Evaluation of Nifurtimox Treatment of Chronic Chagas Disease by Means of Several Parasitological Methods

Muñoz, Catalina; Zulantay, Inés; Apt, Werner; Ortíz, Sylvia; Schijman, Alejandro G.; Bisio, Margarita; Ferrada, V.; Herrera, Cinthya N.; Martínez, Gabriela; Solari, Aldo

doi:10.1128/aac.00227-13

Cited by 26 publications

(21 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The clinical suspicion is directed to other endemic diseases particularly dengue with similar early clinical symptoms. The frequency and the symptoms observed were similar to those in the majority of acute CD outbreaks reported [25, 27, 29, 32, 57, 58]. The histopathological findings of four hearts from patients, showed an intense inflammatory infiltrate in the interstitium, and the presence of amastigote nests in myocardial fibers.…”

Section: Discussionsupporting

confidence: 80%

Acute chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia

et al. 2015

Self Cite

View full text Add to dashboard Cite

BackgroundOutbreaks of acute Chagas disease associated with oral transmission are easily detected nowadays with trained health personnel in areas of low endemicity, or in which the vector transmission has been interrupted. Given the biological and genetic diversity of Trypanosoma cruzi, the high morbidity, mortality, and the observed therapeutic failure, new characteristics of these outbreaks need to be addressed at different levels, both in Trypanosoma cruzi as in patient response. The aim of this work was to evaluate the patient’s features involved in six outbreaks of acute Chagas disease which occurred in Santander, Colombia, and the characteristics of Trypanosoma cruzi clones isolated from these patients, to establish the potential relationship between the etiologic agent features with host behavior.MethodsThe clinical, pathological and epidemiological aspects of outbreaks were analyzed. In addition, Trypanosoma cruzi clones were biologically characterized both in vitro and in vivo, and the susceptibility to the classical trypanocidal drugs nifurtimox and benznidazole was evaluated. Trypanosoma cruzi clones were genotyped by means of mini-exon intergenic spacer and cytochrome b genes sequencing.ResultsAll clones were DTU I, and based on the mini-exon intergenic spacer, belong to two genotypes: G2 related with sub-urban, and G11 with rural outbreaks. Girón outbreak clones with higher susceptibility to drugs presented G2 genotype and C/T transition in Cyt b. The outbreaks affected mainly young population (±25.9 years), and the mortality rate was 10 %. The cardiac tissue showed intense inflammatory infiltrate, myocardial necrosis and abundant amastigote nests. However, although the gastrointestinal tissue was congestive, no inflammation or parasites were observed.ConclusionsAlthough all clones belong to DTU I, two intra-DTU genotypes were found with the sequencing of the mini-exon intergenic spacer, however there is no strict correlation between genetic groups, the cycles of the parasite or the clinical forms of the disease. Trypanosoma cruzi clones from Girón with higher sensitivity to nifurtimox presented a particular G2 genotype and C/T transition in Cyt b. When the diagnosis was early, the patients responded well to antichagasic treatment, which highlights the importance of diagnosis and treatment early to prevent fatal outcomes associated with these acute episodes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1218-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 80%

Acute chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…TcV was the most abundant and TcI the least frequent DTU detected in these patients, even though other not identified DTUs are also circulating in some patients. The presence of mixed DTUs (11/21) and undetermined DTUs (9/21) were also reported in a previous survey (Muñoz et al 2013 )…”

Section: Discussionsupporting

confidence: 81%

Trypanosoma cruzi burden, genotypes, and clinical evaluation of Chilean patients with chronic Chagas cardiopathy

