Early assessment of antibodies decline in Chagas patients following treatment using a serological multiplex immunoassay.

Chagas disease following infection with Trypanosoma cruzi is a major public health issue, with the disease spreading beyond endemic regions and becoming more global due to the migration of infected individuals. The currently available anti-parasitic drugs, nifurtimox and benznidazole, remain insufficiently evaluated for their efficacy in adult patients. A key challenge is the lack of markers for parasitological cure, which also precludes the development of new treatments.

Adverse events associated with benznidazole treatment for Chagas disease in children and adults.

Aims: Chagas disease (ChD) affects approximately 7 million people in Latin America, with benznidazole being the most commonly used treatment.

Methods: Data from a retrospective cohort study in Argentina, covering January 1980 to July 2019, was reanalysed to identify and characterize benznidazole-related adverse drug reactions (ADRs).

Results: The study included 518 patients: 449 children and 69 adults (median age in children: 4 years; adults: 25 years; age ranges: 1 month-17.

Efficacy of short-course treatment for prevention of congenital transmission of Chagas disease: A retrospective cohort study.

Background: In regions with controlled vector transmission of T. cruzi, congenital transmission is the most frequent route of infection. Treatment with benznidazole (BZ) or nifurtimox (NF) for 60 days in girls and women of childbearing age showed to be effective in preventing mother to child transmission of this disease.

An α-Gal antigenic surrogate as a biomarker of treatment evaluation in Trypanosoma cruzi-infected children. A retrospective cohort study.

Background: Proper evaluation of therapeutic responses in Chagas disease is hampered by the prolonged persistence of antibodies to Trypanosoma cruzi measured by conventional serological tests and by the lack of sensitivity of parasitological tests. Previous studies indicated that tGPI-mucins, an α-Gal (α-d-Galp(1→3)-β-d-Galp(1→4)-d-GlcNAc)-rich fraction obtained from T. cruzi trypomastigotes surface coat, elicit a strong and protective antibody response in infected individuals, which disappears soon after successful treatment.

Clinical use of molecular methods for infection in endemic and non-endemic countries: Benefits, limitations and challenges.

infection is diagnosed by parasitological, molecular, and serological tests. Molecular methods based on DNA amplification provide a more sensitive alternative to classical parasitological techniques for detecting evidence of parasitemia, and are the preferred tests for congenital and oral transmission cases and parasite reactivation in chronically infected immunosuppressed individuals. In newborns at risk of vertical transmission, simplified diagnostic algorithms that provide timely results can reduce the high follow-up losses observed with current algorithms.

Deep serological profiling of the Trypanosoma cruzi TSSA antigen reveals different epitopes and modes of recognition by Chagas disease patients.

Background: Trypanosoma cruzi, the agent of Chagas disease, displays a highly structured population, with multiple strains that can be grouped into 6-7 evolutionary lineages showing variable eco-epidemiological traits and likely also distinct disease-associated features. Previous works have shown that antibody responses to 'isoforms' of the polymorphic parasite antigen TSSA enable robust and sensitive identification of the infecting strain with near lineage-level resolution. To optimize the serotyping performance of this molecule, we herein used a combination of immunosignaturing approaches based on peptide microarrays and serum samples from Chagas disease patients to establish a deep linear B-cell epitope profiling of TSSA.

ELISA F29 -A therapeutic efficacy biomarker in Chagas disease: Evaluation in pediatric patients treated with nifurtimox and followed for 4 years post-treatment.

Background: Measurement of the success of antitrypanosomal treatment for Chagas disease is difficult, particularly in the chronic phase of the disease, because anti-Trypanosoma cruzi antibodies persist in serum for prolonged periods. We studied the effects of nifurtimox administered by two different treatment regimens on the T. cruzi calcium-binding flagellar protein F29 in children diagnosed with Chagas disease measured using an enzyme-linked immunosorbent assay (ELISA) technique (ELISA F29).

Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.

Background: There is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi).

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas.

During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown.

Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE).

Nifurtimox is recommended for the treatment of Chagas disease; however, long-term follow-up data are scarce. This prolonged follow-up phase of the prospective, historically controlled, CHICO clinical trial evaluated seronegative conversion in pediatric patients aged <18 years with Chagas disease who were followed for 4 years after nifurtimox treatment. Patients were randomly assigned 2:1 to nifurtimox 60-day or 30-day regimens comprising 10 to 20 mg/kg/day for patients aged <12 years and body weight <40 kg, and 8 to 10 mg/kg/day for those aged ≥12 years and body weight ≥40 kg.

Major benznidazole metabolites in patients treated for Chagas disease: Mass spectrometry-based identification, structural analysis and detoxification pathways.

Benznidazole is the drug of choice for the treatment of Chagas disease, but its metabolism in humans is unclear. Here, we identified and characterized the major benznidazole metabolites and their biosynthetic mechanisms in humans by analyzing the ionic profiles of urine samples from patients and untreated donors through reversed-phase UHPLC-ESI-QTOF-MS and UHPLC-ESI-QqLIT-MS. A strategy for simultaneous detection and fragmentation of characteristic positive and negative ions was employed using information-dependent acquisitions (IDA).

