients (22.6%). All of them had minor disorders of the peristalsis (13 with ineffective esophageal motility and 1 with fragmented peristalsis). Hypotonic lower esophageal sphincter was found more frequently in the CG than in the control group (21% vs 3.3%; p<0.01). Upper esophageal sphincter was hypertonic in 22 (35.5%) and hypotonic in 1 patient. When comparing specific manometric parameters or patterns in the CG according to the presence of symptoms or esophagogram no statistically significant association were seen, except for distal latency. Conclusion The esophageal involvement measured by HRM in patients with chronic Chagas disease in our cohort is 22.6%. All the patients with esophageal alterations had minor disorders of the peristalsis. Symptoms and

  1. [Chagas' disease in patients in chronic hemodialysis. Prevalence and risk of transmission by blood transfusion].

    PubMed

    Lorca, M; Lorca, E; Atías, A; Plubins, L

    1989-06-01

    A serologic study of Chagas disease was performed in 110 patients submitted to chronic hemodialisis and blood transfusions. Immunofluorescence antibody testing (IgG and IgM) was positive in 6 out of 62 patients receiving multiple blood transfusions (9.7%), but negative in all 48 subjects without transfusions. Thus, repeated blood transfusion is a significant risk for T cruzi infection in chronic hemodialized patients. PMID:2501847

  2. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

    PubMed

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease. PMID:27324760

  3. Positive deviance study to inform a Chagas disease control program in southern Ecuador

    PubMed Central

    Nieto-Sanchez, Claudia; Baus, Esteban G; Guerrero, Darwin; Grijalva, Mario J

    2015-01-01

    Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region. PMID:25807468

  4. Chagas disease and housing improvement in northeastern Brazil: a cross-sectional survey.

    PubMed

    Lima, Marli M; Carvalho-Costa, Filipe A; Toma, Helena K; Borges-Pereira, José; de Oliveira, Tiago Guedes; Sarquis, Otília

    2015-05-01

    Chagas disease was investigated in two new settlements of landless rural workers inhabiting prefabricated, triatomine-proof houses and in four neighboring older communities where mud huts were still well suitable for vectors. Through a cross-sectional survey and entomological assessment, we surveyed 148 houses/families in the two new settlements and in 47 houses/families in the four older localities. We determined seroprevalence of Chagas disease through IFI and Elisa (eluates) assays and searched for vectors in the domestic and peridomestic environments. Seroprevalence reached 0.6% (3/466) in the new settlements and 0.8% (1/115) in the older communities. Triatomines were not found in the new settlements, while 7 Triatoma brasiliensis, 4 T. pseudomaculata, 1 Panstrongylus lutzi, and 145 Rhodnius nasutus were collected in the older localities. In addition, a colony of T. brasiliensis (n = 55) was encountered inside a school attended by children of the region. Parasite strains isolated from the insects were characterized as T. cruzi I. Despite the low prevalence of Chagas disease in both scenarios, entomological surveillance must be strengthened and housing improvement reinforced in order to control vector transmission. The risk of infection by the vectors was lower in the settlements of improved homes, where conditions for colonization of the peridomestic environment by transmitting insects were not observed.

  5. Oesophageal motility disorders in infected immigrants with Chagas disease in a non-endemic European area

    PubMed Central

    Valerio, Lluís; Vallès, Xavier; Morales, Betty; Garcia-Diaz, M Immaculada; Pedro-Botet, M Luisa; Serra, Jordi

    2016-01-01

    Background Immigration-related new diseases pose a growing challenge for healthcare services in receptor countries. Following Latin American migration, Chagas disease has inevitably appeared in Europe. Aim To determine the prevalence and characteristics of oesophageal motility disorders in immigrants infected with Trypanosoma cruzi, using high resolution oesophageal manometry (HREM). Methods In all newly-diagnosed cases with chronic Chagas infection referring upper digestive symptoms, a protocolized clinical evaluation and complementary tests including barium oesophagogram and HREM were carried out. As control group, 14 healthy subjects from the same endemic areas were studied with HREM. Results We included 61 patients (46 female, 15 male; age range 26–63 years). Only seven patients (11%) had a minor alteration on barium oesophagogram. By contrast, 23 (37%) patients showed an alteration in oesophageal manometry, mainly minor motility disorders (34%). Only one healthy control (7%) had a minor motility disorder at HREM (p = 0.029 vs. patients). Conclusions Oesophageal motor disorders in infected immigrants with Chagas disease are common, and mainly characterized by a minor motility disorder that is not detected by barium oesophagogram. Hence, as well as barium oesophagogram examination, HREM should be considered, to assess oesophageal damage in this specific group of patients. PMID:27536373

  6. Chagas disease and housing improvement in northeastern Brazil: a cross-sectional survey.

    PubMed

    Lima, Marli M; Carvalho-Costa, Filipe A; Toma, Helena K; Borges-Pereira, José; de Oliveira, Tiago Guedes; Sarquis, Otília

    2015-05-01

    Chagas disease was investigated in two new settlements of landless rural workers inhabiting prefabricated, triatomine-proof houses and in four neighboring older communities where mud huts were still well suitable for vectors. Through a cross-sectional survey and entomological assessment, we surveyed 148 houses/families in the two new settlements and in 47 houses/families in the four older localities. We determined seroprevalence of Chagas disease through IFI and Elisa (eluates) assays and searched for vectors in the domestic and peridomestic environments. Seroprevalence reached 0.6% (3/466) in the new settlements and 0.8% (1/115) in the older communities. Triatomines were not found in the new settlements, while 7 Triatoma brasiliensis, 4 T. pseudomaculata, 1 Panstrongylus lutzi, and 145 Rhodnius nasutus were collected in the older localities. In addition, a colony of T. brasiliensis (n = 55) was encountered inside a school attended by children of the region. Parasite strains isolated from the insects were characterized as T. cruzi I. Despite the low prevalence of Chagas disease in both scenarios, entomological surveillance must be strengthened and housing improvement reinforced in order to control vector transmission. The risk of infection by the vectors was lower in the settlements of improved homes, where conditions for colonization of the peridomestic environment by transmitting insects were not observed. PMID:25673077

  7. A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors

    PubMed Central

    Farrow, Anitra L.; Peng, Binghao J.; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L.

    2016-01-01

    Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi’s amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the “Antigen Capsid-Incorporation” strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

  8. Positive deviance study to inform a Chagas disease control program in southern Ecuador.

    PubMed

    Nieto-Sanchez, Claudia; Baus, Esteban G; Guerrero, Darwin; Grijalva, Mario J

    2015-05-01

    Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region. PMID:25807468

  9. New approach towards the synthesis of selenosemicarbazones, useful compounds for Chagas' disease.

    PubMed

    Pizzo, Chiara; Faral-Tello, Paula; Yaluff, Gloria; Serna, Elva; Torres, Susana; Vera, Ninfa; Saiz, Cecilia; Robello, Carlos; Mahler, Graciela

    2016-02-15

    Herein, we describe a new approach towards the synthesis of selenosemicarbazones. The reaction involves an O-Se exchange of semicarbazones using Ishihara reagent. Eleven selenosemicarbazones were prepared using this methodology, with low to moderate yields. Among the prepared compounds the m-bromo phenyl methyl derivative 1b was selected to be evaluated in vivo, in a murine model of acute Chagas' disease. Compound 1b 10 mg/kg bw/day reduced 50% of parasitaemia profile compared with the control group, but was less effective than Benznidazole (50 mg/kg bw/day reduced 90%) and toxic. These studies are important to guide future Chagas drug design. PMID:26774036

  10. Multi-epitope proteins for improved serological detection of Trypanosoma cruzi infection and Chagas Disease.

    PubMed

    Duthie, Malcolm S; Guderian, Jeffery A; Vallur, Aarthy C; Misquith, Ayesha; Liang, Hong; Mohamath, Raodoh; Luquetti, Alejandro O; Carter, Darrick; Tavares, Suelene N B; Reed, Steven G

    2016-03-01

    We previously reported that tandem repeat (TR) proteins from Trypanosoma cruzi could serve as targets of the antibody response and be useful as diagnostic indicators. To optimize reagents for detecting T. cruzi infection we evaluated individual TR proteins and identified several that were recognized by the majority of Chagas patient's sera collected from individuals form Brazil. We then produced novel, recombinant fusion proteins to combine the reactive TR proteins into a single diagnostic product. Direct comparison of the antibody response of serum samples that were readily detected by the established fusion antigen used in commercial detection of Chagas disease, TcF, revealed strong responses to TcF43 and TcF26 proteins. While the TcF43 and TcF26 antigens enhanced detection and strength of signal, they did not compromise the specificity of detection compared to that obtained with TcF. Finally, it was apparent by testing against a panel of 84 serum samples assembled on the basis of moderate or weak reactivity against TcF (mostly signal:noise <5) that TcF43 and TcF26 could more strongly detected by many of the sera that had low TcF antibody levels. Taken together, these data indicate that TcF43 and TcF26 could be used to enhance the detection of T. cruzi infection as well as supporting a diagnosis of Chagas disease.

  11. Prevalence of Chagas disease in Brazil: a systematic review and meta-analysis.

    PubMed

    Martins-Melo, Francisco Rogerlândio; Ramos, Alberto Novaes; Alencar, Carlos Henrique; Heukelbach, Jorg

    2014-02-01

    Chagas disease is a major public health problem in Brazil and Latin America. During the last years, it has become an emerging problem in North America and Europe due to increasing international migration. Here we describe the prevalence of Chagas disease in Brazil through a systematic review. We searched national and international electronic databases, grey literature and reference lists of selected articles for population-based studies on Chagas disease prevalence in Brazil, performed from 1980 until September 2012. Forty-two articles with relevant prevalence data were identified from a total of 4985 references. Prevalence ranged from 0% to 25.1%. Most surveys were performed in the Northeast region, especially in the state of Piauí. We observed a high degree of heterogeneity in most pooled estimates (I(2)>75%; p<0.001). The pooled estimate of Chagas disease prevalence across studies for the entire period was 4.2% (95% CI: 3.1-5.7), ranging from 4.4% (95% CI: 2.3-8.3) in the 1980s to 2.4% (95% CI: 1.5-3.8) after 2000. Females (4.2%; 95% CI: 2.6-6.8), >60 year-olds (17.7%; 95% CI: 11.4-26.5), Northeast (5.0%; 95% CI: 3.1-8.1) and Southeast (5.0%; CI: 2.4-9.9) regions and mixed (urban/rural) areas (6.4%; 95% CI: 4.2-9.4) had the highest pooled prevalence. About 4.6 million (95% CI: 2.9-7.2 million) of people are estimated to be infected with Trypanosoma cruzi. The small number of studies and small-scale samples of the general population in some areas limit interpretation, and findings of this review do not necessarily reflect the situation of the entire country. Systematic population-based studies at regional and national level are recommended to provide more accurate estimates and better define the epidemiology and risk areas of Chagas disease in Brazil.

  12. Chagas disease as a cause of heart failure and ventricular arrhythmias in patients long removed from endemic areas: an emerging problem in Europe.

    PubMed

    Vannucchi, Vieri; Tomberli, Benedetta; Zammarchi, Lorenzo; Fornaro, Alessandra; Castelli, Gabriele; Pieralli, Filippo; Berni, Andrea; Yacoub, Sophie; Bartoloni, Alessandro; Olivotto, Iacopo

    2015-12-01

    Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi. In endemic areas (South and Central America), Chagas disease represents a relevant public health issue, and is the most frequent cause of cardiomyopathy. In nonendemic areas, such as Europe, Chagas disease represents an emerging problem following the establishment of sizeable communities from Brazil and Bolivia. Chagas cardiomyopathy represents the most frequent and serious complication of chronic Chagas disease, affecting about 20-30% of patients, potentially leading to heart failure, arrhythmias, thromboembolism, stroke and sudden death. Because late complications of Chagas disease may develop several years or even decades after the acute infection, it may be extremely challenging to reach the correct diagnosis in patients long removed from the countries of origin. We report two examples of Chagas cardiomyopathy in South American women permanently residing in Italy for more than 20 years, presenting with cardiac manifestations ranging from left ventricular dysfunction and heart failure to isolated ventricular arrhythmias. The present review emphasizes that Chagas disease should be considered as a potential diagnosis in patients from endemic areas presenting with 'idiopathic' cardiac manifestations, even when long removed from their country of origin, with potential implications for treatment and control of Chagas disease transmission.

  13. FC-TRIPLEX Chagas/Leish IgG1: A Multiplexed Flow Cytometry Method for Differential Serological Diagnosis of Chagas Disease and Leishmaniasis

    PubMed Central

    Teixeira-Carvalho, Andréa; Campos, Fernanda Magalhães Freire; Geiger, Stefan Michael; Rocha, Roberta Dias Rodrigues; de Araújo, Fernanda Fortes; Vitelli-Avelar, Danielle Marquete; Andrade, Mariléia Chaves; Araújo, Márcio Sobreira Silva; Lemos, Elenice Moreira; de Freitas Carneiro Proietti, Anna Bárbara; Sabino, Ester Cerdeira; Caldas, Rafaella Gaiotti; Freitas, Carolina Renata Camargos; Campi-Azevedo, Ana Carolina; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis

    2015-01-01

    Differential serological diagnosis of Chagas disease and leishmaniasis is difficult owing to cross-reactivity resulting from the fact that the parasites that cause these pathologies share antigenic epitopes. Even with optimized serological assays that use parasite-specific recombinant antigens, inconclusive test results continue to be a problem. Therefore, new serological tests with high sensitivity and specificity are needed. In the present work, we developed and evaluated the performance of a new flow cytometric serological method, referred to as FC-TRIPLEX Chagas/Leish IgG1, for the all-in-one classification of inconclusive tests. The method uses antigens for the detection of visceral leishmaniasis, localized cutaneous leishmaniasis, and Chagas disease and is based on an inverted detuned algorithm for analysis of anti-Trypanosomatidae IgG1 reactivity. First, parasites were label with fluorescein isothiocyanate or Alexa Fluor 647 at various concentrations. Then serum samples were serially diluted, the dilutions were incubated with suspensions of mixed labeled parasites, and flow cytometric measurements were performed to determine percentages of positive fluorescent parasites. Using the new method, we obtained correct results for 76 of 80 analyzed serum samples (95% overall performance), underscoring the outstanding performance of the method. Moreover, we found that the fluorescently labeled parasite suspensions were stable during storage at room temperature, 4°C, and –20°C for 1 year. In addition, two different lots of parasite suspensions showed equivalent antigen recognition; that is, the two lots showed equivalent categorical segregation of anti-Trypanosomatidae IgG1 reactivity at selected serum dilutions. In conclusion, we have developed a sensitive and selective method for differential diagnosis of Chagas disease, visceral leishmaniasis, and localized cutaneous leishmaniasis. PMID:25875961

  14. FC-TRIPLEX Chagas/Leish IgG1: a multiplexed flow cytometry method for differential serological diagnosis of chagas disease and leishmaniasis.

    PubMed

    Teixeira-Carvalho, Andréa; Campos, Fernanda Magalhães Freire; Geiger, Stefan Michael; Rocha, Roberta Dias Rodrigues; de Araújo, Fernanda Fortes; Vitelli-Avelar, Danielle Marquete; Andrade, Mariléia Chaves; Araújo, Márcio Sobreira Silva; Lemos, Elenice Moreira; de Freitas Carneiro Proietti, Anna Bárbara; Sabino, Ester Cerdeira; Caldas, Rafaella Gaiotti; Freitas, Carolina Renata Camargos; Campi-Azevedo, Ana Carolina; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis

    2015-01-01

    Differential serological diagnosis of Chagas disease and leishmaniasis is difficult owing to cross-reactivity resulting from the fact that the parasites that cause these pathologies share antigenic epitopes. Even with optimized serological assays that use parasite-specific recombinant antigens, inconclusive test results continue to be a problem. Therefore, new serological tests with high sensitivity and specificity are needed. In the present work, we developed and evaluated the performance of a new flow cytometric serological method, referred to as FC-TRIPLEX Chagas/Leish IgG1, for the all-in-one classification of inconclusive tests. The method uses antigens for the detection of visceral leishmaniasis, localized cutaneous leishmaniasis, and Chagas disease and is based on an inverted detuned algorithm for analysis of anti-Trypanosomatidae IgG1 reactivity. First, parasites were label with fluorescein isothiocyanate or Alexa Fluor 647 at various concentrations. Then serum samples were serially diluted, the dilutions were incubated with suspensions of mixed labeled parasites, and flow cytometric measurements were performed to determine percentages of positive fluorescent parasites. Using the new method, we obtained correct results for 76 of 80 analyzed serum samples (95% overall performance), underscoring the outstanding performance of the method. Moreover, we found that the fluorescently labeled parasite suspensions were stable during storage at room temperature, 4 °C, and -20 °C for 1 year. In addition, two different lots of parasite suspensions showed equivalent antigen recognition; that is, the two lots showed equivalent categorical segregation of anti-Trypanosomatidae IgG1 reactivity at selected serum dilutions. In conclusion, we have developed a sensitive and selective method for differential diagnosis of Chagas disease, visceral leishmaniasis, and localized cutaneous leishmaniasis.

  15. Training Systems Modelers through the Development of a Multi-scale Chagas Disease Risk Model

    NASA Astrophysics Data System (ADS)

    Hanley, J.; Stevens-Goodnight, S.; Kulkarni, S.; Bustamante, D.; Fytilis, N.; Goff, P.; Monroy, C.; Morrissey, L. A.; Orantes, L.; Stevens, L.; Dorn, P.; Lucero, D.; Rios, J.; Rizzo, D. M.

    2012-12-01

    The goal of our NSF-sponsored Division of Behavioral and Cognitive Sciences grant is to create a multidisciplinary approach to develop spatially explicit models of vector-borne disease risk using Chagas disease as our model. Chagas disease is a parasitic disease endemic to Latin America that afflicts an estimated 10 million people. The causative agent (Trypanosoma cruzi) is most commonly transmitted to humans by blood feeding triatomine insect vectors. Our objectives are: (1) advance knowledge on the multiple interacting factors affecting the transmission of Chagas disease, and (2) provide next generation genomic and spatial analysis tools applicable to the study of other vector-borne diseases worldwide. This funding is a collaborative effort between the RSENR (UVM), the School of Engineering (UVM), the Department of Biology (UVM), the Department of Biological Sciences (Loyola (New Orleans)) and the Laboratory of Applied Entomology and Parasitology (Universidad de San Carlos). Throughout this five-year study, multi-educational groups (i.e., high school, undergraduate, graduate, and postdoctoral) will be trained in systems modeling. This systems approach challenges students to incorporate environmental, social, and economic as well as technical aspects and enables modelers to simulate and visualize topics that would either be too expensive, complex or difficult to study directly (Yasar and Landau 2003). We launch this research by developing a set of multi-scale, epidemiological models of Chagas disease risk using STELLA® software v.9.1.3 (isee systems, inc., Lebanon, NH). We use this particular system dynamics software as a starting point because of its simple graphical user interface (e.g., behavior-over-time graphs, stock/flow diagrams, and causal loops). To date, high school and undergraduate students have created a set of multi-scale (i.e., homestead, village, and regional) disease models. Modeling the system at multiple spatial scales forces recognition that

  16. PREVALENCE OF CHAGAS DISEASE IN A RURAL AREA IN THE STATE OF CEARA, BRAZIL

    PubMed Central

    FREITAS, Erlane Chaves; OLIVEIRA, Maria de Fátima; ANDRADE, Mônica Coelho; VASCONCELOS, Arduina Sofia Ortet de Barros; da SILVA, José Damião; CÂNDIDO, Darlan da Silva; PEREIRA, Laíse dos Santos; CORREIA, João Paulo Ramalho; da CRUZ, José Napoleão Monte; CAVALCANTI, Luciano Pamplona de Góes

    2015-01-01

    SUMMARY Chagas disease is caused by Trypanosoma cruzi and affects about two to three million people in Brazil, still figuring as an important public health problem. A study was conducted in a rural area of the municipality of Limoeiro do Norte - CE, northeastern Brazil, aiming to determine the prevalence of T. cruzi infection. Of the inhabitants, 52% were examined, among whom 2.6% (4/154) were seropositive in at least two serological tests. All seropositive individuals were older than 50 years, farmers, with a low education and a family income of less than three minimum wages. Active surveillance may be an alternative for early detection of this disease. PMID:26603232

  17. Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease

    PubMed Central

    da Mota, Fabio Faria; Marinho, Lourena Pinheiro; Moreira, Carlos José de Carvalho; Lima, Marli Maria; Mello, Cícero Brasileiro; Garcia, Eloi Souza; Carels, Nicolas; Azambuja, Patricia

    2012-01-01

    Background Chagas disease is a trypanosomiasis whose agent is the protozoan parasite Trypanosoma cruzi, which is transmitted to humans by hematophagous bugs known as triatomines. Even though insecticide treatments allow effective control of these bugs in most Latin American countries where Chagas disease is endemic, the disease still affects a large proportion of the population of South America. The features of the disease in humans have been extensively studied, and the genome of the parasite has been sequenced, but no effective drug is yet available to treat Chagas disease. The digestive tract of the insect vectors in which T. cruzi develops has been much less well investigated than blood from its human hosts and constitutes a dynamic environment with very different conditions. Thus, we investigated the composition of the predominant bacterial species of the microbiota in insect vectors from Rhodnius, Triatoma, Panstrongylus and Dipetalogaster genera. Methodology/Principal Findings Microbiota of triatomine guts were investigated using cultivation-independent methods, i.e., phylogenetic analysis of 16s rDNA using denaturing gradient gel electrophoresis (DGGE) and cloned-based sequencing. The Chao index showed that the diversity of bacterial species in triatomine guts is low, comprising fewer than 20 predominant species, and that these species vary between insect species. The analyses showed that Serratia predominates in Rhodnius, Arsenophonus predominates in Triatoma and Panstrongylus, while Candidatus Rohrkolberia predominates in Dipetalogaster. Conclusions/Significance The microbiota of triatomine guts represents one of the factors that may interfere with T. cruzi transmission and virulence in humans. The knowledge of its composition according to insect species is important for designing measures of biological control for T. cruzi. We found that the predominant species of the bacterial microbiota in triatomines form a group of low complexity whose structure

  18. American Trypanosomiasis (Also Known as Chagas Disease) Treatment

    MedlinePlus

    ... Disease Among United States Blood Donors Information For: Adoption: Agencies & Parents Blood Banks Travelers Related Links Parasites ... Disease Among United States Blood Donors Information For: Adoption: Agencies & Parents Blood Banks Travelers Related Links Parasites ...

  19. Chronic Chagas' heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine.

    PubMed

    Muñoz-Saravia, Silvia Gilka; Haberland, Annekathrin; Wallukat, Gerd; Schimke, Ingolf

    2012-01-01

    Chagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease.

  20. Chagas disease as a mechanistic model for testing a novel hypothesis.

    PubMed

    Mosovich, Serge A; Mady, Charles; Lopes, Neuza; Ianni, Barbara; Dias, João Carlos Pinto; Correia, Dalmo; Farkouh, Michael E

    2008-01-01

    The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression. PMID:18368274

  1. Combining Public Health Education and Disease Ecology Research: Using Citizen Science to Assess Chagas Disease Entomological Risk in Texas

    PubMed Central

    Curtis-Robles, Rachel; Wozniak, Edward J.; Auckland, Lisa D.; Hamer, Gabriel L.; Hamer, Sarah A.

    2015-01-01

    Background Chagas disease is a zoonotic parasitic disease well-documented throughout the Americas and transmitted primarily by triatomine ‘kissing bug’ vectors. In acknowledgment of the successful history of vector control programs based on community participation across Latin America, we used a citizen science approach to gain novel insight into the geographic distribution, seasonal activity, and Trypanosoma cruzi infection prevalence of kissing bugs in Texas while empowering the public with information about Chagas disease. Methodology/Principal Findings We accepted submissions of kissing bugs encountered by the public in Texas and other states from 2013–2014 while providing educational literature about Chagas disease. In the laboratory, kissing bugs were identified to species, dissected, and tested for T. cruzi infection. A total of 1,980 triatomines were submitted to the program comprised of at least seven species, of which T. gerstaeckeri and T. sanguisuga were the most abundant (85.7% of submissions). Triatomines were most commonly collected from dog kennels and outdoor patios; Overall, 10.5% of triatomines were collected from inside the home. Triatomines were submitted from across Texas, including many counties which were not previously known to harbor kissing bugs. Kissing bugs were captured primarily throughout April-October, and peak activity occurred in June-July. Emails to our dedicated account regarding kissing bugs were more frequent in the summer months (June-August) than the rest of the year. We detected T. cruzi in 63.3% of tested bugs. Conclusions/Significance Citizen science is an efficient approach for generating data on the distribution, phenology, and infection prevalence of kissing bugs—vectors of the Chagas disease parasite—while educating the public and medical community. PMID:26658425

  2. Training the Next Generation of Scientists: System Dynamics Modeling of Chagas Disease (American Trypanosomiasis) transmission.

    NASA Astrophysics Data System (ADS)

    Goff, P.; Hulse, A.; Harder, H. R.; Pierce, L. A.; Rizzo, D.; Hanley, J.; Orantes, L.; Stevens, L.; Justi, S.; Monroy, C.

    2015-12-01

    A computational simulation has been designed as an investigative case study by high school students to introduce system dynamics modeling into high school curriculum. This case study approach leads users through the forensics necessary to diagnose an unknown disease in a Central American village. This disease, Chagas, is endemic to 21 Latin American countries. The CDC estimates that of the 110 million people living in areas with the disease, 8 million are infected, with as many as 300,000 US cases. Chagas is caused by the protozoan parasite, Trypanosoma cruzi, and is spread via blood feeding insect (vectors), that feed on vertebrates and live in crevasses in the walls and roofs of adobe homes. One-third of the infected people will develop chronic Chagas who are asymptomatic for years before their heart or GI tract become enlarged resulting in death. The case study has three parts. Students play the role of WHO field investigators and work collaboratively to: 1) use genetics to identify the host(s) and vector of the disease 2) use a STELLA™ SIR (Susceptible, Infected, Recovered) system dynamics model to study Chagas at the village scale and 3) develop management strategies. The simulations identify mitigation strategies known as Ecohealth Interventions (e.g., home improvements using local materials) to help stakeholders test and compare multiple optima. High school students collaborated with researchers from the University of Vermont, Loyola University and Universidad de San Carlos, Guatemala, working in labs, interviewing researchers, and incorporating mulitple field data as part of a NSF-funded multiyear grant. The model displays stable equilibria of hosts, vectors, and disease-states. Sensitivity analyses show measures of household condition and presence of vertebrates were significant leverage points, supporting other findings by the University research team. The village-scale model explores multiple solutions to disease mitigation for the purpose of producing

  3. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas.

    PubMed

    Péneau, Julie; Nguyen, Anne; Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

    2016-02-01

    The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species. PMID:26867025

  4. Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

    PubMed Central

    Lepesheva, Galina I.

    2013-01-01

    Introduction Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14α-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. PMID:24079515

  5. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas

    PubMed Central

    Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

    2016-01-01

    The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species. PMID:26867025

  6. Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas.

    PubMed

    Péneau, Julie; Nguyen, Anne; Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

    2016-02-01

    The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species.

  7. Bibliometric assessment of the contributions of literature on Chagas disease in Latin America and the Caribbean.

    PubMed

    Delgado-Osorio, Nathalia; Vera-Polania, Felipe; Lopez-Isaza, Andres F; Martinez-Pulgarin, Dayron F; Murillo-Abadia, Jonathan; Munoz-Urbano, Marcela; Cardona-Ospina, Jaime A; Bello, Ricardo; Lagos-Grisales, Guillermo J; Villegas-Rojas, Soraya; Rodriguez-Morales, Alfonso J

    2014-01-01

    Chagas disease, considered a parasitic neglected disease, is endemic in Latin America. Although, its mortality rate has decreased over time, it still represents a public health problem in the region. A bibliometric evaluation of the Latin American contributions on this disease was done. This study used SCI (1980-2013), MEDLINE/GOPUBMED (1802-2013), Scopus (1959-2013), SCIELO (2004-2013), and LILACS (1980-2013). Different study types have been characterized by years, origin city/country, journals and most productive authors, by country, cites and H-index. 2988 articles were retrieved from SCI (30.85% of total). Brazil was found to be the highest producer (31.22%), followed by Argentina (18.14%) and México (9.57%); the region received 47241 citations, 28.60% for Brazil (H-index=52), 18.26% of Argentina (Hindex= 43), 11.40% Bolivia (H-index=37). 4484 were retrieved from Scopus (30.20% of the total), 38.58% of which were from Brazil, 12.40% from Argentina and 8.90% from Mexico. From Medline, 6647 records were retrieved (45.58% Brazil). From SciELO, 917 articles (47.66% Brazil). From LILACS, 2165 articles (60.05% Brazil). Brazil has the highest output in the region. Despite advances in controlling Chagas disease, scientific production is low, particularly for regional bibliographic databases, which calls for more research on this disease.

  8. Clinical and epidemiological study of chronic heart involvment in Chagas' disease*

    PubMed Central

    Puigbó, J. J.; Rhode, J. R. Nava; Barrios, H. García; Suárez, J. A.; Yépez, C. Gil

    1966-01-01

    It has been estimated that, in vast areas of the American continent, there is a high prevalence of human infection by Trypanosoma cruzi. Such infection can lead to a variety of heart diseases, predominantly with involvement of the myocardium. The aim of the present work was to determine the prevalence of heart disease in two rural areas of Venezuela with a high endemicity of Chagas' disease and to try to determine the natural history of the disease. It is shown that a form of chronic myocardial disease in patients with positive specific serology and good functional capacity is highly prevalent. Electrocardiographic patterns typical of the initial and developing stages of the disease, as well as early abnormalities of the cardiac rhythm, are described and illustrated. The present work forms part of a longitudinal study still in progress. ImagesFIG. 2FIG. 8FIG. 9FIG. 6FIG. 7FIG. 3FIG. 5FIG. 4 PMID:4957485

  9. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients.

    PubMed

    Guedes, Paulo Marcos Matta; de Andrade, Cléber Mesquita; Nunes, Daniela Ferreira; de Sena Pereira, Nathalie; Queiroga, Tamyres Bernadete Dantas; Machado-Coelho, George Luiz Lins; Nascimento, Manuela Sales Lima; Do-Valle-Matta, Maria Adelaide; da Câmara, Antônia Cláudia Jácome; Chiari, Egler; Galvão, Lúcia Maria da Cunha

    2016-04-01

    Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease. PMID

  10. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients.

    PubMed

    Guedes, Paulo Marcos Matta; de Andrade, Cléber Mesquita; Nunes, Daniela Ferreira; de Sena Pereira, Nathalie; Queiroga, Tamyres Bernadete Dantas; Machado-Coelho, George Luiz Lins; Nascimento, Manuela Sales Lima; Do-Valle-Matta, Maria Adelaide; da Câmara, Antônia Cláudia Jácome; Chiari, Egler; Galvão, Lúcia Maria da Cunha

    2016-04-01

    Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease.

  11. Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients

    PubMed Central

    Guedes, Paulo Marcos Matta; de Andrade, Cléber Mesquita; Nunes, Daniela Ferreira; de Sena Pereira, Nathalie; Queiroga, Tamyres Bernadete Dantas; Machado-Coelho, George Luiz Lins; Nascimento, Manuela Sales Lima; Do-Valle-Matta, Maria Adelaide; da Câmara, Antônia Cláudia Jácome; Chiari, Egler; Galvão, Lúcia Maria da Cunha

    2016-01-01

    Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease. PMID

  12. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.

    PubMed

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard; Supek, Frantisek

    2015-10-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates.

  13. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.

    PubMed

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard; Supek, Frantisek

    2015-10-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates. PMID:26239982

  14. Chagas' disease parasite-derived neurotrophic factor activates cholinergic gene expression in neuronal PC12 cells.

    PubMed

    Akpan, Nsikan; Caradonna, Kacey; Chuenkova, Marina V; PereiraPerrin, Mercio

    2008-06-27

    A parasite-derived neurotrophic factor (PDNF) produced by the Chagas' disease parasite Trypanosoma cruzi binds nerve growth factor (NGF) receptor TrkA, increasing receptor autophosphorylation, and activating phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK/Erk) pathways, and transcription factor CREB. The end-result is enhanced survival and neuritogenesis of various types of neurons. PDNF also enhances the expression and activity of tyrosine hydroxylase, a rate limiting enzyme in the synthesis of dopamine and other catecholamine neurotransmitters. It remains unknown, however, if PDNF alters expression and metabolism of acetylcholine (ACh), a neurotransmitter thought to play a role in Chagas' disease progression. Here we demonstrate that PDNF stimulates mRNA and protein expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are critical for synthesis and storage of ACh. Stimulation requires functional TrkA because it did not occur in cell mutants that lack the receptor and in TrkA-expressing wild-type cells treated with K252a, an inhibitor of TrkA kinase activity. It also requires TrkA-dependent PI3K and MAPK/Erk signaling pathways because PDNF stimulation of cholinergic transcripts is abolished by specific pharmacological inhibitors. Furthermore, the cholinergic actions of PDNF were reproduced by PDNF-expressing extracellular T. cruzi trypomastigotes at the start of host cell invasion. In contrast, host cells bearing intracellular T. cruzi showed decreased, rather than increased, cholinergic gene expression. These results suggest that T. cruzi invasion of the nervous system alters cholinergic gene expression and that could play a role in neuropathology, and/or lack thereof, in Chagas' disease patients. PMID:18502403

  15. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

    PubMed Central

    Khare, Shilpi; Roach, Steven L.; Barnes, S. Whitney; Hoepfner, Dominic; Walker, John R.; Chatterjee, Arnab K.; Neitz, R. Jeffrey; Arkin, Michelle R.; McNamara, Case W.; Ballard, Jaime; Lai, Yin; Fu, Yue; Molteni, Valentina; Yeh, Vince; McKerrow, James H.; Glynne, Richard J.; Supek, Frantisek

    2015-01-01

    Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease. PMID:26186534

  16. Triatominae species of Suriname (Heteroptera: Reduviidae) and their role as vectors of Chagas disease.

    PubMed

    Hiwat, Hélène

    2014-07-01

    Nine species of Triatominae, representing three tribes and five genera, are currently known in Suriname. An annotated list of the species based on the collections of the Bureau of Public Health (Suriname), the National Zoological Collection Suriname and the National History Museum Leiden (the Netherlands) is provided. Additionally, the results of several years of opportunistic collection in two domestic environments are presented. The most common species are Rhodnius pictipes Stål, 1972, Rhodnius robustus Larrouse, 1972 and Panstrongylus geniculatus (Latreille, 1811). The significance of the species as vectors of Chagas disease in Suriname is discussed.

  17. Triatominae species of Suriname (Heteroptera: Reduviidae) and their role as vectors of Chagas disease

    PubMed Central

    Hiwat, Hélène

    2014-01-01

    Nine species of Triatominae, representing three tribes and five genera, are currently known in Suriname. An annotated list of the species based on the collections of the Bureau of Public Health (Suriname), the National Zoological Collection Suriname and the National History Museum Leiden (the Netherlands) is provided. Additionally, the results of several years of opportunistic collection in two domestic environments are presented. The most common species are Rhodnius pictipes Stål, 1972, Rhodnius robustus Larrouse, 1972 and Panstrongylus geniculatus (Latreille, 1811). The significance of the species as vectors of Chagas disease in Suriname is discussed. PMID:25004146

  18. Distantiae Transmission of Trypanosoma cruzi: A New Epidemiological Feature of Acute Chagas Disease in Brazil

    PubMed Central

    Xavier, Samanta Cristina das Chagas; Roque, André Luiz Rodrigues; Bilac, Daniele; de Araújo, Vitor Antônio Louzada; Neto, Sócrates Fraga da Costa; Lorosa, Elias Seixas; da Silva, Luiz Felipe Coutinho Ferreira; Jansen, Ana Maria

    2014-01-01

    Background The new epidemiological scenario of orally transmitted Chagas disease that has emerged in Brazil, and mainly in the Amazon region, needs to be addressed with a new and systematic focus. Belém, the capital of Pará state, reports the highest number of acute Chagas disease (ACD) cases associated with the consumption of açaí juice. Methodology/Principal Findings The wild and domestic enzootic transmission cycles of Trypanosoma cruzi were evaluated in the two locations (Jurunas and Val-de Cães) that report the majority of the autochthonous cases of ACD in Belém city. Moreover, we evaluated the enzootic cycle on the three islands that provide most of the açaí fruit that is consumed in these localities. We employed parasitological and serological tests throughout to evaluate infectivity competence and exposure to T. cruzi. In Val-de-Cães, no wild mammal presented positive parasitological tests, and 56% seroprevalence was observed, with low serological titers. Three of 14 triatomines were found to be infected (TcI). This unexpected epidemiological picture does not explain the high number of autochthonous ACD cases. In Jurunas, the cases of ACD could not be autochthonous because of the absence of any enzootic cycle of T. cruzi. In contrast, in the 3 island areas from which the açaí fruit originates, 66.7% of wild mammals and two dogs displayed positive hemocultures, and 15.6% of triatomines were found to be infected by T. cruzi. Genotyping by mini-exon gene and PCR-RFLP (1f8/Akw21I) targeting revealed that the mammals and triatomines from the islands harbored TcI and Trypanosoma rangeli in single and mixed infections. Conclusion/Significance These findings show that cases of Chagas disease in the urban area of Belém may be derived from infected triatomines coming together with the açaí fruits from distant islands. We term this new epidemiological feature of Chagas disease as “Distantiae transmission”. PMID:24854494

  19. Protective Human Leucocyte Antigen Haplotype, HLA-DRB1*01-B*14, against Chronic Chagas Disease in Bolivia

    PubMed Central

    del Puerto, Florencia; Nishizawa, Juan Eiki; Kikuchi, Mihoko; Roca, Yelin; Avilas, Cinthia; Gianella, Alberto; Lora, Javier; Velarde, Freddy Udalrico Gutierrez; Miura, Sachio; Komiya, Norihiro; Maemura, Koji; Hirayama, Kenji

    2012-01-01

    Background Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease. Conclusions This is the first report of HLA haplotype association with resistance to chronic Chagas disease. PMID:22448298

  20. Impact of Helminth Infection on the Clinical and Microbiological Presentation of Chagas Diseases in Chronically Infected Patients

    PubMed Central

    Salvador, Fernando; Sulleiro, Elena; Sánchez-Montalvá, Adrián; Martínez-Gallo, Mónica; Carrillo, Eugenia; Molina, Israel

    2016-01-01

    Abstract Background Helminth infections are highly prevalent in tropical and subtropical countries, coexisting in Chagas disease endemic areas. Helminth infections in humans may modulate the host immune system, changing the Th1/Th2 polarization. This immunological disturbance could modify the immune response to other infections. The aim of this study is to evaluate the relationship between clinical, microbiological and epidemiological characteristics of Chagas disease patients, with the presence of helminth infection. Methods A prospective observational study was conducted at Vall d’Hebron University Hospital (Barcelona, Spain). Inclusion criteria were: age over 18 years, diagnosis of Chagas disease, and not having received specific treatment for Chagas disease previously to the inclusion. The study protocol included Chagas disease assessment (cardiac and digestive evaluation, detection of T. cruzi DNA measured by PCR in peripheral blood), and helminth infection diagnosis (detection of IgG anti-Strongyloides stercoralis by ELISA, microscopic examination of stool samples from three different days, and specific faecal culture for S. stercoralis larvae). Results Overall, 65 patients were included, median age was 38 years, 75.4% were women and most of them came from Bolivia. Cardiac and digestive involvement was present in 18.5% and 27.7% of patients respectively. T. cruzi PCR was positive in 28 (43.1%) patients. Helminth infection was diagnosed in 12 (18.5%) patients. No differences were observed in clinical and epidemiological characteristics between patients with and without helminth infection. Nevertheless, the proportion of patients with positive T. cruzi PCR was higher among patients with helminth infection compared with patients without helminth infection (75% vs 35.8%, p = 0.021). Conclusions We observed a high prevalence of S. stercoralis infection among chronic Chagas disease patients attended in our tropical medicine unit. Strongyloidiasis was associated

  1. Electrocardiographic and echocardiographic abnormalities in residents of rural Bolivian communities hyperendemic for Chagas disease

    PubMed Central

    Fernandez, Antonio B.; Nunes, Maria Carmo P.; Clark, Eva H.; Samuels, Aaron; Menacho, Silvio; Gomez, Jesus; Gutierrez, Ricardo W. Bozo; Crawford, Thomas C.; Gilman, Robert H.; Bern, Caryn

    2015-01-01

    Background Chagas disease is a neglected and preventable tropical disease that causes significant cardiac morbidity and mortality in Latin America. Our objective in this study was to describe cardiac findings among inhabitants of rural communities of the Bolivian Chaco. Methods The cardiac study drew participants from an epidemiologic study in 7 indigenous Guarani communities. All infected participants 10 years or older were asked to undergo a brief physical examination and 12-lead electrocardiogram. A subset had echocardiograms (ECGs). ECGs and echocardiograms were read by one or more cardiologists. Results Of 1137 residents 10 years or older, 753 (66.2%) had T. cruzi infection. Cardiac evaluations were performed for 398 infected participants 10 years or older. Fifty-five (13.8%) participants had one or more ECG abnormality suggestive of Chagas cardiomyopathy. The most frequent abnormalities were bundle branch blocks in 42 (11.3%), followed by rhythm disturbances or ventricular ectopy in 13 (3.3%) and atrioventricular blocks (AVB) in 10 (2.6%) participants. The prevalence of any abnormality rose from 1.1% among those 10-19 years old to 14.2%, 17.3% and 26.4% among those 20-39, 40-59 and older than 60 years, respectively. First degree AVB was seen most frequently in participants 60 years or older, but the 4 patients with 3rd degree AVB were all under 50 years old. Eighteen and two participants had a left ventricular ejection fraction of 40-54% and <40%, respectively. An increasing number of ECG abnormalities was associated with progressively larger left ventricular end-diastolic dimensions and lower left ventricular ejection fraction. Conclusions We found a high prevalence of ECG abnormalities and substantial evidence of Chagas cardiomyopathy. Programs to improve access to basic cardiac care (annual ECGs, antiarrhythmics, pacemakers) could have an immediate impact on morbidity and mortality in these highly endemic communities. PMID:26407511

  2. Stairway to Heaven or Hell? Perspectives and Limitations of Chagas Disease Chemotherapy.

    PubMed

    Salomao, Kelly; Menna-Barreto, Rubem Figueiredo Sadok; de Castro, Solange Lisboa

    2016-01-01

    In this review, we intend to provide a general view of the evolution of experimental studies in the area of chemotherapy for Chagas disease. We can follow the process of drug development through three phases. The first phase began almost at the same time as the discovery made by Carlos Chagas and proceeds to 1970, during which time an extensive list of compounds was subjected to preclinical and clinical trials. The second phase began with the introduction of nifurtimox and benznidazole into the clinical setting, followed with the search for alternative drugs. In this phase, a dichotomy existed between rational and empirical approaches in preclinical studies. The third phase began with the unravelling of the T. cruzi genome. The development of transgenic parasites has allowed the development of solid HTS protocols, and the establishment of bioluminescent T. cruzi has allowed in vivo drug evaluations using a reduced number of animals. Among the wide variety of compounds subjected to preclinical studies, we have discovered azolic and non-azolic inhibitors of sterol C14α-demethylase (CYP51) and nitro compounds. Two compounds evaluated during the second phase, namely, MK-436 and allopurinol, could be revisited. Clinical studies of posaconazole and E1224 yielded disappointing results, and it is critical to understand the reason for their failure as a monotherapy. Currently, the combination and repositioning of drugs with different mechanisms of action are complementary approaches. The use of drug combinations, particularly those of nitro compounds with CYP51 inhibitors, is considered a real alternative for the treatment of Chagas disease. PMID:27072716

  3. Stairway to Heaven or Hell? Perspectives and Limitations of Chagas Disease Chemotherapy.

    PubMed

    Salomao, Kelly; Menna-Barreto, Rubem Figueiredo Sadok; de Castro, Solange Lisboa

    2016-01-01

    In this review, we intend to provide a general view of the evolution of experimental studies in the area of chemotherapy for Chagas disease. We can follow the process of drug development through three phases. The first phase began almost at the same time as the discovery made by Carlos Chagas and proceeds to 1970, during which time an extensive list of compounds was subjected to preclinical and clinical trials. The second phase began with the introduction of nifurtimox and benznidazole into the clinical setting, followed with the search for alternative drugs. In this phase, a dichotomy existed between rational and empirical approaches in preclinical studies. The third phase began with the unravelling of the T. cruzi genome. The development of transgenic parasites has allowed the development of solid HTS protocols, and the establishment of bioluminescent T. cruzi has allowed in vivo drug evaluations using a reduced number of animals. Among the wide variety of compounds subjected to preclinical studies, we have discovered azolic and non-azolic inhibitors of sterol C14α-demethylase (CYP51) and nitro compounds. Two compounds evaluated during the second phase, namely, MK-436 and allopurinol, could be revisited. Clinical studies of posaconazole and E1224 yielded disappointing results, and it is critical to understand the reason for their failure as a monotherapy. Currently, the combination and repositioning of drugs with different mechanisms of action are complementary approaches. The use of drug combinations, particularly those of nitro compounds with CYP51 inhibitors, is considered a real alternative for the treatment of Chagas disease.

  4. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole.

    PubMed

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-03-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruzi quantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective.

  5. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole

    PubMed Central

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-01-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective. PMID:26982179

  6. Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease.

    PubMed

    Ayo, Christiane Maria; Reis, Pâmela Guimarães; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Oliveira, Camila de Freitas; de Araújo, Silvana Marques; de Oliveira Marques, Divina Seila; Sell, Ana Maria

    2015-05-01

    The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2+/2DL2-/C1+) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy-CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30-18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2+/2DL2-/KIR2DL3+/C1+ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy.

  7. [Seroprevalence of Chagas disease in 17 rural communities of "Monte Impenetrable", Chaco Province].

    PubMed

    Biancardi, Miguel A; Conca Moreno, Mónica; Torres, Natalia; Pepe, Carolina; Altcheh, Jaime; Freilij, Héctor

    2003-01-01

    In the month of July 1999 and 2000 we studied the presence of Trypanosoma cruzi antibodies in residents of 17 isolated rural communities of "Monte Impenetrable", in Chaco Province. This area has 3,000 km2 inhabited by about 3,000 person and presents all the conditions for the development of Chagas disease. A total of 344 blood samples were analysed for Chagas disease. All samples, stored with SEROKIT, were tested with indirect hemagglutination test, enzyme-linked immunosorbent assay and particle agglutination test. Samples reactive for two assays were considered positive. Serological evidence of human T. cruzi infection was demonstrated in 183 (53.50%) out of 344 individuals. In the 1-15 years age group the percentage of positivity was 45.83% and in the 1-5 years age group 53.85%. a) General infection prevalence in these rural communities was 7 times higher than the national average estimated rate (7.20%). b) Prevalence in the 1-15 years age group was 25 times higher in relation to that found in residents of rural areas under entomology vigilance (1.77%). c) The prevalence in younger than five years old indicated the absence of vectorial control. The Tobas communities presented higher prevalence than Criollos, although the risk factors to acquire the disease were similar in both populational groups. These findings show the urgency of public health policies and sanitary decisions, specially in these zones of the country. PMID:12793080

  8. Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America

    PubMed Central

    Franco-Paredes, Carlos; Von, Anna; Hidron, Alicia; Rodríguez-Morales, Alfonso J; Tellez, Ildefonso; Barragán, Maribel; Jones, Danielle; Náquira, Cesar G; Mendez, Jorge

    2007-01-01

    Background Achieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals. Discussion Health-related Millennium Development Goals need to incorporate a multidimensional approach addressing the specific epidemiologic profile for each region of the globe. In this regard, addressing the cycle of destitution and suffering associated with infection with Trypanosoma cruzi, the causal agent of Chagas disease of American trypanosomiasis, will play a key role to enable the most impoverished populations in Latin America the opportunity to achieve their full potential. Most cases of Chagas disease occur among forgotten populations because these diseases persist exclusively in the poorest and the most marginalized communities in Latin America. Summary Addressing the cycle of destitution and suffering associated with T. cruzi infection will contribute to improve the health of the most impoverished populations in Latin America and will ultimately grant them with the opportunity to achieve their full economic potential. PMID:17725836

  9. Parasite prolyl oligopeptidases and the challenge of designing chemotherapeuticals for Chagas disease, leishmaniasis and African trypanosomiasis.

    PubMed

    Bastos, I M D; Motta, F N; Grellier, P; Santana, J M

    2013-01-01

    The trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp. cause Chagas disease, leishmaniasis and human African trypanosomiasis, respectively. It is estimated that over 10 million people worldwide suffer from these neglected diseases, posing enormous social and economic problems in endemic areas. There are no vaccines to prevent these infections and chemotherapies are not adequate. This picture indicates that new chemotherapeutic agents must be developed to treat these illnesses. For this purpose, understanding the biology of the pathogenic trypanosomatid- host cell interface is fundamental for molecular and functional characterization of virulence factors that may be used as targets for the development of inhibitors to be used for effective chemotherapy. In this context, it is well known that proteases have crucial functions for both metabolism and infectivity of pathogens and are thus potential drug targets. In this regard, prolyl oligopeptidase and oligopeptidase B, both members of the S9 serine protease family, have been shown to play important roles in the interactions of pathogenic protozoa with their mammalian hosts and may thus be considered targets for drug design. This review aims to discuss structural and functional properties of these intriguing enzymes and their potential as targets for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis.

  10. Etanercept Induces Low QRS Voltage and Autonomic Dysfunction in Mice with Experimental Chagas Disease

    PubMed Central

    Rodríguez-Angulo, Héctor; García, Oscar; Castillo, Endher; Cardenas, Edward; Marques, Juan; Mijares, Alfredo

    2013-01-01

    Background Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagasic cardiomyopathy is characterized by disorders of autonomic regulation and action potential conduction in the acute and chronic phases of infection. Although tumor necrosis factor alpha (TNF-α) has been linked to cardiomyopathy in experimental models and in patients with Chagas disease, other reports suggest that TNF-α may exert anti-parasitic actions during the acute phase of infection. Objectives This study aimed to determine the effects of a soluble TNF-α blocker, etanercept, on electrocardiographic parameters in the acute phase of experimental infection with Trypanosoma cruzi. Methods Electrocardiograms were obtained from untreated infected mice and infected mice who were treated with etanercept 7 days after infection. ECG wave and heart rate variability parameters were determined using Chart for Windows. Results Etanercept treatment resulted in a low QRS voltage and decreased heart rate variability compared with no treatment. However, the treated mice exhibited a delay in the fall of the survival curve during the acute phase. Conclusion The results of this study suggest that although etanercept treatment promotes survival in mice infected with a virulent T. cruzi strain, TNF-α blockade generates a low voltage complex and autonomic dysfunction during the acute phase of infection. These findings indicate that mortality during the acute phase can be attributed to a systemic inflammatory response rather than cardiac dysfunction. PMID:23877744

  11. A decade of targets and patented drugs for chemotherapy of Chagas disease.

    PubMed

    Duschak, Vilma G

    2011-09-01

    Chagas disease, a parasitic infection typically spread by triatomine bugs, affects millions of people throughout Latin America. Current chemotherapy based on the nitroaromatic compounds, benzonidazole and nifurtimox provides unsatisfactory results and suffers from considerable side effects. Therefore, there is still an urgent need for new drugs to treat this neglected disease. During the last decade, the advances and understanding in the biology and biochemistry of Trypanosoma cruzi have allowed the identification of multiple new targets for Chagas' disease chemotherapy. Among the most promising targets for antiparasitic drugs are: cruzipain, the main cysteine protease of T. cruzi, essential for parasite survival and proliferation in mammalian host; ergosterol biosynthesis pathway; trypanothione synthesis and thiol-dependant redox metabolism. Specific enzymes of the glycolytic, pentose phosphate, polyisoprenoid (farnesylpyrophosphate synthase) and other particular biosynthetic pathways as well as enzymes from purine salvage (hypoxanthine-guanine phosphoribosyl-transferase, dihydrofolate reductase) have also been intensively studied in T. cruzi. In particular, trypanocidal agents that target the validated biochemical pathways of the parasite including cysteine proteinase inhibitors and inhibitors capable to block ergosterol biosynthesis are currently in the pipeline. Among the latter, posaconazole and ravuconazole, are planned to enter in clinical trials for trypanocidal chemotherapy in the near future. This review will summarize advances on antichagasic agents directed to specific parasite targets such as metabolic pathways or specific enzymes. Related patents filed and issued from 2000 to 2010 claiming inhibitors for specific parasite targets will be also discussed. Among them, the most represented were those related with cysteine proteinase inhibitors. PMID:21824073

  12. Coronary Microvascular Disease in Chronic Chagas Cardiomyopathy Including an Overview on History, Pathology, and Other Proposed Pathogenic Mechanisms

    PubMed Central

    Rossi, Marcos A.; Tanowitz, Herbert B.; Malvestio, Lygia M.; Celes, Mara R.; Campos, Erica C.; Blefari, Valdecir; Prado, Cibele M.

