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1.
PLoS Negl Trop Dis ; 18(1): e0011895, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38252673

RESUMO

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. Reports on short-course treatment (≤30 days) are scarce. METHODS: Retrospective cohort study. Offspring of women with Chagas disease who received short-course treatment (≤30 days) with BZ or NF, attended between 2003 and 2022, were evaluated. Parasitemia (microhaematocrit and/or PCR) was performed at <8 months of age, and serology (ELISA and IHA) at ≥8 months to rule out congenital infection. RESULTS: A total of 27 women receiving ≤30 days of treatment and their children were included in this study. NF was prescribed in 17/27 (63%) women, and BZ in 10/27 (37%). The mean duration of treatment was 29.2 days. None of the women experienced serious adverse events during treatment, and no laboratory abnormalities were observed. Forty infants born to these 27 treated women were included. All newborns were full term, with appropriate weight for their gestational age. No perinatal infectious diseases or complications were observed. DISCUSSION: Several studies have shown that treatment of infected girls and women of childbearing age for 60 days is an effective practice to prevent transplacental transmission of T. cruzi. Our study demonstrated that short-duration treatment (≤30 days) is effective and beneficial in preventing transplacental transmission of Chagas disease.


Assuntos
Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Lactente , Criança , Recém-Nascido , Humanos , Feminino , Masculino , Estudos Retrospectivos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Doença de Chagas/tratamento farmacológico , Doença de Chagas/prevenção & controle , Nifurtimox/uso terapêutico , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico
2.
PLoS Negl Trop Dis ; 17(5): e0010850, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37256863

RESUMO

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). METHODS: 81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment. RESULTS: Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95-11.8; range 1.79-19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25-3.77; range 0.14-7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7-8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance). CONCLUSION: We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs. TRIAL REGISTRATION: Registered in clinicaltrials.gov #NCT01549236.


Assuntos
Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Adulto , Humanos , Criança , Lactente , Recém-Nascido , Pré-Escolar , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Reação em Cadeia da Polimerase , Tripanossomicidas/uso terapêutico
3.
Toxicol Lett ; 377: 71-82, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36775077

RESUMO

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). Selected precursor ions, neutral losses, and MS3 experiments complemented the study. A total of six phase-I and ten phase-II metabolites were identified and structurally characterized in urine of benznidazole-treated patients. Based on creatinine-corrected ion intensities, nitroreduction to amino-benznidazole (M1) and its subsequent N-glucuronidation to M5 were the main metabolic pathways, followed by imidazole-ring cleavage, oxidations, and cysteine conjugations. This extensive exploration of benznidazole metabolites revealed potentially toxic structures in the form of glucuronides and glutathione derivatives, which may be associated with recurrent treatment adverse events; this possibility warrants further exploration in future clinical trials. Incorporation of this knowledge of the benznidazole metabolic profile into clinical pharmacology trials could lead to improved treatments, facilitate the study of possible drug-drug interactions, and even mitigation of adverse drug reactions.


Assuntos
Doença de Chagas , Nitroimidazóis , Humanos , Espectrometria de Massas , Doença de Chagas/tratamento farmacológico , Doença de Chagas/induzido quimicamente , Nitroimidazóis/uso terapêutico , Íons , Cromatografia Líquida de Alta Pressão
4.
Arch. argent. pediatr ; 121(1): e202102500, feb. 2023. ilus
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1413458

RESUMO

La hidatidosis pancreática representa el 0,2-0,6 % de los casos, siendo la población pediátrica la de mayor riesgo. Las lesiones suelen localizarse en cabeza del páncreas (50-58 %); la localización en cuerpo y cola del páncreas se encuentra en el 24-34 % y el 19 %, respectivamente. Dada la posibilidad de complicaciones, suele realizarse tratamiento quirúrgico. Se sugiriere indicar albendazol antes y después del acto quirúrgico por los riesgos de ruptura y diseminación de los protoescólices. Se presenta el caso de una niña de 5 años de edad con dolor abdominal progresivo y lesión quística en páncreas compatible con hidatidosis en la ultrasonografía. En la tomografía computada se observa compresión de la vía biliar. La hemoaglutinación indirecta fue negativa. Presentó elevación de la bilirrubina total, con franco predominio de bilirrubina directa, y aumento de enzimas hepáticas. Se realizó laparotomía exploradora, colecistectomía y destechamiento del quiste. Evolucionó favorablemente, continuó con albendazol durante 3 meses luego de la cirugía.


Pancreatic echinococcosis accounts for 0.2­0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50­58%); and in the body and tail in 24­34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominal pain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.


Assuntos
Humanos , Feminino , Pré-Escolar , Pancreatopatias/cirurgia , Pancreatopatias/complicações , Pancreatopatias/diagnóstico , Equinococose/cirurgia , Equinococose/complicações , Equinococose/diagnóstico , Pâncreas , Albendazol/uso terapêutico , Abdome
5.
Arch Argent Pediatr ; 121(1): e202102500, 2023 02 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36194666

RESUMO

Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50-58%); and in the body and tail in 24-34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominalpain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.


La hidatidosis pancreática representa el 0,2-0,6 % de los casos, siendo la población pediátrica la de mayor riesgo. Las lesiones suelen localizarse en cabeza del páncreas (50-58 %); la localización en cuerpo y cola del páncreas se encuentra en el 24-34 % y el 19 %, respectivamente. Dada la posibilidad de complicaciones, suele realizarse tratamiento quirúrgico. Se sugiriere indicar albendazol antes y después del acto quirúrgico por los riesgos de ruptura y diseminación de los protoescólices. Se presenta el caso de una niña de 5 años de edad con dolor abdominal progresivo y lesión quística en páncreas compatible con hidatidosis en la ultrasonografía. En la tomografía computada se observa compresión de la vía biliar. La hemoaglutinación indirecta fue negativa. Presentó elevación de la bilirrubina total, con franco predominio de bilirrubina directa, y aumento de enzimas hepáticas. Se realizó laparotomía exploradora, colecistectomía y destechamiento del quiste. Evolucionó favorablemente, continuó con albendazol durante 3 meses luego de la cirugía.


Assuntos
Equinococose , Pancreatopatias , Feminino , Humanos , Criança , Pré-Escolar , Albendazol/uso terapêutico , Pancreatopatias/diagnóstico , Pancreatopatias/cirurgia , Pancreatopatias/complicações , Equinococose/diagnóstico , Equinococose/cirurgia , Equinococose/complicações , Abdome , Pâncreas
6.
PLoS Negl Trop Dis ; 16(12): e0010968, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36534647

RESUMO

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. The objective was to evaluate cardiac involvement in patients with Chagas disease with a minimum follow-up of 6 years post-treatment. METHODOLOGY: A descriptive study of a cohort of pediatric patients with CD treated with benznidazole (Bz) or nifurtimox (Nf) was conducted. Children (N = 234) with at least 6 years post CD treatment followed at the Parasitology and Chagas Service, Buenos Aires Children's Hospital (Argentina) were enrolled. By convenience sampling, children who attended a clinical visit between August 2015 and November 2019 were also invited to participate for additional cardiovascular studies like 24-hour Holter monitoring and speckle-tracking 2D echocardiogram (STE). Benznidazole was prescribed in 171 patients and nifurtimox in 63 patients. Baseline parasitemia data was available for 168/234 patients. During the follow-up period, alterations in routine ECG were observed in 11/234 (4.7%, 95% CI [2-7.4%]) patients. In only four patients, with complete right bundle branch block (cRBBB) and left anterior fascicular block (LAFB), ECG alterations were considered probably related to CD. During follow-up, 129/130 (99%) treated patients achieved persistent negative parasitemia by qPCR. Also decrease in T.cruzi antibodies titers was observed in all patients and negative seroconversion occurred in 123/234 (52%) patients. CONCLUSIONS: A low incidence of cardiological lesions related to CD was observed in patients treated early for pediatric CD. This suggests a protective effect of parasiticidal treatment on the development of cardiological lesions and highlights the importance of early treatment of infected children. TRIAL REGISTRATION: ClinicalTrials.gov NCT04090489.


