Case 4/2019 - 26-Year-Old Man with Congenital Chagas Disease and Heart Transplantation

Pinesi, Henrique Trombini; Strabelli, Tânia Mara Varejão; Aiello, Vera Demarchi

doi:10.5935/abc.20190162

Cited by 3 publications

(1 citation statement)

References 17 publications

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“…As proposed in immunocompromised CD patients, it is probable that trypomastigotes can flourish from ‘dormant forms’ located in different organs, including the gastrointestinal tract. 49 , 50 Our present assays argue in favour of dormant forms since even though it was not able to lyse trypomastigotes, Cpd 1 impairs their ability to establish a successful in vitro infection. Despite outstanding efficacy against intracellular forms ( Figure 7 ), Cpd 1 is not able to induce in vitro sterilization possibly due to its inefficacy against low metabolic latent (e.g.…”

Section: Discussionmentioning

confidence: 75%

7-Aryl-7-deazapurine 3′-deoxyribonucleoside derivative as a novel lead for Chagas’ disease therapy: in vitro and in vivo pharmacology

Cardoso-Santos

Fiuza

Silva

et al. 2021

JAC-Antimicrobial Resistance

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Background The protozoan Trypanosoma cruzi is auxotrophic for purines and causes Chagas’ disease (CD), a neglected illness affecting >6 million people. Combining the 3-deoxyribofuranose part of cordycepin with the modified purine ring of a nucleoside ‘hit’ led to the discovery of 4-amino-5-(4-chlorophenyl)-N7-(3′-deoxy-β-d-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine (Cpd1), revealing promising anti-T. cruzi activity. Objectives To further evaluate Cpd1 in vitro and in vivo to fully assess its therapeutic potential against CD, covering cell culture sterilization through washout assays, drug combination with benznidazole and long-term administration in T. cruzi-infected mice. Results Although less susceptible to Cpd1 than amastigotes, trypomastigotes present an impaired capacity to successfully establish intracellular infection of cardiac cultures. Combination of benznidazole with Cpd1 indicated no interaction (additive effect) (FIC index = 0.72) while administration to mice at one-tenth of the optimal dose (2.5 mg/kg and 10 mg/kg for Cpd1 and benznidazole, respectively) suppressed parasitaemia but failed to avoid mortality. Long-term treatment (60 days) gave a rapid drop of the parasitaemia (>98% decline) and 100% mice survival but only 16% cure. In vitro washout experiments demonstrated that although parasite release into the supernatant of infected cardiac cultures was reduced by >94%, parasite recrudescence did occur after treatment. Conclusions Parasite recrudescence did occur after treatment corroborating the hypothesis of therapeutic failure due to subpopulations of dormant forms and/or genetic factors in persister parasites involved in natural drug resistance.

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Section: Discussionmentioning

confidence: 75%

7-Aryl-7-deazapurine 3′-deoxyribonucleoside derivative as a novel lead for Chagas’ disease therapy: in vitro and in vivo pharmacology

Cardoso-Santos

Fiuza

Silva

et al. 2021

JAC-Antimicrobial Resistance

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Chagas disease in immunocompromised patients

Clark,

Messenger,

Whitman

et al. 2024

Clin Microbiol Rev

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SUMMARY As Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

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Chagas Disease Maternal Seroprevalence and Maternal–Fetal Health Outcomes in a Parturition Cohort in Western El Salvador

et al. 2023

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Congenital Chagas disease is a growing concern, prioritized by the World Health Organization for public health action. El Salvador is home to some of the highest Chagas disease (Trypanosoma cruzi infection) burdens in the Americas, yet pregnancy screening remains neglected. This pilot investigation performed a maternal T. cruzi surveillance study in Western El Salvador among women presenting for labor and delivery. From 198 consented and enrolled pregnant women, 6% were T. cruzi positive by serology or molecular diagnosis. Half of the infants born to T. cruzi-positive women were admitted to the NICU for neonatal complications. Geospatial statistical clustering of cases was noted in the municipality of Jujutla. Older women and those knowing an infected relative or close friend were significantly more likely to test positive for T. cruzi infection at the time of parturition. In closing, maternal T. cruzi infections were significantly higher than national HIV or syphilis maternal rates, creating an urgent need to add T. cruzi to mandatory pregnancy screening programs.

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Case 4/2019 - 26-Year-Old Man with Congenital Chagas Disease and Heart Transplantation

Cited by 3 publications

References 17 publications

7-Aryl-7-deazapurine 3′-deoxyribonucleoside derivative as a novel lead for Chagas’ disease therapy: in vitro and in vivo pharmacology

7-Aryl-7-deazapurine 3′-deoxyribonucleoside derivative as a novel lead for Chagas’ disease therapy: in vitro and in vivo pharmacology

Chagas disease in immunocompromised patients

Chagas Disease Maternal Seroprevalence and Maternal–Fetal Health Outcomes in a Parturition Cohort in Western El Salvador

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