    2010-01-01

    This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease. PMID:20824217

  13. Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

    PubMed Central

    Dutra, Walderez Ornelas; Menezes, Cristiane Alves Silva; Villani, Fernanda Nobre Amaral; da Costa, Germano Carneiro; da Silveira, Alexandre Barcelos Morais; d’Ávila Reis, Débora; Gollob, Kenneth J

    2012-01-01

    Perhaps one of the most intriguing aspects of human Chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. While most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. Although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenesis of Chagas disease. It is clear that the host’s immune response is decisive in this process. While characteristics of the parasite influence the immune response, it is becoming evident that the host genetic background plays a fundamental role in the establishment of pathogenic versus protective responses. The involvement of three complex organisms, host, parasite and vector, is certainly one of the key aspects that calls for multidisciplinary approaches towards the understanding of Chagas disease. We believe that now, one hundred years after the discovery of Chagas disease, it is imperative to continue with highly interactive research in order to elucidate the immune response associated with disease evolution, which will be essential in designing prophylactic or therapeutic interventions. PMID:19753476

  14. [Epidemiological status of Chagas disease in the endemic area from Region II of Antofagasta].

    PubMed

    Cáceres, J; Burchard, L; Bahamonde, M I; Contreras, M C; García, A; Rojas, A; Schenone, H; Lorca, M

    1999-01-01

    During 1997 a seroepidemiological study on Chagas' disease was carried out in 18 localities of three provinces (Tocopilla, El Loa and Antofagasta) of Region II (20 degrees 56'-26 degrees South Lat.; 70 degrees 38'-67 degrees West Long.), in order to assess the impact of the control program against Triatoma infestans launched in 1988, based on insecticide spraying of dwellings. By means of ELISA and an indirect hemagglutination test for Chagas' disease blood samples from 1,034 children under 10 years of age were examined, arising a 0.5% (3 cases) positivity. Test resulted positive in 2 (0.9%) children from the locality of San Pedro de Atacama and 1 (0.4%) from Calama city, all in the age group 6-10 year-old. However, none of their dwellings were found infested with T. infestants. These results indicate that the control program has a good possibility to prevent new human infections. It is advisable to continue the seroepidemiological and entomological vigilance and remark the necessity of increasing the effort in the study of transmission through other routes, to adopt or reinforce the pertinent preventive measures.

  15. Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

    PubMed Central

    Campos, Michel Leandro; Rosa, Talita Atanazio; Padilha, Elias Carvalho; Alzate, Alejandro Henao; Rolim, Larissa Araújo; Rolim-Neto, Pedro José

    2016-01-01

    Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentration in vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease. PMID:26883698

  16. Diagnostic electrocardiography in epidemiological studies of Chagas' disease: multicenter evaluation of a standardized method.

    PubMed

    Lázzari, J O; Pereira, M; Antunes, C M; Guimarães, A; Moncayo, A; Chávez Domínguez, R; Hernández Pieretti, O; Macedo, V; Rassi, A; Maguire, J; Romero, A

    1998-11-01

    An electrocardiographic recording method with an associated reading guide, designed for epidemiological studies on Chagas' disease, was tested to assess its diagnostic reproducibility. Six cardiologists from five countries each read 100 electrocardiographic (ECG) tracings, including 30 from chronic chagasic patients, then reread them after an interval of 6 months. The readings were blind, with the tracings numbered randomly for the first reading and renumbered randomly for the second reading. The physicians, all experienced in interpreting ECGs from chagasic patients, followed printed instructions for reading the tracings. Reproducibility of the readings was evaluated using the kappa (kappa) index for concordance. The results showed a high degree of interobserver concordance with respect to the diagnosis of normal vs. abnormal tracings (kappa = 0.66; SE 0.02). While the interpretations of some categories of ECG abnormalities were highly reproducible, others, especially those having a low prevalence, showed lower levels of concordance. Intraobserver concordance was uniformly higher than interobserver concordance. The findings of this study justify the use by specialists of the recording of readings method proposed for epidemiological studies on Chagas' disease, but warrant caution in the interpretation of some categories of electrocardiographic alterations.

  17. Phenyl-alpha-tert-butyl nitrone reverses mitochondrial decay in acute Chagas' disease.

    PubMed

    Wen, Jian-Jun; Bhatia, Vandanajay; Popov, Vsevolod L; Garg, Nisha Jain

    2006-12-01

    In this study, we investigated the mechanism(s) of mitochondrial functional decline in acute Chagas' disease. Our data show a substantial decline in respiratory complex activities (39 to 58%) and ATP (38%) content in Trypanosoma cruzi-infected murine hearts compared with normal controls. These metabolic alterations were associated with an approximately fivefold increase in mitochondrial reactive oxygen species production rate, substantial oxidative insult of mitochondrial membranes and respiratory complex subunits, and >60% inhibition of mtDNA-encoded transcripts for respiratory complex subunits in infected myocardium. The antioxidant phenyl-alpha-tert-butyl nitrone (PBN) arrested the oxidative damage-mediated loss in mitochondrial membrane integrity, preserved redox potential-coupled mitochondrial gene expression, and improved respiratory complex activities (47 to 95% increase) and cardiac ATP level (>or=40% increase) in infected myocardium. Importantly, PBN resulted twofold decline in mitochondrial reactive oxygen species production rate in infected myocardium. Taken together, our data demonstrate the pathological significance of oxidative stress in metabolic decay and energy homeostasis in acute chagasic myocarditis and further suggest that oxidative injuries affecting mitochondrial integrity-dependent expression and activity of the respiratory complexes initiate a feedback cycle of electron transport chain inefficiency, increased reactive oxygen species production, and energy homeostasis in acute chagasic hearts. PBN and other mitochondria-targeted antioxidants may be useful in altering mitochondrial decay and oxidative pathology in Chagas' disease.

  18. Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study.

    PubMed

    Davanço, Marcelo Gomes; Campos, Michel Leandro; Rosa, Talita Atanazio; Padilha, Elias Carvalho; Alzate, Alejandro Henao; Rolim, Larissa Araújo; Rolim-Neto, Pedro José; Peccinini, Rosângela Gonçalves

    2016-04-01

    Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease. PMID:26883698

  19. EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE

    PubMed Central

    MARIM, Ricardo Guimarães; de GUSMÃO, Alex Silva; CASTANHO, Roberto Esteves Pires; DEMINICE, Rafael; THEREZO, Altino Luiz Silva; JORDÃO, Alceu Afonso; de ASSIS, Marcos Renato; TAIPEIRO, Elane de Fátima; MARTINS, Luciamare Perinetti Alves

    2015-01-01

    Introduction: In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain. Methods: Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle. Results: Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever. Conclusion: Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory. PMID:26200966

  20. Do Brazilian scientific journals promote the adherence of Chagas disease researchers to international ethical principles?

    PubMed

    Malafaia, Guilherme; Guilhem, Dirce; Talvani, André

    2013-01-01

    The ethical aspects of the Brazilian publications about human Chagas disease (CD) developed between 1996 and 2010 and the policy adopted by Brazilian medical journals were analyzed. Articles were selected on the SciELO Brazil data basis, and the evaluation of ethical aspects was based on the normative contents about ethics in research involving human experimentation according to the Brazilian resolution of the National Health Council no. 196/1996. The editorial policies of the section "Instructions to authors" were analyzed. In the period of 1996-2012, 58.9% of articles involving human Chagas disease did not refer to the fulfillment of the ethical aspects concerning research with human beings. In 80% of the journals, the requirements and confirmation of the information about ethical aspects in the studies of human CD were not observed. Although a failure in this type of service is still observed, awareness has been raised in federal agencies, educational institutions/research and publishing groups to standardize the procedures and ethical requirements for the Brazilian journals, reinforcing the fulfillment of the ethical parameters, according to the resolution of NHC no. 196/1996.

  1. Impact of Chagas Disease in Bolivian Immigrants Living in Europe and the Risk of Stigmatization

    PubMed Central

    Ortí-Lucas, Rafael M.; Parada-Barba, María C.; de la Rubia-Ortí, José E.; Carrillo-Ruiz, Alejandra; Beso-Delgado, María; Boone, An L. D.

    2014-01-01

    Background. The prevalence of Chagas disease in endemic countries varies with the kind of vector involved and the socioeconomic conditions of the population of origin. Due to recent immigration it is an emerging public health problem in Europe, especially in those countries which receive immigrant populations with a high prevalence of carriers. The study reviews the impact of the disease on Bolivian immigrants living in Europe, the preventive measures and regulations applied in European countries, and their repercussion on possible stigmatization of certain population groups. Methods. The Bolivian immigrant population resident in 2012 was estimated and the affected population in different European countries was calculated with data on carrier prevalence that were recently published. The preventive measures and regulations available in Europe were also reviewed. MEDLINE-PubMed, GoPubMed, and Embase were consulted for the literature review. Results. The Bolivian immigrant population has the highest prevalence of Chagas carriers (6.7%–25%) compared to the overall Latin American population (1.3%–2.4%). Only in Spain, France, Belgium, UK, Portugal, Italy, Switzerland, The Netherlands, and Germany, preventive measures are applied to this population. The established regulations are insufficient and completely different criteria are applied in the different countries and this could reflect a certain degree of stigmatization. PMID:24719753

  2. Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

    PubMed

    Rodríguez-Angulo, H; Thomas, L E; Castillo, E; Cárdenas, E; Mogollón, F; Mijares, A

    2013-08-01

    Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase. PMID:23684908

  3. Current and developing therapeutic agents in the treatment of Chagas disease

    PubMed Central

    Apt, Werner

    2010-01-01

    Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF) and benznidazole (BNZ) are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30–60 days. Other useful drugs are itraconazole and posaconazole. The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished. At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease. In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole. PMID:20957215

  4. [Epidemiological status of Chagas disease in the endemic area from Region II of Antofagasta].

    PubMed

    Cáceres, J; Burchard, L; Bahamonde, M I; Contreras, M C; García, A; Rojas, A; Schenone, H; Lorca, M

    1999-01-01

    During 1997 a seroepidemiological study on Chagas' disease was carried out in 18 localities of three provinces (Tocopilla, El Loa and Antofagasta) of Region II (20 degrees 56'-26 degrees South Lat.; 70 degrees 38'-67 degrees West Long.), in order to assess the impact of the control program against Triatoma infestans launched in 1988, based on insecticide spraying of dwellings. By means of ELISA and an indirect hemagglutination test for Chagas' disease blood samples from 1,034 children under 10 years of age were examined, arising a 0.5% (3 cases) positivity. Test resulted positive in 2 (0.9%) children from the locality of San Pedro de Atacama and 1 (0.4%) from Calama city, all in the age group 6-10 year-old. However, none of their dwellings were found infested with T. infestants. These results indicate that the control program has a good possibility to prevent new human infections. It is advisable to continue the seroepidemiological and entomological vigilance and remark the necessity of increasing the effort in the study of transmission through other routes, to adopt or reinforce the pertinent preventive measures. PMID:10488587

  5. Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas' Disease Treatment ▿

    PubMed Central

    Batista, Denise da Gama Jaén; Batista, Marcos Meuser; Oliveira, Gabriel Melo de; Amaral, Patrícia Borges do; Lannes-Vieira, Joseli; Britto, Constança Carvalho; Junqueira, Angela; Lima, Marli Maria; Romanha, Alvaro José; Sales Junior, Policarpo Ademar; Stephens, Chad E.; Boykin, David W.; Soeiro, Maria de Nazaré Correia

    2010-01-01

    Chagas' disease, a neglected tropical illness for which current therapy is unsatisfactory, is caused by the intracellular parasite Trypanosoma cruzi. The goal of this work is to investigate the in vitro and in vivo effects of the arylimidamide (AIA) DB766 against T. cruzi. This arylimidamide exhibits strong trypanocidal activity and excellent selectivity for bloodstream trypomastigotes and intracellular amastigotes (Y strain), giving IC50s (drug concentrations that reduce 50% of the number of the treated parasites) of 60 and 25 nM, respectively. DB766 also exerts striking effects upon different parasite stocks, including those naturally resistant to benznidazole, and displays higher activity in vitro than the reference drugs. By fluorescent and transmission electron microscopy analyses, we found that this AIA localizes in DNA-enriched compartments and induces considerable damage to the mitochondria. DB766 effectively reduces the parasite load in the blood and cardiac tissue and presents efficacy similar to that of benznidazole in mouse models of T. cruzi infection employing the Y and Colombian strains, using oral and intraperitoneal doses of up to 100 mg/kg/day that were given after the establishment of parasite infection. This AIA ameliorates electrocardiographic alterations, reduces hepatic and heart lesions induced by the infection, and provides 90 to 100% protection against mortality, which is similar to that provided by benznidazole. Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment. PMID:20457822

  6. Bacterial symbiosis and paratransgenic control of vector-borne Chagas disease.

    PubMed

    Beard, C B; Dotson, E M; Pennington, P M; Eichler, S; Cordon-Rosales, C; Durvasula, R V

    2001-05-01

    The triatomine vectors of Chagas disease are obligate haematophagous insects, feeding on vertebrate blood throughout their entire developmental cycle. As a result of obtaining their nutrition from a single food source, their diet is devoid of certain vitamins and nutrients. Consequently, these insects harbour populations of bacterial symbionts within their intestinal tract, which provide the required nutrients that are lacking from their diet. We have isolated and characterised symbiont cultures from various triatomine species and developed a method for genetically transforming them. We can then reintroduce them into their original host species, thereby producing stable paratransgenic insects in which we are able to express heterologous gene products. Using this methodology, we have generated paratransgenic Rhodnius prolixus that are refractory for infection with Trypanosoma cruzi. Two examples of potentially refractory genes are currently being expressed in paratransgenic insects. These include the insect immune peptide cecropin A and active single chain antibody fragments. We have also developed an approach that would allow introduction of genetically modified bacterial symbionts into natural populations of Chagas disease vectors. This approach utilises the coprophagic behaviour of these insects, which is the way in which the symbionts are transmitted among bug populations in nature. The production and ultimate release of transgenic or paratransgenic insects for public health applications is potentially very promising but also worthy of much careful consideration with respect to environmental, political, and human safety concerns.

  7. Evidence of Autochthonous Chagas Disease in Southeastern Texas

    PubMed Central

    Garcia, Melissa N.; Aguilar, David; Gorchakov, Rodion; Rossmann, Susan N.; Montgomery, Susan P.; Rivera, Hilda; Woc-Colburn, Laila; Hotez, Peter J.; Murray, Kristy O.

    2015-01-01

    Autochthonous transmission of Trypanosoma cruzi in the United States is rarely reported. Here, we describe five newly identified patients with autochthonously acquired infections from a small pilot study of positive blood donors in southeast Texas. Case-patients 1–4 were possibly infected near their residences, which were all in the same region ∼100 miles west of Houston. Case-patient 5 was a young male with considerable exposure from routine outdoor and camping activities associated with a youth civic organization. Only one of the five autochthonous case-patients received anti-parasitic treatment. Our findings suggest an unrecognized risk of human vector-borne transmission in southeast Texas. Education of physicians and public health officials is crucial for identifying the true disease burden and source of infection in Texas. PMID:25371187

  8. Evidence of autochthonous Chagas disease in southeastern Texas.

    PubMed

    Garcia, Melissa N; Aguilar, David; Gorchakov, Rodion; Rossmann, Susan N; Montgomery, Susan P; Rivera, Hilda; Woc-Colburn, Laila; Hotez, Peter J; Murray, Kristy O

    2015-02-01

    Autochthonous transmission of Trypanosoma cruzi in the United States is rarely reported. Here, we describe five newly identified patients with autochthonously acquired infections from a small pilot study of positive blood donors in southeast Texas. Case-patients 1-4 were possibly infected near their residences, which were all in the same region ∼100 miles west of Houston. Case-patient 5 was a young male with considerable exposure from routine outdoor and camping activities associated with a youth civic organization. Only one of the five autochthonous case-patients received anti-parasitic treatment. Our findings suggest an unrecognized risk of human vector-borne transmission in southeast Texas. Education of physicians and public health officials is crucial for identifying the true disease burden and source of infection in Texas.

  9. Correlation between infection rate of triatominies and Chagas Disease in Southwest of Bahia, Brazil: a warning sign?

    PubMed

    Silveira, Eliezer A DA; Ribeiro, Israel S; Amorim, Miguel S; Rocha, Dalva V; Coutinho, Helder S; Freitas, Leandro M DE; Tomazi, Laize; Silva, Robson A A DA

    2016-07-11

    Chagas disease, caused by the Trypanosoma cruzi, has a wide distribution in South America, and its main method of control is the elimination of triatomines. It is presented here the geographic distribution and the rate of natural infection by T. cruzi of triatomines collected and evaluated from 2008 to 2013 in southwest of Bahia. Triatomines were captured in the intradomiciliary and peridomiciliary areas of five cities located in the southwest of Bahia state, identified, and analyzed for the presence of trypanosomatids in their feces. During the study period the number of patients suspected for acute Chagas disease was recovered from the Notifiable Diseases Information System (SINAN). 8966 triatomines were captured and identified as belonging to eight species. Twenty-six presented themselves infected, being Triatoma sordida the most abundant and with the highest percentage of infection by T. cruzi. Tremedal was the city with the highest number of cases of acute Chagas' disease reported to SINAN. All cities showed triatomines infected with T. cruzi, so there is considerable risk of vectorial transmission of Chagas disease in the southwestern Bahia state, evidencing the need for vector transmission control programs and preventive surveillance measures.

  10. Correlation between infection rate of triatominies and Chagas Disease in Southwest of Bahia, Brazil: a warning sign?

    PubMed

    Silveira, Eliezer A DA; Ribeiro, Israel S; Amorim, Miguel S; Rocha, Dalva V; Coutinho, Helder S; Freitas, Leandro M DE; Tomazi, Laize; Silva, Robson A A DA

    2016-07-11

    Chagas disease, caused by the Trypanosoma cruzi, has a wide distribution in South America, and its main method of control is the elimination of triatomines. It is presented here the geographic distribution and the rate of natural infection by T. cruzi of triatomines collected and evaluated from 2008 to 2013 in southwest of Bahia. Triatomines were captured in the intradomiciliary and peridomiciliary areas of five cities located in the southwest of Bahia state, identified, and analyzed for the presence of trypanosomatids in their feces. During the study period the number of patients suspected for acute Chagas disease was recovered from the Notifiable Diseases Information System (SINAN). 8966 triatomines were captured and identified as belonging to eight species. Twenty-six presented themselves infected, being Triatoma sordida the most abundant and with the highest percentage of infection by T. cruzi. Tremedal was the city with the highest number of cases of acute Chagas' disease reported to SINAN. All cities showed triatomines infected with T. cruzi, so there is considerable risk of vectorial transmission of Chagas disease in the southwestern Bahia state, evidencing the need for vector transmission control programs and preventive surveillance measures. PMID:27411071

  11. Opportunities for Improved Chagas Disease Vector Control Based on Knowledge, Attitudes and Practices of Communities in the Yucatan Peninsula, Mexico

    PubMed Central

    Rosecrans, Kathryn; Cruz-Martin, Gabriela; King, Ashley; Dumonteil, Eric

    2014-01-01

    Background Chagas disease is a vector-borne parasitic disease of major public health importance. Current prevention efforts are based on triatomine vector control to reduce transmission to humans. Success of vector control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to improved vector control strategies in the Yucatan peninsula, Mexico. Methodology/principal findings We employed a sequence of qualitative and quantitative research methods to investigate knowledge, attitudes and practices surrounding Chagas disease, triatomines and vector control in three rural communities. Our combined data show that community members are well aware of triatomines and are knowledgeable about their habits. However, most have a limited understanding of the transmission dynamics and clinical manifestations of Chagas disease. While triatomine control is not a priority for community members, they frequently use domestic insecticide products including insecticide spray, mosquito coils and plug-in repellents. Families spend about $32 US per year on these products. Alternative methods such as yard cleaning and window screens are perceived as desirable and potentially more effective. Screens are nonetheless described as unaffordable, in spite of a cost comparable to the average annual spending on insecticide products. Conclusion/Significance Further education campaigns and possibly financing schemes may lead families to redirect their current vector control spending from insecticide products to window screens. Also, synergism with mosquito control efforts should be further explored to motivate community involvement and ensure sustainability of Chagas disease vector control. PMID:24676038

  12. Polymorphic Sites at the Immunoregulatory CTLA-4 Gene Are Associated with Chronic Chagas Disease and Its Clinical Manifestations

    PubMed Central

    Mendes-Junior, Celso T.; Dantas, Roberto O.; Pissetti, Cristina W.; Rodrigues Junior, Virmondes; Dellalibera-Joviliano, Renata; Marin-Neto, José A.; Gutierrez, Fredy R. S.; Moreau, Philippe; Silva, João S.; Donadi, Eduardo A.

    2013-01-01

    Background Chagas disease affects approximately 10 million people mainly in Latin America. The immune regulation by the host seems to be an essential factor for disease evolution, and immune system inhibitory molecules such as CTLA-4 and PD-1 favor the maintenance of peripheral tolerance. Considering that polymorphisms at the immunoregulatory CTLA-4 and PDCD1 genes may alter their inhibitory function, we investigated the association of alleles, genotypes and haplotypes of polymorphic sites observed at the CTLA-4 and PDCD1 genes with different clinical manifestations of chronic Chagas disease (indeterminate, cardiac, digestive and mixed). Methods The polymorphisms at the CTLA-4 (-1722T/C, -318C/T and +49A/G) and PDCD1 (PD-1.3G/A) genes were typed using TaqMan methodology in 277 chronic Chagas disease patients classified into four groups, according to clinical characteristics, and 326 non-infected controls. Results Our results showed that CTLA-4 -1722CC genotype (22%), -1722C allele (27%) and CTLA-4 TCG (8.6%), TCA (26%) and CCA (15%) haplotypes were strongly associated with the indeterminate form, while the CTLA-4 -318CT genotype (82%) and CTLA-4 -318T allele (47%) were found mainly in patients with the mixed form of the disease. The CTLA-4 TCG haplotype (10.2%) was associated with the digestive form. On the other hand, the PD-1.3G/A polymorphism was not associated with chronic Chagas disease and its clinical manifestations. Conclusions Here, we showed that alleles, genotypes and haplotypes reported to increase the expression of the regulatory molecule CTLA-4 were associated with the indeterminate form of the disease. Taken together, our data support the idea that polymorphic sites at immunoregulatory genes may influence the development of Chagas disease variants. PMID:24205212

  13. Regulatory T Cells Phenotype in Different Clinical Forms of Chagas' Disease

    PubMed Central

    Teixeira-Carvalho, Andréa; Renato Zuquim Antas, Paulo; Assis Silva Gomes, Juliana; Sathler-Avelar, Renato; Otávio Costa Rocha, Manoel; Elói-Santos, Silvana Maria; Pinho, Rosa Teixeira; Correa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis

    2011-01-01

    CD25High CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In this review, we summarize data obtained by the investigation of Treg cells in different clinical forms of Chagas' disease. Ex vivo immunophenotyping of whole blood, as well as after stimulation with Trypanosoma cruzi antigens, demonstrated that individuals in the indeterminate (IND) clinical form of the disease have a higher frequency of Treg cells, suggesting that an expansion of those cells could be beneficial, possibly by limiting strong cytotoxic activity and tissue damage. Additional analysis demonstrated an activated status of Treg cells based on low expression of CD62L and high expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. cruzi antigenic stimulation. Moreover, there was an increase in the frequency of the population of Foxp3+ CD25HighCD4+ cells that was also IL-10+ in the IND group, whereas in the cardiac (CARD) group, there was an increase in the percentage of Foxp3+ CD25High CD4+ cells that expressed CTLA-4. These data suggest that IL-10 produced by Treg cells is effective in controlling disease development in IND patients. However, in CARD patients, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient to control the progression of the disease. These data suggest that Treg cells may play an important role in controlling the immune response in Chagas' disease and the balance between regulatory and effector T cells may be important for the progression and development of the disease. Additional detailed analysis of the mechanisms on how these cells are activated and exert their function will certainly give insights for the rational design of procedure to achieve the appropriate balance between protection and pathology during parasite

  14. Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries.

    PubMed

    Moncayo, Alvaro

    2003-07-01

    Chagas disease, named after Carlos Chagas who first described it in 1909, exists only on the American Continent. It is caused by a parasite, Trypanosoma cruzi, transmitted to humans by blood-sucking triatomine bugs and by blood transfusion. Chagas disease has two successive phases, acute and chronic. The acute phase lasts 6 to 8 weeks. After several years of starting the chronic phase, 20% to 35% of the infected individuals, depending on the geographical area will develop irreversible lesions of the autonomous nervous system in the heart, esophagus, colon and the peripheral nervous system. Data on the prevalence and distribution of Chagas disease improved in quality during the 1980's as a result of the demographically representative cross-sectional studies carried out in countries where accurate information was not available. A group of experts met in Bras lia in 1979 and devised standard protocols to carry out countrywide prevalence studies on human T. cruzi infection and triatomine house infestation. Thanks to a coordinated multi-country program in the Southern Cone countries the transmission of Chagas disease by vectors and by blood transfusion has been interrupted in Uruguay in1997, in Chile in 1999, and in 8 of the 12 endemic states of Brazil in 2000 and so the incidence of new infections by T. cruzi in the whole continent has decreased by 70%. Similar control multi-country initiatives have been launched in the Andean countries and in Central America and rapid progress has been recorded to ensure the interruption of the transmission of Chagas disease by 2005 as requested by a Resolution of the World Health Assembly approved in 1998. The cost-benefit analysis of the investments of the vector control program in Brazil indicate that there are savings of US$17 in medical care and disabilities for each dollar spent on prevention, showing that the program is a health investment with good return. Since the inception in 1979 of the Steering Committee on Chagas Disease

  15. Chemokine receptor CCR5 polymorphisms and Chagas' disease cardiomyopathy.

    PubMed

    Calzada, J E; Nieto, A; Beraún, Y; Martín, J

    2001-09-01

    In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Delta32 deletion and CCR5 59029 A-->G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Delta32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029-A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10-0.94). In addition, the presence of the CCR5 59029-G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12-0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.

  16. [Risk of Chagas disease through transfusions in the Americans].