Assuntos
Cardiologia , Cardiomiopatia Chagásica , Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Adulto , Humanos , Criança , Nifurtimox/uso terapêutico , Parasitemia/epidemiologia , Tripanossomicidas/uso terapêutico , Doença de Chagas/parasitologia , Nitroimidazóis/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/parasitologia
7.
Future Microbiol ; 17: 1295-1305, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36094429

RESUMO

Background: There are scarce data of Treponema pallidum subsp. pallidum (TPA) characterization in children with syphilis. Nonsexually acquired transmission (NSAT) of TPA is possible in infants through close contact. Methods: A descriptive study in five families with NSAT of syphilis was conducted. Polymerase chain reaction detection of TPA in pediatric index cases (n = 6) and their relatives (n = 44) were conducted followed by multilocus sequence typing (MLST). Results: TPA was detected in swab samples in 16 cases and 12 were characterized by MLST. Nichols lineage was identified in two of five families and SS14-lineage in three of five. In four families, MLST profiles linked index cases to relatives. Conclusion: This is the first report of TPA characterization in children infected by NSAT.


Syphilis is a disease caused by the bacterium Treponema pallidum subsp. pallidum (TPA). Although it is considered a sexually transmitted disease, syphilis can also be transmitted by nonsexual close contact with active lesions. There are clinical reports of this route of transmissions in children; however, there are no molecular characterizations of TPA in this population. A multidisciplinary study (epidemiological, clinical, social and molecular) was performed in six children from five families with clinical diagnosis of nonsexually transmitted syphilis. As a result, 18 infected persons were detected. In 16 individuals the presence of the bacterium genetic material was confirmed by molecular biology techniques, and in 12, its strain was analyzed. When we compared the data, we observed that in four families, the child's strain coincided with the one found in close contact, while in one family, this could not be determined. To our knowledge, this is the first report of TPA characterization in children, which underscore the importance of including molecular biology techniques in complex clinical scenarios such as these.


Assuntos
Sífilis , Treponema pallidum , Criança , Globo Pálido , Humanos , Lactente , Tipagem de Sequências Multilocus , Sífilis/diagnóstico , Treponema pallidum/genética
8.
Pediatr Infect Dis J ; 41(8): e329-e331, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35389935

RESUMO

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.


Assuntos
Síndrome de Guillain-Barré , Toxoplasmose , Adulto , Antiparasitários/uso terapêutico , Pré-Escolar , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/diagnóstico , Humanos , Masculino , Toxoplasmose/complicações , Toxoplasmose/diagnóstico , Toxoplasmose/tratamento farmacológico
9.
Diagn Microbiol Infect Dis ; 102(3): 115608, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34942587

RESUMO

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.


Assuntos
Toxoplasma , Toxoplasmose Congênita , Toxoplasmose , Anticorpos Antiprotozoários , Antígenos de Protozoários/genética , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G , Lactente , Sensibilidade e Especificidade , Toxoplasma/genética , Toxoplasmose/diagnóstico , Toxoplasmose Congênita/diagnóstico
10.
Mol Diagn Ther ; 25(6): 791-801, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34426953

RESUMO

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. Blood samples were collected for microscopic examination and molecular diagnosis at baseline. If negative, infants were followed up until 9 months of age to determine a final diagnosis by serology. In-house qPCR and LAMP previously validated were challenged as index tests. RESULTS: A total of 154 participants were potentially eligible, 120 of whom were enrolled. Finally, 102 (66.2%) of them fulfilled the follow-up. The diagnosis of congenital Chagas disease was confirmed in 13 infants and excluded in 89. Both the sensitivity and specificity of the qPCR were 100.0% (95% confidence interval 75.3-100.0 and 95% confidence interval 95.9-100.0, respectively), whereas the sensitivity and specificity of LAMP were 69.2% (95% confidence interval 38.6-90.9) and 100% (95% confidence interval 95.9-100.0), respectively. CONCLUSIONS: The qPCR agreed with the current diagnostic algorithm, and was a reliable and sensitive tool to detect congenital Chagas disease earlier, providing an appropriate and timely identification of infected infants requiring treatment. LAMP was able to detect congenital Chagas disease in infected infants by naked-eye visualization in accordance with a microscopic examination. The advantages of molecular diagnostic tools should be taken into account by the health system to improve congenital Chagas disease diagnosis.


Assuntos
Doença de Chagas , Trypanosoma cruzi , Doença de Chagas/congênito , Doença de Chagas/diagnóstico , Feminino , Humanos , Lactente , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Trypanosoma cruzi/genética
11.
Pediatr Infect Dis J ; 40(10): 892-898, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34310503

RESUMO

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. Sexual transmission was ruled out after a careful medical and psychosocial evaluation of the patient and his/her family. RESULTS: Twenty-four patients were included in the study. Mean age at diagnosis was 4.2 years old. All of them came from overcrowded households with poor hygiene conditions. The most frequent reason for consultations was secondary syphilis skin lesions (79.2%). The psychosocial evaluation of children and their families did not reveal signs of sexual abuse in any of the cases. Seventy-eight families and their cohabitants were evaluated, 23 (29.5%) resulted positive for rapid plasma reagin and treponemal test of hemagglutination; 60.9% of the cases were asymptomatic. The symptomatic relatives showed lesions of secondary syphilis. A sustained fall on nontreponemal antibodies titer (rapid plasma reagin) was observed after treatment, becoming negative in 6/24 (25%) cases within 12 months posttreatment. DISCUSSION: Following evaluation, it was considered that sexual abuse was unlikely. However, if examination and psychosocial evaluation do not support it, other ways of transmission must be considered. Overcrowded and poor household conditions boost the risks for nonsexual treponema transmission. An infected member of the family or a caretaker are a particular risk to an infant due to common practices such as using saliva to moisten the rubber nipples of the milk bottles or trying the food temperature using the lips before feeding the infants.


Assuntos
Anticorpos Antibacterianos/sangue , Família , Pele/microbiologia , Sífilis/etiologia , Sífilis/transmissão , Criança , Pré-Escolar , Aglomeração , Características da Família , Feminino , Humanos , Higiene , Masculino , Pobreza , Estudos Prospectivos , Pele/patologia , Sífilis/sangue , Sífilis/diagnóstico , Sorodiagnóstico da Sífilis , Treponema pallidum/imunologia
12.
PLoS Negl Trop Dis ; 15(1): e0009010, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406082

RESUMO

In spite of being preventable, Congenital syphilis (CS) is still an important, and growing health problem worldwide. Fetal infection can be particularly aggressive, but newborns can be asymptomatic at birth and, if left untreated, develop systemic compromise afterwards with poor prognosis. We analyzed 61 CS diagnosis cases between 1987-2019 presenting at the Buenos Aires Children' Hospital. The distribution of cases showed a bimodal curve, with a peak in 1992-1993 and in 2014-2017. Median age at diagnosis was 2 months (IQ 1-6 months). The main clinical findings were: bone alterations (59%); hepatosplenomegaly (54.1%); anemia (62.8%); skin lesions (42.6%) and renal compromise (33.3%). Cerebrospinal fluid (CSF) was abnormal in 5 patients, normal in 45 and was not available for 11 patients. Remarkably, spinal lumbar puncture did not modify therapeutic decisions in any case. Between mothers, only 46% have been tested for syphilis during pregnancy and 60.5% patients had non-treponemal titers equal to or less than fourfold the maternal titer. Intravenous penicillin G was prescribed for all except one patient, who received ceftriaxone with good therapeutic response. During follow-up, 1.6% infants died, 6.5% had persistent kidney disorders and 1.6% showed bone sequelae damage. RPR titers decreased after treatment, reaching negative seroconversion in 43% subjects at a median of 26.4 months. Low adherence to follow up was observed due to inherent vulnerable and low-income population characteristics in our cohort. Our results highlight a rising tendency in cases referred for CS in our population with high morbidity related to delayed diagnosis. A good therapeutic response was observed. CS requires a greater effort from the health system to adequately screen for this disease during pregnancy, and to detect cases earlier, to provide an adequate diagnosis and treatment.


Assuntos
Sífilis Congênita/diagnóstico , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Sífilis Congênita/complicações , Sífilis Congênita/tratamento farmacológico , Sífilis Congênita/epidemiologia
13.
PLoS Negl Trop Dis ; 13(8): e0007647, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31415566

