Cruzi Transmission Research Articles

Low seroprevalence of Trypanosoma cruzi infection and chronic chagasic cardiomyopathy in a region with abundance of triatomine vectors in Yucatan Peninsula of Mexico.

The Yucatan Peninsula of Mexico is endemic with Chagas disease. The main vector responsible for Trypanosoma cruzi transmission is Triatoma dimidiata which is abundant in domestic, peridomestic and sylvan cycles. The abundance of vectors favours T. cruzi transmission and is a high risk for developing chronic chagasic cardiomyopathy (CCC). In the past 10 years, little information was available on parasite seroprevalence and the prevalence of CCC in the Yucatan Peninsula. In the present work, we studied two Mayan communities with a high abundance of T. dimidiata and a random serial sample of 233 patients with an altered electrocardiogram or cardiac failure admitted to the Regional Hospital. A homemade enzyme-linked immunosorbent assay and indirect immunofluorescence standardized techniques were used to detect anti-T. cruzi IgG. In addition, Mayan volunteers were monitored by electrocardiography. In the Mayan communities, 4.8% (3/63) subjects were positive for T. cruzi antibodies none of them presented electrocardiographic alterations, however in seronegative subjects were detected right or left ventricle hypertrophy in 25% (16/63). A remarkable finding was that 90% of the Mayan population recognized the vector and 65% of them had experienced contact with triatomines bites. At the Regional Hospital 0.42% (1/233) were positive for T. cruzi antibodies showing compatible diagnosis with CCC; the most frequent pathology in this population was hypertension in 65% (151/233) and the less frequent was dilated myocardiopathy 6% (14/233). In conclusion, the prevalence of T. cruzi infection and CCC can be considered low in Yucatan, Mexico.

Host switching vs. host sharing in overlapping sylvatic Trypanosoma cruzi transmission cycles

ABSTRACTThe principle of competitive exclusion is well established for multiple populations competing for the same resource, and simple models for multistrain infection exhibit it as well when cross-immunity precludes coinfections. However, multiple hosts provide niches for different pathogens to occupy simultaneously. This is the case for the vector-borne parasite Trypanosoma cruzi in overlapping sylvatic transmission cycles in the Americas, where it is enzootic. This study uses cycles in the USA involving two different hosts but the same vector species as a context for the study of the mechanisms behind the communication between the two cycles. Vectors dispersing in search of new hosts may be considered to move between the two cycles (host switching) or, more simply, to divide their time between the two host types (host sharing). Analysis considers host switching as an intermediate case between isolated cycles and intermingled cycles (host sharing) in order to examine the role played by the host-switching rate in permitting coexistence of multiple strains in a single-host population. Results show that although the population dynamics (demographic equilibria) in host-switching models align well with those in the limiting models (host sharing or isolated cycles), infection dynamics differ significantly, in ways that sometimes illuminate the underlying epidemiology (such as differing host susceptibilities to infection) and sometimes reveal model limitations (such as host switching dominating the infection dynamics). Numerical work suggests that the model explains the trace presence of TcI in raccoons but not the more significant co-persistence observed in woodrats.

Eco-epidemiology of Chagas disease in an endemic area of Colombia: risk factor estimation, Trypanosoma cruzi characterization and identification of blood-meal sources in bugs.

The Sierra Nevada de Santa Marta (SNSM) is a mountainous area in Colombia that is highly endemic to Chagas disease. We explored some eco-epidemiological attributes involved in the Chagas disease transmission scenario in three Indigenous communities. An epidemiological survey was done, where parasite infection in reservoirs and insects, Trypanosoma cruzi genotyping, identification of blood-meal sources in intradomiciliary insects using the high-resolution melting technique, and some risk factors were evaluated. The results suggest that several dwelling conditions such as thatched palm roofs and mud walls carried the highest risk of finding intradomiciliary Rhodnius prolixus, which 56.41% were infected with T. cruzi and fed with human blood. Moreover, T. cruzi Ia was the most frequent haplotype found in insects. These results indicate the existence of a domestic T. cruzi transmission cycle that does not overlap with the sylvatic cycle, and highlight the need for efficient entomological control focused to this area.

