scholarly journals New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-Up

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
María Gabriela Álvarez ◽  
Juan Carlos Ramírez ◽  
Graciela Bertocchi ◽  
Marisa Fernández ◽  
Yolanda Hernández ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Nuclear Dna ◽  
Parasite Load ◽  
Serological Tests ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Specific Antibodies ◽  
Intermittent Administration ◽  
Low Rate

ABSTRACT In a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two daily doses every 5 days. Parasite load, Trypanosoma cruzi-specific antibodies, and serum chemokine levels were measured prior to treatment and after a median follow-up of 36 months posttreatment by DNA minicircle kinetoplastid and nuclear DNA satellite sequence qPCR methods, conventional serological techniques, a Luminex-based assay with recombinant T. cruzi proteins, and a cytometric bead array. At the end of follow-up, 14 of 17 (82%) patients had negative qPCR findings, whereas three of 17 (18%) had detectable nonquantifiable findings by at least one of the qPCR techniques. A decline in parasite-specific antibodies at 12 months posttreatment was confirmed by conventional serological tests and the Luminex assays. Monocyte chemoattractant protein 1 levels increased after treatment, whereas monokine induced by gamma interferon levels decreased. New posttreatment electrocardiographic abnormalities were observed in only one patient who had cardiomyopathy prior to treatment. Together, these data strengthen our previous findings by showing that the intermittent administration of benznidazole results in a low rate of treatment suspension, with treatment efficacy comparable to that of a daily dose of 5 mg/kg for 60 days.

scholarly journals The Trypomastigote Small Surface Antigen from Trypanosoma cruzi Improves Treatment Evaluation and Diagnosis in Pediatric Chagas Disease

2017 ◽  
Vol 55 (12) ◽  
pp. 3444-3453 ◽  
Author(s):  
Virginia Balouz ◽  
Luciano J. Melli ◽  
Romina Volcovich ◽  
Guillermo Moscatelli ◽  
Samanta Moroni ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Surface Antigen ◽  
Rapid Assessment ◽  
Drug Efficacy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serological Tests ◽  
Small Surface ◽  
Content Type

ABSTRACTChagas disease is caused by the protozoan parasiteTrypanosoma cruzi. Assessment of parasitological cure upon treatment with available drugs relies on achieving consistent negative results in conventional parasitological and serological tests, which may take years to assess. Here, we evaluated the use of a recombinantT. cruziantigen termed trypomastigote small surface antigen (TSSA) as an early serological marker of drug efficacy inT. cruzi-infected children. A cohort of 78 pediatric patients born toT. cruzi-infected mothers was included in this study. Only 39 of the children were infected withT. cruzi, and they were immediately treated with trypanocidal drugs. Serological responses against TSSA were evaluated in infected and noninfected populations during the follow-up period using an in-house enzyme-linked immunosorbent assay (ELISA) and compared to conventional serological methods. Anti-TSSA antibody titers decreased significantly faster than anti-whole parasite antibodies detected by conventional serology both inT. cruzi-infected patients undergoing effective treatment and in those not infected. The differential kinetics allowed a significant reduction in the required follow-up periods to evaluate therapeutic responses or to rule out maternal-fetal transmission. Finally, we present the case of a congenitally infected patient with an atypical course in whom TSSA provided an early marker forT. cruziinfection. In conclusion, we showed that TSSA was efficacious both for rapid assessment of treatment efficiency and for early negative diagnosis in infants at risk of congenitalT. cruziinfection. Based upon these findings we propose the inclusion of TSSA for refining the posttherapeutic cure criterion and other diagnostic needs in pediatric Chagas disease.

scholarly journals Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission

2009 ◽  
Vol 42 (5) ◽  
pp. 484-487 ◽  
Author(s):  
Sergio Sosa-Estani ◽  
Estela Cura ◽  
Elsa Velazquez ◽  
Cristina Yampotis ◽  
Elsa Leonor Segura
Keyword(s):  
Trypanosoma Cruzi ◽  
Young Women ◽  
Serological Tests ◽  
Congenital Transmission ◽  
Cruzi Infection ◽  
Efficacy Of Treatment

The objective was to detect Trypanosoma cruzi infection in 32 children in Salta, Argentina, born to 16 chronically infected young women who were treated with benznidazole. Tests were performed to assess the efficacy of treatment after 14 years. At the end of the follow up, 87.5% of the women were non-reactive to EIA tests, 62.5% to IHA and 43.8% to IFA. 62.5% of the women were non-reactive according to two or three serological tests. No infected children were detected among the newborns of mothers treated before their pregnancy.

