Genotypic Trypanosoma cruzi distribution and parasite load differ ecotypically and according to parasite genotypes in Triatoma brasiliensis from endemic and outbreak areas in Northeastern Brazil

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

Download Full-text

Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

Cell Death and Disease ◽

10.1038/s41419-021-03964-6 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Marcela Hernández-Torres ◽

Rogério Silva do Nascimento ◽

Monica Cardozo Rebouças ◽

Alexandra Cassado ◽

Kely Catarine Matteucci ◽

...

Keyword(s):

T Cells ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Parasite Load ◽

Peritoneal Macrophages ◽

T Cell Response ◽

No Production ◽

Similar Reduction ◽

Ifn Γ

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.

Download Full-text

Infection patterns of helminths in Norops brasiliensis (Squamata, Dactyloidae) from a humid forest, Northeastern Brazil and their relation with body mass, sex, host size, and season

Helminthologia ◽

10.2478/helm-2019-0011 ◽

2019 ◽

Vol 56 (2) ◽

pp. 168-174 ◽

Cited By ~ 1

Author(s):

D. M. Amorim ◽

R. W. Ávila

Keyword(s):

Body Size ◽

Ecological Factors ◽

Parasite Load ◽

Helminth Fauna ◽

Northeastern Brazil ◽

Rainfall Regime ◽

New Host ◽

Humid Forest ◽

Host Sex ◽

New Host Records

SummaryClimatic and ecological factors can influence the parasite load of a host. Variation in rainfall, body size, and sex of the hosts may be related to the abundance of parasites. This study investigated the helminth fauna associated with a population of Norops brasiliensis, together with the effect of host biology (sex, body size, and mass) and variation in rainfall regime on the abundance of helminths. Species of three groups of endoparasites were found (Nematoda, Cestoda, and Trematoda), with nematodes as the most representative taxa with eight species, prevalence of 63.2 %, mean intensity of 4.0 ± 0.58 (1 – 25), and mean abundance of 2.66 ± 0.44 (0 – 25). Nine helminth species are new host records for N. brasiliensis. The nematode Rhabdias sp. had the highest prevalence (53.3 %). There was no significant relationship between abundance of the trematode Mesocoelium monas and host sex or season, although the abundance of this parasite increased significantly with host body size and mass, while abundance of nematodes was related to season and host mass. This study increases the knowledge about the diversity of helminth fauna associated with N. brasiliensis, revealing infection levels of hosts from northeastern Brazil.

Download Full-text

A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02436-18 ◽

2019 ◽

Vol 63 (10) ◽

Cited By ~ 4

Author(s):

Adriana Egui ◽

M. Carmen Thomas ◽

Ana Fernández-Villegas ◽

Elena Pérez-Antón ◽

Inmaculada Gómez ◽

...

Keyword(s):

T Cells ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Parasite Load ◽

Drastic Reduction ◽

Content Type ◽

Short Period ◽

Before And After ◽

Cruzi Infection

ABSTRACT One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and after benznidazole treatment. The results showed that the reactivity against these antigens decreased at 9, 24, and 48 months after treatment. Moreover, the 42.4% and 68.75% of IND patients met the established standard criteria of therapeutic efficacy (STEC) at 24 and 48 months posttreatment, respectively. Meeting the STEC implied that there was a continuous decrease in the reactivity of the patient sera against the four antigens after treatment and that there was a substantial decrease in the reactivity for at least two of the antigens. This important decrease in reactivity may be associated with a drastic reduction in the parasite load, but it is not necessarily associated with a parasitological cure. After treatment, a positive PCR result was only obtained in patients who did not meet the STEC. The percentage of granzyme B+/perforin+ CD8+ T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%; P < 0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8+ T cells compared with that in the patients who did not meet the STEC.

Download Full-text

The palm tree Copernicia cerifera (carnaúba) as an ecotope of Rhodnius nasutus in rural areas of the State of Piauí Northeastern Brazil

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821986000400008 ◽

1986 ◽

Vol 19 (4) ◽

pp. 243-245 ◽

Cited By ~ 10

Author(s):

Artur da S. Pinto ◽

Dalva N. da C. Bento

Keyword(s):

Trypanosoma Cruzi ◽

Rural Areas ◽

The State ◽

Northeastern Brazil ◽

Palm Tree ◽

Palm Trees ◽

Triatomine Species

The C. cerifera palm tree (carnaúba) is widely distributed in the Northeastem Brazil, including the State of Piauí. This investigation revealed that R. nasutus is the ortly triatomine species captured on that palm tree, in five different localities. 78% of palm trees were infested with triatomines, and 4.0% were infected with flagellates morphologically and biologically indistinguishable from Trypanosoma cruzi. Birds, rodents and marsupials were found as major blood meai sources for R. nasutus.

Download Full-text

Genetic analyses of Trypanosoma cruzi isolates from naturally infected triatomines and humans in northeastern Brazil

Acta Tropica ◽

10.1016/j.actatropica.2010.03.003 ◽

2010 ◽

Vol 115 (3) ◽

pp. 205-211 ◽

Cited By ~ 27

Author(s):

A.C.J. Câmara ◽

A.A. Varela-Freire ◽

H.M.S. Valadares ◽

A.M. Macedo ◽

D.A. D’Ávila ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Northeastern Brazil ◽

Genetic Analyses

Download Full-text

Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02098-16 ◽

2017 ◽

Vol 61 (4) ◽

Cited By ~ 20

Author(s):

F. H. Guedes-da-Silva ◽

D. G. J. Batista ◽

C. F. Da Silva ◽

J. S. De Araújo ◽

B. P. Pavão ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Day Treatment ◽

Parasite Load ◽

Comparative Investigation ◽

Pcr Analysis ◽

Cytochrome P450 Enzyme ◽

Animal Group ◽

Reference Drug ◽

Content Type

ABSTRACT Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi. The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of T. cruzi. The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other T. cruzi strains and in combination with other drugs.