Ecological, social and biological risk factors for continued Trypanosoma cruzi transmission by Triatoma dimidiata in Guatemala.

BackgroundChagas disease transmission by Triatoma dimidiata persists in Guatemala and elsewhere in Central America under undefined ecological, biological and social (eco-bio-social) conditions.MethodologyEco-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 FindingsBlood 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/SignificancePersistent 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 peridomestic animals in transmission and community memberś level of knowledge, attitudes and practices associated with the disease and transmission process.

Trypanosoma cruzi transmission in a Colombian Caribbean region suggests that secondary vectors play an important epidemiological role.

BackgroundColombia, as part of The Andean Countries Initiative has given priority to triatomine control programs to eliminate primary (domiciliated) vector species such as Rhodnius prolixus and Triatoma dimidiata. However, recent events of Trypanosoma cruzi transmission in localities where R. prolixus and T. dimidiata are not present suggest that other species are involved in the T. cruzi transmission cycle.MethodsWe studied T. cruzi transmission on Margarita Island, located on the Magdalena River in the Colombian Caribbean region, where a high number of non-domiciliated triatomines infected with T. cruzi inside human dwellings have been observed. A cross-sectional survey including serological studies in humans and parasitological and molecular methods in vectors and reservoirs was conducted. We investigated risk factors for human infection and house infestation, and evaluated the association between abundance of wild triatomines in palm trees (Attalea butyracea) across municipalities, seasons and anthropogenic land use.ResultsThe T. cruzi seroprevalence rate in humans was 1.7% (13/743) and autochthonous active T. cruzi transmission was detected. The infection risk was associated with the capture of triatomines in human dwellings. Five wild mammal species were infected with T. cruzi, where Didelphis marsupialis was the main reservoir host with an 86.3% (19/22) infection rate. TcIb was the only genotype present among vectors. Triatomine abundance was significantly higher in Ecosystem 2, as well as in the dry season. Despite the absence of triatomine domiciliation in this area, T. cruzi active transmission was registered with a human seroprevalence rate similar to that reported in areas with domesticated R. prolixus.ConclusionsThis study illustrates the importance of secondary and household invading triatomines in Chagas disease epidemiology in the Caribbean lowlands of Colombia.

Circulation of Tc Ia discrete type unit Trypanosoma cruzi in Yucatan Mexico.

The etiologic agent Trypanosoma cruzi (Tc) has been grouped into six discrete type units (DTU I-VI); within DTU-I exists four subgroups defined Ia-Id. In Colombia, the genotype Ia is associated with human infection and domiciliated Rhodnius vector. In the Yucatan Peninsula of Mexico, the main vector involved in T. cruzi transmission is Triatoma dimidiata predominantly via sylvatic and peridomiciliated cycles. In this study, multiple sequence analysis of mini-exon intergenic regions of T. cruzi isolates obtained from T. dimidiata in the Yucatan Peninsula of Mexico revealed they belonged to Tc Ia DTU along with two additional Mexican strains located 1,570km away from Yucatan. In conclusion Tc Ia circulates in the Yucatan peninsula in T. dimidiata vector and likewise in the northwest region of Mexico.

Wild Trypanosoma cruzi I genetic diversity in Brazil suggests admixture and disturbance in parasite populations from the Atlantic Forest region.