    PubMed

    Schmuñis, G A

    1999-01-01

    . In absolute numbers, the highest potential for occurrence of cases of T. cruzi infection were present in Bolivia, the greatest number of HVC cases in Colombia, and the most cases of HVB in Nicaragua. Only in two countries, Bolivia and Colombia, HIV could be potentially transmitted by blood transfusion. Although the situation has improved since 1993, and 100% of donors are being screened for T. cruzi in Argentina, Colombia, Ecuador, El Salvador, Honduras, Paraguay, Uruguay and Venezuela, success will only be assured by: total enforcement of the law by governments; implementation of altruistic and volunteer blood donations, exclusively; 100% of donors are screened for communicable diseases; the collection, processing and use of blood strictly follow quality control norms; reagents used in diagnosis are adequate, and the use of blood and blood derivatives is limited to cases where it is only absolutely necessary. PMID:10668254

  17. The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease.

    PubMed

    Marin-Neto, J Antonio; Rassi, Anis; Avezum, Alvaro; Mattos, Antonio C; Rassi, Anis; Morillo, Carlos A; Sosa-Estani, Sergio; Yusuf, Salim

    2009-07-01

    Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project--Benznidazole Evaluation for Interrupting Trypanosomiasis--is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease. PMID:19753491

  18. Aptamer-based detection of disease biomarkers in mouse models for chagas drug discovery.

    PubMed

    de Araujo, Fernanda Fortes; Nagarkatti, Rana; Gupta, Charu; Marino, Ana Paula; Debrabant, Alain

    2015-01-01

    Drug discovery initiatives, aimed at Chagas treatment, have been hampered by the lack of standardized drug screening protocols and the absence of simple pre-clinical assays to evaluate treatment efficacy in animal models. In this study, we used a simple Enzyme Linked Aptamer (ELA) assay to detect T. cruzi biomarker in blood and validate murine drug discovery models of Chagas disease. In two mice models, Apt-29 ELA assay demonstrated that biomarker levels were significantly higher in the infected group compared to the control group, and upon Benznidazole treatment, their levels reduced. However, biomarker levels in the infected treated group did not reduce to those seen in the non-infected treated group, with 100% of the mice above the assay cutoff, suggesting that parasitemia was reduced but cure was not achieved. The ELA assay was capable of detecting circulating biomarkers in mice infected with various strains of T. cruzi parasites. Our results showed that the ELA assay could detect residual parasitemia in treated mice by providing an overall picture of the infection in the host. They suggest that the ELA assay can be used in drug discovery applications to assess treatment efficacy in-vivo.

  19. Geographic Distribution of Chagas Disease Vectors in Brazil Based on Ecological Niche Modeling

    PubMed Central

    Gurgel-Gonçalves, Rodrigo; Galvão, Cléber; Costa, Jane; Peterson, A. Townsend

    2012-01-01

    Although Brazil was declared free from Chagas disease transmission by the domestic vector Triatoma infestans, human acute cases are still being registered based on transmission by native triatomine species. For a better understanding of transmission risk, the geographic distribution of Brazilian triatomines was analyzed. Sixteen out of 62 Brazilian species that both occur in >20 municipalities and present synanthropic tendencies were modeled based on their ecological niches. Panstrongylus geniculatus and P. megistus showed broad ecological ranges, but most of the species sort out by the biome in which they are distributed: Rhodnius pictipes and R. robustus in the Amazon; R. neglectus, Triatoma sordida, and T. costalimai in the Cerrado; R. nasutus, P. lutzi, T. brasiliensis, T. pseudomaculata, T. melanocephala, and T. petrocchiae in the Caatinga; T. rubrovaria in the southern pampas; T. tibiamaculata and T. vitticeps in the Atlantic Forest. Although most occurrences were recorded in open areas (Cerrado and Caatinga), our results show that all environmental conditions in the country are favorable to one or more of the species analyzed, such that almost nowhere is Chagas transmission risk negligible. PMID:22523500

  20. Genetic variants in the chemokines and chemokine receptors in Chagas disease.

    PubMed

    Flórez, Oscar; Martín, Javier; González, Clara Isabel

    2012-08-01

    Clinical symptoms of Chagas' disease occur in 30% of the individuals infected with Trypanosoma cruzi and are characterised by heart inflammation and dysfunction. Chemokines and chemokine receptors control the migration of leukocytes during the inflammatory process and are involved in the modulation of Th1 or Th2 responses. To determine their influence, we investigated the possible role of CCL5/RANTES and CXCL8/IL8 chemokines, and CCR2 and CCR5 chemokines receptors cluster gene polymorphisms with the development of chagasic cardiomyopathy. Our study included 260 Chagas seropositive individuals (asymptomatic, n=130; cardiomyopathic, n=130) from an endemic area of Colombia. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP genotyping assay. We found statistically significant differences in the distribution of the CCR5 human haplogroup (HH)-A (p=0.027; OR=3.78, 95% CI=1.04-13.72). Moreover, we found that the CCR5-2733 G and CCR5-2554 T alleles are associated, respectively, with a reduced risk of susceptibility and severity to develop chagasic cardiomyopathy. No other associations were found to be significant for the other polymorphisms analysed in the CCR5, CCR2, CCL5/RANTES and CXCL8/IL8 genes. Our data suggest that the analysed chemokines and chemokine receptor genetic variants have a weak but important association with the development of chagasic cardiomyopathy in the population under study.

  1. Aspirin Treatment of Mice Infected with Trypanosoma cruzi and Implications for the Pathogenesis of Chagas Disease

    PubMed Central

    Mukherjee, Shankar; Machado, Fabiana S.; Huang, Huang; Oz, Helieh S.; Jelicks, Linda A.; Prado, Cibele M.; Koba, Wade; Fine, Eugene J.; Zhao, Dazhi; Factor, Stephen M.; Collado, J. Elias; Weiss, Louis M.

    2011-01-01

    Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected mice. To distinguish the effects of ASA on the parasite and host bio-synthetic pathways we infected cyclooxygenase-1 (COX-1) null mice with the Brazil-strain of T. cruzi. Infected COX-1 null mice displayed a reduction in circulating levels of thromboxane (TX)A2 and prostaglandin (PG)F2α. Parasitemia was increased in COX-1 null mice compared with parasitemia and mortality in ASA-treated infected mice indicating the effects of ASA on mortality potentially had little to do with inhibition of prostaglandin metabolism. Expression of SOCS-2 was enhanced, and TRAF6 and TNFα reduced, in the spleens of infected ASA-treated mice. Ablation of the initial innate response to infection may cause the increased mortality in ASA-treated mice as the host likely succumbs more quickly without the initiation of the “cytokine storm” during acute infection. We conclude that ASA, through both COX inhibition and other “off-target” effects, modulates the progression of acute and chronic Chagas disease. Thus, eicosanoids present during acute infection may act as immunomodulators aiding the transition to and maintenance of the chronic phase of the disease. A deeper understanding of the mechanism of ASA action may provide clues to the differences

  2. Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Medina, R.; Jugo, D.; Nunez, T. J.; Borrego, A.; Arellano, E.; Arenare, B.; DePalma, J. L.; Greco, E. C.; Starc, V.

    2007-01-01

    Some individuals with Chagas disease develop right precordial lead ST segment elevation in response to an ajmaline challenge test, and the prevalence of right bundle branch block (RBBB) is also high in Chagas disease. Because these same electrocardiographic abnormalities occur in the Brugada syndrome, which involves genetically defective cardiac sodium channels, acquired damage to cardiac sodium channels may also occur in Chagas disease. We studied several conventional and advanced resting 12-lead/derived Frank-lead ECG parameters in 34 patients with Chagas -related heart disease (mean age 39 14 years) and in 34 age-/gender-matched healthy controls. All ECG recordings were of 5-10 min duration, obtained in the supine position using high fidelity hardware/software (CardioSoft, Houston, TX). Even after excluding those Chagas patients who had resting BBBs, tachycardia and/or pathologic arrhythmia (n=8), significant differences remained in multiple conventional and advanced ECG parameters between the Chagas and control groups (n=26/group), especially in their respective QT interval variability indices, maximal spatial QRS-T angles and low frequency HRV powers (p=0.0006, p=0.0015 and p=0.0314 respectively). In relation to the issue of potential damage to cardiac sodium channels, the Chagas patients had: 1) greater than or equal to twice the incidence of resting ST segment elevation in leads V1-V3 (n=10/26 vs. n=5/26) and of both leftward (n=5/26 versus n=0/26) and rightward (n=7/26 versus n=3/26) QRS axis deviation than controls; 2) significantly increased filtered (40-250 Hz) QRS interval durations (92.1 8.5 versus 85.3 plus or minus 9.0 ms, p=0.022) versus controls; and 3) significantly decreased QT and especially JT interval durations versus controls (QT interval: 387.5 plus or minus 26.4 versus 408.9 plus or minus 34.6 ms, p=0.013; JT interval: 290.5 plus or minus 26.3 versus 314.8 plus or minus 31.3 ms; p=0.0029). Heart rates and Bazett-corrected QTc/JTc intervals

  3. Antigenicity and Diagnostic Potential of Vaccine Candidates in Human Chagas Disease

    PubMed Central

    Gupta, Shivali; Wan, Xianxiu; Zago, Maria P.; Martinez Sellers, Valena C.; Silva, Trevor S.; Assiah, Dadjah; Dhiman, Monisha; Nuñez, Sonia; Petersen, John R.; Vázquez-Chagoyán, Juan C.; Estrada-Franco, Jose G.; Garg, Nisha Jain

    2013-01-01

    Background Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease. Methods and Results Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1st-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2nd-phase for antibody response to the recombinant antigens (individually or mixed) by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n = 175). The IgG antibodies to TcG1, TcG2, and TcG4 (individually) and TcGmix were present in 62–71%, 65–78% and 72–82%, and 89–93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%), TcG2- (96%), TcG4- (94.6%) and TcGmix- (98%) based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8%) in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects. Conclusions Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations. PMID

  4. A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

    PubMed Central

    Hunter, Gabrielle C.; Borrini-Mayorí, Katty; Ancca Juárez, Jenny; Castillo Neyra, Ricardo; Verastegui, Manuela R.; Malaga Chavez, Fernando S.; Cornejo del Carpio, Juan Geny; Córdova Benzaquen, Eleazar; Náquira, César; Gilman, Robert H.; Bern, Caryn; Levy, Michael Z.

    2012-01-01

    Background Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment. Methods We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m) around seropositive individuals, and collected data on costs of implementation for each strategy. Results Infection was detected in 21 of 923 (2.28%) participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively). Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041), time lived in a rural location (OR 1.04; p = 0.022), and time lived in an infested area (OR 1.04; p = 0.008). No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others. Conclusions Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the epidemiology that

  5. FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO STATE, BRAZIL

    PubMed Central

    SANGENIS, Luiz Henrique Conde; DE SOUSA, Andréa Silvestre; SPERANDIO DA SILVA, Gilberto Marcelo; XAVIER, Sérgio Salles; MACHADO, Carolina Romero Cardoso; BRASIL, Patrícia; DE CASTRO, Liane; DA SILVA, Sidnei; GEORG, Ingebourg; SARAIVA, Roberto Magalhães; do BRASIL, Pedro Emmanuel Alvarenga Americano; HASSLOCHER-MORENO, Alejandro Marcel

    2015-01-01

    SUMMARY Chagas disease (CD) is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro. PMID:26422165

  6. Dendritic Cells: A Double-Edged Sword in Immune Responses during Chagas Disease.

    PubMed

    Gil-Jaramillo, Natalia; Motta, Flávia N; Favali, Cecília B F; Bastos, Izabela M D; Santana, Jaime M

    2016-01-01

    Dendritic cells (DCs) are the most important member of the antigen presenting cells group due to their ability to recognize antigen at the infection site and their high specialized antigen internalization capacity. These cells have central role in connecting the innate and adaptive immune responses against Trypanosoma cruzi, the causative agent of Chagas disease. These first line defense cells modulate host immune response depending on type, maturation level, cytokine milieu and DC receptor involved in the interactions with T. cruzi, influencing the development of the disease clinic forms. Here, we present a review of DCs-T. cruzi interactions both in human and murine models, pointing out the parasite ability to manipulate DCs activity for the purpose of evading innate immune response and assuring its own survival and persistence. PMID:27471496

  7. Dendritic Cells: A Double-Edged Sword in Immune Responses during Chagas Disease

    PubMed Central

    Gil-Jaramillo, Natalia; Motta, Flávia N.; Favali, Cecília B. F.; Bastos, Izabela M. D.; Santana, Jaime M.

    2016-01-01

    Dendritic cells (DCs) are the most important member of the antigen presenting cells group due to their ability to recognize antigen at the infection site and their high specialized antigen internalization capacity. These cells have central role in connecting the innate and adaptive immune responses against Trypanosoma cruzi, the causative agent of Chagas disease. These first line defense cells modulate host immune response depending on type, maturation level, cytokine milieu and DC receptor involved in the interactions with T. cruzi, influencing the development of the disease clinic forms. Here, we present a review of DCs–T. cruzi interactions both in human and murine models, pointing out the parasite ability to manipulate DCs activity for the purpose of evading innate immune response and assuring its own survival and persistence. PMID:27471496

  8. Successful Treatment with Posaconazole of a Patient with Chronic Chagas Disease and Systemic Lupus Erythematosus

    PubMed Central

    Pinazo, María-Jesús; Espinosa, Gerard; Gállego, Montserrat; López-Chejade, Paulo Luis; Urbina, Julio A.; Gascón, Joaquim

    2010-01-01

    American Trypanosomiasis or Chagas disease (CD) is a neglected disease that affects Latin American people worldwide. Two old antiparasitic drugs, benznidazole and nifurtimox, are currently used for specific CD treatment with limited efficacy in chronic infections and frequent side effects. New drugs are needed for patients with chronic CD as well as for immunosuppressed patients, for whom the risk of reactivation is life-threatening. We describe a case of chronic CD and systemic lupus erythematosus (SLE) that required immunosuppression to control the autoimmune process. It was found that benznidazole induced a reduction, but not an elimination, of circulating Trypanosoma cruzi levels, whereas subsequent treatment with posaconazole led to a successful resolution of the infection, despite the maintenance of immunosuppressive therapy. PMID:20348503

  9. Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease

    PubMed Central

    2013-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development. PMID:24304150

  10. Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological Confirmation of Chagas Disease

    PubMed Central

    Granjon, Elodie; Dichtel-Danjoy, Marie-Laure; Saba, Esber; Sabino, Ester; Campos de Oliveira, Lea; Zrein, Maan

    2016-01-01

    Background Chagas disease is due to the parasite Trypanosoma cruzi, a protist disseminated by a Triatome vector. This disease is endemic to Latin America and considered by WHO as one of the 17 world’s neglected diseases. In Europe and in North America, imported cases are also detected, due to migration of population outside of the endemic region. Diagnosis of T. cruzi infection is usually made indirectly by the detection of specific antibodies to T. cruzi antigens. Following initial diagnostic evaluation or screening test (qualifying or discarding blood donation), a confirmation test is performed for samples initially reactive. The test presented in this study aims at the confirmation/refutation of the infectious status of human blood samples and will permit taking appropriate clinical measures. Methodology/Principal Findings We designed a novel array of twelve antigens and printed these antigens onto 96-well plates. We tested 248 positive samples T. cruzi, 94 unscreened blood donors’ samples from non-endemic area, 49 seronegative blood donors, 7 false-positive and 3 doubtful samples. The observed reactivities were analyzed to propose a decision-tree algorithm that correctly classifies all the samples, with the potential to discriminate false-positive results and sticky samples. We observed that antibodies levels (Sum of all antigens) was significantly higher for PCR positive than for PCR negative samples in all studied groups with Multi-cruzi. Conclusion/Significance The results described in this study indicate that the Multi-cruzi improves the serological confirmation of Chagas disease. Moreover the “sum of all antigens” detected by Multi-cruzi could reflect parasitemia level in patients–like PCR signals does—and could serve as an indicator of parasite clearance in longitudinal follow-ups. Validation of this assay is still required on an independent large collection of well characterized samples including typical false-reactive samples such as

  11. Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic, Clinical, and Serological Evolution of Chagas Disease

    PubMed Central

    Fragata-Filho, Abilio Augusto; França, Francisco Faustino; Fragata, Claudia da Silva; Lourenço, Angela Maria; Faccini, Cristiane Castro; Costa, Cristiane Aparecida de Jesus

    2016-01-01

    Introduction Chagas disease is one of the most important endemic parasitic diseases in Latin America. In its chronic phase, progression to cardiomyopathy has high morbidity and mortality. The persistence of a normal electrocardiogram (ECG) provides a similar prognosis to that of a non-diseased population. Benznidazole (BNZ) is the only drug with trypanocidal action available in Brazil. Materials/Methods/Results A group of 310 patients with chronic Chagas disease who had normal ECGs at the first medical visit performed before 2002 were included. There were 263 patients treated with BNZ and 47 untreated. The follow-up period was 19.59 years. Univariate analyses showed that those treated were younger and predominantly male. As many as 79.08% of those treated and 46.81% of those untreated continued with normal electrocardiograms (p <0.0001). The occurrence of electrocardiographic abnormalities and relevant clinical events (heart failure, stroke, total mortality, and cardiovascular death) was less prevalent in treated patients (p <0.001, p: 0.022, p: 0.047 respectively). In multivariate analyses, the parasiticide treatment was an independent variable for persistence of a normal ECG pattern, which was an independent variable in the prevention of significant clinical events. The immunofluorescence titers decreased with the parasitological treatment. However, the small number of tests in untreated patients did not allow the correlation of the decrease of these titers with electrocardiographic alterations. Conclusion These data suggest that treatment with benznidazole prevents the occurrence of electrocardiographic alterations. On the other hand, patients who develop ECG abnormalities present with more significant clinical events. PMID:26974551

  12. Comparison of seven diagnostic tests to detect Trypanosoma cruzi infection in patients in chronic phase of Chagas disease

    PubMed Central

    Duarte, Luisa Fernanda; Flórez, Oscar; Rincón, Giovanna

    2014-01-01

    Objective: To compare the diagnostic performance of seven methods to determine Trypanosoma cruzi infection in patients with chronic Chagas disease. Methods: Analytical study, using the case-control design, which included 205 people (patients with Chagasic cardiomyopathy, n= 100; control group, n= 105). Three enzyme linked immunosorbent assays, one indirect hemagglutination assay and one immunochromatographic test were assessed. Additionally, DNA amplification was performed via the PCR method using kinetoplast and nuclear DNA as target sequences. For the comparative analysis of diagnostic tests, the parameters used were sensitivity, specificity, positive and negative predictive values, Receiver Operator Characteristic (ROC), positive and negative likelihood ratio, as well as κ quality analysis. Results: The commercial Bioelisa Chagas test showed the highest sensitivity (98%), specificity (100%), and positive and negative predictive values; ​​additionally, it had the highest discriminatory power. Otherwise, the amplification of T. cruzi DNA in blood samples showed low values of sensitivity (kinetoplast DNA = 51%, nuclear DNA = 22%), but high values of specificity (100%), and moderate to low discriminatory ability. Conclusion: The comparative analysis among the different methods suggests that the diagnostic strategy of T. cruzi infection in patients with chronic Chagas disease can be performed using ELISA assays based on recombinant proteins and/or synthetic peptides, which show higher diagnosis performance and can confirm and exclude the diagnosis of T. cruzi infection. The molecular methods show poor performance when used in the diagnosis of patients with chronic Chagas disease. PMID:25100890

  13. Chagas Disease

    MedlinePlus

    ... if they: ■ Have lived in rural areas of Mexico, Central America or South America, in countries such ... El Salvador, Ecuador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay or Venezuela ■ ...

  14. Immunoglobulin A antibodies to Trypanosoma cruzi antigens in digestive forms of Chagas' disease.

    PubMed Central

    Primavera, K S; Hoshino-Shimizu, S; Umezawa, E S; Peres, B A; Manigot, D A; Camargo, M E

    1988-01-01

    In an attempt to find a serological marker for the diagnosis of chronic digestive forms of Chagas' disease, we compared amastigote and trypomastigote antigens obtained from immunosuppressed mice infected with Trypanosoma cruzi (Y strain) with conventional epimastigote antigens to search for immunoglobulin A (IgA) antibodies. A total of 255 serum samples from patients with acute and chronic (indeterminate, digestive, and cardiac) forms of Chagas' disease and with nonchagasic diseases and from healthy individuals were studied. Amastigote antigens proved to be the most adequate for our purpose, since IgA antibodies could be detected in 23 of 25 serum samples from patients with digestive forms, with relative indices of sensitivity, specificity, and efficiency of 0.920, 0.911, and 0.912, respectively. These antigens also showed high reactivity with IgA antibodies, with a geometric mean titer of 16,635 (12.7 log2). IgA antibodies were detected in 16 of 28 serum samples from patients with the acute form as well, but this clinical form is easily distinguished from the chronic form by the demonstration of IgM antibodies. Poor results were seen with trypomastigote and epimastigote antigens. The finding of IgA antibodies in about 20% of indeterminate forms and 20% of cardiac forms, although in low titers, requires further investigation to ascertain their role as an early signal of gastrointestinal lesions. In addition, the amastigote antigens described here seem more convenient for use in endemic areas than those obtained from cell cultures because of their lower cost. PMID:3141458

  15. Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

    PubMed Central

    Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

    2014-01-01

    Background Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. Objective To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Methods Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. Results In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). Conclusion The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction. PMID:24553982

  16. Increased type 1 chemokine expression in experimental Chagas disease correlates with cardiac pathology in beagle dogs.

    PubMed

    Guedes, Paulo M M; Veloso, Vanja M; Talvani, André; Diniz, Livia F; Caldas, Ivo S; Do-Valle-Matta, Maria A; Santiago-Silva, Juliana; Chiari, Egler; Galvão, Lucia M C; Silva, João S; Bahia, Maria T

    2010-11-15

    Chemokines and chemokine receptors interaction have presented important role in leukocyte migration to specific immune reaction sites. Recently, it has been reported that chemokine receptors CXC (CXCR3) and CC (CCR5) were preferentially expressed on Th1 cells while CCR3 and CCR4 were preferentially expressed on Th2 cells. This study evaluated the mRNA expression of type 1 and type 2 chemokine and chemokine receptors in the cardiac tissue of Beagle dogs infected with distinct genetic groups of Trypanosoma cruzi (Y, Berenice-78 and ABC strains) during acute and chronic phases. To analyze the correlation between chemokine and chemokine receptors expression and the development of heart pathology, the chronic infected animals were divided into groups, according to the parasite strain and based on the degree of heart damage: cardiac and indeterminate form of Chagas disease. Our results indicated that cardiac type1/2 chemokines and their receptors were partially dependent on the genetic diversity of parasites as well as the polarization of clinical forms. Also, dogs presenting cardiac form showed lower heart tissue mRNA expression of CCL24 (type 2) and higher expression of CCL5, CCL4 and CXCR3 (type 1) when compared with those with indeterminate form of disease. Together, these data reinforce a close-relation between T. cruzi genetic population and the host specific type 1 immune response and, for the first time, we show the distribution of type 1/2 chemokines associated with the development of cardiac pathology using dogs, a well similar model to study human Chagas disease.

  17. Chagas' disease: an emergent urban zoonosis. The caracas valley (Venezuela) as an epidemiological model.

    PubMed

    Urdaneta-Morales, Servio

    2014-01-01

    The unprecedented emergence of important public health and veterinary zoonoses is usually a result of exponential population growth and globalization of human activities. I characterized Chagas' disease as an emergent zoonosis in the Caracas Valley (Venezuela) due to the following findings: the presence of reservoirs (Didelphis marsupialis, Rattus rattus) and vectors (Panstrongylus geniculatus, Panstrongylus rufotuberculatus) infected with Trypanosoma cruzi in urbanized or marginalized areas; the elevated contact between P. geniculatus and human beings detected by parasitological and molecular examinations of triatomine feces demonstrated the possibility of transmission risks; a study of outbreaks of urban Chagas' disease reported the first proven case of oral transmission of T. cruzi to human beings; the risk of transmission of glandular metacyclic stages from marsupials by experimental ocular and oral instillation; mice genitalia infected with T. cruzi contaminated blood resulted in the formation of amastigotes very close to the lumen suggesting that there may be a possibility of infection via their release into the urine and thence to the exterior; the ubiquitous histotropism and histopathology of T. cruzi was demonstrated using a mouse model; the presence of experimental T. cruzi pseudocysts in adipose, bone-cartilage, and eye tissue indicated a potential risk for transplants. Socio-sanitary programs that include improvements in housing, vector control, and access to medical treatment, as well as strategies aimed at combating social inequalities, poverty, and underdevelopment should be undertaken in those areas where zoonoses are most prevalent. Disciplines, such as Ecology, Epidemiology, Medical Entomology, Human and Veterinary Medicine, Environmental Studies, Public Health, Social and Political Studies, Immunology, Microbiology, and Pharmacology could all provide important contributions that aim to reduce the occurrence of factors governing the spread of

  18. Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease

    PubMed Central

    Messenger, Louisa A; Miles, Michael A; Bern, Caryn

    2015-01-01

    Over the last 30 years, concomitant with successful transnational disease control programs across Latin America, Chagas disease has expanded from a neglected, endemic parasitic infection of the rural poor to an urbanized chronic disease, and now a potentially emergent global health problem. Trypanosoma cruzi infection has a highly variable clinical course, ranging from complete absence of symptoms to severe and often fatal cardiovascular and/or gastrointestinal manifestations. To date, few correlates of clinical disease progression have been identified. Elucidating a putative role for T. cruzi strain diversity in Chagas disease pathogenesis is complicated by the scarcity of parasites in clinical specimens and the limitations of our contemporary genotyping techniques. This article systematically reviews the historical literature, given our current understanding of parasite genetic diversity, to evaluate the evidence for any association between T. cruzi genotype and chronic clinical outcome, risk of congenital transmission or reactivation and orally transmitted outbreaks. PMID:26162928

  19. Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease.

    PubMed

    Messenger, Louisa A; Miles, Michael A; Bern, Caryn

    2015-08-01

    Over the last 30 years, concomitant with successful transnational disease control programs across Latin America, Chagas disease has expanded from a neglected, endemic parasitic infection of the rural poor to an urbanized chronic disease, and now a potentially emergent global health problem. Trypanosoma cruzi infection has a highly variable clinical course, ranging from complete absence of symptoms to severe and often fatal cardiovascular and/or gastrointestinal manifestations. To date, few correlates of clinical disease progression have been identified. Elucidating a putative role for T. cruzi strain diversity in Chagas disease pathogenesis is complicated by the scarcity of parasites in clinical specimens and the limitations of our contemporary genotyping techniques. This article systematically reviews the historical literature, given our current understanding of parasite genetic diversity, to evaluate the evidence for any association between T. cruzi genotype and chronic clinical outcome, risk of congenital transmission or reactivation and orally transmitted outbreaks.

  20. A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera)

    PubMed Central

    Ribeiro, José M. C.; Schwarz, Alexandra; Francischetti, Ivo M. B.

