scholarly journals The economic value of identifying and treating Chagas disease patients earlier and the impact on Trypanosoma cruzi transmission

2018 ◽  
Vol 12 (11) ◽  
pp. e0006809 ◽  
Author(s):  
Sarah M. Bartsch ◽  
Cameron M. Avelis ◽  
Lindsey Asti ◽  
Daniel L. Hertenstein ◽  
Martial Ndeffo-Mbah ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Economic Value ◽  
The Impact

Population structure and genetic typing of Trypanosoma cruzi, the agent of Chagas disease: a multilocus enzyme electrophoresis approach

Parasitology ◽  
2000 ◽  
Vol 120 (5) ◽  
pp. 513-526 ◽  
Author(s):  
C. BARNABÉ ◽  
S. BRISSE ◽  
M. TIBAYRENC
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Natural Populations ◽  
Enzyme Electrophoresis ◽  
Strong Linkage Disequilibrium ◽  
Multilocus Enzyme Electrophoresis ◽  
Routine Identification ◽  
Genetic Clusters ◽  
Phylogenetic Lineages ◽  
The Impact

A set of 434 Trypanosoma cruzi stocks from a wide ecogeographical range was analysed by Multilocus Enzyme Electrophoresis for 22 genetic loci. Strong linkage disequilibrium, not associated with geographical distance, and 2 main genetic clusters each considerably heterogeneous, was observed. These results support the hypotheses previously proposed that T. cruzi natural populations are composed of highly diversified genetic clones distributed into 2 main phylogenetic lineages: lineage 1, the most ubiquitous in the endemic area, was more frequently observed in sylvatic cycles, whereas lineage 2, predominant in humans and domestic cycles, in the southern part of the area surveyed, was further partitioned into 5 lesser genetic subdivisions. T. cruzi appears therefore subdivided into at least 6 ‘discrete typing units’ or DTUs (Tibayrenc, 1998a–c). We have identified various specific isoenzyme markers (‘tags’; Tibayrenc, op. cit.) suitable for the routine identification of these DTUs for epidemiological tracking purposes. We discuss the correspondence with previous classifications and with the recent recommendations of the 90th anniversary of the discovery of Chagas disease symposium, as well as the impact of T. cruzi genetic variability on this parasite's biomedical diversity.

scholarly journals Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1

2015 ◽  
Vol 59 (5) ◽  
pp. 2666-2677 ◽  
Author(s):  
Nayara Cristina Fonseca ◽  
Luana Faria da Cruz ◽  
Filipe da Silva Villela ◽  
Glaécia Aparecida do Nascimento Pereira ◽  
Jair Lage de Siqueira-Neto ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Schistosoma Mansoni ◽  
Trypanosoma Brucei ◽  
Chagas Disease ◽  
Cysteine Proteases ◽  
Content Type ◽  
Structure Activity ◽  
Biochemical Assays ◽  
The Impact

ABSTRACTThe pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, andSchistosoma mansoniCB1 (SmCB1), the major cysteine proteases fromTrypanosoma cruzi,Trypanosoma brucei, andS. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50= 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluatedin vitroagainst the parasitesT. cruzi,T. brucei, andS. mansoni, revealing active compounds among this series.

scholarly journals Purinergic Antagonist Suramin Aggravates Myocarditis and Increases Mortality by Enhancing Parasitism, Inflammation, and Reactive Tissue Damage in Trypanosoma cruzi-Infected Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Rômulo D. Novaes ◽  
Eliziária C. Santos ◽  
Marli C. Cupertino ◽  
Daniel S. S. Bastos ◽  
Andréa A. S. Mendonça ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Tissue Damage ◽  
Mammalian Cells ◽  
Negative Impact ◽  
Purinergic Signaling ◽  
Host Cells ◽  
Antioxidant Defenses ◽  
The Impact