BackgroundTrypanosoma cruzi (Kinetoplastida, Trypanosomatidae) infection is an ancient and widespread zoonosis distributed throughout the Americas. Ecologically, Brazil comprises several distinct biomes: Amazonia, Cerrado, Caatinga, Pantanal and the Atlantic Forest. Sylvatic T. cruzi transmission is known to occur throughout these biomes, with multiple hosts and vectors involved. Parasite species-level genetic diversity can be a useful marker for ecosystem health. Our aims were to: investigate sylvatic T. cruzi genetic diversity across different biomes, detect instances of genetic exchange, and explore the possible impact of ecological disturbance on parasite diversity at an intra-species level.MethodsWe characterised 107 isolates of T. cruzi I (TcI; discrete typing unit, DTU I) from different major Brazilian biomes with twenty-seven nuclear microsatellite loci. A representative subset of biologically cloned isolates was further characterised using ten mitochondrial gene loci. We compared these data generated from Brazilian TcI isolates from around America.ResultsGenetic diversity was remarkably high, including one divergent cluster that branched outside the known genetic diversity of TcI in the Americas. We detected evidence for mitochondrial introgression and genetic exchange between the eastern Amazon and Caatinga. Finally, we found strong signatures of admixture among isolates from the Atlantic Forest region by comparison to parasites from other study sites.ConclusionsAtlantic Forest sylvatic TcI populations are highly fragmented and admixed by comparison to others around Brazil. We speculate on: the possible causes of Atlantic Forest admixture; the role of T. cruzi as a sentinel for ecosystem health, and the impact disrupted sylvatic transmission cycles might have on accurate source attribution in oral outbreaks.

Graphical analysis of evolutionary trade-off in sylvatic Trypanosoma cruzi transmission modes

The notion of evolutionary trade-off (one attribute increasing at the expense of another) is central to the evolution of traits, well-studied especially in life-history theory, where a framework first developed by Levins illustrates how internal (genetics) and external (fitness landscapes) forces interact to shape an organism׳s ongoing adaptation. This manuscript extends this framework to the context of vector-borne pathogens, with the example of Trypanosoma cruzi (the etiological agent of Chagas׳ disease) adapting via trade-off among three different infection routes to hosts—stercorarian, vertical, and oral—in response to an epidemiological landscape that involves both hosts and vectors (where, in particular, parasite evolution depends not on parasite density but on relative host and vector densities). Using a fitness measure derived from an invasion reproductive number, this study analyzes several different trade-off scenarios in cycles involving raccoons or woodrats, including a proper three-way trade-off (two independent parameters). Results indicate that selection favors oral transmission to raccoons but classical stercorarian transmission to woodrats even under the same predation rate, with vertical (congenital) transmission favored only when aligned with dominant oral transmission or (at trace levels) under a weak (convex) trade-off.

Trypanosoma cruzi infection in neotropical wild carnivores (Mammalia: Carnivora): at the top of the T. cruzi transmission chain.

Little is known on the role played by Neotropical wild carnivores in the Trypanosoma cruzi transmission cycles. We investigated T. cruzi infection in wild carnivores from three sites in Brazil through parasitological and serological tests. The seven carnivore species examined were infected by T. cruzi, but high parasitemias detectable by hemoculture were found only in two Procyonidae species. Genotyping by Mini-exon gene, PCR-RFLP (1f8/Akw21I) and kDNA genomic targets revealed that the raccoon (Procyon cancrivorus) harbored TcI and the coatis (Nasua nasua) harbored TcI, TcII, TcIII-IV and Trypanosoma rangeli, in single and mixed infections, besides four T. cruzi isolates that displayed odd band patterns in the Mini-exon assay. These findings corroborate the coati can be a bioaccumulator of T. cruzi Discrete Typing Units (DTU) and may act as a transmission hub, a connection point joining sylvatic transmission cycles within terrestrial and arboreal mammals and vectors. Also, the odd band patterns observed in coatis’ isolates reinforce that T. cruzi diversity might be much higher than currently acknowledged. Additionally, we assembled our data with T. cruzi infection on Neotropical carnivores’ literature records to provide a comprehensive analysis of the infection patterns among distinct carnivore species, especially considering their ecological traits and phylogeny. Altogether, fifteen Neotropical carnivore species were found naturally infected by T. cruzi. Species diet was associated with T. cruzi infection rates, supporting the hypothesis that predator-prey links are important mechanisms for T. cruzi maintenance and dispersion in the wild. Distinct T. cruzi infection patterns across carnivore species and study sites were notable. Musteloidea species consistently exhibit high parasitemias in different studies which indicate their high infectivity potential. Mesocarnivores that feed on both invertebrates and mammals, including the coati, a host that can be bioaccumulator of T. cruzi DTU’s, seem to take place at the top of the T. cruzi transmission chain.