RESUMO

BACKGROUND: Treatment with nifurtimox (NF) for Chagas disease is discouraged during breast-feeding because no information on NF transfer into breast milk is available. NF is safe and effective for paediatric and adult Chagas disease. We evaluated the degree of NF transfer into breast milk in lactating women with Chagas disease. PATIENTS AND METHODS: Prospective study of a cohort of lactating women with Chagas disease. Patients were treated with NF for 1 month. NF was measured in plasma and milk by high performance liquid chromatography (HPLC). Breastfed infants were evaluated at admission, 7th and 30th day of treatment (and monthly thereafter, for 6 months). RESULTS: Lactating women with chronic Chagas disease (N = 10) were enrolled (median age 28 years, range 17-36). Median NF dose was 9.75 mg/kg/day three times a day (TID). Six mothers had mild adverse drug reactions (ADRs), but no ADRs were observed in any of the breastfed infants. No interruption of breastfeeding was observed. Median NF concentrations were 2.15 mg/L (Inter quartil range (IQR) 1.32-4.55) in milk and 0.30 mg/L (IQR 0.20-0.95) in plasma. Median NF milk/plasma ratio was 16 (range 8.75-30.25). Median relative infant NF dose (assuming a daily breastmilk intake of 150 mL/kg/day) was 6.7% of the maternal dose/kg/day (IQR 2.35-7.19%). CONCLUSIONS: The low concentrations of NF in breast milk and the normal clinical evaluation of the breastfed babies imply that maternal NF treatment for Chagas disease during breastfeeding is unlikely to lead to clinically relevant exposures in the breastfed infants. TRIAL REGISTRATION: Clinical trial registry name and registration number: ClinicalTrials.gov NCT01744405.


Assuntos
Doença de Chagas/tratamento farmacológico , Leite Humano/química , Nifurtimox/administração & dosagem , Nifurtimox/análise , Tripanossomicidas/administração & dosagem , Tripanossomicidas/análise , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lactente , Masculino , Plasma/química , Estudos Prospectivos , Adulto Jovem
14.
PLoS Negl Trop Dis ; 13(8): e0007668, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31465522

RESUMO

BACKGROUND: Evaluation of therapeutic response in chronic Chagas disease is a major challenge, due to prolonged persistence of Trypanosoma cruzi-specific antibodies, lack of sensitivity of parasitological tests, and need for long-term follow-up to observe negative seroconversion of conventional serological tests (CS). The objective of this study was to evaluate F2/3-ELISA serology, a promising early biomarker of therapeutic response, and T.cruzi Polymerase chain reaction (PCR) for T. cruzi Deoxyribonucleic acid (DNA), for neonatal diagnosis and evaluation of parasitemia after treatment. METHODS: Prospective cohort study, with three-year clinical, serological and parasitological follow-up of pediatric Chagas disease patients treated with benznidazole. Serology was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA), Indirect hemagglutination (IHA) and F2/3-ELISA; Parasitemia by microhematocrit (MH) and PCR. RESULTS: A cohort of 107 pediatric patients treated with benznidazole was enrolled in the study. ELISA and IHA were initially reactive in 100% of patients, F2/3-ELISA serology was reactive in 80% (86/107) and 91% (97/107) had detectable parasitemia. Seventy-six (71%) patients completed at least 36 months of serological follow up after treatment. Although a similar decreasing linear trend was observed for all serological tests, F2/3-ELISA presented earlier, age dependent, negative seroconversion compared to CS. All patients reaching undetectable CS titers had previously seroreverted by F2/3-ELISA. All patients with persistently decreasing antibody titers had negative PCRs throughout the follow up period. No new cardiological lesions were observed during the 3 years follow-up period. CONCLUSIONS: The data reported here, using CS, F2/3 ELISA and PCR provide support for the efficacy of benznidazole in congenital Chagas diseases. These results provide support for scaling up of screening, diagnosis and access to benznidazole treatment. TRIAL REGISTRATION: ClinicalTrials.gov 0028/04 in the Research Council, Secretary of Health Buenos Aires city Goberment.


Assuntos
Anticorpos Antiprotozoários/sangue , Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/imunologia , Trypanosoma cruzi/imunologia , Adolescente , Formação de Anticorpos , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Nitroimidazóis/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
15.
Open Forum Infect Dis ; 5(11): ofy236, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30397621

