Parasitological, serological and molecular diagnosis of acute and chronic Chagas disease: from field to laboratory

Schijman, Alejandro G.; Alonso-Padilla, Julio; Longhi, Silvia Andrea; Picado, Albert

doi:10.1590/0074-02760200444

Cited by 19 publications

(8 citation statements)

References 107 publications

(126 reference statements)

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“…Like ELISA, CMIAs are recommended for the diagnosis of chronic Chagas and donor screening ( World Health Organization, 2019 ). CMIAs use recombinant antigens ( Schijman et al, 2022 ). Typically automated, CMIAs allow higher throughput and quicker turnaround times, making them preferable for large centers and those conducting donor screening.…”

Section: Discussionmentioning

confidence: 99%

“…There are 18 genera and 154 species of triatomine bugs ( Shi et al, 2020 ). Triatomines inhabit in tropical and subtropical areas of the Americas, from Southern United States to Argentina, Asia, Africa, and Oceania ( Shi et al, 2020 ; Schijman et al, 2022 ; Zhao et al, 2023 ). However, vector transmission only occurs in the Americas.…”

Section: Introductionmentioning

confidence: 99%

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In vitro diagnostic methods of Chagas disease in the clinical laboratory: a scoping review

Ascanio,

Carroll,

Paniz-Mondolfi

et al. 2024

Front. Microbiol.

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BackgroundChagas disease (CD), caused by Trypanosoma cruzi, is a global health concern with expanding geographical reach. Despite improved and accessible test methods, diagnosing CD in its various phases remains complex. The existence of clinical scenarios, including immunosuppressed patients, transplant-related CD reactivation, transfusion-associated cases, and orally transmitted acute infections, adds to the diagnostic challenge. No singular gold standard test exists for all phases, and recommendations from PAHO and the CDC advocate for the use of two serological methods for chronic CD diagnosis, while molecular methods or direct parasite detection are suggested for the acute phase. Given the complexity in the diagnostic landscape of CD, the goal of this scoping review is to characterize available diagnostic tests for CD in the clinical laboratory.MethodsA literature search in PubMed was conducted on studies related to In vitro diagnosis (IVD) in humans published in English, Spanish, or Portuguese language as of 28 August 2023, and extended backward with no predefined time frame. Studies underwent title and abstract screening, followed by full-text review. Studies included were classified based on the diagnostic method used. Test methods were grouped as serological, molecular, and other methods. Performance, availability, and regulatory status were also characterized.ResultsOut of 85 studies included in the final review, 115 different tests were identified. These tests comprised 89 serological test types, 21 molecular test types, and 5 other test methods. Predominant serological tests included ELISA (38 studies, 44.70%), Rapid tests (19 studies, 22.35%), and chemiluminescence (10 studies, 11.76%). Among molecular tests, Polymerase Chain Reaction (PCR) assays were notable. Twenty-eight tests were approved globally for IVD or donor testing, all being serological methods. Molecular assays lacked approval for IVD in the United States, with only European and Colombian regulatory acceptance.Discussion and conclusionSerological tests, specifically ELISAs, remain the most used and commercially available diagnostic methods. This makes sense considering that most Chagas disease diagnoses occur in the chronic phase and that the WHO gold standard relies on 2 serological tests to establish the diagnosis of chronic Chagas. ELISAs are feasible and relatively low-cost, with good performance with sensitivities ranging between 77.4% and 100%, and with specificities ranging between 84.2% and 100%. Molecular methods allow the detection of specific variants but rely on the parasite’s presence, which limits their utility to parasitemia levels. Depending on the PCR method and the phase of the disease, the sensitivity ranged from 58.88 to 100% while the mean specificity ranged from 68.8% to 100%. Despite their performance, molecular testing remains mostly unavailable for IVD use. Only 3 molecular tests are approved for IVD, which are available only in Europe. Six commercial serological assays approved by the FDA are available for blood and organ donor screening. Currently, there are no guidelines for testing CD oral outbreaks. Although more evidence is needed on how testing methods should be used in special clinical scenarios, a comprehensive approach of clinical assessment and diagnostics tests, including not IVD methods, is required for an accurate CD diagnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro diagnostic methods of Chagas disease in the clinical laboratory: a scoping review

Ascanio,

Carroll,

Paniz-Mondolfi

et al. 2024

Front. Microbiol.