et al. 2015

Self Cite

View full text Add to dashboard Cite

There are currently no biomarkers to assess which patients with chronic indeterminate Chagas disease will develop heart disease and which will spend their entire life in this state. We hypothetize that the parasite burden and Trypanosoma cruzi genotypes are related to the presence of heart disease in patients with Chagas disease. This study is aimed to investigate the parasite burden and T. cruzi genotypes in chagasic cardiopaths versus chagasic individuals without cardiac involvement according to the New York Heart Association. Patients with chronic Chagas disease, 50 with and 50 without cardiopathy (controls), groups A and B, respectively, were submitted to anamnesis, physical examination, and electrocardiogram. Echo-Doppler was performed for group A; all important known causes of cardiopathy were discarded. Xenodiagnosis, conventional PCR, and quantitative PCR were performed on patients of both groups. T. cruzi genotyping was done for 25 patients of group A and 20 of group B. The 50 cardiopaths had 80 electrocardiographic alterations, most of them in grade II of the New York Heart Association classification; 49 were classified in grade I by Echo-Doppler, and only one patient was in grade III. The difference in average parasitemia in patients of groups A and B was not significant. The most frequent T. cruzi DTU found was TcV. The parasite burden and genotype of the groups with and without cardiopathy were similar.Graphical abstractImagen 1 Chronic chagas cardiopathy chest X-ray heart enlargementFigure 2 Chronic Chagas cardiopathy microaneurism of left ventricle. Cineangiography

show abstract

“…Twenty studies (37%) included adults [ 22 , 29 , 31 , 33 , 35 , 36 , 38 , 43 , 44 , 46 , 48 , 50 , 52 , 61 , 66 , 69 , 70 , 73 – 75 ], sixteen studies (30%) included only children [ 23 – 25 , 27 , 32 , 41 , 54 , 49 , 51 , 54 – 56 , 59 , 62 , 64 , 65 ], and thirteen (24%) included both children and adults [ 28 , 30 , 34 , 37 , 39 , 40 , 42 , 47 , 57 , 60 , 63 , 68 , 72 ]. The age of study sample was not clearly reported in five studies (9%), but it can be assumed that they involved adults as well [ 26 , 53 , 58 , 67 , 71 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

BackgroundChagas disease is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). It is endemic in Latin American countries outside the Caribbean. The current criterion for cure in the chronic phase of the disease is the negativization of at least two serological tests such as enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect hemagglutination assay (IHA). The serological evolution of treated subjects with chronic T. cruzi infection is variable. Treatment failure is indicated by a positive parasitological and/or molecular test (persistence of parasitemia).ObjectivesTo summarize the pattern of response to treatment of parasitological, molecular and serological tests performed during the follow-up of subjects with chronic T. cruzi infection.MethodsElectronic searches in relevant databases and screening of citations of potentially eligible articles were accomplished. Organizations focusing on neglected infectious diseases were asked for help in identifying relevant studies.Included studies were randomized controlled trials (RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic infection who received trypanocidal treatment (benznidazole or nifurtimox) and were followed over time. The assessment of risk of bias was performed separately for each study design. The Cochrane Collaboration’s tool and the guidelines developed by Hayden et al. were used. Two reviewers extracted all data independently. A third review author was consulted in case of discordant opinion.Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of positive parasitological and molecular tests and for negative serological tests were developed by using the lowess curve technique. Heterogeneity was measured by I2.The protocol was registered in PROSPERO, an international prospective register of systematic review protocols (Registration Number CRD42012002162).ResultsOut of 2,136 citations screened, 54 studies (six RCTs and 48 cohort studies) were included. The smoothed curves for positive xenodiagnosis and positive polymerase chain reaction (PCR) were characterized by a sharp decrease at twelve month posttreatment. Afterwards, they reached 10–20% and 40% for xenodiagnosis and PCR, respectively. The smoothed curves for negative conventional serological tests increased up to 10% after 48 months of treatment. In the long-term, the rate of negativization was between 20% and 45%.The main sources of bias identified across cohort studies were the lack of control for confounding and attrition bias. In general, RCTs were judged as low risk of bias in all domains. The level of heterogeneity across included studies was moderate to high.Additional analysis were incomplete because of the limited availability of data. In this regard, the country of origin of study participants might affect the results of parasitological and molecular tests, while the level of risk of bias might affect serological outcomes. Subgroup analysis suggested that seronegativization occurs...

show abstract

Evaluation of Nifurtimox Treatment of Chronic Chagas Disease by Means of Several Parasitological Methods

Cited by 26 publications

References 45 publications

Acute chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia

Acute chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia

Trypanosoma cruzi burden, genotypes, and clinical evaluation of Chilean patients with chronic Chagas cardiopathy

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

Contact Info

Product

Resources

About