    2015-01-01

    Saliva of blood-sucking arthropods contains a complex cocktail of pharmacologically active compounds that assists feeding by counteracting their hosts’ hemostatic and inflammatory reactions. Panstrongylus megistus (Burmeister) is an important vector of Chagas disease in South America, but despite its importance there is only one salivary protein sequence publicly deposited in GenBank. In the present work, we used Illumina technology to disclose and publicly deposit 3,703 coding sequences obtained from the assembly of >70 million reads. These sequences should assist proteomic experiments aimed at identifying pharmacologically active proteins and immunological markers of vector exposure. A supplemental file of the transcriptome and deducted protein sequences can be obtained from http://exon.niaid.nih.gov/transcriptome/P_megistus/Pmeg-web.xlsx. PMID:26334808

  1. A simple, biologically sound, and potentially useful working classification of Chagas disease vectors

    PubMed Central

    Abad-Franch, Fernando

    2016-01-01

    Current working classifications of Chagas disease vectors rely on a loose mix-up of biological and operational matters. They are therefore confusing and ineffective. I propose a very simple classification that makes biological sense and can be operationally useful. It considers a four-level hierarchy of species (which can be native or non-native); populations (either wild or non-wild); infestation foci (natural, domestic or peridomestic); and individual bugs (which can be solitary house-invaders or part of a hidden infestation focus). This classification translates into a clear, algorithmic scheme for triatomine control-surveillance that may be useful at every operationally relevant scale, from multi-country initiatives to on-site control-surveillance action. PMID:27759764

  2. A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera).

    PubMed

    Ribeiro, José M C; Schwarz, Alexandra; Francischetti, Ivo M B

    2015-05-01

    Saliva of blood-sucking arthropods contains a complex cocktail of pharmacologically active compounds that assists feeding by counteracting their hosts' hemostatic and inflammatory reactions. Panstrongylus megistus (Burmeister) is an important vector of Chagas disease in South America, but despite its importance there is only one salivary protein sequence publicly deposited in GenBank. In the present work, we used Illumina technology to disclose and publicly deposit 3,703 coding sequences obtained from the assembly of >70 million reads. These sequences should assist proteomic experiments aimed at identifying pharmacologically active proteins and immunological markers of vector exposure. A supplemental file of the transcriptome and deducted protein sequences can be obtained from http://exon.niaid.nih.gov/transcriptome/P_megistus/Pmeg-web.xlsx.

  3. Trypanosoma cruzi, the Causal Agent of Chagas Disease: Boundaries between Wild and Domestic Cycles in Venezuela

    PubMed Central

    Herrera, Leidi

    2014-01-01

    Trypanosoma cruzi the etiological agent of American Trypanosomiasis or Chagas disease (ChD) is transmitted by triatomines vectors between mammals including man. T. cruzi has existed for circa 150 Ma in the Americas and nearly 10 million people are currently infected. The overlap between wild and domestic ecotopes where T. cruzi circulates is increasing. Host–parasite interactions have been determined by infection patterns in these cycles, all under natural or laboratorial conditions. This mini-review describes specific parasite niches, such as plant communities or biological corridors between domestic and wild landscapes, in order to help identify risk factors for ChD and define the boundaries between wild and domestic transmission cycles, with an emphasis on research undertaken in Venezuela. PMID:25506587

  4. Human Trypanosomiasis in the Eastern Region of the Panama Province: New Endemic Areas for Chagas Disease

    PubMed Central

    Calzada, José E.; Pineda, Vanesa; Garisto, Juan D.; Samudio, Franklyn; Santamaria, Ana Maria; Saldaña, Azael

    2010-01-01

    The epidemiology of Chagas disease was studied in five rural communities located in the eastern region of the Panama Province. Serological tests for Trypanosoma cruzi infection revealed a prevalence of 5.88% (12/204). Hemocultures coupled with polymerase chain reaction (PCR) analysis showed a Trypanosoma rangeli infection rate of 5.88% (12/204). An overall trypanosome infection index of 11.76% (24/204) was detected in this population. A total of 121 triatomine specimens were collected in domestic and peridomestic habitats. Rhodnius pallescens was confirmed as the predominant species. Molecular analysis showed that 17.8% (13/73) of the examined insects were positive for T. cruzi, 17.8% (13/73) for T. rangeli, and 35.6% (26/73) presented mixed infections. Among 73 R. pallescens evaluated, 16.4% (12/73) contained opossum blood meals. The epidemiological implications of these findings are discussed. PMID:20348502

  5. Familial Analysis of Seropositivity to Trypanosoma cruzi and of Clinical Forms of Chagas Disease

    PubMed Central

    Silva-Grecco, Roseane L.; Balarin, Marly A. S.; Correia, Dalmo; Prata, Aluízio; Rodrigues, Virmondes

    2010-01-01

    A cross-sectional study was carried out in Água Comprida, MG, Brazil, a region previously endemic to Chagas disease whose vectorial transmission was interrupted around 20 year ago. A total of 998 individuals were examined for anti-Trypanosoma cruzi antibodies. Seropositivity was observed in 255 subjects (25.5%), and 743 subjects were negative. Forty-one families with 5–80 individuals with similar environmental conditions were selected for familial analysis. In 15 families, seropositivity to T. cruzi was observed in > 50% of individuals. The segregation analysis confirmed family aggregation for the seropositivity to the T. cruzi. Heart commitment was the major clinical form observed, and in six families, > 50% of the individuals display cardiopathy that may be attributed to T. cruzi infection. Our results support the hypothesis that there is a family aggregation for the seropositivity but without the effect of one major gene. PMID:20064994

  6. Lineage Analysis of Circulating Trypanosoma cruzi Parasites and Their Association with Clinical Forms of Chagas Disease in Bolivia

    PubMed Central

    del Puerto, Ramona; Nishizawa, Juan Eiki; Kikuchi, Mihoko; Iihoshi, Naomi; Roca, Yelin; Avilas, Cinthia; Gianella, Alberto; Lora, Javier; Gutierrez Velarde, Freddy Udalrico; Renjel, Luis Alberto; Miura, Sachio; Higo, Hiroo; Komiya, Norihiro; Maemura, Koji; Hirayama, Kenji

    2010-01-01

    Background The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. Methods and Findings Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease. Conclusions None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia. PMID:20502516

  7. Safety Profile of Nifurtimox and Treatment Interruption for Chronic Chagas Disease in Colombian Adults

    PubMed Central

    Olivera, Mario Javier; Cucunubá, Zulma M.; Álvarez, Carlos Arturo; Nicholls, Rubén Santiago

    2015-01-01

    Nifurtimox (NFX) is one of the approved drugs used to treat Chagas disease. Safety profile studies and models on risk factors for treatment interruption in adults are scarce in Latin America. This study evaluated retrospectively the medical records of adult Chagas disease patients treated with NFX between 2007 and 2012 in Bogotá, Colombia. An accelerated failure time model was used, and associations were expressed as time ratio (TR). In total, 76 adult patients with NFX were included: 60 (79.0%) completed 60 days of treatment, 61 (80.3%) presented adverse drug reactions (ADRs), and 16 (21.0%) required treatment interruption. The predominant symptoms were epigastric pain (23.7%), nauseas (18.4%), sleep disturbances (18.4%), loss of appetite (17.1%), and temporary loss of memory (15.2%). ADRs were classified as mild (64.5%), moderate (30.4%), and severe (5.1%). Time of treatment was significantly longer when presenting ≤ 3 ADRs (TR: 1.78; 95% CI: 1.04–3.03), presence of non-severe ADRs (TR: 6.52; 95% CI: 3.24–13.1), doses of NFX ≤ 8 mg/kg/day (TR: 1.78; 95% CI: 0.90–3.49), and age < 48 years (TR: 1.57; 95% CI: 0.90–2.74). Treatment with NFX in adults caused a high frequency of ADRs, but most of the cases were mild and did not require treatment interruption. Severity and number of ADRs were the main predictors for treatment interruption. PMID:26392162

  8. Epidemiology of and Impact of Insecticide Spraying on Chagas Disease in Communities in the Bolivian Chaco

    PubMed Central

    Galdos-Cardenas, Gerson; Wiegand, Ryan E.; Ferrufino, Lisbeth; Menacho, Silvio; Gil, Jose; Spicer, Jennifer; Budde, Julia; Levy, Michael Z.; Bozo, Ricardo W.; Gilman, Robert H.; Bern, Caryn

    2013-01-01

    Background Chagas disease control campaigns relying upon residual insecticide spraying have been successful in many Southern American countries. However, in some areas, rapid reinfestation and recrudescence of transmission have occurred. Methodology/Principal Findings We conducted a cross-sectional survey in the Bolivian Chaco to evaluate prevalence of and risk factors for T. cruzi infection 11 years after two rounds of blanket insecticide application. We used a cubic B-spline model to estimate change in force of infection over time based on age-specific seroprevalence data. Overall T. cruzi seroprevalence was 51.7%. The prevalence was 19.8% among children 2–15, 72.7% among those 15–30 and 97.1% among participants older than 30 years. Based on the model, the estimated annual force of infection was 4.3% over the two years before the first blanket spray in 2000 and fell to 0.4% for 2001–2002. The estimated annual force of infection for 2004–2005, the 2 year period following the second blanket spray, was 4.6%. However, the 95% bootstrap confidence intervals overlap for all of these estimates. In a multivariable model, only sleeping in a structure with cracks in the walls (aOR = 2.35; 95% CI = 1.15–4.78), age and village of residence were associated with infection. Conclusions/Significance As in other areas in the Chaco, we found an extremely high prevalence of Chagas disease. Despite evidence that blanket insecticide application in 2000 may have decreased the force of infection, active transmission is ongoing. Continued spraying vigilance, infestation surveillance, and systematic household improvements are necessary to disrupt and sustain interruption of infection transmission. PMID:23936581

  9. Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease.

    PubMed

    García, Mónica Cristina; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Manzo, Rubén Hilario; Jimenez-Kairuz, Alvaro Federico; Aoki, Maria Pilar

    2016-06-01

    Chagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the in vitro and in vivo anti-Trypanosoma cruzi effects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ. In vitro studies, carried out using a checkerboard technique on trypomastigotes (T. cruzi strain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety.

  10. Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response.

    PubMed

    Pinazo, Maria-Jesus; Posada, Elizabeth de Jesus; Izquierdo, Luis; Tassies, Dolors; Marques, Alexandre-Ferreira; de Lazzari, Elisa; Aldasoro, Edelweiss; Muñoz, Jose; Abras, Alba; Tebar, Silvia; Gallego, Montserrat; de Almeida, Igor Correia; Reverter, Joan-Carles; Gascon, Joaquim

    2016-01-01

    Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole. PMID:26727000

  11. Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease.

    PubMed

    García, Mónica Cristina; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Manzo, Rubén Hilario; Jimenez-Kairuz, Alvaro Federico; Aoki, Maria Pilar

    2016-06-01

    Chagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the in vitro and in vivo anti-Trypanosoma cruzi effects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ. In vitro studies, carried out using a checkerboard technique on trypomastigotes (T. cruzi strain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety. PMID:27067322

  12. Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response

    PubMed Central

    Pinazo, Maria-Jesus; Posada, Elizabeth de Jesus; Izquierdo, Luis; Tassies, Dolors; Marques, Alexandre-Ferreira; de Lazzari, Elisa; Aldasoro, Edelweiss; Muñoz, Jose; Abras, Alba; Tebar, Silvia; Gallego, Montserrat; de Almeida, Igor Correia; Reverter, Joan-Carles; Gascon, Joaquim

    2016-01-01

    Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole. PMID:26727000

  13. Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease

    PubMed Central

    Moretti, Nilmar Silvio; da Silva Augusto, Leonardo; Clemente, Tatiana Mordente; Antunes, Raysa Paes Pinto; Yoshida, Nobuko; Torrecilhas, Ana Claudia; Cano, Maria Isabel Nogueira

    2015-01-01

    Acetylation of lysine is a major posttranslational modification of proteins and is catalyzed by lysine acetyltransferases, while lysine deacetylases remove acetyl groups. Among the deacetylases, the sirtuins are NAD+-dependent enzymes, which modulate gene silencing, DNA damage repair, and several metabolic processes. As sirtuin-specific inhibitors have been proposed as drugs for inhibiting the proliferation of tumor cells, in this study, we investigated the role of these inhibitors in the growth and differentiation of Trypanosoma cruzi, the agent of Chagas disease. We found that the use of salermide during parasite infection prevented growth and initial multiplication after mammalian cell invasion by T. cruzi at concentrations that did not affect host cell viability. In addition, in vivo infection was partially controlled upon administration of salermide. There are two sirtuins in T. cruzi, TcSir2rp1 and TcSir2rp3. By using specific antibodies and cell lines overexpressing the tagged versions of these enzymes, we found that TcSir2rp1 is localized in the cytosol and TcSir2rp3 in the mitochondrion. TcSir2rp1 overexpression acts to impair parasite growth and differentiation, whereas the wild-type version of TcSir2rp3 and not an enzyme mutated in the active site improves both. The effects observed with TcSir2rp3 were fully reverted by adding salermide, which inhibited TcSir2rp3 expressed in Escherichia coli with a 50% inhibitory concentration (IC50) ± standard error of 1 ± 0.5 μM. We concluded that sirtuin inhibitors targeting TcSir2rp3 could be used in Chagas disease chemotherapy. PMID:26014945

  14. Safety Profile of Nifurtimox and Treatment Interruption for Chronic Chagas Disease in Colombian Adults.

    PubMed

    Olivera, Mario Javier; Cucunubá, Zulma M; Álvarez, Carlos Arturo; Nicholls, Rubén Santiago

    2015-12-01

    Nifurtimox (NFX) is one of the approved drugs used to treat Chagas disease. Safety profile studies and models on risk factors for treatment interruption in adults are scarce in Latin America. This study evaluated retrospectively the medical records of adult Chagas disease patients treated with NFX between 2007 and 2012 in Bogotá, Colombia. An accelerated failure time model was used, and associations were expressed as time ratio (TR). In total, 76 adult patients with NFX were included: 60 (79.0%) completed 60 days of treatment, 61 (80.3%) presented adverse drug reactions (ADRs), and 16 (21.0%) required treatment interruption. The predominant symptoms were epigastric pain (23.7%), nauseas (18.4%), sleep disturbances (18.4%), loss of appetite (17.1%), and temporary loss of memory (15.2%). ADRs were classified as mild (64.5%), moderate (30.4%), and severe (5.1%). Time of treatment was significantly longer when presenting ≤ 3 ADRs (TR: 1.78; 95% CI: 1.04-3.03), presence of non-severe ADRs (TR: 6.52; 95% CI: 3.24-13.1), doses of NFX ≤ 8 mg/kg/day (TR: 1.78; 95% CI: 0.90-3.49), and age < 48 years (TR: 1.57; 95% CI: 0.90-2.74). Treatment with NFX in adults caused a high frequency of ADRs, but most of the cases were mild and did not require treatment interruption. Severity and number of ADRs were the main predictors for treatment interruption. PMID:26392162

  15. Dynamics of Sylvatic Chagas Disease Vectors in Coastal Ecuador Is Driven by Changes in Land Cover

    PubMed Central

    Grijalva, Mario J.; Terán, David; Dangles, Olivier

    2014-01-01

    Background Chagas disease is a serious public health problem in Latin America where about ten million individuals show Trypanosoma cruzi infection. Despite significant success in controlling domiciliated triatomines, sylvatic populations frequently infest houses after insecticide treatment which hampers long term control prospects in vast geographical areas where vectorial transmission is endemic. As a key issue, the spatio-temporal dynamics of sylvatic populations is likely influenced by landscape yet evidence showing this effect is rare. The aim of this work is to examine the role of land cover changes in sylvatic triatomine ecology, based on an exhaustive field survey of pathogens, vectors, hosts, and microhabitat characteristics' dynamics. Methodology and Principal Findings The study was performed in agricultural landscapes of coastal Ecuador as a study model. Over one year, a spatially-randomized sampling design (490 collection points) allowed quantifying triatomine densities in natural, cultivated and domestic habitats. We also assessed infection of the bugs with trypanosomes, documented their microhabitats and potential hosts, and recorded changes in landscape characteristics. In total we collected 886 individuals, mainly represented by nymphal stages of one triatomine species Rhodnius ecuadoriensis. As main results, we found that 1) sylvatic triatomines had very high T. cruzi infection rates (71%) and 2) densities of T. cruzi-infected sylvatic triatomines varied predictably over time due to changes in land cover and occurrence of associated rodent hosts. Conclusion We propose a framework for identifying the factors affecting the yearly distribution of sylvatic T. cruzi vectors. Beyond providing key basic information for the control of human habitat colonization by sylvatic vector populations, our framework highlights the importance of both environmental and sociological factors in shaping the spatio-temporal population dynamics of triatomines. A better

  16. Treatment of Chagas Cardiomyopathy

    PubMed Central

    Botoni, Fernando A.; Ribeiro, Antonio Luiz P.; Marinho, Carolina Coimbra; Lima, Marcia Maria Oliveira; Nunes, Maria do Carmo Pereira; Rocha, Manoel Otávio C.

    2013-01-01

    Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities. PMID:24350293

  17. [Sword of Damocles or Russian roulette ... what everyone knows or ought to know about Chagas disease].

    PubMed

    Pays, J F

    2009-12-01

    In 2006 the Pan American Health Organisation (PAHO) roughly estimated the prevalence of Chagas disease or American Human Trypanosomiasis, due to Trypanosoma cruzi, still to be eight million cases. The migration of people from the country into towns has resulted, in recent decades, in the urbanisation of this rural disease. Up to the mid-20th century, the epidemiology of the disease was closely linked to the extreme poverty of the peasant population and to their housing, the rancho, which offers a suitable habitat for the vectors and encourages their proliferation. A further barrier has recently been crossed with the arrival in non-endemic areas of numerous seropositive individuals. We shall draw attention in this article to the main clinical signs and to the manner of progression of the disease as well as to the problems posed by treatment of the different phases of this unique condition. It is not fanciful to describe it as resembling an adventure story, because of the place and manner of its discovery and of how the disease unfolds.

  18. The importance of the multidisciplinary approach to deal with the new epidemiological scenario of Chagas disease (global health).

    PubMed

    Pinazo, Maria-Jesus; Gascon, Joaquim

    2015-11-01

    There are currently two major factors that have modified the epidemiology of Chagas disease in the last decades: climate change and migration flows. In this new scenario, there are new challenges to control and prevent Trypanosoma cruzi infection in endemic countries, such as the control of a wider distribution of triatomine vectors or the reinforcement of vertical transmission programs. In non-endemic areas, few countries are aware of the emergence of this new disease and have established changes in their health systems. To address this new public health challenge, the priorities should be control programs to avoid new cases of T. cruzi infection acquired through vertical transmission, blood transfusion or organ transplant. In both, endemic and non-endemic areas, the international community and all the actors involved in Chagas disease must join efforts mainly in two directions: better management of the infection in affected individuals and more research to cover the knowledge gap mainly in physiopathology, diagnosis and treatment.

  19. The importance of the multidisciplinary approach to deal with the new epidemiological scenario of Chagas disease (global health).

    PubMed

    Pinazo, Maria-Jesus; Gascon, Joaquim

    2015-11-01

    There are currently two major factors that have modified the epidemiology of Chagas disease in the last decades: climate change and migration flows. In this new scenario, there are new challenges to control and prevent Trypanosoma cruzi infection in endemic countries, such as the control of a wider distribution of triatomine vectors or the reinforcement of vertical transmission programs. In non-endemic areas, few countries are aware of the emergence of this new disease and have established changes in their health systems. To address this new public health challenge, the priorities should be control programs to avoid new cases of T. cruzi infection acquired through vertical transmission, blood transfusion or organ transplant. In both, endemic and non-endemic areas, the international community and all the actors involved in Chagas disease must join efforts mainly in two directions: better management of the infection in affected individuals and more research to cover the knowledge gap mainly in physiopathology, diagnosis and treatment. PMID:26187358

  20. Knowledge and experiences of Chagas disease in Bolivian women living in Spain: a qualitative study

    PubMed Central

    Blasco-Hernández, Teresa; Miguel, Lucía García-San; Navaza, Bárbara; Navarro, Miriam; Benito, Agustín

    2016-01-01

    Background In Europe, Spain has the highest number of people with Chagas disease (CD). Bolivian migrants account for 81% of the reported cases. One of the priorities in controlling the disease is prevention of mother-to-child transmission. Despite under-diagnosis in Spain being estimated at 90%, there are currently few studies that explore the social and cultural dimensions of this disease. Objective The aim of this study was to explore the knowledge and experiences of Bolivian women with CD, in order to generate a useful understanding for the design and implementation of public health initiatives. Design Qualitative study based on semi-structured interviews, triangular groups, and field notes. Participants Fourteen Bolivian women with CD living in Madrid. Results The participants were aware that the disease was transmitted through the vector, that it could be asymptomatic, and that it could also be associated with sudden death by heart failure. They opined that the treatment as such could not cure the disease but only slow it down. There was a sense of indifference along with a lack of understanding of the risk of contracting the disease. Participants who presented with symptoms, or those with relatives suffering from the disease, were concerned about fatalities, cardiac problems, and possible vertical transmission. There was also a fear of being rejected by others. The disease was described as something that affected a large number of people but only showed up in a few cases and that too after many years. There was a widespread assumption that it was better not to know because doing so, allows the disease to take hold. Conclusions Disease risk perception was very low in Bolivian women living in Madrid. This factor, together with the fear of being screened, may be contributing to the current rate of under-diagnosis. PMID:26976265

  1. Environmental and socio-economic risk modelling for Chagas disease in Bolivia.

    PubMed

    Mischler, Paula; Kearney, Michael; McCarroll, Jennifer C; Scholte, Ronaldo G C; Vounatsou, Penelope; Malone, John B

    2012-09-01

    Accurately defining disease distributions and calculating disease risk is an important step in the control and prevention of diseases. Geographical information systems (GIS) and remote sensing technologies, with maximum entropy (Maxent) ecological niche modelling computer software, were used to create predictive risk maps for Chagas disease in Bolivia. Prevalence rates were calculated from 2007 to 2009 household infection survey data for Bolivia, while environmental data were compiled from the Worldclim database and MODIS satellite imagery. Socio-economic data were obtained from the Bolivian National Institute of Statistics. Disease models identified altitudes at 500-3,500 m above the mean sea level (MSL), low annual precipitation (45-250 mm), and higher diurnal range of temperature (10-19 °C; peak 16 °C) as compatible with the biological requirements of the insect vectors. Socio-economic analyses demonstrated the importance of improved housing materials and water source. Home adobe wall materials and having to fetch drinking water from rivers or wells without pump were found to be highly related to distribution of the disease by the receiver operator characteristic (ROC) area under the curve (AUC) (0.69 AUC, 0.67 AUC and 0.62 AUC, respectively), while areas with hardwood floors demonstrated a direct negative relationship (-0.71 AUC). This study demonstrates that Maxent modelling can be used in disease prevalence and incidence studies to provide governmental agencies with an easily learned, understandable method to define areas as either high, moderate or low risk for the disease. This information may be used in resource planning, targeting and implementation. However, access to high-resolution, sub-municipality socio-economic data (e.g. census tracts) would facilitate elucidation of the relative influence of poverty-related factors on regional disease dynamics. PMID:23032284

  2. Environmental and socio-economic risk modelling for Chagas disease in Bolivia.

    PubMed

    Mischler, Paula; Kearney, Michael; McCarroll, Jennifer C; Scholte, Ronaldo G C; Vounatsou, Penelope; Malone, John B

    2012-09-01

    Accurately defining disease distributions and calculating disease risk is an important step in the control and prevention of diseases. Geographical information systems (GIS) and remote sensing technologies, with maximum entropy (Maxent) ecological niche modelling computer software, were used to create predictive risk maps for Chagas disease in Bolivia. Prevalence rates were calculated from 2007 to 2009 household infection survey data for Bolivia, while environmental data were compiled from the Worldclim database and MODIS satellite imagery. Socio-economic data were obtained from the Bolivian National Institute of Statistics. Disease models identified altitudes at 500-3,500 m above the mean sea level (MSL), low annual precipitation (45-250 mm), and higher diurnal range of temperature (10-19 °C; peak 16 °C) as compatible with the biological requirements of the insect vectors. Socio-economic analyses demonstrated the importance of improved housing materials and water source. Home adobe wall materials and having to fetch drinking water from rivers or wells without pump were found to be highly related to distribution of the disease by the receiver operator characteristic (ROC) area under the curve (AUC) (0.69 AUC, 0.67 AUC and 0.62 AUC, respectively), while areas with hardwood floors demonstrated a direct negative relationship (-0.71 AUC). This study demonstrates that Maxent modelling can be used in disease prevalence and incidence studies to provide governmental agencies with an easily learned, understandable method to define areas as either high, moderate or low risk for the disease. This information may be used in resource planning, targeting and implementation. However, access to high-resolution, sub-municipality socio-economic data (e.g. census tracts) would facilitate elucidation of the relative influence of poverty-related factors on regional disease dynamics.

  3. Chagas Disease among the Latin American Adult Population Attending in a Primary Care Center in Barcelona, Spain

    PubMed Central

    Roca, Carme; Pinazo, María Jesús; López-Chejade, Paolo; Bayó, Joan; Posada, Elizabeth; López-Solana, Jordi; Gállego, Montserrat; Portús, Montserrat; Gascón, Joaquim

    2011-01-01

    Background/Aims The epidemiology of Chagas disease, until recently confined to areas of continental Latin America, has undergone considerable changes in recent decades due to migration to other parts of the world, including Spain. We studied the prevalence of Chagas disease in Latin American patients treated at a health center in Barcelona and evaluated its clinical phase. We make some recommendations for screening for the disease. Methodology/Principal Findings We performed an observational, cross-sectional prevalence study by means of an immunochromatographic test screening of all continental Latin American patients over the age of 14 years visiting the health centre from October 2007 to October 2009. The diagnosis was confirmed by serological methods: conventional in-house ELISA (cELISA), a commercial kit (rELISA) and ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). Of 766 patients studied, 22 were diagnosed with T. cruzi infection, showing a prevalence of 2.87% (95% CI, 1.6–4.12%). Of the infected patients, 45.45% men and 54.55% women, 21 were from Bolivia, showing a prevalence in the Bolivian subgroup (n = 127) of 16.53% (95% CI, 9.6–23.39%). All the infected patients were in a chronic phase of Chagas disease: 81% with the indeterminate form, 9.5% with the cardiac form and 9.5% with the cardiodigestive form. All patients infected with T. cruzi had heard of Chagas disease in their country of origin, 82% knew someone affected, and 77% had a significant history of living in adobe houses in rural areas. Conclusions We found a high prevalence of T. cruzi infection in immigrants from Bolivia. Detection of T. cruzi–infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems. PMID:21572511

  4. Under-Expression of Chemosensory Genes in Domiciliary Bugs of the Chagas Disease Vector Triatoma brasiliensis

    PubMed Central

    Marchant, Axelle; Mougel, Florence; Jacquin-Joly, Emmanuelle; Costa, Jane; Almeida, Carlos Eduardo; Harry, Myriam

    2016-01-01

    Background In Latin America, the bloodsucking bugs Triatominae are vectors of Trypanosoma cruzi, the parasite that causes Chagas disease. Chemical elimination programs have been launched to control Chagas disease vectors. However, the disease persists because native vectors from sylvatic habitats are able to (re)colonize houses—a process called domiciliation. Triatoma brasiliensis is one example. Because the chemosensory system allows insects to interact with their environment and plays a key role in insect adaption, we conducted a descriptive and comparative study of the chemosensory transcriptome of T. brasiliensis samples from different ecotopes. Methodology/Principal Finding In a reference transcriptome built using de novo assembly, we found transcripts encoding 27 odorant-binding proteins (OBPs), 17 chemosensory proteins (CSPs), 3 odorant receptors (ORs), 5 transient receptor potential channel (TRPs), 1 sensory neuron membrane protein (SNMPs), 25 takeout proteins, 72 cytochrome P450s, 5 gluthatione S-transferases, and 49 cuticular proteins. Using protein phylogenies, we showed that most of the OBPs and CSPs for T. brasiliensis had well supported orthologs in the kissing bug Rhodnius prolixus. We also showed a higher number of these genes within the bloodsucking bugs and more generally within all Hemipterans compared to the other species in the super-order Paraneoptera. Using both DESeq2 and EdgeR software, we performed differential expression analyses between samples of T. brasiliensis, taking into account their environment (sylvatic, peridomiciliary and domiciliary) and sex. We also searched clusters of co-expressed contigs using HTSCluster. Among differentially expressed (DE) contigs, most were under-expressed in the chemosensory organs of the domiciliary bugs compared to the other samples and in females compared to males. We clearly identified DE genes that play a role in the chemosensory system. Conclusion/Significance Chemosensory genes could be good

  5. Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

    PubMed Central

    Morrot, Alexandre; Villar, Silvina R.; González, Florencia B.; Pérez, Ana R.

    2016-01-01

    Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease. PMID:27242726

  6. [Immunodiagnostic findings in sera of patients with leishmaniasis, Chagas' disease, malaria and amebiasis in endemic regions of Venezuela (author's transl)].

    PubMed

    Salfelder, A; Mannweiler, E

    1981-09-01

    66 serum samples from patients suffering from mucocutaneous leishmaniasis (20), Chagas' disease (12), malaria (16) or amebiasis (18) were collected and examined with five different protozoic antigens (L. donovani, T. cruzi, P. fieldi, P. falciparum, E. histolytica) by means of the indirect fluorescent antibody test, the complement fixation test, the indirect hemagglutination test and the latex agglutination. Cross-reactions were observed only between the sera from patients with leishmaniasis and Chagas' disease, both groups, however, showed stronger reactions with the homologous antigen. There were no cross-reactions among the other antigens and antibodies. The results obtained in this study together with facts already proved by literature show the usefulness of the employed antigens for epidemiological surveys. PMID:6285563

  7. [Consensus document for the detection and management of Chagas disease in primary health care in a non-endemic areas].

    PubMed

    Roca Saumell, Carme; Soriano-Arandes, Antoni; Solsona Díaz, Lluís; Gascón Brustenga, Joaquim

    2015-05-01

    Chagas disease is caused by the protozoan Trypanosoma cruzi. Although it is commonly transmitted by an insect vector in continental Latin-America, in recent decades, due migration, has been diagnosed in other countries such Spain, the European country with a largest immigrant population of Latin American. For a long time, the patient remains asymptomatic, but some years after this stage, the symptoms can be serious (dilated cardiomyopathy, megacolon, megaesophagus). In addition, detection in pregnant women has a high priority because of the route of vertical transmission. Several specific guidelines about Chagas disease has been developed on the Banks of blood, maternal hospitals, HIV co-infection, organ transplant. But due to the detection of lack of information to primary care professionals, we consider to will be useful this document written and agreed to by family phisicians, pediatricians and specialists in International Health.

  8. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole.

    PubMed

    Fernández, Marisa Liliana; Marson, Maria Elena; Ramirez, Juan Carlos; Mastrantonio, Guido; Schijman, Alejandro Gabriel; Altcheh, Jaime; Riarte, Adelina Rosa; Bournissen, Facundo García

    2016-03-01

    Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruzi quantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective. PMID:26982179

  9. Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country.

    PubMed

    González-Ramos, J; Noguera-Morel, L; Tong, H Y; Ramírez, E; Ruiz-Bravo, E; Bellón, T; Cabañas, R; Cachafeiro, L; Herranz-Pinto, P

    2016-09-01

    Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk. PMID:26851874

  10. Population structure of the Chagas disease vector Triatoma infestans in an urban environment.

    PubMed

    Khatchikian, Camilo E; Foley, Erica A; Barbu, Corentin M; Hwang, Josephine; Ancca-Juárez, Jenny; Borrini-Mayori, Katty; Quıspe-Machaca, Victor R; Naquira, Cesar; Brisson, Dustin; Levy, Michael Z

    2015-02-01

    Chagas disease is a vector-borne disease endemic in Latin America. Triatoma infestans, a common vector of this disease, has recently expanded its range into rapidly developing cities of Latin America. We aim to identify the environmental features that affect the colonization and dispersal of T. infestans in an urban environment. We amplified 13 commonly used microsatellites from 180 T. infestans samples collected from a sampled transect in the city of Arequipa, Peru, in 2007 and 2011. We assessed the clustering of subpopulations and the effect of distance, sampling year, and city block location on genetic distance among pairs of insects. Despite evidence of genetic similarity, the majority of city blocks are characterized by one dominant insect genotype, suggesting the existence of barriers to dispersal. Our analyses show that streets represent an important barrier to the colonization and dispersion of T. infestans in Arequipa. The genetic data describe a T. infestans infestation history characterized by persistent local dispersal and occasional long-distance migration events that partially parallels the history of urban development.

  11. Population Structure of the Chagas Disease Vector Triatoma infestans in an Urban Environment

    PubMed Central

    Khatchikian, Camilo E.; Foley, Erica A.; Barbu, Corentin M.; Hwang, Josephine; Ancca-Juárez, Jenny; Borrini-Mayori, Katty; Quıspe-Machaca, Victor R.; Naquira, Cesar; Brisson, Dustin; Levy, Michael Z.

    2015-01-01

    Chagas disease is a vector-borne disease endemic in Latin America. Triatoma infestans, a common vector of this disease, has recently expanded its range into rapidly developing cities of Latin America. We aim to identify the environmental features that affect the colonization and dispersal of T. infestans in an urban environment. We amplified 13 commonly used microsatellites from 180 T. infestans samples collected from a sampled transect in the city of Arequipa, Peru, in 2007 and 2011. We assessed the clustering of subpopulations and the effect of distance, sampling year, and city block location on genetic distance among pairs of insects. Despite evidence of genetic similarity, the majority of city blocks are characterized by one dominant insect genotype, suggesting the existence of barriers to dispersal. Our analyses show that streets represent an important barrier to the colonization and dispersion of T. infestans in Arequipa. The genetic data describe a T. infestans infestation history characterized by persistent local dispersal and occasional long-distance migration events that partially parallels the history of urban development. PMID:25646757

  12. Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

    PubMed Central

    Pinazo, Maria-Jesus; Thomas, Maria-Carmen; Bustamante, Juan; de Almeida, Igor Correia; Lopez, Manuel-Carlos; Gascon, Joaquim

    2015-01-01

    The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed. PMID:25946151

  13. Trypanosoma cruzi ubiquitin as an antigen in the differential diagnosis of Chagas disease and leishmaniasis.

    PubMed

    Telles, Senobia; Abate, Teresa; Slezynger, Thelma; Henriquez, Diana A

    2003-06-10

    In the present report we describe Trypanosoma cruzi ubiquitin as an antigen to be utilized in the differential diagnosis of Chagas disease and leishmaniasis. Initially, recombinant T. cruzi ubiquitin was evaluated against a panel of sera by phage dot immunoassay, showing a good performance against chagasic sera. However, the presence of a carboxy-terminal tail region encoding a ribosomal protein homologous to a related protein present in the genome of Leishmania sp. gave significant cross-reactivity with leishmanial sera. Therefore, ubiquitin was purified by a simple biochemical protocol and its immunoreactivity was studied by enzyme-linked immunosorbent assay. Analysis of 104 sera indicates that the response to ubiquitin is very sensitive towards chronic chagasic sera (98%) and, more important, highly species-specific, presenting better performance compared to the use of the recombinant protein or the total epimastigote extracts when tested against a panel of leishmanial sera, where out of a total of 70 sera tested, only five sera from the mucocutaneous form of the disease reacted with T. cruzi ubiquitin. On the other hand, Leishmania ubiquitin was not recognized by chagasic sera, but was recognized by sera from different forms of leishmaniasis. These results make ubiquitin an excellent candidate to be used in the differential diagnosis of these two parasitic diseases. The molecular basis for this highly species-specific response is discussed.

  14. Use of tumor necrosis factor alpha (TNF α) antagonists in a patient with psoriasis and Chagas disease*

    PubMed Central

    Navarrete-Dechent, Cristián; Majerson, Daniela; Torres, Marisa; Armijo, Daniela; Patel, Mahir; Menter, Alan; de la Cruz, Claudia

    2015-01-01

    There are several studies on the benefits of using TNFα antagonists in the treatment of psoriasis, but few studies addressing the interaction of these drugs with chronic infections. We report the case of a 52-year-old patient diagnosed with psoriasis refractory to traditional systemic agents, who was treated with biologic therapies. After one year of treatment with biologic agents, the patient was diagnosed with Chagas Disease. PMID:26312707

  15. Congenital Chagas disease as an ecological model of interactions between Trypanosoma cruzi parasites, pregnant women, placenta and fetuses.

    PubMed

    Carlier, Yves; Truyens, Carine

    2015-11-01

    The aim of this paper is to discuss the main ecological interactions between the parasite Trypanosoma cruzi and its hosts, the mother and the fetus, leading to the transmission and development of congenital Chagas disease. One or several infecting strains of T. cruzi (with specific features) interact with: (i) the immune system of a pregnant woman whom responses depend on genetic and environmental factors, (ii) the placenta harboring its own defenses, and, finally, (iii) the fetal immune system displaying responses also susceptible to be modulated by maternal and environmental factors, as well as his own genetic background which is different from her mother. The severity of congenital Chagas disease depends on the magnitude of such final responses. The paper is mainly based on human data, but integrates also complementary observations obtained in experimental infections. It also focuses on important gaps in our knowledge of this congenital infection, such as the role of parasite diversity vs host genetic factors, as well as that of the maternal and placental microbiomes and the microbiome acquisition by infant in the control of infection. Investigations on these topics are needed in order to improve the programs aiming to diagnose, manage and control congenital Chagas disease.

  16. Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas' Heart Disease

    PubMed Central

    Pereira, Isabela Resende; Vilar-Pereira, Glaucia; Silva, Andrea Alice; Moreira, Otacilio Cruz; Britto, Constança; Sarmento, Ellen Diana Marinho

    2014-01-01

    Background. Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure. Aim of the Study. To challenge the hypothesis that TNF plays a key role in Trypanosoma cruzi-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas' heart disease. Results. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFNγ levels; diminished the frequency of IL-17A+ but increased IL-10+ CD4+ T-cells; reduced TNF+ but augmented IL-10+ Ly6C+ and F4/80+ cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFNγ-producing VNHRFTLV-specific CD8+ T-cells in spleen and reduced the number of perforin+ cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue. Conclusions. Our data support that TNF is a crucial player in the pathogenesis of Chagas' heart disease fueling immunological unbalance which contributes to cardiac abnormalities. PMID:25140115

  17. [Chagas disease in a non endemic country: a study in the district of Bologna (Italy). Multidisciplinary analysis of the disease in the Latin American migrant population].

    PubMed

    Di Girolamo, C; Marta, B L; Ciannameo, A; Cacciatore, F; Balestra, G L; Bodini, C; Taroni, F

    2010-01-01

    Chagas disease is a parasitic illness endemic in 21 countries of Central and South America, affecting over 10 million people. Due to the increase of migration flows to Europe, Chagas disease is an emerging public health issue in non endemic countries. In Italy, where no specific policy has yet been developed, the Centre for International Health of the University of Bologna is carrying out the project "Chagas disease in a non endemic country: a study in the district of Bologna". A multidisciplinary and multi-method approach was adopted to estimate the problem and its impact in our territory. A retrospective analysis was performed searching several databases in order to collect information concerning the demographic and epidemiological profile of Latin American migrants coming from endemic countries. At the same time, a preliminary ethnographic research was conducted to start unveiling the main socio-anthropological characteristics of this population, thanks to the involvement of key informants and community associations. According to preliminary findings, Chagas disease is a present and possibly increasing reality in our territory. Due to the particular features of the affected population, socio-cultural variables have to be considered for their impact on the visibility of the condition and on health seeking behaviors.

  18. First report of a family outbreak of Chagas disease in French Guiana and posttreatment follow-up.

    PubMed

    Blanchet, Denis; Brenière, Simone Frédérique; Schijman, Alejandro G; Bisio, Margarita; Simon, Stéphane; Véron, Vincent; Mayence, Claire; Demar-Pierre, Magalie; Djossou, Félix; Aznar, Christine

    2014-12-01

    The outbreak of acute Chagas disease due to oral transmission of the parasite is a well-known phenomenon mainly occurring in the Amazon. Such an event is described here for the first time in French Guiana. Eight patients of the same family, presenting epidemiological and clinical histories compatible with recent Trypanosoma cruzi infection of Chagas disease due to the ingestion of palm Oenocarpus bacaba juice were, rather late after the putative date of infection, underwent four parasitological and two serological specific tests for confirmation of the diagnosis. Real-time PCR results were positive for all the patients; strains were isolated by hemoculture from four patients, PCR identification of TcI DTU was made for six patients, while parasites were not detected in any of the patients by direct microscopic examination. The results of two serologic tests were positive. All patients were treated with benznidazole, and two patients were additionally given nifurtimox. A 6-year follow-up was possible for six patients. Real-time PCR was negative for these patients after 1 year, while the antibody rates decreased slowly and serology results were negative only after several years (1-5 years). Our findings confirm the occurrence of an outbreak of Chagas infection in members of the same family, with the oral mode of infection being the most likely hypothesis to explain this group of cases. Our results show the successful treatment of patients infected by TcI and the usefulness of real-time PCR for the emergency diagnosis of recent Chagas disease cases and in posttreatment follow-up.

  19. Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease.

    PubMed

    Ramsey, Janine M; Peterson, A Townsend; Carmona-Castro, Oscar; Moo-Llanes, David A; Nakazawa, Yoshinori; Butrick, Morgan; Tun-Ku, Ezequiel; la Cruz-Félix, Keynes de; Ibarra-Cerdeña, Carlos N

    2015-05-01

    Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species, Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzi transmission. PMID:25993505

  20. Population structure of the Chagas disease vector, Triatoma infestans, at the urban-rural interface

    PubMed Central

    Foley, Erica A.; Khatchikian, Camilo E.; Hwang, Josephine; Ancca-Juárez, Jenny; Borrini-Mayori, Katty; Quıspe-Machaca, Victor R.; Levy, Michael Z.; Brisson, Dustin

    2013-01-01

    The increasing rate of biological invasions resulting from human transport or human-mediated changes to the environment have had devastating ecologic and public health consequences. The kissing bug, Triatoma infestans, has dispersed through the Peruvian city of Arequipa. The biological invasion of this insect has resulted in a public health crisis, putting thousands of residents of this city at risk of infection by Trypanosoma cruzi and subsequent development of Chagas disease. Here we show that populations of Tria. Infestans in geographically distinct districts within and around this urban center share a common recent evolutionary history although current gene flow is restricted even between proximal sites. The population structure among the Tria. Infestans in different districts is not correlated with the geographic distance between districts. These data suggest that migration among the districts is mediated by factors beyond the short-range migratory capabilities of Tria. Infestans and that human movement has played a significant role in the structuring of the Tria. Infestans population in the region. Rapid urbanization across southern South America will continue to create suitable environments for Tria. Infestans and knowledge of its urban dispersal patterns may play a fundamental role in mitigating human disease risk. PMID:24103030

  1. Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease

    PubMed Central

    Francisco, Amanda Fortes; de Abreu Vieira, Paula Melo; Arantes, Jerusa Marilda; Silva, Maisa; Pedrosa, Maria Lúcia; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; Araújo, Márcio Sobreira Silva; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2010-01-01

    Oxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite. PMID:20663295

  2. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease

    PubMed Central

    Miyazaki, Márcia I.; Chiminacio Neto, Nelson; Padeski, Marcela C.; Barros, Ana Cláudia M.

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy. PMID:26745156

  3. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease.

    PubMed

    Luz, Paola Rosa; Miyazaki, Márcia I; Chiminacio Neto, Nelson; Padeski, Marcela C; Barros, Ana Cláudia M; Boldt, Angelica B W; Messias-Reason, Iara J

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy.

  4. Mortality Due to Chagas Disease in Brazil According to a Specific Cause

    PubMed Central

    da Nóbrega, Aglaêr Alves; de Araújo, Wildo Navegantes; Vasconcelos, Ana Maria Nogales

    2014-01-01

    A century after its discovery, Chagas disease (CD) is still considered a public health problem. Mortality caused by CD between 2000 and 2010 was described according to the specific underlying cause, year of occurrence, gender, age range, and region of Brazil. The standardized mortality rate decreased 32.4%, from 3.4% in 2000 to 2.3% in 2010. Most of the deaths (85.9%) occurred in male patients who were > 60 years of age caused by cardiac involvement. The mortality rate caused by cardiac involvement decreased in all regions of Brazil, except in the North region, where it increased by 1.6%. The Northeast had the smallest and the Central-West had the largest decrease. The mortality rate caused by a compromised digestive tract increased in all regions. Despite the control of transmission by vector and blood transfusions, CD should remain on the list of priority diseases for the public health service in Brazil, and surveillance actions cannot be interrupted. PMID:25002301

  5. Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease.

    PubMed

    Ramsey, Janine M; Peterson, A Townsend; Carmona-Castro, Oscar; Moo-Llanes, David A; Nakazawa, Yoshinori; Butrick, Morgan; Tun-Ku, Ezequiel; la Cruz-Félix, Keynes de; Ibarra-Cerdeña, Carlos N

    2015-05-01

    Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species, Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzi transmission.

  6. Population structure of the Chagas disease vector, Triatoma infestans, at the urban-rural interface.

    PubMed

    Foley, Erica A; Khatchikian, Camilo E; Hwang, Josephine; Ancca-Juárez, Jenny; Borrini-Mayori, Katty; Quıspe-Machaca, Victor R; Levy, Michael Z; Brisson, Dustin

    2013-10-01

    The increasing rate of biological invasions resulting from human transport or human-mediated changes to the environment has had devastating ecological and public health consequences. The kissing bug, Triatoma infestans, has dispersed through the Peruvian city of Arequipa. The biological invasion of this insect has resulted in a public health crisis, putting thousands of residents of this city at risk of infection by Trypanosoma cruzi and subsequent development of Chagas disease. Here, we show that populations of Tria. infestans in geographically distinct districts within and around this urban centre share a common recent evolutionary history although current gene flow is restricted even between proximal sites. The population structure among the Tria. infestans in different districts is not correlated with the geographical distance between districts. These data suggest that migration among the districts is mediated by factors beyond the short-range migratory capabilities of Tria. infestans and that human movement has played a significant role in the structuring of the Tria. infestans population in the region. Rapid urbanization across southern South America will continue to create suitable environments for Tria. infestans, and knowledge of its urban dispersal patterns may play a fundamental role in mitigating human disease risk. PMID:24103030

  7. Field trial of vaccination against American trypanosomiasis (Chagas' disease) in dogs.

    PubMed

    Basombrio, M A; Segura, M A; Mora, M C; Gomez, L

    1993-07-01

    In Santiago del Estero, an area endemic for Chagas' disease in northwestern Argentina, household dogs were vaccinated with live-attenuated Trypanosoma cruzi, and the prospective incidence of natural infection by this parasite was assessed during a two-year followup period. Vaccinated dogs received 10(7) attenuated, TCC strain T. cruzi epimastigotes and were given booster vaccinations two and 14 months later. The number of animals that could be evaluated in vaccinated versus control groups was 73 and 75 after one year and 49 and 40 after two years, respectively. Parasitologic evaluation by xenodiagnosis indicated that vaccination had reduced natural T. cruzi infection from 26.7% to 12.3% after one year (P = 0.015). The preventive effect of vaccination after the second year was less significant in spite of the booster vaccinations. Inclusion of indirect hemagglutination data for the diagnosis of infection slightly increased the number of infected dogs without affecting the evidence for protection in the first year. Serologic, parasitologic, and isoenzyme studies indicated that protection was mediated by an attenuated, self-cured infection. In 15 dogs in which the vaccination failed to completely prevent natural infection, immunization nevertheless impaired their ability to infect the natural insect vectors of the disease in humans. PMID:8352387

  8. Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease

    PubMed Central

    Ramsey, Janine M; Peterson, A Townsend; Carmona-Castro, Oscar; Moo-Llanes, David A; Nakazawa, Yoshinori; Butrick, Morgan; Tun-Ku, Ezequiel; de la Cruz-Félix, Keynes; Ibarra-Cerdeña, Carlos N

    2015-01-01

    Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species, Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzi transmission. PMID:25993505

  9. Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas' disease

    PubMed Central

    1995-01-01

    Trypanosoma cruzi, the etiological agent of Chagas' disease, expresses a trans-sialidase at highest levels in infective trypomastigotes, where it attaches to the plasma membrane by a glycophosphoinositol linkage. Bound enzyme sheds into the extracellular milieu in a soluble form. Experiments performed in vitro suggest that the trans-sialidase participates in several parameters of T. cruzi-host interactions, like cell adhesion and complement resistance. However, the role that membrane-bound and soluble trans-sialidase plays in the infection of mammals is not understood. To begin to study the role the enzyme may play in vivo, T. cruzi trypomastigotes were inoculated subcutaneously into mice that had been sensitized for various times with the purified protein. A single dose of either endogenous or recombinant trans- sialidase injected into the connective tissues of BALB/c mice greatly enhanced parasitemia and mortality. Maximum enhancement was achieved with 1-2-h priming. Injection of the enzyme after the parasites had been established in the inoculation site had little, if any, consequence in modifying virulence. The enhancement did not seem to be through a direct effect of the enzyme on trypomastigote-host cell interactions because it occurred when the sites of trans-sialidase sensitization and parasite inoculation were physically separate. Rather, virulence enhancement seemed to depend on inflammatory cells, since priming with trans-sialidase had no significant effect in severe combined immunodeficiency mice, which lack functional T and B lymphocytes. However, antibody response to T. cruzi in the trans- sialidase-primed BALB/c mice was the same as in the control animals. Virulence enhancement was specific for the trans-sialidase because it did not occur in mice primed with Newcastle virus sialidase, which has the same substrate specificity as the T. cruzi enzyme, or with the sialidase from the bacterium Vibrio cholerae, whose substrate specificity is broader than

  10. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

    PubMed Central

    de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; Brandão de Mattos, Cinara Cássia; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

    2015-01-01

    The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region—rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD. PMID:26599761

  11. Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

    PubMed

    de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

    2015-01-01

    The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

  12. Social Representations and Practices Towards Triatomines and Chagas Disease in Calakmul, México.

    PubMed

    Valdez-Tah, Alba; Huicochea-Gómez, Laura; Ortega-Canto, Judith; Nazar-Beutelspacher, Austreberta; Ramsey, Janine M

    2015-01-01

    Vector-borne transmission of Trypanosoma cruzi (VBTTc) is dependent on the concomitant interaction between biological and environmental hazard over the entire landscape, and human vulnerability. Representations and practices of health-disease-care-seeking and territorial appropriation and use were analyzed for VBTTc in a qualitative ethnographic study in the Zoh-Laguna landscape, Campeche, Mexico. In-depth interviews and participatory observation explored representations and practices regarding ethno-ecological knowledge related to vector-transmission, health-disease-care-seeking, and land use processes. The population has a broad knowledge of biting insects, which they believe are all most abundant in the rainy season; the community´s proximity to natural areas is perceived as a barrier to control their abundance. Triatomines are mostly recognized by men, who have detailed knowledge regarding their occurrence and association with mammals in non-domestic fragments, where they report being bitten. Women emphasize the dermal consequences of triatomine bites, but have little knowledge about the disease. Triatomine bites and the chinchoma are "normalized" events which are treated using home remedies, if at all. The neglected condition of Chagas disease in Mexican public health policies, livelihoods which are dependent on primary production, and gender-related knowledge (or lack thereof) are structural circumstances which influence the environment and inhabitants´ living conditions; in turn, these trigger triatomine-human contact. The most important landscape practices producing vulnerability are the activities and mobility within and between landscape fragments causing greater exposure of inhabitants primarily in the dry season. A landscape approach to understanding vulnerability components of VBTTc from health-disease-care-seeking perspectives and based on territorial appropriation and use, is essential where there is continuous movement of vectors between and

  13. Modelling geographic variation in the cost-effectiveness of control policies for infectious vector diseases: the example of Chagas disease.

    PubMed

    Castillo-Riquelme, Marianela; Chalabi, Zaid; Lord, Joanne; Guhl, Felipe; Campbell-Lendrum, Diarmid; Davies, Clive; Fox-Rushby, Julia

    2008-03-01

    Few cost-effectiveness analysis (CEA) models have accounted for geographic variation in input parameters. This paper describes a deterministic discrete-time multi-state model to estimate the cost-effectiveness of vector control policies for Chagas disease, where implementation varies according to village characteristics. The model outputs include the total number of new infections, disability adjusted life years (DALYs) incurred, costs of associated healthcare, and total costs of the Ministry of Health's control policy for house surveillance and spraying. Incremental net benefits were estimated to determine Colombian villages in which it is cost-effective to implement the control policy. The robustness of these conclusions was evaluated by deterministic sensitivity analyses. The model should help provide a decision-support system to compare control policies and to allocate resources geographically. PMID:18222556

  14. Trypanosoma cruzi (Chagas' disease agent) reduces HIV-1 replication in human placenta

    PubMed Central

    Dolcini, Guillermina Laura; Solana, María Elisa; Andreani, Guadalupe; Celentano, Ana María; Parodi, Laura María; Donato, Ana María; Elissondo, Natalia; Cappa, Stella Maris González; Giavedoni, Luis David; Peralta, Liliana Martínez

    2008-01-01

    Background Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level. Results Simple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers) and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain), either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues. Conclusion Our results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence viral transduction in this

  15. Mortality profiles of Rhodnius prolixus (Heteroptera: Reduviidae), vector of Chagas disease.

    PubMed

    Chaves, Luis Fernando; Hernandez, Maria-Josefina; Revilla, Tomás A; Rodríguez, Diego J; Rabinovich, Jorge E

    2004-10-01

    Life table data of Rhodnius prolixus (Heteroptera: Reduviidae) kept at laboratory conditions were analysed in search for mortality patterns. Gompertz and Weibull mortality models seem adequate to explain the sigmoid shape of the survivorship curve. A significant fit was obtained with both models for females (R(2) = 0.70, P < 0.0005 for the Gompertz model; R(2) = 0.78, P < 0.0005 for the Weibull model) and for males (R(2) = 0.39, P < 0.0005 for the Gompertz model; R(2) = 0.48, P < 0.0005 for the Weibull model). The mortality parameter (b) is higher for females in Gompertz and Weibull models, using smoothed and non-smoothed data (P < 0.05), revealing a significant sex mortality differential. Given the particular life history of this insect, the non-linear relationship between the force of mortality and age may have an important impact in the vectorial capacity of R. prolixus as Chagas disease vector, and its consideration should be included as an important factor in the transmission of Trypanosoma cruzi by triatomines.