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“…Hemoculture is another indirect method, in which the examination should be performed monthly for as long as six months. However, both xenodiagnosis and hemoculture have low sensitivity [35,36] (around 20%) and are best suited for the chronic phase of the disease [15,34].…”

Section: Discussionmentioning

confidence: 99%

An outbreak of Chagas disease through oral transmission: 115 years after discovery by Carlos Chagas, the disease is still hard to manage

Alves Simões-Neto,

Santos,

Bomfim

et al. 2024

Preprint

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BackgroundOrally transmitted acute Chagas disease (ACD) mostly affects low-visibility and low-income individuals, mainly in tropical and subtropical zones. However, even more than 100 years after Carlos Chagas’ discovery, several difficulties in managing ACD are still faced. Ita expansion to other, non-endemic areas through globalization processes has transformed it into a global health problem.Methodology and findingsThis report addresses an outbreak of 39 cases of ACD due to oral transmission. A clinical-epidemiological investigation with an entomological search was performed. Laboratory criteria (positive peripheral blood smear (PBS), seroconversion of IgG and 2x increase in IgG titer) and clinical-epidemiological criteria (clinical findings, epidemiological exposure and at least one positive IgG) were used for diagnoses. In-house conventional polymerase chain reaction (PCR) was performed on 33 samples. All patients were treated with benznidazole. After 4.5 years, IgG was investigated in 26 individuals. Their mean age was 33.6 years, with no difference in gender distribution; the mean incubation period was 13.8 days and mean time between symptom onset and treatment was 16.6 days. The most frequent symptoms were fever and lymphadenopathy (90%). For 66.6%, laboratory criteria yielded the diagnosis and for 23%, clinical-epidemiological criteria, while 10.2% showed negative tests but were treated due to high clinical suspicion. Test positivity rates: PBS 69.7%; serology 91.4%; PCR 100%. There were no deaths. Serological cure was achieved for 34.6% and decreased IgG titers for 15.3%.Conclusions and significanceWe present all the barriers encountered in managing real-life situations: vulnerability of the population; dependence on old diagnostic techniques; lack of standardization of molecular biology techniques; and few therapeutic options. We demonstrated the importance of rapid surveillance action with early treatment, such that this outbreak did not give rise to deaths. We also propose that conventional PCR should become standardized within the diagnostic routine.AUTHOR SUMMARYIn this study we present an outbreak of orally transmitted acute Chagas disease (ACD), a neglected tropical disease. The source of transmission was bacaba juice served at a celebration held in a quilombola community and 39 individuals were affected. The focus of this study was clinical-epidemiological investigation and diagnostic tools. There were no deaths due to this event, probably because of the quick action of the surveillance team and the early start of treatment. We show all the difficulties facing a real-life situation (vulnerability of population affected, weaknesses regarding good food safety practices and obstacles to following what guidelines recommend), discuss the performance and executability of the diagnostic method used and address the global threat that Chagas disease may pose. Furthermore, we propose that the polymerase chain reaction should become standardized in diagnosing acute disease, given that this was the only method with 100% positivity, even among patients whose other tests were all negative.

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“…Newer serological tests use recombinant antigens specific to Trypanosoma cruzi, reducing cross-reactivity with other parasites (Carine et al 2021). This enhances the accuracy of results and improves sensitivity and specificity compared to tests using whole parasite extracts (Gabriel et al 2022;Pilar et al 2023).…”

Section: Serological Tests With Recombinant Antigensmentioning

confidence: 99%

Chagas Disease: An Overview of Current Understanding and Future Perspectives

2023

IJAB

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Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is a life-threatening infection transmitted primarily by triatomine bugs. Originating in rural Latin America, CD has spread globally through various transmission routes, including organ transplantation, blood transfusion, contaminated food and drink, and hereditary transfer. Millions in vulnerable stages face poverty and inadequate medical care due to unawareness and resource constraints. The acute phase presents symptoms like fever, anorexia, fatigue, and tachycardia, progressing to the chronic phase with severe health issues, including congenital heart diseases and neurological damage. It remains a neglected tropical disease recognized by the World Health Organization. Diagnosis involves serological, molecular, and parasitological tests, with challenges such as underdiagnosis. Antiparasitic medications, including Benznidazole and Nifurtimox, offer limited effectiveness, and drug resistance is emerging. Ongoing research explores new drugs, immunotherapies, gene therapy, and combination therapies. Diagnostic advances include nucleic acid amplification tests and serological tests with recombinant antigens. Vector control is crucial, focusing on insecticide use, housing improvements, and community education. Blood screening, organ transplantation screening, and prenatal interventions contribute to prevention. The disease's global burden affects millions, with challenges in endemic and non-endemic regions. Future research must address disease mechanisms, enhance diagnostic methods, explore new treatment options, and develop effective prevention strategies. Genomics, drug discovery, immunotherapy, vector control, and health system strengthening offer opportunities. Eradication potential lies in comprehensive public health strategies, targeting vectors, blood screening, and prenatal care, underscoring the need for sustained efforts and research innovations in the fight against Chagas disease.

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Parasitological, serological and molecular diagnosis of acute and chronic Chagas disease: from field to laboratory

Cited by 19 publications

References 107 publications

In vitro diagnostic methods of Chagas disease in the clinical laboratory: a scoping review

In vitro diagnostic methods of Chagas disease in the clinical laboratory: a scoping review

An outbreak of Chagas disease through oral transmission: 115 years after discovery by Carlos Chagas, the disease is still hard to manage

Chagas Disease: An Overview of Current Understanding and Future Perspectives

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