Suramin (Sur) acts as an ecto-NTPDase inhibitor in Trypanosoma cruzi and a P2-purinoceptor antagonist in mammalian cells. Although the potent antitrypanosomal effect of Sur has been shown in vitro, limited evidence in vivo suggests that this drug can be dangerous to T. cruzi-infected hosts. Therefore, we investigated the dose-dependent effect of Sur-based chemotherapy in a murine model of Chagas disease. Seventy uninfected and T. cruzi-infected male C57BL/6 mice were randomized into five groups: SAL = uninfected; INF = infected; SR5, SR10, and SR20 = infected treated with 5, 10, or 20 mg/kg Sur. In addition to its effect on blood and heart parasitism, the impact of Sur-based chemotherapy on leucocytes myocardial infiltration, cytokine levels, antioxidant defenses, reactive tissue damage, and mortality was analyzed. Our results indicated that animals treated with 10 and 20 mg/kg Sur were disproportionally susceptible to T. cruzi, exhibiting increased parasitemia and cardiac parasitism (amastigote nests and parasite load (T. cruzi DNA)), intense protein, lipid and DNA oxidation, marked myocarditis, and mortality. Animals treated with Sur also exhibited reduced levels of nonprotein antioxidants. However, the upregulation of catalase, superoxide dismutase, and glutathione-S-transferase was insufficient to counteract reactive tissue damage and pathological myocardial remodeling. It is still poorly understood whether Sur exerts a negative impact on the purinergic signaling of T. cruzi-infected host cells. However, our findings clearly demonstrated that through enhanced parasitism, inflammation, and reactive tissue damage, Sur-based chemotherapy contributes to aggravating myocarditis and increasing mortality rates in T. cruzi-infected mice, contradicting the supposed relevance attributed to this drug for the treatment of Chagas disease.

scholarly journals The Potential Economic Value of a Trypanosoma cruzi (Chagas Disease) Vaccine in Latin America

2010 ◽  
Vol 4 (12) ◽  
pp. e916 ◽  
Author(s):  
Bruce Y. Lee ◽  
Kristina M. Bacon ◽  
Diana L. Connor ◽  
Alyssa M. Willig ◽  
Rachel R. Bailey
Keyword(s):  
Latin America ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Economic Value

scholarly journals Spatial metabolomics identifies localized chemical changes in heart tissue during chronic cardiac Chagas disease

2020 ◽  
Author(s):  
Danya A. Dean ◽  
Gautham ◽  
Jair L. Siqueira-Neto ◽  
James H. McKerrow ◽  
Pieter C. Dorrestein ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Burden ◽  
Heart Tissue ◽  
Blood Transfusions ◽  
Organ Transplants ◽  
Chronic Stage ◽  
Congenital Transmission ◽  
Cardiac Symptoms ◽  
The Impact

AbstractChagas disease (CD) is one of thirteen neglected tropical diseases caused by the parasite Trypanosoma cruzi. CD is a vector-borne disease transmitted by triatomines but CD can also be transmitted through blood transfusions, organ transplants and congenital transmission. While endemic to Latin America, T. cruzi infects 7-8 million people worldwide and can induce severe cardiac symptoms including apical aneurysms, thromboembolisms and arrhythmias during the chronic stage of CD. However, these cardiac clinical manifestations and CD disease pathogenesis are not fully understood. Using spatial metabolomics (chemical cartography), we sought to understand the localized impact of infection on the cardiac metabolome of mice chronically infected with two divergent T. cruzi strains. Our data showed chemical differences in localized cardiac regions upon chronic T. cruzi infection, indicating that parasite infection changes the host metabolome at select sites in chronic CD. These sites were distinct from the sites of highest parasite burden. In addition, we identified acylcarnitines and phosphocholines as discriminatory chemical families within each heart region, comparing infected and uninfected samples. Overall, our study indicated overall and positional metabolic differences common to infection with different T. cruzi strains, and identified select infection-modulated pathways. These results provide further insight into CD pathogenesis and demonstrate the advantage of a spatial perspective to understand infectious disease tropism.Author SummaryChagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi. CD originated in South America; however, there are now 7-8 million people infected worldwide due to population movements. CD is transmitted through a triatomine vector, organ transplants, blood transfusions and congenital transmission. It occurs in two stages, an acute stage (usually asymptomatic) and the chronic stage. Chronic stage CD presents with severe cardiac symptoms such as heart failure, localized aneurysms and cardiomyopathy. Unfortunately, what causes severe cardiac symptoms in some individuals in chronic CD is not fully understood. Therefore, we used liquid chromatography-tandem mass spectrometry to analyze the heart tissue of chronically T. cruzi-infected and uninfected mice, to understand the impact of infection on the tissue metabolome. We identified discriminatory small molecules related to T. cruzi infection. We also determined that regions with the highest parasite burden are distinct from the regions with the largest changes in overall metabolite profile; these locations of high metabolic perturbation provide a molecular mechanism to why localized cardiac symptoms occur in CD. Overall, our work gives insight to chronic cardiac CD symptom development and shapes a framework for novel treatment and biomarker development.

scholarly journals Genomics and High-Resolution Typing Confirm Predominant Clonal Evolution Down to a Microevolutionary Scale in Trypanosoma cruzi

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 356 ◽  
Author(s):  
Michel Tibayrenc ◽  
Francisco J. Ayala
Keyword(s):  
High Resolution ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Genetic Recombination ◽  
Phylogenetic Signal ◽  
Clonal Evolution ◽  
Natural Populations ◽  
Evolutionary Patterns ◽  
The Impact ◽  
Evolutionary Units

Trypanosoma cruzi, the agent of Chagas disease, is a paradigmatic case of the predominant clonal evolution (PCE) model, which states that the impact of genetic recombination in pathogens’ natural populations is not sufficient to suppress a persistent phylogenetic signal at all evolutionary scales. In spite of indications for occasional recombination and meiosis, recent genomics and high-resolution typing data in T. cruzi reject the counterproposal that PCE does not operate at lower evolutionary scales, within the evolutionary units (=near-clades) that subdivide the species. Evolutionary patterns in the agent of Chagas disease at micro- and macroevolutionary scales are strikingly similar (“Russian doll pattern”), suggesting gradual, rather than saltatory evolution.

Water in the economy of Tamil Nadu, India: more flexible water allocation policies offer a possible way out of water-induced economic stagnation and will be good for the environment and the poor

Water Policy ◽  
2006 ◽  
Vol 8 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Ramesh Bhatia ◽  
John Briscoe ◽  
R. P. S. Malik ◽  
Lindy Miller ◽  
Smita Misra ◽  
...  
Keyword(s):  
Water Allocation ◽  
Water Policy ◽  
Tamil Nadu ◽  
Economic Value ◽  
The State ◽  
Allocation Policy ◽  
Rural And Urban ◽  
State Income ◽  
Important Exception ◽  
The Impact

The state of Tamil Nadu, India, is in the grips of a water crisis, with demand far outstripping supply. As the economy of the state grows, this crisis is going to become ever more serious. To date the focus of state water policy has been on trying to augment supplies, from within the state (even from desalinization) and from neighboring states. In addition, the water use is regulated in a way that does not encourage the highest value uses. International experience shows that supply-side measures must be complemented by demand-side measures and that practice must move away from fixed, command-and-control allocation policies towards flexible allocation mechanisms, which facilitate the voluntary movement of water from low to high-value uses. This study addresses the question of whether such a change in allocation policies is worth doing. It addresses this question by developing optimization models for each of the 17 river basins in Tamil Nadu (including an assessment of the economic value of water in different end-uses – agriculture, domestic and industry), then using an input–output model embedded in a social accounting matrix (SAM), to assess the impact of these changes on the state economy and on different rural and urban employment groups. The results suggest that a shift to a flexible water allocation system would bring major environmental, economic and social benefits to the state. Compared with the current “fixed sectoral allocation” policy, a flexible allocation policy would, in 2020, result in 15% less overall water used; 24% less water pumped from aquifers; 20% higher state income; with all strata, rich and poor, benefiting similarly, with one important exception, that of agricultural laborers.

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