  16. A Deep Insight into the Sialome of Rhodnius neglectus, a Vector of Chagas Disease

    PubMed Central

    Santiago, Paula Beatriz; Assumpção, Teresa C. F.; de Araújo, Carla Nunes; Bastos, Izabela Marques Dourado; Neves, David; da Silva, Ionizete Garcia; Charneau, Sébastien; Queiroz, Rayner Myr L.; Raiol, Tainá; Oliveira, João Victor de Araújo; de Sousa, Marcelo Valle; Calvo, Eric; Ribeiro, José M. C.; Santana, Jaime M.

    2016-01-01

    Background Triatomines are hematophagous insects that act as vectors of Chagas disease. Rhodnius neglectus is one of these kissing bugs found, contributing to the transmission of this American trypanosomiasis. The saliva of hematophagous arthropods contains bioactive molecules responsible for counteracting host haemostatic, inflammatory, and immune responses. Methods/Principal Findings Next generation sequencing and mass spectrometry-based protein identification were performed to investigate the content of triatomine R. neglectus saliva. We deposited 4,230 coding DNA sequences (CDS) in GenBank. A set of 636 CDS of proteins of putative secretory nature was extracted from the assembled reads, 73 of them confirmed by proteomic analysis. The sialome of R. neglectus was characterized and serine protease transcripts detected. The presence of ubiquitous protein families was revealed, including lipocalins, serine protease inhibitors, and antigen-5. Metalloproteases, disintegrins, and odorant binding protein families were less abundant. Conclusions/Significance The data presented improve our understanding of hematophagous arthropod sialomes, and aid in understanding hematophagy and the complex interplay among vectors and their vertebrate hosts. PMID:27129103

  17. Chagas Disease Control Programme in Brazil: a study of the effectiveness of 13 years of intervention.

    PubMed Central

    Costa, F. C.; Vitor, R. W.; Antunes, C. M.; Carneiro, M.

    1998-01-01

    Reported is an evaluation of 13 years of intervention by the Chagas Disease Control Programme in an endemic area (Montalvania) in the State of Minas Gerais, Brazil. The design used was an epidemiological panel study. The reduction of Trypanosoma cruzi infection rates was estimated from data collected on three separate occasions: a serological survey in 1975-80, a quasi-experimental study in 1987, and the present investigation. A random sample of 156 households was selected and blood samples were collected from 653 inhabitants. The data routinely collected by the control programme were analysed to correlate the results with the incidence of T. cruzi. The overall prevalence of infection was 2.3%; however, no participant under 14 years of age was found to have a positive serological test. The total reduction in T. cruzi infection rates in this area from the start of the programme's activities was estimated to be 83.5%. Cross-sectional comparisons for the age groups 2-6 years and 7-14 years indicated a 100% reduction in T. cruzi incidence rates; but cohort comparisons showed that 100% reduction was achieved only for the 2-6-years age group. PMID:9803589

  18. Molecular phylogeography of the Chagas' disease vector Triatoma infestans in Argentina

    PubMed Central

    Pérez de Rosas, A R; Segura, E L; García, B A

    2011-01-01

    Triatoma infestans is the main vector of Chagas' disease in South America between latitudes 10°S and 46°S. A multilocus microsatellite data set of 836 individuals from 27 populations of T. infestans, from all its range of distribution in Argentina, was analyzed. Our results favor the hypothesis of two independent migration events of colonization in Argentina and secondary contacts. The majority of the populations of the western provinces of Catamarca, La Rioja, San Juan and the west of Cordoba province, had almost no shared ancestry with the rest of the populations analyzed. Probably those populations, belonging to localities close to the Andean region, could have been established by the dispersal line of T. infestans that would have arrived to Argentina through the Andes, whereas most of the rest of the populations analyzed may have derived from the dispersal line of T. infestans in non-Andean lowlands. Among them, those from the provinces of Formosa, Chaco, Santiago del Estero and Santa Fe shared different percentages of ancestry and presented lower degree of genetic differentiation. The migratory movement linked to regional economies and possibly associated with passive dispersal, would allow a higher genetic exchange among these populations of T. infestans. This study, using microsatellite markers, provides a new approach for evaluating the validity of the different hypotheses concerning the evolutionary history of this species. Two major lineages of T. infestans, an Andean and non-Andean, are suggested. PMID:21224874

  19. Barriers to Testing and Treatment for Chagas Disease among Latino Immigrants in Georgia

    PubMed Central

    Minneman, Rebecca M.; Hennink, Monique M.; Nicholls, Andrea; Salek, Sahar S.; Palomeque, Francisco S.; Khawja, Amina; Albor, Lauren C.; Pennock, Chester C.; Leon, Juan S.

    2012-01-01

    Background. The lack of testing and treatment of Chagas disease (CD), caused by Trypanosoma cruzi, amongst infected immigrants in the USA increases the risk of serious health complications and transmission (congenital or via blood transfusions). Goal. Our goal was to identify the barriers to testing and treatment of CD and understand the process of seeking healthcare amongst Latino immigrants in Georgia. Methods. In this qualitative study, eleven focus group discussions were conducted with 82 Latino immigrants, including migrant farm workers. Grounded theory was used to collect and analyze the data to develop an inductive conceptual framework to explain the context and process of seeking healthcare for CD amongst this at-risk population. Results. Participants were not aware of CD. Three healthcare seeking behaviors were identified: delaying treatment, using traditional remedies, and using either mainstream or alternative health providers. Behaviors and motivations differed by gender, and the use of licensed medical providers was considered a last resort due to the cost of healthcare, loss of earnings while seeking care, and fear of diagnosis with fatal illness. Discussion. Providing free or low cost services, mobile clinics, and education regarding CD is critical to increase testing and treatment of CD in the US. PMID:23326646

  20. Inheritance of resistance to pyrethroids in Triatoma infestans, the main Chagas disease vector in South America.

    PubMed

    Cardozo, R M; Panzera, F; Gentile, A G; Segura, M A; Pérez, R; Díaz, R A; Basombrío, M A

    2010-12-01

    An outbreak of pyrethroid resistance was recently detected in Triatoma infestans from northern Argentina. To analyze the inheritance of the resistant phenotype, we carried out experimental crosses between resistant (R) and susceptible (S) strains captured in Argentina during 2005. The R strain was collected from sprayed houses in the north of the province of Salta while the S strain was collected in the province of Chaco. Both strains were bred in the laboratory for reciprocal crosses (F1), intercrosses (F2) and backcrosses (BC). The descendents were tested by a standard insecticide resistance bioassay. Resistance ratios were 1 for S strain, 103.36 for R strain and 18.34 for F1. The regression lines of F1 generations (R×S and S×R) showed no significant differences and were closer to that of the R parents, indicating that inheritance of deltamethrin resistance in T. infestans is autosomal and incompletely dominant (D=0.20). Chi-square analysis from responses of intercross and backcross progenies rejected the hypothesis of a single gene being responsible for resistance. The minimum number of independent segregation genes was three, as calculated with Lande's method. The genetic basis here described for the resistant phenotype indicate that, under pyrethroid selective pressure, the resistant genotypes could be easily spread to susceptible insects from resistant individuals, posing a major threat to vectorial control of Chagas disease.

  1. Barriers to Testing and Treatment for Chagas Disease among Latino Immigrants in Georgia.

    PubMed

    Minneman, Rebecca M; Hennink, Monique M; Nicholls, Andrea; Salek, Sahar S; Palomeque, Francisco S; Khawja, Amina; Albor, Lauren C; Pennock, Chester C; Leon, Juan S

    2012-01-01

    Background. The lack of testing and treatment of Chagas disease (CD), caused by Trypanosoma cruzi, amongst infected immigrants in the USA increases the risk of serious health complications and transmission (congenital or via blood transfusions). Goal. Our goal was to identify the barriers to testing and treatment of CD and understand the process of seeking healthcare amongst Latino immigrants in Georgia. Methods. In this qualitative study, eleven focus group discussions were conducted with 82 Latino immigrants, including migrant farm workers. Grounded theory was used to collect and analyze the data to develop an inductive conceptual framework to explain the context and process of seeking healthcare for CD amongst this at-risk population. Results. Participants were not aware of CD. Three healthcare seeking behaviors were identified: delaying treatment, using traditional remedies, and using either mainstream or alternative health providers. Behaviors and motivations differed by gender, and the use of licensed medical providers was considered a last resort due to the cost of healthcare, loss of earnings while seeking care, and fear of diagnosis with fatal illness. Discussion. Providing free or low cost services, mobile clinics, and education regarding CD is critical to increase testing and treatment of CD in the US. PMID:23326646

  2. Sustainable vector control and management of Chagas disease in the Gran Chaco, Argentina

    PubMed Central

    Gürtler, Ricardo E.; Kitron, Uriel; Cecere, M. Carla; Segura, Elsa L.; Cohen, Joel E.

    2007-01-01

    Chagas disease remains a serious obstacle to health and economic development in Latin America, especially for the rural poor. We report the long-term effects of interventions in rural villages in northern Argentina during 1984–2006. Two community-wide campaigns of residual insecticide spraying immediately and strongly reduced domestic infestation and infection with Trypanosoma cruzi in Triatoma infestans bugs and dogs and more gradually reduced the seroprevalence of children <15 years of age. Because no effective surveillance and control actions followed the first campaign in 1985, transmission resurged in 2–3 years. Renewed interventions in 1992 followed by sustained, supervised, community-based vector control largely suppressed the reestablishment of domestic bug colonies and finally led to the interruption of local human T. cruzi transmission. Human incidence of infection was nearly an order of magnitude higher in peripheral rural areas under pulsed, unsupervised, community-based interventions, where human transmission became apparent in 2000. The sustained, supervised, community-based strategy nearly interrupted domestic transmission to dogs but did not eliminate T. infestans despite the absence of pyrethroid-insecticide resistance. T. infestans persisted in part because of the lack of major changes in housing construction and quality. Sustained community participation grew out of establishing a trusted relationship with the affected communities and the local schools. The process included health promotion and community mobilization, motivation, and supervision in close cooperation with locally nominated leaders. PMID:17913895

  3. Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

    PubMed Central

    Waleckx, Etienne; Gourbière, Sébastien; Dumonteil, Eric

    2015-01-01

    Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions. PMID:25993504

  4. Trypanosoma cruzi culture used as vaccine to prevent chronic Chagas' disease in mice.

    PubMed Central

    Basombrío, M A; Besuschio, S

    1982-01-01

    The development of chronic pathology in mice at 2 to 10 months after inoculation of 10(2) T. cruzi trypomastigotes can be prevented by preimmunization with live, attenuated culture parasites (strain TCC). Swiss mice received one or three immunizing inoculations of 10(6) TCC organisms and were challenged with 10(2) Tulahuén blood trypomastigotes. Control groups received only the immunizing or the challenge inoculations. Immunized groups as compared with nonimmunized controls had lower mortality rates at 2 months postchallenge (9% versus 23%; P = 0.059), lower early peaks of parasitemia, lower percentages of positive xenodiagnoses at 5.5 months (40 versus 80%; P = 0.061), and lower incidences of tissue lesions in the skeletal muscle (P less than 0.005) at 2,6, and 10 months postchallenge. Tissue lesions in the heart and smooth muscle were also reduced, reaching statistical significance after 10 months (P less than 0.02). Chronic pathology parameters were never enhanced in preimmunized groups. In spite of the putative role that autoimmunity may play in the development of chronic chagasic lesions, the preventive effect of vaccination is readily exerted upon the chronic murine model of Chagas' disease. Images PMID:6804390

  5. Barriers to Testing and Treatment for Chagas Disease among Latino Immigrants in Georgia.

    PubMed

    Minneman, Rebecca M; Hennink, Monique M; Nicholls, Andrea; Salek, Sahar S; Palomeque, Francisco S; Khawja, Amina; Albor, Lauren C; Pennock, Chester C; Leon, Juan S

    2012-01-01

    Background. The lack of testing and treatment of Chagas disease (CD), caused by Trypanosoma cruzi, amongst infected immigrants in the USA increases the risk of serious health complications and transmission (congenital or via blood transfusions). Goal. Our goal was to identify the barriers to testing and treatment of CD and understand the process of seeking healthcare amongst Latino immigrants in Georgia. Methods. In this qualitative study, eleven focus group discussions were conducted with 82 Latino immigrants, including migrant farm workers. Grounded theory was used to collect and analyze the data to develop an inductive conceptual framework to explain the context and process of seeking healthcare for CD amongst this at-risk population. Results. Participants were not aware of CD. Three healthcare seeking behaviors were identified: delaying treatment, using traditional remedies, and using either mainstream or alternative health providers. Behaviors and motivations differed by gender, and the use of licensed medical providers was considered a last resort due to the cost of healthcare, loss of earnings while seeking care, and fear of diagnosis with fatal illness. Discussion. Providing free or low cost services, mobile clinics, and education regarding CD is critical to increase testing and treatment of CD in the US.

  6. Analysis of Children's Perception of Triatomine Vectors of Chagas Disease through Drawings: Opportunities for Targeted Health Education

    PubMed Central

    Yevstigneyeva, Violetta; Camara-Mejia, Javier; Dumonteil, Eric

    2014-01-01

    Background Chagas disease is a tropical parasitic disease affecting about 10 million people, mostly in the Americas, and transmitted mainly by triatomine bugs. Insect vector control with indoor residual insecticides and the promotion of housing improvement is the main control intervention. The success of such interventions relies on their acceptance and appropriation by communities, which depends on their knowledge and perceptions of both the disease and the vector. In this study, we investigated school-aged children's knowledge and perception on triatomine vectors and Chagas disease to further understand how communities view this vector and the disease in Yucatan, Mexico. Methodology/Principal findings We performed an analysis of children's drawings on the theme of triatomines and their house in several rural villages, to explore in an open-ended manner their views, understanding and misconceptions. A total of 261 drawings were collected from children ages 6–12 from four villages. We found that children are very familiar with triatomine vectors, and know very well many aspects of their biology and ecology, and in particular their blood-feeding habits. On the other hand, their drawings suggest that the role of triatomines as vectors of a chronic and severe cardiac disease is less understood, and the main perceived health threat appears limited to the bite itself, as previously observed in adults. Conclusions/Significance These results have important implications for the specific design of future education materials and campaigns, and for the promotion of the inclusion of children in raising Chagas disease awareness in these endemic communities. PMID:25275321

  7. A Practical Green Synthesis, and Biological Evaluation of Benzimidazoles Against Two Neglected Tropical Diseases: Chagas and Leishmaniasis.

    PubMed

    Bandyopadhyay, Debasish; Samano, Selina; Villalobos-Rocha, Juan C; Sanchez-Torres, Luvia E; Nogueda-Torres, Benjamín; Rivera, Gildardo; Banik, Bimal K

    2013-01-01

    Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and its estimated there are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas' disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described. PMID:23317160

  8. Proteome Expression and Carbonylation Changes During Trypanosoma cruzi Infection and Chagas Disease in Rats*

    PubMed Central

    Wen, Jian-Jun; Garg, Nisha Jain

    2012-01-01

    cardiac disease in human chagasic patients. Together, these results demonstrate the plasma oxidative and inflammatory response profile, and plasma detection of cardiac proteins parallels the pathologic events contributing to Chagas disease development, and is of potential utility in diagnosing disease severity and designing suitable therapy for management of human chagasic patients. PMID:22199233

  9. Trypanosoma cruzi in the Chicken Model: Chagas-Like Heart Disease in the Absence of Parasitism

    PubMed Central

    Teixeira, Antonio R. L.; Gomes, Clever; Nitz, Nadjar; Sousa, Alessandro O.; Alves, Rozeneide M.; Guimaro, Maria C.; Cordeiro, Ciro; Bernal, Francisco M.; Rosa, Ana C.; Hejnar, Jiri; Leonardecz, Eduardo; Hecht, Mariana M.

    2011-01-01

    Background The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis. Methodology/Principal Findings To understand the origin of clinical manifestations of the heart disease we used a chicken model system in which infection can be initiated in the egg, but parasite persistence is precluded. T. cruzi inoculation into the air chamber of embryonated chicken eggs generated chicks that retained only the parasite mitochondrial kinetoplast DNA minicircle in their genome after eight days of gestation. Crossbreeding showed that minicircles were transferred vertically via the germ line to chicken progeny. Minicircle integration in coding regions was shown by targeted-primer thermal asymmetric interlaced PCR, and detected by direct genomic analysis. The kDNA-mutated chickens died with arrhythmias, shortness of breath, cyanosis and heart failure. These chickens with cardiomyopathy had rupture of the dystrophin and other genes that regulate cell growth and differentiation. Tissue pathology revealed inflammatory dilated cardiomegaly whereby immune system mononuclear cells lyse parasite-free target heart fibers. The heart cell destruction implicated a thymus-dependent, autoimmune; self-tissue rejection carried out by CD45+, CD8γδ+, and CD8α lymphocytes. Conclusions/Significance These results suggest that genetic alterations resulting from kDNA integration in the host genome lead to autoimmune-mediated destruction of heart tissue in the absence of T. cruzi parasites. PMID:21468314

  10. Geospatial Risk Factors of Canine American Trypanosomiasis (Chagas Disease) (42 Cases: 2000-2012).

    PubMed

    Raghavan, Ram K; Saunders, Ashley B; Goodin, Doug G; Anderson, Gary A; Harkin, Kenneth R

    2015-10-01

    American trypanosomiasis or Chagas disease caused by Trypanosoma cruzi affects many mammals, including humans and dogs, in all Latin American countries outside the Caribbean and increasingly also in the southern United States. Dogs are considered as reliable sentinels and have been identified as an important risk factor for the disease in humans in endemic countries. Factors that determine American trypanosomiasis in dogs may therefore have public health relevance. Associations of different environmental, locational, and pet owner socioeconomic conditions were evaluated retrospectively as potential risk factors for American trypanosomiasis status in dogs in a case-control study. Laboratory-confirmed cases received at the Texas A&M University Veterinary Medical Teaching Hospital between the years 2000 and 2012 and candidate risk factor variables extracted from publicly available environmental data and 2010 US Census Bureau were used. The sample included 42 dogs serologically positive and 82 dogs serologically negative determined by indirect immunofluorescent assay. The diagnostic titer was 1:160 (case). Univariate logistic regressions followed by stepwise multivariate logistic modeling were used for variable screening and to determine the strengths of variable associations with case status. Total Edge Contrast Index (odds ratio [OR] = 3.35, 95% confidence interval [CI] 3.10, 3.62), residing in homes that had rural addresses (OR = 2.48, 95% CI 2.43, 2.53), total number of owner occupied housing units in a neighborhood with a householder who is Hispanic or Latino (OR = 1.66, 95% CI 1.04, 2.66), and the total number of housing units in a neighborhood that were built on or prior to year 1980 (OR = 2.22, 95% CI 1.94, 2.55) were identified as risk factors. Suitable awareness campaigns and future research that considers pet owner housing and socioeconomic circumstances are necessary for effective prevention and control of this disease among dogs.

  11. Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation

    PubMed Central

    Guimaro, Maria C.; Alves, Rozeneide M.; Rose, Ester; Sousa, Alessandro O.; de Cássia Rosa, Ana; Hecht, Mariana M.; Sousa, Marcelo V.; Andrade, Rafael R.; Vital, Tamires; Plachy, Jiří; Nitz, Nadjar; Hejnar, Jiří; Gomes, Clever C.; L. Teixeira, Antonio R.

    2014-01-01

    Background Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. Methods/Principal Findings To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. Conclusions/Significance Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. PMID:25521296

  12. Effect of mild aerobic training on the myocardium of mice with chronic Chagas disease

    PubMed Central

    Preto, Emerson; Lima, Nathalia EA; Simardi, Lucila; Fonseca, Fernando Luiz Affonso; Filho, Abílio Augusto Fragata; Maifrino, Laura Beatriz Mesiano

    2015-01-01

    Background Chronic chagasic heart disease represents extensive remodeling of the cardiovascular system, manifested as cardiac denervation, interstitial mononuclear infiltrate, myocyte and vascular degenerative changes, fibrosis, and hypertrophy. Moreover, aerobic exercises are widely indicated for the treatment of various disorders of the cardiovascular system. Purpose To evaluate the right and left ventricles of BALB/c mice with chronic Chagas disease, undergoing mild exercise, by using morphometric and stereological methods. Materials and methods A total of 20 male mice at 4 months of age were used for experiments. The animals were divided into four groups (n=5 in each group): untrained control, trained control, untrained infected (UI), and trained infected (TI). Animals of UI and TI groups were inoculated with 1,000 trypomastigote forms of Trypanosoma cruzi (Y strain), and after 40 days, animals entered chronic phase of the disease. Physical exercise, which included swimming, was performed for 30 minutes daily, five times a week for 8 consecutive weeks at a bath temperature of 30°C. After the trial period, euthanasia and subsequent withdrawal of the heart were done. The organ was prepared by histological staining procedures with hematoxylin–eosin and picrosirius red. Results We found that the physical training used in our experimental model promoted increase in volume density of capillaries and decrease in volume density of collagen fibers and cross-sectional area of cardiomyocytes in chagasic animals (TI group). By histopathological analysis, we found differences in the inflammatory infiltrate, which was lower in animals of TI group. The training program promoted a recovery of these parameters in the TI group. Conclusion Our results suggest that low-intensity aerobic exercise acts on morphological and morphometric parameters of the left and right ventricles in mice infected with T. cruzi, reducing the changes caused by the organism and making the results

  13. Carlos Chagas: biographical sketch.

    PubMed

    Moncayo, Alvaro

    2010-01-01

    Carlos Chagas was born on 9 July 1878 in the farm "Bon Retiro" located close to the City of Oliveira in the interior of the State of Minas Gerais, Brazil. He started his medical studies in 1897 at the School of Medicine of Rio de Janeiro. In the late XIX century, the works by Louis Pasteur and Robert Koch induced a change in the medical paradigm with emphasis in experimental demonstrations of the causal link between microbes and disease. During the same years in Germany appeared the pathological concept of disease, linking organic lesions with symptoms. All these innovations were adopted by the reforms of the medical schools in Brazil and influenced the scientific formation of Chagas. Chagas completed his medical studies between 1897 and 1903 and his examinations during these years were always ranked with high grades. Oswaldo Cruz accepted Chagas as a doctoral candidate and directed his thesis on "Hematological studies of Malaria" which was received with honors by the examiners. In 1903 the director appointed Chagas as research assistant at the Institute. In those years, the Institute of Manguinhos, under the direction of Oswaldo Cruz, initiated a process of institutional growth and gathered a distinguished group of Brazilian and foreign scientists. In 1907, he was requested to investigate and control a malaria outbreak in Lassance, Minas Gerais. In this moment Chagas could not have imagined that this field research was the beginning of one of the most notable medical discoveries. Chagas was, at the age of 28, a Research Assistant at the Institute of Manguinhos and was studying a new flagellate parasite isolated from triatomine insects captured in the State of Minas Gerais. Chagas made his discoveries in this order: first the causal agent, then the vector and finally the human cases. These notable discoveries were carried out by Chagas in twenty months. At the age of 33 Chagas had completed his discoveries and published the scientific articles that gave him world

  14. Innovative community-based ecosystem management for dengue and Chagas disease prevention in low and middle income countries in Latin America and the Caribbean.

    PubMed

    Finkelman, Jacobo

    2015-02-01

    In 2009, the WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the International Development Research Centre (IDRC) launched a call for innovative community-based ecosystem management research projects for dengue and Chagas disease prevention in low and middle income countries in Latin America and the Caribbean. Eight research institutions were selected. The outputs of these projects led to a better understanding of the interaction between ecological, biological, social and economic (eco-bio-social) determinants of dengue and Chagas disease in Latin America and the Caribbean. Both diseases are considered highly relevant in the regional health agendas.

  15. Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

    PubMed Central

    Ayo, Christiane Maria; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Reis, Pâmela Guimarães; Jarduli, Luciana Ribeiro; Alves, Hugo Vicentin; Sell, Ana Maria

    2013-01-01

    Chagas disease, which is caused by the flagellate parasite Trypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during human T. cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC, KIR, and cytokine host genetic factors on the infection by T. cruzi and the clinical course of Chagas disease. PMID:24069594

  16. Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

    PubMed Central

    Santos, Astrid Meireles; Scanavacca, Mauricio Ibrahim; Darrieux, Francisco; Ianni, Bárbara; de Melo, Sissy Lara; Pisani, Cristiano; Santos Neto, Francisco; Sosa, Eduardo; Hachul, Denise Tessariol

    2014-01-01

    Background Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence. Objective To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias. Method Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram). Results GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028). Conclusion The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias. PMID:25004420

  17. Cost-Effectiveness of Chagas Disease Vector Control Strategies in Northwestern Argentina

    PubMed Central

    Vazquez-Prokopec, Gonzalo M.; Spillmann, Cynthia; Zaidenberg, Mario; Kitron, Uriel; Gürtler, Ricardo E.

    2009-01-01

    Background Control and prevention of Chagas disease rely mostly on residual spraying of insecticides. In Argentina, vector control shifted from a vertical to a fully horizontal strategy based on community participation between 1992 and 2004. The effects of such strategy on Triatoma infestans, the main domestic vector, and on disease transmission have not been assessed. Methods and Findings Based on retrospective (1993–2004) records from the Argentinean Ministry of Health for the Moreno Department, Northwestern Argentina, we performed a cost-effectiveness (CE) analysis and compared the observed CE of the fully horizontal vector control strategy with the expected CE for a vertical or a mixed (i.e., vertical attack phase followed by horizontal surveillance) strategy. Total direct costs (in 2004 US$) of the horizontal and mixed strategies were, respectively, 3.3 and 1.7 times lower than the costs of the vertical strategy, due to reductions in personnel costs. The estimated CE ratios for the vertical, mixed and horizontal strategies were US$132, US$82 and US$45 per averted human case, respectively. When per diems were excluded from the costs (i.e., simulating the decentralization of control activities), the CE of vertical, mixed and horizontal strategies was reduced to US$60, US$42 and US$32 per averted case, respectively. Conclusions and Significance The mixed strategy would have averted between 1.6 and 4.0 times more human cases than the fully horizontal strategy, and would have been the most cost-effective option to interrupt parasite transmission in the Department. In rural and dispersed areas where waning vertical vector programs cannot accomplish full insecticide coverage, alternative strategies need to be developed. If properly implemented, community participation represents not only the most appealing but also the most cost-effective alternative to accomplish such objectives. PMID:19156190

  18. The importance of exercise gated blood pool imaging in Chagas Disease

    SciTech Connect

    Meneguetti, J.C.; Neto, J.E.; Hironaka, F.H.; Netto, M.P.; Gomes, J.R.; Goldbaum, M.; Pileggi, F.; Camargo, E.E.