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

2019 ◽  
Vol 63 (10) ◽  
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.

scholarly journals 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

2017 ◽  
Vol 61 (4) ◽  
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.

scholarly journals Course of Chronic Trypanosoma cruzi Infection after Treatment Based on Parasitological and Serological Tests: A Systematic Review of Follow-Up Studies

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0139363 ◽  
Author(s):  
Yanina Sguassero ◽  
Cristina B. Cuesta ◽  
Karen N. Roberts ◽  
Elizabeth Hicks ◽  
Daniel Comandé ◽  
...  
Keyword(s):  
Systematic Review ◽  
Trypanosoma Cruzi ◽  
Serological Tests ◽  
Follow Up Studies ◽  
Cruzi Infection

scholarly journals Parasite-Derived Neurotrophic Factor/trans-Sialidase of Trypanosoma cruzi Links Neurotrophic Signaling to Cardiac Innate Immune Response

2014 ◽  
Vol 82 (9) ◽  
pp. 3687-3696 ◽  
Author(s):  
Ryan Salvador ◽  
Daniel Aridgides ◽  
Mercio PereiraPerrin
Keyword(s):  
Innate Immunity ◽  
Trypanosoma Cruzi ◽  
Neurotrophic Factor ◽  
Neutralizing Antibodies ◽  
Tissue Growth ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neurotrophic Signaling ◽  
Neurotrophic Receptors ◽  
Dose Dependent Increase

ABSTRACTThe Chagas' disease parasiteTrypanosoma cruzielicits a potent inflammatory response in acutely infected hearts that keeps parasitism in check and triggers cardiac abnormalities. A most-studied mechanism underlying innate immunity inT. cruziinfection is Toll-like receptor (TLR) activation by lipids and other parasite molecules. However, yet-to-be-identified pathways should exist. Here, we show thatT. cruzistrongly upregulates monocyte chemoattractant protein 1 (MCP-1)/CCL2 and fractalkine (FKN)/CX3CL1 in cellular and mouse models of heart infection. Mechanistically, upregulation of MCP-1 and FKN stems from the interaction of parasite-derived neurotrophic factor (PDNF)/trans-sialidase with neurotrophic receptors TrkA and TrkC, as assessed by pharmacological inhibition, neutralizing antibodies, and gene silencing studies. Administration of a single dose of intravenous PDNF to naive mice results in a dose-dependent increase in MCP-1 and FKN in the heart and liver with pulse-like kinetics that peak at 3 h postinjection. Intravenous PDNF also augments MCP-1 and FKN in TLR signaling-deficient MyD88-knockout mice, underscoring the MyD88-independent action of PDNF. Although single PDNF injections do not increase MCP-1 and FKN receptors, multiple PDNF injections at short intervals up the levels of receptor transcripts in the heart and liver, suggesting that sustained PDNF triggers cell recruitment at infection sites. Thus, given that MCP-1 and FKN are chemokines essential to the recruitment of immune cells to combat inflammation triggers and to enhance tissue repair, our findings uncover a new mechanism in innate immunity againstT. cruziinfection mediated by Trk signaling akin to an endogenous inflammatory and fibrotic pathway resulting from cardiomyocyte-TrkA recognition by matricellular connective tissue growth factor (CTGF/CCN2).

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

2016 ◽  
Vol 60 (6) ◽  
pp. 3355-3364 ◽  
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.

scholarly journals Trypanosoma cruzi: avirulence of the PF strain to Callithrix marmosets

1981 ◽  
Vol 14 (1) ◽  
pp. 73-80
Author(s):  
Humberto Menezes
Keyword(s):  
Body Weight ◽  
Trypanosoma Cruzi ◽  
Callithrix Jacchus ◽  
Blood Cultures ◽  
Serological Tests

Callithrix jacchus geoffroy marmosets (HumBol. 1812) were injected once subcutaneously with 10.000 parasites/g body weight and followed for a period of six months. The PF strain of Trypanosoma cruzi was used. Follow-up was done through blood cultures, xenodiagnosis, serological tests, and ECG. A small number of normaI animais served as control.

Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children

2021 ◽  
pp. ASN.2021010094
Author(s):  
Jason H. Greenberg ◽  
Alison G. Abraham ◽  
Yunwen Xu ◽  
Jeffrey R. Schelling ◽  
Harold I. Feldman ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Ckd Progression ◽  
Creatinine Concentration ◽  
Clinical Model ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Urine Biomarkers ◽  
Urine Creatinine ◽  
Kidney Injury Molecule 1

BackgroundNovel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression.MethodsWe investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30–90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4–7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period.ResultsOverall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression.ConclusionsAfter multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

scholarly journals Towards a New Strategy for Diagnosis of Congenital Trypanosoma cruzi Infection

2017 ◽  
Vol 55 (5) ◽  
pp. 1396-1407 ◽  
Author(s):  
Alba Abras ◽  
Carmen Muñoz ◽  
Cristina Ballart ◽  
Pere Berenguer ◽  
Teresa Llovet ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Latin American ◽  
Serological Test ◽  
Igg Antibodies ◽  
Childbearing Age ◽  
Serological Tests ◽  
Content Type ◽  
Congenital Transmission ◽  
Screening Programs ◽  
New Strategy

ABSTRACTThe immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenitalTrypanosoma cruziinfection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis ofT. cruziinfection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenitalT. cruziinfection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.

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