RESUMO

BACKGROUND: No reliable tests or validated biomarkers exist to ensure parasitological cure following treatment of Chagas disease (CD) patients chronically infected with Trypanosoma cruzi. As seroreversion, the only marker of cure, happens more quickly in children, we investigated the correlation between previously identified biomarkers and seroreversion in children. METHODS: Thirty CD children (age 1 month to 10 years) diagnosed as T. cruzi positive (time point S0) were treated with benznidazole (BZ) 5-8 mg/kg/d for 60 days. At least 2 serological tests were used to evaluate treatment efficacy from the end of treatment (S1) until seroreversion (S2). Thirty children (age 1 month to 10 years) and 15 adults were used as healthy controls (HCs). Immunoblot and a proteomic-based assay were used to validate previously identified fragments of apolipoprotein A-1 (ApoA1) and fibronectin (FBN) as CD biomarkers. RESULTS: Correlation between seroreversion and absence of ApoA1 and FBN fragments by immunoblot was observed in 30/30 (100%) and 29/30 (96.6%) CD children, respectively. ApoA1 and FBN fragments were absent at the end of BZ treatment in 20/30 (66.6%) and 16/30 (53.3%) children, respectively. Absence of fragments in serum profiles was confirmed by mass spectrometry. Using intact protein analysis, a 28 109-Da protein identified as full-length ApoA1 by tandem mass spectrometry was detected in HC serum samples. CONCLUSIONS: These data confirm that ApoA1 and FBN fragments can discriminate between healthy and T. cruzi-infected samples. Correlation with seroreversion was shown for the first time; results suggest predictive capacity potentially superior to serology, making them potentially useful as surrogate biomarkers.

16.
J Clin Microbiol ; 55(12): 3444-3453, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28978686

RESUMO

Chagas disease is caused by the protozoan parasite Trypanosoma 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 recombinant T. cruzi antigen termed trypomastigote small surface antigen (TSSA) as an early serological marker of drug efficacy in T. cruzi-infected children. A cohort of 78 pediatric patients born to T. cruzi-infected mothers was included in this study. Only 39 of the children were infected with T. 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 in T. 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 for T. cruzi infection. 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 congenital T. cruzi infection. Based upon these findings we propose the inclusion of TSSA for refining the posttherapeutic cure criterion and other diagnostic needs in pediatric Chagas disease.


Assuntos
Anticorpos Antiprotozoários/sangue , Doença de Chagas/diagnóstico , Monitoramento de Medicamentos/métodos , Testes Sorológicos/métodos , Glicoproteínas Variantes de Superfície de Trypanosoma/imunologia , Doença de Chagas/tratamento farmacológico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Tripanossomicidas/administração & dosagem , Trypanosoma cruzi
17.
PLoS One ; 11(9): e0160472, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27589236

RESUMO

INTRODUCTION: Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. OBJECTIVE: To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. POPULATION AND METHODS: Patients (0-18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10-15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. RESULTS: A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. CONCLUSION: Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Equinococose/tratamento farmacológico , Adolescente , Animais , Argentina , Criança , Pré-Escolar , Equinococose/cirurgia , Feminino , Humanos , Masculino , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
18.
Mem. Inst. Oswaldo Cruz ; 110(5): 644-648, Aug. 2015. tab, ilus
Artigo em Inglês | LILACS | ID: lil-755901

RESUMO

The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruziinfection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate.

.


Assuntos
Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Gravidez , Adulto Jovem , Doença de Chagas/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Argentina/epidemiologia , Estudos Transversais , Doença de Chagas/diagnóstico , Prevalência , População Urbana
19.
Mem Inst Oswaldo Cruz ; 110(5): 644-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26222020

RESUMO

The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate.


Assuntos
Doença de Chagas/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Adolescente , Adulto , Animais , Argentina/epidemiologia , Doença de Chagas/diagnóstico , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Gravidez , Prevalência , População Urbana , Adulto Jovem
20.
Mem. Inst. Oswaldo Cruz ; 110(4): 507-509, 09/06/2015. tab
Artigo em Inglês | LILACS | ID: lil-748867

RESUMO

It is currently unknown whether treatment of Chagas disease decreases the risk of congenital transmission from previously treated mothers to their infants. In a cohort of women with Chagas disease previously treated with benznidazole, no congenital transmission of the disease was observed in their newborns. This finding provides support for the treatment of Chagas disease as early as possible.


Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Gravidez , Adulto Jovem , Doença de Chagas/transmissão , Transmissão Vertical de Doenças Infecciosas , Nitroimidazóis/uso terapêutico , Complicações Parasitárias na Gravidez , Tripanossomicidas/uso terapêutico , Estudos de Coortes , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Prevenção Primária , Complicações Parasitárias na Gravidez/tratamento farmacológico , Trypanosoma cruzi
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