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)

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.

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)

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.

Vector migration and dispersal rates for sylvatic Trypanosoma cruzi transmission

The spread of vector-borne diseases are greatly increased by a vector's ability to migrate. Recent studies of sylvatic Trypanosoma cruzi transmission have motivated the study of vector migration across geographic regions. Due to the natural mechanisms in which vector-borne diseases are transmitted between vectors and hosts, vector dispersal among different host populations is a critical factor in the ability of the parasite to be spread across large regions. In this study we develop a general framework for deriving large-scale, discrete-space migration rates from small-scale, continuous-space dispersal data. We identify three defining characteristics of vector migration: distance, preferred direction of dispersal, and strength of preference for a particular direction. We consider several migration scenarios in which vectors may have no preference for dispersal in a particular direction or may disperse with a preferred direction, such as northeast. We examine what effect preferred direction has on the migration rate, as well as use the local to global framework to calculate numerical estimates for vector migration rates for the primary vectors in the southeast U.S. and northern Mexico, Triatoma sanguisuga and Triatoma gerstaeckeri, based on biological and experimental data. Results from this study can be applied to metapopulation models for species that migrate.

Trypanosoma cruzi among wild and domestic mammals in different areas of the Abaetetuba municipality (Pará State, Brazil), an endemic Chagas disease transmission area

The presence of acute Chagas disease (ACD) due to oral transmission is growing and expanding in several South American countries. Within the Amazon basin, the Abaetetuba municipality has been a site of recurrent cases spanning across distinct landscapes. Because Chagas disease is primarily a zoonotic infection, we compared the enzootic Trypanosoma cruzi transmission cycles in three different environmental areas of Abaetetuba to better understand this new epidemiological situation. Philander opossum was the most abundant mammalian species collected (38% of the collected mammals) with a T. cruzi prevalence of 57%, as determined by hemocultures. Didelphis marsupialis was abundant only in the area with the higher level of environmental disturbance (approximately 42%) and did not yield detectable parasitemia. Despite similarities observed in the composition of the small mammalian fauna and the prevalence of T. cruzi infection among the studied areas, the potential of these hosts to infect vectors differed significantly according to the degree of land use (with prevalences of 5%, 41%, and 64% in areas A3, A1 and A2, respectively). Domestic mammals were also found to be infected, and one canine T. cruzi isolate was obtained. Our data demonstrated that the transmission of T. cruzi in the Amazon basin is far more complex than had been previously taught and showed that the probability of humans and domestic mammals coming into contact with infected bugs can vary dramatically, even within the same municipality. The exposure of dogs to T. cruzi infection (indicated by positive serology) was the common feature among the studied localities, stressing the importance of selecting domestic mammals as sentinels in the identification of T. cruzi transmission hotspots.

Trypanosoma cruzi Infection in an Indigenous Kariña Community in Eastern Venezuela

We investigated the seroprevalence of Trypanosoma cruzi infection in an indigenous Kariña population in eastern Venezuela. A total of 175 serum samples were collected in the community of Piñantal during February 2009. Interviews targeting socioeconomic and environmental factors associated with the T. cruzi transmission were also conducted. Samples were evaluated using trypomastigote excreted/secreted antigens (TESAs) in an ELISA format. TESA-ELISA positive samples were confirmed by indirect haemagglutination (HAI) (Wiener). A nonsystematic collection of vectors was also undertaken. T. cruzi seroprevalence was 7.43% according to both assays, and the mean age of infected patients was 48.61±10.40 years (range 34 to 73 years). The vector infection rate was 20.00% (2/10). T. cruzi seropositivity was associated with a history of triatomine bites, the ability to recognize the vector and poor knowledge about Chagas disease, but no associations were found with gender, house type, knowledge of how the disease is transmitted, or the presence of vectors or animals inside dwellings. To our knowledge, this is the first study of the seroprevalence of T. cruzi in an indigenous population in eastern Venezuela. All of the epidemiological variables required for the establishment of active vectorial transmission of T. cruzi were present in this community.

