Chagas disease in immunocompromised patients.

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

Chagas disease.

Chagas disease persists as a global public health problem due to the high morbidity and mortality burden. Despite the possibility of a cure and advances in transmission control, epidemiological transformations, such as urbanisation and globalisation, and the emerging importance of oral and vertical transmission mean that Chagas disease should be considered an emerging disease, with new cases occurring worldwide. Important barriers to diagnosis, treatment, and care remain, resulting in repressed numbers of reported cases, which in turn leads to inadequate public policies. The validation of new diagnostic tools and treatment options is needed, as existing tools pose serious limitations to access to health care. Integrated models of surveillance, with community and intersectional participation, embedded in the concept of One Health, are essential for control. In addition, mitigation strategies for the main social determinants of health, including difficulties imposed by migration, are important to improve access to comprehensive health care in a globalised scenario.

Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

Adaptation of Chagas Disease Screening Recommendations for a Community of At-risk HIV in the United States.

Chagas disease (CD), caused by Trypanosoma cruzi, is underdiagnosed in the United States. Improved screening strategies are needed, particularly for people at risk for life-threatening sequelae of CD, including people with human immunodeficiency virus (HIV, PWH). Here we report results of a CD screening strategy applied at a large HIV clinic serving an at-risk population.

The use of peptides for immunodiagnosis of human Chagas disease.

Chagas disease, caused by the protozoa Trypanosoma cruzi, continues to be a serious public health problem in Latin America, worsened by the limitations in its detection. Given the importance of developing new diagnostic methods for this disease, the present review aimed to verify the number of publications dedicated to research on peptides that demonstrate their usefulness in serodiagnosis. To this end, a bibliographic survey was conducted on the PubMed platform using the keyword "peptide" or "epitope" combined with "Chagas disease" or "Trypanosoma cruzi"; "diagno*" or "serodiagnosis" or "immunodiagnosis", without period restriction. An increasing number of publications on studies employing peptides in ELISA and rapid tests assays was verified, which confirms the expansion of research in this field. It is possible to observe that many of the peptides tested so far originate from proteins widely used in the diagnosis of Chagas, and many of them are part of commercial tests developed. In this sense, as expected, promising results were obtained for several peptides when tested in ELISA, as many of them exhibited sensitivity and specificity values above 90%. Furthermore, some peptides have been tested in several studies, confirming their diagnostic potential. Despite the promising results observed, it is possible to emphasize the need for extensive testing of peptides, using different serological panels, in order to confirm their potential. The importance of producing an effective assay capable of detecting the clinical stages of the disease, as well as new immunogenic antigens that enable new serological diagnostic tools for Chagas disease, is evident.

Outcomes of patients in Chagas disease of the central nervous system: a systematic review.

Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi. One of the complications of the disease is the infection of the central nervous system (CNS), as it can result from either the acute phase or by reactivation during the chronic phase, exhibiting high mortality in immunocompromised patients. This systematic review aimed to determine clinical and paraclinical characteristics of patients with Chagas disease in the CNS. Articles were searched from PubMed, Scopus and LILACS until January 2023. From 2325 articles, 59 case reports and 13 case series of patients with Chagas in the CNS were retrieved from which 138 patients were identified. In this population, 77% of the patients were male, with a median age of 35 years old, from which most of them came from Argentina and Brazil. Most of the individuals were immunocompromised from which 89% were HIV-positive, and 54 patients had an average of 48 cells per mm3 CD4+ T cells. Motor deficits and seizures were the most common manifestation of CNS compromise. Furthermore, 90 patients had a documented CNS lesion by imaging from which 89% were supratentorial and 86% were in the anterior/middle cranial fossa. The overall mortality was of 74%. Among patients who were empirically treated with anti-toxoplasma drugs, 70% died. This review shows how Chagas disease in the CNS is a devastating complication requiring prompt diagnosis and treatment to improve patients' outcomes.

A simplified molecular tool for detecting the Chagas etiological agent using a vector feces sample in field conditions.