Long-term cardiology outcomes in children after early treatment for Chagas disease, an observational study.

Background: Parasite persistence after acute infection with Trypanosoma cruzi is an important factor in the development of Chagas disease (CD) cardiomyopathy. Few studies have investigated the clinical effectiveness of CD treatment through the evaluation of cardiological events by long term follow-up of treated children. Cardiological evaluation in children is challenging since features that would be diagnosed as abnormal in an adult's ECG may be normal, age-related findings in a pediatric ECG trace.

[Patient with pulmonary cysts and diagnosis of co-infection with tuberculosis and hydatidosis. Pediatric cases report].

Numerous entities in the pediatric population can present in the form of cysts or as lesions with similar characteristics. Of the pathologies that can cause these images in children, infectious diseases are the most frequent. We present the case of a native of Bolivia with recent immigration to Argentina who presented a pulmonary co-infection with tuberculosis and hydatidosis.

Pancreatic echinococcosis in a 5-year-old girl.

Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk.

Multilocus sequence typing of in children with acquired syphilis by nonsexual contact.

There are scarce data of subsp. (TPA) characterization in children with syphilis. Nonsexually acquired transmission (NSAT) of TPA is possible in infants through close contact.

Randomized, direct comparison study of Saccharomyces boulardii CNCM I-745 versus multi-strained Bacillus clausii probiotics for the treatment of pediatric acute gastroenteritis.

Background: The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE.

Methods: A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina.

Miltefosine and Benznidazole Combination Improve Anti- and Efficacy.

Drug repurposing and combination therapy have been proposed as cost-effective strategies to improve Chagas disease treatment. Miltefosine (MLT), a synthetic alkylphospholipid initially developed for breast cancer and repositioned for leishmaniasis, is a promising candidate against infection. This study evaluates the efficacy of MLT as a monodrug and combined with benznidazole (BZ) in both and models of infection with (VD strain, DTU TcVI).

Effectiveness of Nifurtimox in the Treatment of Chagas Disease: a Long-Term Retrospective Cohort Study in Children and Adults.

Chagas disease (ChD), caused by Trypanosoma cruzi, has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF.

Guillain-Barré Syndrome Associated With Acute Toxoplasmosis in a 3-Year-old Boy.

Few clinical cases of Guillain-Barré syndrome have been described following acute Toxoplasma gondii infection, all in adult patients. We report a case of a 3-year-old boy who developed this syndrome with a good response to antiparasitic treatment.

Evaluation of Toxoplasma gondii recombinant antigens for early diagnosis of congenital toxoplasmosis.

The performance of Toxoplasma rGra8, rMic1, and the chimeric rGra4-Gra7 antigens for early congenital toxoplasmosis (CT) diagnosis was evaluated. Sera from CT patients showed high IgG reactivity to rMic1, rGra8, and rGra4-Gra7. The seroreactivity of samples from uninfected infants was lost within 2 months of age.

Evaluation of the Chagas Western Blot IgG Assay for the Diagnosis of Chagas Disease.

Chagas disease is a debilitating and often fatal pathology resulting from infection by the protozoan parasite . In its recommendations, the World Health Organization states that the diagnosis of infection is usually based on the detection of antibodies against antigens and performed with two methodologically different assays. An inconclusive result can be resolved with a third "confirmatory" assay.

Diagnostic Accuracy of Two Molecular Tools for Diagnosis of Congenital Chagas Disease.

Background And Objective: The real prevalence of congenital Chagas disease is undefined because of difficulties in the detection of Trypanosoma cruzi by microscopic examination. The aim of this study was to determine the diagnostic accuracy of two molecular diagnostic tools, qPCR and LAMP, in the diagnosis of congenital Chagas disease in a clinical setting.

Methods: To this end, we conducted a prospective cohort study in a tertiary care center, of infants under 9 months of age, born in Buenos Aires to women with Chagas disease.

Optimization and biological validation of an assay using the transfected Dm28c/pLacZ strain.

There is an urgent need to develop safer and more effective drugs for Chagas disease, as the current treatment relies on benznidazole (BZ) and nifurtimox (NFX). Using the Dm28c strain genetically engineered to express the β-galactosidase gene, lacZ, we have adapted and validated an easy, quick and reliable assay suitable for high-throughput screening for candidate compounds with anti- activity. studies were conducted to determine trypomastigotes sensitivity to BZ and NFX from Dm28c/pLacZ strain by comparing the conventional labour-intensive microscopy counting method with the colourimetric assay.

Acquired Syphilis by Nonsexual Contact in Childhood.

Background: Children may acquire syphilis by nonsexual contact as a consequence of close and repetitive contact with mucosal or skin lesions of people with active syphilis.

Methods: Prospective cohort study of pediatric patients with acquired syphilis by nonsexual contact. Demographics, clinical findings, posttreatment serology development and general laboratory data were collected.

[Argentine consensus of congenital toxoplasmosis].

Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diagnosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage.