Kinetoplastids:
            <i>Trypanosoma cruzi</i>
            (Chagas disease)

Tarleton, Rick L.

doi:10.1002/9781118393321.ch9

Cited by 3 publications

(3 citation statements)

References 50 publications

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“…Indeed a positive parasitological result after treatment is considered unequivocal evidence of failure to clear the parasite and thus ineffective treatment [ 21 ]. However, PCR negative results do not ensure the absence of infection given that the parasitemia fluctuates between detectable and undetectable concentrations in blood [ 21 ] and the parasite may persist in host tissues like muscle or may intermittently circulate at a very low or undetectable levels in blood [ 22 ]. Another technique that has been evaluated for the follow-up of treatment efficacy is serology testing.…”

Section: Introductionmentioning

confidence: 99%

A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients

Zrein¹,

Granjon²,

Gueyffier³

et al. 2018

PLoS Negl Trop Dis

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BackgroundTrypanosoma cruzi parasite, the causative agent of Chagas disease, infects about six million individuals in more than 20 countries. Monitoring parasite persistence in infected individuals is of utmost importance to develop and evaluate treatments to control the disease. Routine screening for infected human individuals is achieved by serological assays; PCR testing to monitor spontaneous or therapy-induced parasitological cure has limitations due to the low and fluctuating parasitic load in circulating blood. The aim of the present study is to evaluate a newly developed antibody profiling assay as an indirect method to assess parasite persistence based on waning of antibodies following spontaneous or therapy-induced clearance of the infection.Methodology/Principal findingsWe designed a multiplex serology assay, an array of fifteen optimized T. cruzi antigens, to evaluate antibody diversity in 1654 serum samples from chronic Chagas patients. One specific antibody response (antibody 3, Ab3) showed a strong correlation with T. cruzi parasite persistence as determined by T. cruzi PCR positive results. High and sustained Ab3 signal was strongly associated with PCR positivity in untreated patients, whereas significant decline in Ab3 signals was observed in BZN-treated patients who cleared parasitemia based on blood PCR results.Conclusion/SignificanceAb3 is a new surrogate biomarker that strongly correlates with parasite persistence in chronic and benznidazole-treated Chagas patients. We hypothesize that Ab3 is induced and maintained by incessant stimulation of the immune system by tissue-based and shed parasites that are not consistently detectable by blood based PCR techniques. Hence, a simple immunoassay measurement of Ab3 could be beneficial for monitoring the infectious status of seropositive patients.

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Section: Introductionmentioning

confidence: 99%

A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients

Zrein¹,

Granjon²,

Gueyffier³

et al. 2018

PLoS Negl Trop Dis

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“…After the acute phase which lasts few months, most patients enter chronic Chagas disease. During this phase, parasites are less abundant and may be confined to certain host tissues like muscle or fat [ 3 ]. About 70% of chronic patients will never develop severe clinical complications.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological Confirmation of Chagas Disease

Granjon¹,

Dichtel-Danjoy²,

Saba³

et al. 2016

PLoS Negl Trop Dis

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BackgroundChagas disease is due to the parasite Trypanosoma cruzi, a protist disseminated by a Triatome vector. This disease is endemic to Latin America and considered by WHO as one of the 17 world’s neglected diseases. In Europe and in North America, imported cases are also detected, due to migration of population outside of the endemic region. Diagnosis of T. cruzi infection is usually made indirectly by the detection of specific antibodies to T. cruzi antigens. Following initial diagnostic evaluation or screening test (qualifying or discarding blood donation), a confirmation test is performed for samples initially reactive. The test presented in this study aims at the confirmation/refutation of the infectious status of human blood samples and will permit taking appropriate clinical measures.Methodology/Principal FindingsWe designed a novel array of twelve antigens and printed these antigens onto 96-well plates. We tested 248 positive samples T. cruzi, 94 unscreened blood donors’ samples from non-endemic area, 49 seronegative blood donors, 7 false-positive and 3 doubtful samples. The observed reactivities were analyzed to propose a decision-tree algorithm that correctly classifies all the samples, with the potential to discriminate false-positive results and sticky samples. We observed that antibodies levels (Sum of all antigens) was significantly higher for PCR positive than for PCR negative samples in all studied groups with Multi-cruzi.Conclusion/SignificanceThe results described in this study indicate that the Multi-cruzi improves the serological confirmation of Chagas disease. Moreover the “sum of all antigens” detected by Multi-cruzi could reflect parasitemia level in patients–like PCR signals does—and could serve as an indicator of parasite clearance in longitudinal follow-ups. Validation of this assay is still required on an independent large collection of well characterized samples including typical false-reactive samples such as Leishmaniasis.

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“…After the acute and relatively asymptomatic blood stage of T. cruzi infection, parasites are primarily confined to myocytes and adipocytes [133]. Anti-parasitic drugs become ineffective and control of Chagas disease becomes all about treating the chronic symptoms including cardiac and gastrointestinal problems.…”

Section: Chronic Infectionmentioning

confidence: 99%

Role of Chemokines and Trafficking of Immune Cells in Parasitic Infections

McGovern¹,

Wilson²

2014

CIR

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Parasites are diverse eukaryotic pathogens that can have complex life cycles. Their clearance, or control within a mammalian host requires the coordinated effort of the immune system. The cell types recruited to areas of infection can combat the disease, promote parasite replication and survival, or contribute to disease pathology. Location and timing of cell recruitment can be crucial. In this review, we explore the role chemokines play in orchestrating and balancing the immune response to achieve optimal control of parasite replication without promoting pathology.

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Kinetoplastids: Trypanosoma cruzi (Chagas disease)

Cited by 3 publications

References 50 publications

A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients

A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients

Development of a Novel Multiplex Immunoassay Multi-cruzi for the Serological Confirmation of Chagas Disease

Role of Chemokines and Trafficking of Immune Cells in Parasitic Infections

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