Adverse Events After the Use of Benznidazole in Infants and Children With Chagas Disease

Altcheh, Jaime; Moscatelli, Guillermo; Moroni, Samanta; Garcia‐Bournissen, Facundo; Freilij, Héctor

doi:10.1542/peds.2010-1172

Cited by 141 publications

(120 citation statements)

References 34 publications

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“…This result is in accordance with recent findings presented by Lobo et al (43), in which a greater incidence rate of ADRs was observed in adults than in children and older patients (61.0% versus 18.9% and 20.0%, respectively; P ϭ 0.0001) in a cohort of hospitalized patients at a tertiary care hospital in Northern Brazil. However, previous studies have shown a higher incidence of ADRs related to BZN in elderly patients (14), while a low incidence of ADRs was described for children and adolescents (44)(45)(46). As our study did not include individuals older than 65 years, this could explain the higher incidence of ADRs found by us among adults.…”

Section: Discussionmentioning

confidence: 58%

A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

Silva

Mediano

Brasil

et al. 2014

Antimicrob Agents Chemother

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Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease, and the evidence supporting the benefits of BZN use during the chronic phase of the disease will favor its use in millions of individuals. However, more than 30% of patients treated with BZN may suffer adverse drug reactions (ADRs), and the development of tools to identify those patients at risk is highly desirable. In the present study, we aimed to identify predictive factors for ADRs in Chagas disease patients treated with BZN. Among 195 patients included in the study, 48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation were more common among women and in those who graduated from elementary school. Overall ADRs were also less frequent among black individuals. Based on logistic regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to 3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1 to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3; 95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment discontinuation. Graduation from elementary school also presented a tendency to predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to 3.6). The logistic regression (LR) models to predict ADRs to BZN described in this study may become important tools to minimize ADRs and improve patients' compliance and thus assist physicians treating patients with Chagas disease with BZN. E ven 100 years after it was first reported (1), Chagas disease remains a serious public health problem in Latin America, with a high social and economic burden (2, 3). Moreover, the prevalence of Chagas disease is increasing, mainly due to migration, in countries where it is not endemic, such as the United States and European countries (4-7).Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease (8, 9), and the parasitological cure rate when patients are treated with BZN during the acute phase of the disease is almost 80% (10, 11). Although BZN effectiveness during the chronic phase of the disease remains uncertain (12)(13)(14), there is compelling evidence supporting the beneficial use of BZN even during the chronic phase of Chagas disease (13, 15), and some international guidelines are now advocating the use of BZN even among adults with chronic disease (16-18). However, adverse drug reactions (ADRs) occur in 30% to 87% of the patients treated with BZN (19-21), and 12% to 29% of patients fail to complete their full course of treatment (19-21). Therefore, the development of tools to identify patients with high probabilities of developing ADRs to BZN is highly desirable, as this strategy would improve compliance to BZN treatment and minimize complications (21,22).Logistic regression (LR) is a method often used to predict outcomes in health studies (23,24), and...

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Section: Discussionmentioning

confidence: 58%

A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

Silva

Mediano

Brasil

et al. 2014

Antimicrob Agents Chemother

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“…The prevalence of Chagas disease in pregnant women in Latin America ranges from 5% to 40% depending on the geographical area, and the rate of vertical transmission is esti- mated to be 4% to 10% (32). Due to the shortage of biomarkers specific for the acute stage (32,33), the current serologic tests are misleading in the early diagnosis of congenital T. cruzi infections, and a parasitological test should be performed on newborns for diagnosis (22). Within this framework, we evaluated the potential use of TSSA-CL in the serodiagnosis of congenital infections.…”

Section: Resultsmentioning

confidence: 99%

“…Serum samples were collected from infected and noninfected subjects. Clotted blood was obtained by venipuncture and analyzed for T. cruzi-specific antibodies by 2 commercially available kits, an ELISA using total parasite homogenate and IHA (both from the Wiener lab, Argentina) (22). Different panels of serum samples were used in this work.…”

Section: Methodsmentioning

confidence: 99%

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide-and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acidlong peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. Chagas disease is a major health and economic problem in Latin America, for which no vaccine or appropriate drugs for largescale public health interventions are yet available (1). It is caused by the protozoan Trypanosoma cruzi, found throughout the American continents in a variety of wild and domestic mammalian reservoirs, and it is transmitted by the bite of infected bloodsucking triatomine bugs. It is estimated that 8 to 10 million people are currently infected with T. cruzi and that up to 120 million individuals living in areas that are endemic for the parasite are at risk of infection (1). Increasing travel and immigration have also brought the risk of T. cruzi infection into countries that are not endemic for the parasite (2). Several efforts have successfully been undertaken to control transmission in Latin America, with a concomitant decrease in the actual numbers of acute vector-borne infections (3). However, humans can also become infected with T. cruzi through the ingestion of tainted food and fluids, receipt of contaminated blood transfusion or organ transplantation, and from mother-to-child during pregnancy/delivery (4).The diagnosis of Chagas disease is challenging because it is often asymptomatic in its acute phase and evolves into a chronic stage in which the disease course takes different clinical forms (1). In addition, and due to a major decline in parasitemia during the chronic phase, the detection of T. cruzi in blood sample...

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“…11 Nonetheless, when newborns are treated before 1 year of age, infection is cleared in almost all cases without the secondary effects common among adults. 11,13 Diagnosis in neonates is possible immediately after birth through parasitological methods, such as visualization of trypomastigotes on peripheral or cord blood, as well as blood concentration techniques (Strout or microhematocrit 14 ), whereas serologic diagnosis is possible starting at 8 months after birth, when potentially confounding maternal antibodies have disappeared. 11 Additionally, recent data suggest that parasitological treatment of young infected women may help prevent congenital transmission later in life.…”

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confidence: 99%

A National Survey to Determine Prevalence of Trypanosoma cruzi Infection Among Pregnant Women in Ecuador

Costales¹,

Sánchez-Gómez²,

Ayçaguer³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. A nationwide survey was conducted to obtain an estimate of Chagas disease prevalence among pregnant women in Ecuador. As part of a national probability sample, 5,420 women seeking care for delivery or miscarriage at 15 healthcare facilities were recruited into the study. A small minority of participants reported knowing about Chagas disease or recognized the vector. A national seroprevalence of 0.1% (95% confidence interval [95% CI] = 0.0-0.2%) was found; cases were concentrated in the coastal region (seroprevalence = 0.2%; 95% CI = 0.0-0.4%). No cases of transmission to neonates were identified in the sample. Seropositive participants were referred to the National Chagas Program for evaluation and treatment. Additional studies are necessary to determine if areas of higher prevalence exist in well-known endemic provinces and guide the development of a national strategy for elimination of mother-to-child transmission of Chagas disease in Ecuador.Chagas disease, caused by Trypanosoma cruzi, is spread mainly by hematophagous triatomine vectors, blood transfusion, and congenital transmission.

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Adverse Events After the Use of Benznidazole in Infants and Children With Chagas Disease

Cited by 141 publications

References 34 publications

A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

A Clinical Adverse Drug Reaction Prediction Model for Patients with Chagas Disease Treated with Benznidazole

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

A National Survey to Determine Prevalence of Trypanosoma cruzi Infection Among Pregnant Women in Ecuador

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