    1984-01-01

    Myocardial involvement in Chagas Disease (CD) often leads to cardiomyopathy and heart failure. Patients (pts) with the indeterminate form (IF) have positive complement fixation test as the only abnormality. Cardiac form (CF) pts have positive serology, abnormal ECG with or without clinical symptoms. To investigate the degree of cardiac involvement in IF pts, exercise (handgrip) gated blood pool (EGBP) was performed on 77 CD male workers (46 IF, 17-50 yrs; 31 CF, 24-61 yrs) and 28 male (22-46 yrs) normal volunteers (NV). Regional wall motion (RWM), ventricular volumes (VV) and percent EF variation (..delta..%) were analysed. NV group shoed ..delta..% - 3.51 +- 4.86 with normal RWM and VV. IF pts showed ..delta..% - 4.27 +- 7.46 with >-10% drop in 22% of pts; RWM and VV were abnormal in 43% and 30%, respectively; at least one parameter was abnormal in 59% of pts. CF pts showed ..delta..%-10.52 +- 7.37 with >-10% drop in 59%; RWM and VV were abnormal in 79% and 83%, respectively; at least one parameter was abnormal in 86% of pts. No ..delta..% difference was found between NV and IF groups, but there was a significant difference between these two groups and CF pts. When EGBP is considered, only 41% of IF pts are normal. Also, 14% CF pts with ECG and serologic abnormalities have no cardiac dysfunction. This suggests that EGBP study should be included as a routine procedure in CD pts and used as a basis for a new classification of the disease.

  19. Physiopathology of Chagas' heart disease: correlations between clinical and experimental findings*

    PubMed Central

    Anselmi, Alfonso; Moleiro, Federico

    1971-01-01

    In penetrating the heart and developing in it, Trypanosoma cruzi produces an immunoallergic reaction that leads to changes in the histological structure of the myocardium; these changes alter the fundamental properties of the heart, causing fundamental dynamic disorders and morphological changes in the organ. In Chagas' cardiomyopathy, the velocity of impulse propagation diminishes in the auricular and ventricular musculature, altering the activation mechanism, this being shown by changes in the P-wave and in ventricular focal blocks. The functional refractory period (FRP) is shortened in the auricular and ventricular tissue and constitutes, together with changes in conductivity, the physiopathological basis that explains the circus movement—the fundamental factor of the arrhythmias of this stage of the disease. Localization of the inflammation in the A-V conduction system increases the duration of the FRP, producing all types of A-V block. The oedema and the cellular interstitial infiltration seen during this acute phase reduce the distensibility of the fibres; this, in turn, limits their contractility, producing a decrease in systolic volume and an increase in the final diastolic pressure in the chambers of the heart—fundamental factors in reducing kinesia and in increasing the heart's volume. In the chronic phase, destruction of the contractile tissue and fibroblastic proliferation bring into play compensatory mechanisms that maintain the strength of cardiac contractions; the elongation of the fibres and the nature of the dynamic pressure—volume curves explain the dilatation of the chambers of the heart and the dynamic changes seen in this phase of the disease. PMID:5003721

  20. Interactions Between Trypanosoma cruzi the Chagas Disease Parasite and Naturally Infected Wild Mepraia Vectors of Chile.

    PubMed

    Campos-Soto, Ricardo; Ortiz, Sylvia; Cordova, Ivan; Bruneau, Nicole; Botto-Mahan, Carezza; Solari, Aldo

    2016-03-01

    Chagas disease, which ranks among the world's most neglected diseases, is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi. Mepraia species are the wild vectors of this parasite in Chile. Host-parasite interactions can occur at several levels, such as co-speciation and ecological host fitting, among others. Thus, we are exploring the interactions between T. cruzi circulating in naturally infected Mepraia species in all areas endemic of Chile. We evaluated T. cruzi infection rates of 27 different haplotypes of the wild Mepraia species and identified their parasite genotypes using minicircle PCR amplification and hybridization tests with genotype-specific DNA probes. Infection rates were lower in northern Chile where Mepraia gajardoi circulates (10-35%); in central Chile, Mepraia spinolai is most abundant, and infection rates varied in space and time (0-55%). T. cruzi discrete typing units (DTUs) TcI, TcII, TcV, and Tc VI were detected. Mixed infections with two or more DTUs are frequently found in highly infected insects. T. cruzi DTUs have distinct, but not exclusive, ecological and epidemiological associations with their hosts. T. cruzi infection rates of M. spinolai were higher than in M. gajardoi, but the presence of mixed infection with more than one T. cruzi DTU was the same. The same T. cruzi DTUs (TcI, TcII, TcV, and TcVI) were found circulating in both vector species, even though TcI was not equally distributed. These results suggest that T. cruzi DTUs are not associated with any of the two genetically related vector species nor with the geographic area. The T. cruzi vectors interactions are discussed in terms of old and recent events. By exploring T. cruzi DTUs present in Mepraia haplotypes and species from northern to central Chile, we open the analysis on these invertebrate host-parasite interactions.

  1. MnSODtg Mice Control Myocardial Inflammatory and Oxidative Stress and Remodeling Responses Elicited in Chronic Chagas Disease

    PubMed Central

    Dhiman, Monisha; Wan, Xianxiu; Popov, Vsevolod L.; Vargas, Gracie; Garg, Nisha Jain

    2013-01-01

    Background We utilized genetically modified mice equipped with a variable capacity to scavenge mitochondrial and cellular reactive oxygen species to investigate the pathological significance of oxidative stress in Chagas disease. Methods and Results C57BL/6 mice (wild type, MnSODtg, MnSOD+/−, GPx1−/−) were infected with Trypanosoma cruzi and harvested during the chronic disease phase. Chronically infected mice exhibited a substantial increase in plasma levels of inflammatory markers (nitric oxide, myeloperoxidase), lactate dehydrogenase, and myocardial levels of inflammatory infiltrate and oxidative adducts (malondialdehyde, carbonyls, 3‐nitrotyrosine) in the order of wild type=MnSOD+/−>GPx1−/−>MnSODtg. Myocardial mitochondrial damage was pronounced and associated with a >50% decline in mitochondrial DNA content in chronically infected wild‐type and GPx1−/− mice. Imaging of intact heart for cardiomyocytes and collagen by the nonlinear optical microscopy techniques of multiphoton fluorescence/second harmonic generation showed a significant increase in collagen (>10‐fold) in chronically infected wild‐type mice, whereas GPx1−/− mice exhibited a basal increase in collagen that did not change during the chronic phase. Chronically infected MnSODtg mice exhibited a marginal decline in mitochondrial DNA content and no changes in collagen signal in the myocardium. P47phox−/− mice lacking phagocyte‐generated reactive oxygen species sustained a low level of myocardial oxidative stress and mitochondrial DNA damage in response to Trypanosoma cruzi infection. Yet chronically infected p47phox−/− mice exhibited increase in myocardial inflammatory and remodeling responses, similar to that noted in chronically infected wild‐type mice. Conclusions Inhibition of oxidative burst of phagocytes was not sufficient to prevent pathological cardiac remodeling in Chagas disease. Instead, enhancing the mitochondrial reactive oxygen species scavenging

  2. Surveillance, health promotion and control of Chagas disease in the Amazon Region--Medical attention in the Brazilian Amazon Region: a proposal.

    PubMed

    Coura, José Rodrigues; Junqueira, Angela C V

    2015-11-01

    We refer to Oswaldo Cruz's reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients' samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care.

  3. Surveillance, health promotion and control of Chagas disease in the Amazon Region - Medical attention in the Brazilian Amazon Region: a proposal

    PubMed Central

    Coura, José Rodrigues; Junqueira, Angela CV

    2015-01-01

    We refer to Oswaldo Cruz's reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients' samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care. PMID:26560976

  4. Social Representations and Practices Towards Triatomines and Chagas Disease in Calakmul, México.

    PubMed

    Valdez-Tah, Alba; Huicochea-Gómez, Laura; Ortega-Canto, Judith; Nazar-Beutelspacher, Austreberta; Ramsey, Janine M

    2015-01-01

    Vector-borne transmission of Trypanosoma cruzi (VBTTc) is dependent on the concomitant interaction between biological and environmental hazard over the entire landscape, and human vulnerability. Representations and practices of health-disease-care-seeking and territorial appropriation and use were analyzed for VBTTc in a qualitative ethnographic study in the Zoh-Laguna landscape, Campeche, Mexico. In-depth interviews and participatory observation explored representations and practices regarding ethno-ecological knowledge related to vector-transmission, health-disease-care-seeking, and land use processes. The population has a broad knowledge of biting insects, which they believe are all most abundant in the rainy season; the community´s proximity to natural areas is perceived as a barrier to control their abundance. Triatomines are mostly recognized by men, who have detailed knowledge regarding their occurrence and association with mammals in non-domestic fragments, where they report being bitten. Women emphasize the dermal consequences of triatomine bites, but have little knowledge about the disease. Triatomine bites and the chinchoma are "normalized" events which are treated using home remedies, if at all. The neglected condition of Chagas disease in Mexican public health policies, livelihoods which are dependent on primary production, and gender-related knowledge (or lack thereof) are structural circumstances which influence the environment and inhabitants´ living conditions; in turn, these trigger triatomine-human contact. The most important landscape practices producing vulnerability are the activities and mobility within and between landscape fragments causing greater exposure of inhabitants primarily in the dry season. A landscape approach to understanding vulnerability components of VBTTc from health-disease-care-seeking perspectives and based on territorial appropriation and use, is essential where there is continuous movement of vectors between and

  5. Social Representations and Practices Towards Triatomines and Chagas Disease in Calakmul, México

    PubMed Central

    Valdez-Tah, Alba; Huicochea-Gómez, Laura; Ortega-Canto, Judith; Nazar-Beutelspacher, Austreberta; Ramsey, Janine M.

    2015-01-01

    Vector-borne transmission of Trypanosoma cruzi (VBTTc) is dependent on the concomitant interaction between biological and environmental hazard over the entire landscape, and human vulnerability. Representations and practices of health-disease-care-seeking and territorial appropriation and use were analyzed for VBTTc in a qualitative ethnographic study in the Zoh-Laguna landscape, Campeche, Mexico. In-depth interviews and participatory observation explored representations and practices regarding ethno-ecological knowledge related to vector-transmission, health-disease-care-seeking, and land use processes. The population has a broad knowledge of biting insects, which they believe are all most abundant in the rainy season; the community´s proximity to natural areas is perceived as a barrier to control their abundance. Triatomines are mostly recognized by men, who have detailed knowledge regarding their occurrence and association with mammals in non-domestic fragments, where they report being bitten. Women emphasize the dermal consequences of triatomine bites, but have little knowledge about the disease. Triatomine bites and the chinchoma are “normalized” events which are treated using home remedies, if at all. The neglected condition of Chagas disease in Mexican public health policies, livelihoods which are dependent on primary production, and gender-related knowledge (or lack thereof) are structural circumstances which influence the environment and inhabitants´ living conditions; in turn, these trigger triatomine-human contact. The most important landscape practices producing vulnerability are the activities and mobility within and between landscape fragments causing greater exposure of inhabitants primarily in the dry season. A landscape approach to understanding vulnerability components of VBTTc from health-disease-care-seeking perspectives and based on territorial appropriation and use, is essential where there is continuous movement of vectors between and

  6. Here, There, and Everywhere: The Ubiquitous Distribution of the Immunosignaling Molecule Lysophosphatidylcholine and Its Role on Chagas Disease.

    PubMed

    Silva-Neto, Mário Alberto C; Lopes, Angela H; Atella, Georgia C

    2016-01-01

    Chagas disease is a severe illness, which can lead to death if the patients are not promptly treated. The disease is caused by the protozoan parasite Trypanosoma cruzi, which is mostly transmitted by a triatomine insect vector. There are 8-10 million people infected with T. cruzi in the world, but the transmission of such disease by bugs occurs only in the Americas, especially Latin America. Chronically infected patients will develop cardiac diseases (30%) and up digestive, neurological, or mixed disorders (10%). Lysophosphatidylcholine (LPC) is the major phospholipid component of oxidized low-density lipoproteins associated with atherosclerosis-related tissue damage. Insect-derived LPC powerfully attracts inflammatory cells to the site of the insect bite, enhances parasite invasion, and inhibits the production of nitric oxide by T. cruzi-stimulated macrophages. The recognition of the ubiquitous presence of LPC on the vector saliva, its production by the parasite itself and its presence both on patient plasma and its role on diverse host × parasite interaction systems lead us to compare its distribution in nature with the title of the famous Beatles song "Here, There and Everywhere" recorded exactly 50 years ago in 1966. Here, we review the major findings pointing out the role of such molecule as an immunosignaling modulator of Chagas disease transmission. Also, we believe that future investigation of the connection of this ubiquity and the immune role of such molecule may lead in the future to novel methods to control parasite transmission, infection, and pathogenesis.

  7. Genetically modifying the insect gut microbiota to control Chagas disease vectors through systemic RNAi.

    PubMed

    Taracena, Mabel L; Oliveira, Pedro L; Almendares, Olivia; Umaña, Claudia; Lowenberger, Carl; Dotson, Ellen M; Paiva-Silva, Gabriela O; Pennington, Pamela M

    2015-02-01

    Technologies based on RNA interference may be used for insect control. Sustainable strategies are needed to control vectors of Chagas disease such as Rhodnius prolixus. The insect microbiota can be modified to deliver molecules to the gut. Here, Escherichia coli HT115(DE3) expressing dsRNA for the Rhodnius heme-binding protein (RHBP) and for catalase (CAT) were fed to nymphs and adult triatomine stages. RHBP is an egg protein and CAT is an antioxidant enzyme expressed in all tissues by all developmental stages. The RNA interference effect was systemic and temporal. Concentrations of E. coli HT115(DE3) above 3.35 × 10(7) CFU/mL produced a significant RHBP and CAT gene knockdown in nymphs and adults. RHBP expression in the fat body was reduced by 99% three days after feeding, returning to normal levels 10 days after feeding. CAT expression was reduced by 99% and 96% in the ovary and the posterior midgut, respectively, five days after ingestion. Mortality rates increased by 24-30% in first instars fed RHBP and CAT bacteria. Molting rates were reduced by 100% in first instars and 80% in third instars fed bacteria producing RHBP or CAT dsRNA. Oviposition was reduced by 43% (RHBP) and 84% (CAT). Embryogenesis was arrested in 16% (RHBP) and 20% (CAT) of laid eggs. Feeding females 105 CFU/mL of the natural symbiont, Rhodococcus rhodnii, transformed to express RHBP-specific hairpin RNA reduced RHBP expression by 89% and reduced oviposition. Modifying the insect microbiota to induce systemic RNAi in R. prolixus may result in a paratransgenic strategy for sustainable vector control. PMID:25675102

  8. Genetically Modifying the Insect Gut Microbiota to Control Chagas Disease Vectors through Systemic RNAi

    PubMed Central

    Taracena, Mabel L.; Oliveira, Pedro L.; Almendares, Olivia; Umaña, Claudia; Lowenberger, Carl; Dotson, Ellen M.; Paiva-Silva, Gabriela O.; Pennington, Pamela M.

    2015-01-01

    Technologies based on RNA interference may be used for insect control. Sustainable strategies are needed to control vectors of Chagas disease such as Rhodnius prolixus. The insect microbiota can be modified to deliver molecules to the gut. Here, Escherichia coli HT115(DE3) expressing dsRNA for the Rhodnius heme-binding protein (RHBP) and for catalase (CAT) were fed to nymphs and adult triatomine stages. RHBP is an egg protein and CAT is an antioxidant enzyme expressed in all tissues by all developmental stages. The RNA interference effect was systemic and temporal. Concentrations of E. coli HT115(DE3) above 3.35 × 107 CFU/mL produced a significant RHBP and CAT gene knockdown in nymphs and adults. RHBP expression in the fat body was reduced by 99% three days after feeding, returning to normal levels 10 days after feeding. CAT expression was reduced by 99% and 96% in the ovary and the posterior midgut, respectively, five days after ingestion. Mortality rates increased by 24-30% in first instars fed RHBP and CAT bacteria. Molting rates were reduced by 100% in first instars and 80% in third instars fed bacteria producing RHBP or CAT dsRNA. Oviposition was reduced by 43% (RHBP) and 84% (CAT). Embryogenesis was arrested in 16% (RHBP) and 20% (CAT) of laid eggs. Feeding females 105 CFU/mL of the natural symbiont, Rhodococcus rhodnii, transformed to express RHBP-specific hairpin RNA reduced RHBP expression by 89% and reduced oviposition. Modifying the insect microbiota to induce systemic RNAi in R. prolixus may result in a paratransgenic strategy for sustainable vector control. PMID:25675102

  9. Adaptive Developmental Delay in Chagas Disease Vectors: An Evolutionary Ecology Approach

    PubMed Central

    Menu, Frédéric; Ginoux, Marine; Rajon, Etienne; Lazzari, Claudio R.; Rabinovich, Jorge E.

    2010-01-01

    Background The developmental time of vector insects is important in population dynamics, evolutionary biology, epidemiology and in their responses to global climatic change. In the triatomines (Triatominae, Reduviidae), vectors of Chagas disease, evolutionary ecology concepts, which may allow for a better understanding of their biology, have not been applied. Despite delay in the molting in some individuals observed in triatomines, no effort was made to explain this variability. Methodology We applied four methods: (1) an e-mail survey sent to 30 researchers with experience in triatomines, (2) a statistical description of the developmental time of eleven triatomine species, (3) a relationship between development time pattern and climatic inter-annual variability, (4) a mathematical optimization model of evolution of developmental delay (diapause). Principal Findings 85.6% of responses informed on prolonged developmental times in 5th instar nymphs, with 20 species identified with remarkable developmental delays. The developmental time analysis showed some degree of bi-modal pattern of the development time of the 5th instars in nine out of eleven species but no trend between development time pattern and climatic inter-annual variability was observed. Our optimization model predicts that the developmental delays could be due to an adaptive risk-spreading diapause strategy, only if survival throughout the diapause period and the probability of random occurrence of “bad” environmental conditions are sufficiently high. Conclusions/Significance Developmental delay may not be a simple non-adaptive phenotypic plasticity in development time, and could be a form of adaptive diapause associated to a physiological mechanism related to the postponement of the initiation of reproduction, as an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) strategy. We identify a series of parameters that can be measured in the field and laboratory to test

  10. Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease

    PubMed Central

    Matthews, Qiana L.; Farrow, Anitra L.; Rachakonda, Girish; Gu, Linlin; Nde, Pius; Krendelchtchikov, Alexandre; Pratap, Siddharth; Sakhare, Shruti S.; Sabbaj, Steffanie; Lima, Maria F.; Villalta, Fernando

    2016-01-01

    Background Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi) trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi infection. The purpose of this work was to design an improved vaccine for T. cruzi using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the T. cruzi amastigote surface protein 2. Methods Protein IX (pIX)-modified Ad vector (Ad5-pIX-ASP-M) was generated, characterized, and validated. C3H/He mice were immunized with Ad5-pIX-ASP-M and Ad5-gp83 and the cell-mediated responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and intracellular staining. Immunized mice were challenged with T. cruzi to evaluate the vaccine efficacy. Results Our findings indicate that Ad5-pIX-ASP-M was viable. Specific CD8+ T-cell mediated responses prior to the challenge show an increase in IFNγ and TNFα production. A single immunization with Ad5-pIX-ASP-M provided protection from T. cruzi infection, but co-immunizations with Ad5-pIX-ASP-M and Ad5-gp83 provided a higher immunoprotection and increased survival rate of mice. Conclusions Overall, these results suggest that the combination of gp83 and ASP-M specific epitopes onto the capsid-incorporated adenoviruses would provide superior protection against Chagas disease as compared with Ad5-gp83 alone.

  11. Type 1 chemokine receptor expression in Chagas' disease correlates with morbidity in cardiac patients.

    PubMed

    Gomes, Juliana A S; Bahia-Oliveira, Lilian M G; Rocha, Manoel Otávio C; Busek, Solange C U; Teixeira, Mauro M; Silva, João Santana; Correa-Oliveira, Rodrigo

    2005-12-01

    Chemokines and chemokine receptors (CKRs) control the migration of leukocytes during the inflammatory process and are important immunological markers of type 1 (CCR5 and CXCR3) and type 2 (CCR3 and CCR4) responses. The coexpression of CKRs (CCR2, CCR3, CCR5, CXCR3, and CXCR4) and intracellular cytokines (interleukin-10 [IL-10], IL-4, tumor necrosis factor alpha [TNF-alpha], and gamma interferon [IFN-gamma]) on T CD4+ and CD8+ peripheral cells from individuals with indeterminate (IND) or cardiac (CARD) clinical forms of Chagas' disease after in vitro stimulation with Trypanosoma cruzi antigens, were evaluated in this study. The percentage of T CD4+ and CD8+ cells coexpressing CCR5 and IFN-gamma, CXCR3 and IFN-gamma, and CXCR3 and TNF-alpha were higher in CARD than in IND individuals; on the other hand, the percentage of T CD4+ or CD8+ cells coexpressing CCR3 and IL-10 or coexpressing CCR3 and IL-4 were lower in CARD individuals than in IND individuals. In addition, a significant positive correlation between the expression of CCR5 or CXCR3 and IFN-gamma was observed in CARD individuals contrasting with a significant positive correlation between the expression of CCR3 and IL-4 and of CCR3 and IL-10 in IND patients. These results reinforce the hypothesis that a T. cruzi-exacerbated specific type 1 immune response developed by CARD chagasic patients is associated with the development of heart pathology.

  12. NADPH oxidase inhibition ameliorates Trypanosoma cruzi-induced myocarditis during Chagas disease

    PubMed Central

    Dhiman, Monisha; Garg, Nisha Jain

    2015-01-01

    Trypanosoma cruzi, the aetiological agent of Chagas disease, invades nucleated mammalian cells including macrophages. In this study, we investigated the crosstalk between T. cruzi-induced immune activation of reactive oxygen species (ROS) and pro-inflammatory responses, and their role in myocardial pathology. Splenocytes of infected mice (C3H/HeN) responded to Tc-antigenic stimulus by more than a two-fold increase in NADPH oxidase (NOX) activity, ROS generation, cytokine production (IFN-γ > IL-4 > TNFα > IL1-β ≈ IL6), and predominant expansion of CD4+ and CD8+ T cells. Inhibition of NOX, but not of myeloperoxidase and xanthine oxidase, controlled the ROS (>98%) and cytokine (70–89%) release by Tc-stimulated splenocytes of infected mice. Treatment of infected mice with apocynin (NOX inhibitor) in drinking water resulted in a 50–90% decline in endogenous NOX/ROS and cytokine levels, and splenic phagocytes’ proliferation. The splenic percentage of T cells was maintained, though more than a 40% decline in splenic index (spleen weight/body weight) indicated decreased T-cell proliferation in apocynin-treated/infected mice. The blood and tissue parasite burden were significantly increased in apocynin-treated/infected mice, yet acute myocarditis, ie inflammatory infiltrate consisting of macrophages, neutrophils, and CD8+ T cells, and tissue oxidative adducts (eg 8-isoprostanes, 3-nitrotyrosine, and 4-hydroxynonenal) were diminished in apocynin-treated/infected mice. Consequently, hypertrophy (increased cardiomyocytes’ size and β-MHC, BNP, and ANP mRNA levels) and fibrosis (increased collagen, glycosaminoglycans, and lipid contents) of the heart during the chronic phase were controlled in apocynin-treated mice. We conclude that NOX/ROS is a critical regulator of the splenic response (phagocytes, T cells, and cytokines) to T. cruzi infection, and bystander effects of heart-infiltrating phagocytes and CD8+ T cells resulting in cardiac remodelling in chagasic

  13. Safety Profile of Nifurtimox for Treatment of Chagas Disease in the United States

    PubMed Central

    Forsyth, Colin J.; Hernandez, Salvador; Olmedo, Wilman; Abuhamidah, Adieb; Traina, Mahmoud I.; Sanchez, Daniel R.; Soverow, Jonathan; Meymandi, Sheba K.

    2016-01-01

    Background. Nifurtimox is 1 of only 2 medications available for treating Chagas disease (CD) and currently the only drug available in the United States, but its safety and tolerance have not been extensively studied. This is the first study to evaluate tolerance of nifurtimox in US patients with CD. Methods. This investigation assessed side effects in a sample of 53 patients with CD, all Latin American immigrants, who underwent treatment with nifurtimox (8–10 mg/kg in 3 daily doses for 12 weeks) from March 2008 to July 2012. The frequency and severity of adverse events (AEs) was recorded. Results. A total of 435 AEs were recorded; 93.8% were mild, 3.0% moderate, and 3.2% severe. Patients experienced a mean of 8.2 AEs; the most frequent were anorexia (79.2%), nausea (75.5%), headache (60.4%), amnesia (58.5%), and >5% weight loss (52.8%). Eleven patients (20.8%) were unable to complete treatment. Experiencing a moderate or severe AE (odds ratio [OR], 3.82; P < .05) and Mexican nationality (OR, 2.29; P < .05) were significant predictors of treatment discontinuation, but sex and cardiac progression at baseline were not. Patients who did not complete treatment experienced nearly 3 times more AEs per 30-day period (P = .05). Conclusions. Nifurtimox produces frequent side effects, but the majority are mild and can be managed with dose reduction and/or temporary suspension of medication. The high frequency of gastrointestinal symptoms and weight loss mirrors results from prior investigations. Special attention should be paid during the early stages of treatment to potentially severe symptoms including depression, rash, and anxiety. PMID:27432838

  14. Right Ventricular Doppler Echocardiographic Study of Indeterminate Form of Chagas Disease

    PubMed Central

    Furtado, Rogério Gomes; Frota, Daniela do Carmo Rassi; Silva, João Batista Masson; Romano, Minna Moreira Dias; de Almeida, Oswaldo César; Schmidt, André; Rassi, Salvador

    2015-01-01

    Background Patients with indeterminate form of Chagas disease/cardiac normality (ICD/CN) exhibited normal electrocardiograms and chest X-rays; however, more sophisticated tests detected some degree of morphological and functional changes in the heart. Objective To assess the prevalence of systolic and diastolic dysfunction of the right ventricle (RV) in patients with ICD/CN. Methods This was a case–control and prevalence study. Using Doppler two-dimensional echocardiography (2D), 92 patients were assessed and divided into two groups: group I (normal, n = 31) and group II (ICD/CN, n = 61). Results The prevalence of RV systolic dysfunction in patients in groups I and II was as follows: fractional area change (0.0%