Lower Richness of Small Wild Mammal Species and Chagas Disease Risk

A new epidemiological scenario involving the oral transmission of Chagas disease, mainly in the Amazon basin, requires innovative control measures. Geospatial analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have been scarce. We applied interpolation and map algebra methods to evaluate mammalian fauna variables related to small wild mammals and the T. cruzi infection pattern in dogs to identify hotspot areas of transmission. We also evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease. Dogs (n = 649) were examined by two parasitological and three distinct serological assays. kDNA amplification was performed in patent infections, although the infection was mainly sub-patent in dogs. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 11–89% in different localities. The interpolation method and map algebra were employed to test the associations between the lower richness in mammal species and the risk of exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the reduction of the mammal fauna (richness and abundance) was associated with higher parasitemia in small wild mammals and higher exposure of dogs to infection. A Generalized Linear Model (GLM) demonstrated that species richness and positive hemocultures in wild mammals were associated with T. cruzi infection in dogs. Domestic canine infection rates differed significantly between areas with and without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by interpolation and map algebra methods proved to be a powerful tool in the evaluation of areas of T. cruzi transmission. Dog infection was shown to not only be an efficient indicator of reduction of wild mammalian fauna richness but to also act as a signal for the presence of small wild mammals with high parasitemia. The lower richness of small mammal species is discussed as a risk factor for the re-emergence of Chagas disease.

The role of adaptations in two-strain competition for sylvatic Trypanosoma cruzi transmission

This study presents a continuous-time model for the sylvatic transmission dynamics of two strains of Trypanosoma cruzi enzootic in North America, in order to study the role that adaptations of each strain to distinct modes of transmission (classical stercorarian transmission on the one hand, and vertical and oral transmission on the other) may play in the competition between the two strains. A deterministic model incorporating contact process saturation predicts competitive exclusion, and reproductive numbers for the infection provide a framework for evaluating the competition in terms of adaptive trade-off between distinct transmission modes. Results highlight the importance of oral transmission in mediating the competition between horizontal (stercorarian) and vertical transmission; its presence as a competing contact process advantages vertical transmission even without adaptation to oral transmission, but such adaptation appears necessary to explain the persistence of (vertically-adapted) T. cruzi IV in raccoons and woodrats in the southeastern United States.

Study on Chagas disease occurrence in the municipality of Monte Negro, State of Rondônia, Brazilian Amazon

Studies on Chagas disease deal with the perspective of its occurrence in the Amazon region, which is directly correlated to the population growth and the spread of the bug biotope. The state of Rondônia has an immense source of vectors (Triatomine) and reservoirs of Trypanosoma cruzi. Environmental changes brought forth by the deforestation in the region may cause vector behavior changes and bring these vectors to a closer contact with humans, increasing the probability of vector infection. This study was carried out to check the occurrence of Chagas disease in the municipality of Monte Negro, Rondônia, Brazil, based on a random sampling of the farms and people wherein blood collection from the population and capturing triatomines were done. The blood samples were submitted to serologic tests to detect antibodies of the IgG class against T. cruzi. The triatomines that were collected had their digestive tract checked for the presence of trypanosomatidae with morphology resembling that of the T. cruzi. The population examined was mostly from other states. From the 322 bugs examined on the microscope, 50% showed parasites with morphology compatible with T. cruzi. From the serology of 344 random samples of human blood, 1.2% was found positive, 6% showed inconclusive results, and 92.8% were negative. Monte Negro shows low prevalence of human infection by T. cruzi and none active vector transmission; however, preventive and surveying measures, which are not performed until now, shall be taken due to the abundance of vectors infected by trypanosomatidae.

Attraction of Chagas disease vectors (Triatominae) to artificial light sources in the canopy of primary Amazon rainforest

Adult triatomines occasionally fly into artificially lit premises in Amazonia. This can result in Trypanosoma cruzi transmission to humans either by direct contact or via foodstuff contamination, but the frequency of such behaviour has not been quantified. To address this issue, a light-trap was set 45 m above ground in primary rainforest near Manaus, state of Amazonas, Brazil and operated monthly for three consecutive nights over the course of one year (432 trap-hours). The most commonly caught reduviids were triatomines, including 38 Panstrongylus geniculatus, nine Panstrongylus lignarius, three Panstrongylus rufotuberculatus, five Rhodnius robustus, two Rhodnius pictipes, one Rhodnius amazonicus and 17 Eratyrus mucronatus. Males were collected more frequently than females. The only month without any catches was May. Attraction of most of the known local T. cruzi vectors to artificial light sources is common and year-round in the Amazon rainforest, implying that they may often invade premises built near forest edges and thus become involved in disease transmission. Consequently, effective Chagas disease prevention in Amazonia will require integrating entomological surveillance with the currently used epidemiological surveillance.

Chagas Disease: Progress and New Perspectives

Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite Trypanosoma cruzi. The Pan American Health Organization (PAHO) estimates that currently 7.7 million of people have Trypanosoma cruzi infection in the 21 endemic countries from the southern and southwestern United States to central Argentina and Chile. The only approved therapeutics for the treatment of Chagas disease are two nitroheterocyclic compounds as a nitrofuran (nifurtimox; Lampit) and a nitroimidazole (benznidazole; Rochagan). However, the anti-Trypanosoma cruzi activities of these compounds were discovered empirically over three decades ago. The treatment of Chagas disease with nifurtimox or benznidazole is unsatisfactory because of their limited efficacy in the prevalent chronic stage of the disease and their toxic side effects. In this context, this article will review the current knowledge of the different aspects involved in this illness, such as Trypanosoma cruzi transmission, physiology and biochemistry of the etiological agent, epidemiological aspects and current treatments for American trypanosomiasis. An important section of this review will focus on the different strategies in drug discovery for Chagas disease, including methodology, in vitro screening studies against whole parasites, novel rationally developed approaches on the basis of the increasing knowledge of the biochemistry of Trypanosoma cruzi and the recent progress in the understanding and validation of several targets for the therapy of Chagas's disease. A summary of the most relevant drug targets such as sterol biosynthesis pathway, cysteine protease pathway, pyrophosphate metabolism and purine salvage pathway will be reviewed. Moreover, recent studies regarding other strategies currently under development including thiol-dependent redox metabolism, lysophospholipid analogues and DNA binders will also be discussed.

Microdistribution of Sylvatic Triatomine Populations in Central-Coastal Ecuador

Chagas disease is a serious public health problem in Ecuador, where nearly 230,000 individuals show Trypanosoma cruzi infection. Sylvatic T. cruzi transmission is a threat to current control strategies. This is because of the possibility of house reinfestation by sylvatic triatomines after insecticide treatment. This work quantified the spatial distribution of triatomines in sylvatic habitats and its relationship with nearby human dwellings. A simple random sampling design using live-baited traps and manual searches for triatomines was used in areas near human communities in Manabi province, Ecuador, during June and July 2007. We identified risk factors associated with triatomine density using generalized linear models, and developed predictive maps for triatomine density interpolation. There were 345 triatomines belonging to the species Rhodnius ecuadoriensis and Panstrongylus howardi collected in sylvatic areas. Spatial analyses revealed an aggregated distribution pattern of the sylvatic triatomine populations (clustered mostly at a distance smaller than 100 m). Generalized linear models showed that the distance from the nearest house, nest type, and height from ground level were the main factors explaining triatomine densities. Squirrel nests (Sciurus stramineus), located in plants other than palms, above 5 m and close to the domicile presented higher infestation. Interpolation maps of triatomine microdistribution are presented as potential tools to predict triatomine occurrence. The presence of sylvatic populations and the synanthropic tendency of the vectors highlight the need for continuous active and passive entomological surveillance for the long-term control of Chagas disease.