Download Full-text

Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00343-16 ◽

2016 ◽

Vol 60 (6) ◽

pp. 3355-3364 ◽

Cited By ~ 25

Author(s):

Rômulo Dias Novaes ◽

Marcus Vinicius Pessoa Sartini ◽

João Paulo Ferreira Rodrigues ◽

Reggiani Vilela Gonçalves ◽

Eliziária Cardoso Santos ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Liver Toxicity ◽

Cardiac Injury ◽

Parasite Load ◽

Interleukin 4 ◽

Myocardial Inflammation ◽

Cure Rate ◽

Content Type ◽

Complementary Strategy

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected withTrypanosoma cruzi. Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI),T. cruziinfected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruziIgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

Download Full-text

Seasonal distribution of gastrointestinal nematode infections in sheep in a semiarid region, northeastern Brazil

Revista Brasileira de Parasitologia Veterinária ◽

10.1590/s1984-29612013000300006 ◽

2013 ◽

Vol 22 (3) ◽

pp. 351-359 ◽

Cited By ~ 4

Author(s):

Maria de Fátima de Souza ◽

Manoel Pimentel-Neto ◽

André Luís Santos de Pinho ◽

Rízia Maria da Silva ◽

Albeísa Cleyse Batista Farias ◽

...

Keyword(s):

Gastrointestinal Nematode ◽

Parasite Load ◽

Nematode Species ◽

Seasonal Distribution ◽

Northeastern Brazil ◽

Semiarid Region ◽

Parasitic Infections ◽

P Value ◽

Fecal Egg Count ◽

Gastrointestinal Nematode Parasite

The objective of this study was to determine the seasonal distribution and gastrointestinal nematode parasite load in crossbred Santa Inês tracer lambs, and to correlate the rainfall during the study period with occurrences of parasitic infections. Sixty-four male tracer lambs between the ages of four and eight months were used in the study. Two tracer lambs were inserted into the herd every 28 days to determine the pattern of infective larvae available in the environment. Variation in the fecal egg count (FEC) of nematodes was observed at the study site, with many samples containing undetectable parasite loads during the dry season. The larvae identified in coprocultures wereHaemonchus sp., Trichostrongylus sp.,Cooperia sp., Strongyloides sp. andOesophagostomum sp. The nematodes recovered at necropsy were Haemonchus contortus, Trichostrongylus colubriformis, Cooperia punctata, C. pectinata, Trichuris sp.,Oesophagostomum sp. and Skrajabinema ovis. The total number of larvae and the total number of immature and adult forms recovered from the tracers showed seasonal distributions that significantly correlated with the amount of rainfall received that month (p value ≅ 0.000 in all cases ). The species H. contortus was predominant in the herd and should be considered to be main pathogenic nematode species in these hosts under these conditions.

Download Full-text

Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi

Infection and Immunity ◽

10.1128/iai.00400-07 ◽

2007 ◽

Vol 76 (1) ◽

pp. 443-451 ◽

Cited By ~ 18

Author(s):

M. Paola Zago ◽

Alejandra B. Barrio ◽

Rubén M. Cardozo ◽

Tomás Duffy ◽

Alejandro G. Schijman ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Genetic Manipulation ◽

Antibiotic Resistance Genes ◽

Parasite Burden ◽

Parasite Load ◽

Single Copy ◽

Protein Product ◽

Host Cells ◽

Insect Vector ◽

Null Mutant

ABSTRACT Trypanosoma cruzi infection of host cells is a complex process in which many proteins participate but only a few of these proteins have been identified experimentally. One parasite factor likely to be involved is the protein product of LYT1, a single-copy gene cloned, sequenced, and characterized by Manning-Cela et al. (Infect. Immun. 69:3916-3923, 2001). This gene was potentially associated with infectivity, since the deletion of both LYT1 alleles in the CL Brenner strain (the wild type [WT]) resulted in a null mutant T. cruzi clone (L16) that shows an attenuated phenotype in cell culture models. The aim of this work was to characterize the infective behavior of L16 in the insect vector and murine models. The infection of adult Swiss mice with 103 trypomastigotes of both clones revealed a significant reduction in infective behavior of L16, as shown by direct parasitemia, spleen index, and quantitation of tissue parasite burden, suggesting the loss of virulence in the null mutant clone. Although L16 blood counts were almost undetectable, blood-based PCRs indicated the presence of latent and persistent infection during all of the study period and epimastigotes were reisolated from hemocultures until 12 months postinfection. Nevertheless, virulence was not restored in L16 by serial passages in mice, and reisolated parasites lacking the LYT1 gene and bearing the antibiotic resistance genes revealed the stability of the genetic manipulation. Histopathological studies showed a strong diminution in the muscle inflammatory response triggered by L16 compared to that triggered by the WT group, consistent with a lower tissue parasite load. A strong protection against a virulent challenge in both L16- and WT-infected mice was observed; however, the immunizing infection by the genetically modified parasite was highly attenuated.

Download Full-text