Benznidazole treatment in chronic children infected with Trypanosoma cruzi: Serological and molecular follow-up of patients and identification of Discrete Typing Units

Rumi, Mercedes; Brandán, Cecilia Pérez; Gil, José Fernando; D’Amato, Anahí M. Alberti; Ragone, Paula G.; Lauthier, Juan José; Tomasini, Nicolás; Cimino, Rubén O.; Orellana, Viviana; Lacunza, Carlos D.; Nasser, Julio R.; Basombrío, Miguel Á.; Diosque, Patricio

doi:10.1016/j.actatropica.2013.07.003

Cited by 22 publications

(22 citation statements)

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“…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

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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...

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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

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“…18,19 Nevertheless, the Discrete Typing Unit TcI was found infecting humans mainly in organ explants such as human cardiac or brain tissues 20 -23 and in patients who had undergone immunosuppressive therapy, suggesting that TcI parasites circulate at low parasitemia levels, which makes it difficult to detect this DTU in peripheral blood. 22 In congenital human infections, in our endemic region, no TcI parasites have been detected, 23,24 except for the case report presented in this article, which was first described in a previous study 10 and in a few more cases. 21,25 This case report poses 2 main differences with previous studies from our laboratory.…”

Section: Discussionmentioning

confidence: 77%

Some Limitations for Early Diagnosis of Congenital Chagas Infection by PCR

et al. 2018

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, the causing agent of Chagas disease, can be transmitted to the offspring of infected pregnant women, thus being an epidemiologically important way of parasite transmission in humans. In addition, the migration of infected women from endemic areas to nonendemic countries may export this parasite infection. The diagnosis of congenital Chagas disease relies on the detection of the parasite because maternal antibodies are passively transferred to infants during pregnancy. The diagnosis of congenital infection can also be confirmed by detection of infant-specific anti- antibodies at 10 months after delivery. Because early detection of infection in newborns allows an efficient trypanocidal treatment and cure, more sensitive molecular techniques such as DNA amplification are being used for a prompt parasitological diagnosis of children born to seropositive mothers. In this report, we describe a diagnosis case of a child congenitally infected with who tested negative for parasite detection both by microscopic observation and DNA amplification at 20 days and 6 months after delivery. However, at 7 months of age, a hemoculture was made from the infant's blood, and the infective parasite was finally isolated and classified as discrete typing unit I. In a retrospective study, real-time polymerase chain reaction also allowed detecting the parasite but failed to detect any parasite load in earlier control samples. This case report stresses that even when molecular techniques are negative, a long-term follow-up is necessary for the diagnosis of infants congenitally infected with.

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“…Is important to note that the DTUs studied in this work have epidemiological relevance, since the TcV and TcVI are more prevalent in domestic cycles [ 34 , 42 , 47 , 48 ], whereas the TcIII DTU was found in domestic animals [ 34 ]. It is clear that the extrapolation of co-infection results obtained from animal models to the natural occurrence of the phenomena in other hosts should be carefully considered.…”

Section: Discussionmentioning

confidence: 99%

“…It is clear that the extrapolation of co-infection results obtained from animal models to the natural occurrence of the phenomena in other hosts should be carefully considered. We emphasize the predominance of TcVI in the mixture TcV + TcVI since this mixture was found in human blood samples in endemics areas of Argentina [ 42 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

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Experimental Evidence of Biological Interactions among Different Isolates of Trypanosoma cruzi from the Chaco Region

et al. 2015

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Many infectious diseases arise from co-infections or re-infections with more than one genotype of the same pathogen. These mixed infections could alter host fitness, the severity of symptoms, success in pathogen transmission and the epidemiology of the disease. Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits a high biological variability often correlated with its genetic diversity. Here, we developed an experimental approach in order to evaluate biological interaction between three T. cruzi isolates belonging to different Discrete Typing Units (DTUs TcIII, TcV and TcVI). These isolates were obtained from a restricted geographical area in the Chaco Region. Different mixed infections involving combinations of two isolates (TcIII + TcV, TcIII + TcVI and TcV + TcVI) were studied in a mouse model. The parameters evaluated were number of parasites circulating in peripheral blood, histopathology and genetic characterization of each DTU in different tissues by DNA hybridization probes. We found a predominance of TcVI isolate in blood and tissues respect to TcIII and TcV; and a decrease of the inflammatory response in heart when the damage of mice infected with TcVI and TcIII + TcVI mixture were compared. In addition, simultaneous presence of two isolates in the same tissue was not detected. Our results show that biological interactions between isolates with different biological behaviors lead to changes in their biological properties. The occurrence of interactions among different genotypes of T. cruzi observed in our mouse model suggests that these phenomena could also occur in natural cycles in the Chaco Region.

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Benznidazole treatment in chronic children infected with Trypanosoma cruzi: Serological and molecular follow-up of patients and identification of Discrete Typing Units

Cited by 22 publications

References 35 publications

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

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

Some Limitations for Early Diagnosis of Congenital Chagas Infection by PCR

Experimental Evidence of Biological Interactions among Different Isolates of Trypanosoma cruzi from the Chaco Region

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