Triatomine bugs are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease in the American continent. Here, we have tested a loop-mediated isothermal amplification (LAMP) test for a direct detection of T. cruzi in feces of Triatoma infestans, the main vector of this parasite in the Southern Cone of America. The analytical evaluation showed positive results with samples of triatomine feces artificially inoculated with DNA from strains of T. cruzi corresponding to each Discrete Typing Units (I-VI), with a sensitivity of up to one parasite per reaction. Conversely, the reaction yielded negative results when tested with DNA from Trypanosoma rangeli and other phylogenetically related and unrelated organisms. In triatomines captured under real field conditions (from urban households), and defined as positive or negative for T. cruzi using the reference microscopy technique, the LAMP test achieved a concordance of 100 %. Our results demonstrate that this LAMP reaction exhibits excellent analytical specificity and sensitivity without interference from the fecal matrix, since all the reactions were conducted without purification steps. This simple molecular diagnostic technique can be easily used by vector control agencies under field conditions.

Chagas Disease.

Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi, is a leading neglected tropical disease in the United States. An estimated 240 000 to 350 000 persons in the United States are infected, primarily immigrants from Mexico, Central America, and South America, where the disease is endemic. The parasite is transmitted by the triatomine bug but can also be passed through blood transfusion, via organ transplant, or congenitally. Approximately 30% of infected persons later develop cardiac and/or gastrointestinal complications. Health care providers should consider screening at-risk patients with serologic testing. Early diagnosis and treatment with benznidazole or nifurtimox can help prevent complications.

Chagas Disease: Epidemiology, Diagnosis, and Treatment.

PURPOSE OF REVIEW: This review seeks to describe the updates in the literature - particularly with regards to the epidemiology and diagnosis of Chagas disease. Additionally, this paper describes updates to the antiparasitic treatment for Chagas disease. RECENT FINDINGS: With regards to changing epidemiology, autochthonous cases are being found within the USA in addition to Latin America. Additionally, there appears to be more intermixing of discrete typing units-meaning, they are not confined to specific geographic regions. Screening for Chagas disease is recommended in persons who lived in areas with endemic Chagas, persons wtih family member diagnosed with Chagas Disease, persons who have lived in homes of natural material in Latin America, and persons with history of kissing bug bites. Treatment for the parasitic infection remains limited to benznidazole and nifurtimox, and the role of these treatments in Chagas cardiomyopathy has not yet been definitively defined. Finally, indications for and management of heart transplant in the setting of Chagas disease are discussed. FUTURE RESEARCH: Use of antiparasitics during chronic chagas disease should be further explored. Additionally, future research identifying other markers of infection would be valuable to defining cure from infection.

Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease.

Chagas disease is caused by the parasite Trypanosoma cruzi. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel T. cruzi antigen named Tc323 (TcCLB.504087.20), recognized by a single-chain monoclonal antibody (scFv 6B6) isolated from the B cells of patients with cardiomyopathy related to chronic Chagas disease. Tc323, a ~323 kDa protein, is an uncharacterized protein showing putative quinoprotein alcohol dehydrogenase-like domains. A computational molecular docking study revealed that the scFv 6B6 binds to an internal domain of Tc323. Immunofluorescence microscopy and Western Blot showed that Tc323 is expressed in the main developmental forms of T. cruzi, localized intracellularly and exhibiting a membrane-associated pattern. According to phylogenetic analysis, Tc323 is highly conserved throughout evolution in all the lineages of T. cruzi so far identified, but it is absent in Leishmania spp. and Trypanosoma brucei. Most interestingly, only plasma samples from patients infected with T. cruzi and those with mixed infection with Leishmania spp. reacted against Tc323. Collectively, our findings demonstrate that Tc323 is a promising candidate for the differential serodiagnosis of chronic Chagas disease in areas where T. cruzi and Leishmania spp. infections coexist.

The Development of a One-Step RT-qPCR for the Detection and Quantification of Viable Forms of Trypanosoma cruzi in Açai Samples from Areas at Risk of Chagas Disease through Oral Transmission.

Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to control the spread of the disease. The methods utilized to conduct quality control for food associated with outbreaks and to assess the potential for the oral transmission of CD through consuming açaí primarily rely on isolating the parasite or inoculating food into experimental animals, restricting the analyses to major research centers. While there are existing studies in the literature on the detection and quantification of T. cruzi DNA in açaí, the evaluation of parasites' viability using molecular methods in this type of sample and differentiating between live and dead parasites in açaí pulp remain challenging. Consequently, we developed a molecular methodology based on RT-qPCR for detecting and quantifying viable T. cruzi in açaí pulp samples. This protocol enables the stabilization and preservation of nucleic acids in açaí, along with incorporating an exogenous internal amplification control. The standardization of the RNA extraction method involved a simple and reproducible approach, coupled with a one-step RT-qPCR assay. The assay underwent validation with various T. cruzi DTUs and demonstrated sensitivity in detecting up to 0.1 viable parasite equivalents/mL in açaí samples. Furthermore, we investigated the effectiveness of a bleaching method in eliminating viable parasites in açaí samples contaminated with T. cruzi by comparing the detection of DNA versus RNA. Finally, we validated this methodology using açaí pulp samples positive for T. cruzi DNA, which were collected in a municipality with a history of oral CD outbreaks (Coari-AM). This validation involved comparing the detection and quantification of total versus viable T. cruzi. Collectively, our findings demonstrate the feasibility of this methodology in detecting viable forms of T. cruzi in açaí pulp samples, emerging as a crucial tool for monitoring oral outbreaks of Chagas disease resulting from açaí consumption.

A Multi-Epitope Protein for High-Performance Serodiagnosis of Chronic Chagas Disease in ELISA and Lateral Flow Platforms.

We developed a protein to rapidly and accurately diagnose Chagas disease, a life-threatening illness identified by the WHO as a critical worldwide public health risk. Limitations in present day serological tests are complicating the current health situation and contributing to most infected persons being unaware of their condition and therefore untreated. To improve diagnostic testing, we developed an immunological mimic of the etiological agent, Trypanosoma cruzi, by combining ten pathogen-specific epitopes within the beta-barrel protein structure of Thermal Green Protein. The resulting multi-epitope protein, DxCruziV3, displayed high specificity and sensitivity as the antibody capture reagent in an ELISA platform with an analytical sensitivity that exceeds WHO recommendations. Within an immunochromatographic platform, DxCruziV3 showed excellent performance for the point of application diagnosis in a region endemic for multiple diseases, the municipality of Barcelos in the state of Amazonas, Brazil. In total, 167 individuals were rapidly tested using whole blood from a finger stick. As recommended by the Brazilian Ministry of Health, venous blood samples were laboratory tested by conventional assays for comparison. Test results suggest utilizing DxCruziV3 in different assay platforms can confidently diagnose chronic infections by T. cruzi. Rapid and more accurate results will benefit everyone but will have the most noticeable impact in resource-limited rural areas where the disease is endemic.

Chagas disease stroke and associated risk factors: A case-control study.

INTRODUCTION: The intricate relationship between Chagas disease and ischemic stroke remains unclear. Limited evidence exists concerning secondary prophylaxis, etiological diagnosis, and stroke-related determinants. This study aims to discern factors linked to stroke in Chagas disease by contrasting patients with and without a history of ischemic stroke. METHODS: Retrospective data from all outpatient Chagas disease patients from two Brazilian hospitals - one Chagas center and one stroke clinic - were examined. Descriptive analyses were conducted to identify stroke-associated factors. Variables were compared between patients with and without ischemic stroke history. RESULTS: Among 678 subjects, 72 had experienced stroke. Univariate associations with stroke included male gender, heart failure, prior or ongoing alcoholism, electrocardiographic features (non-sinus rhythm, left bundle branch, right bundle branch block, left anterosuperior fascicular block, atrial fibrillation), as well as echocardiographic findings indicative of reduced left ventricular ejection fraction and segmental abnormalities. After logistic regression (multivariate analysis), congestive heart failure, right bundle branch block, left anterosuperior divisional block, and atrial fibrillation retained independent associations. CONCLUSION: In this study, cardiac involvement emerged as the predominant factor correlated with stroke in Chagas disease. While atherosclerosis-related risk factors were prevalent, their influence on ischemic stroke in Chagas disease appeared limited.

Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection.

Population movements have turned Chagas disease (CD) into a global public health problem. Despite the successful implementation of subregional initiatives to control vectorial and transfusional Trypanosoma cruzi transmission in Latin American settings where the disease is endemic, congenital CD (cCD) remains a significant challenge. In countries where the disease is not endemic, vertical transmission plays a key role in CD expansion and is the main focus of its control. Although several health organizations provide general protocols for cCD control, its management in each geopolitical region depends on local authorities, which has resulted in a multitude of approaches. The aims of this review are to (i) describe the current global situation in CD management, with emphasis on congenital infection, and (ii) summarize the spectrum of available strategies, both official and unofficial, for cCD prevention and control in countries of endemicity and nonendemicity. From an economic point of view, the early detection and treatment of cCD are cost-effective. However, in countries where the disease is not endemic, national health policies for cCD control are nonexistent, and official regional protocols are scarce and restricted to Europe. Countries of endemicity have more protocols in place, but the implementation of diagnostic methods is hampered by economic constraints. Moreover, most protocols in both countries where the disease is endemic and those where it is not endemic have yet to incorporate recently developed technologies. The wide methodological diversity in cCD diagnostic algorithms reflects the lack of a consensus. This review may represent a first step toward the development of a common strategy, which will require the collaboration of health organizations, governments, and experts in the field.

Recurrent Chagas' disease meningomyelitis in an HIV-infected patient.

Chagas' disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.

A Case of Chagas Disease in South Dakota: Diagnosis and Treatment.

Chagas disease is a chronic, systemic parasitic infection caused by the protozoan Trypanosoma cruzi. The primary mode of transmission to humans is by the Reduviid insect, endemic to South America. Recent migration of the vector has led to increased cases in the southern United States and has prompted increased surveillance and blood donation screening. It is unusual to diagnose and treat individuals with Chagas disease in the northern United States. This case describes an immigrant female from El Salvador that was informed she had Chagas disease from a blood bank screening. Confirmation and treatment of the disease were performed by her South Dakota primary care provider thus demonstrating the importance of identifying Chagas disease in the immigrant population in regions where Chagas disease infection is uncommon.

Quantitative PCR-Based Diagnosis and Follow-up of Chagas Disease Primary Infection After Solid Organ Transplant: A Multicentre Study.

Chagas disease in solid organ transplant recipients may present as a primary infection (PI). Early detection is crucial for timely treatment. This is the largest observational multicentre study evaluating qPCR for early diagnosis and treatment monitoring of PI in seronegative recipients of organs from seropositive donors. Of 34 patients admitted at 5 health centers, PI was detected by qPCR in 8 (23.5%) within a posttransplant period of 40 days (interquartile range [IQR], 31-50 days). No PI was detected by the Strout test or clinical symptoms/signs. All patients had favorable treatment outcome with negative qPCR 31 days (IQR, 18-35 days) after treatment, with no posttreatment relapse episodes.

Activation-induced marker assays for identification of Trypanosoma cruzi-specific CD4 or CD8 T cells in chronic Chagas disease patients.

Antigen-specific T cells are central to the adaptive immune response against T. cruzi infection and underpin the efficacy of on-going vaccine strategies. In this context, the present study focuses on T-cell assays that define the parasite-specificity on the basis of upregulation of TCR stimulation-induced surface markers. For this purpose, we tested different dual marker combinations (OX40, CD25, CD40L, CD137, CD69, PD-L1, CD11a, CD49d, HLA-DR, CD38) to reliably identify activated CD4+ and CD8+ T-cell populations from PBMCs of chronic Chagas disease (CCD) patients after 12 or 24 h of stimulation with T. cruzi lysate. Results demonstrated that activation-induced markers (AIM) assays combining the expression of OX40, CD25, CD40L, CD137, CD69 and/or PD-L1 surface markers are efficient at detecting T. cruzi-specific CD4+ T cells in CCD patients, in comparison to non-infected donors, after both stimulation times. For CD8+ T cells, only PD-L1/OX40 after 24 h of antigen exposure resulted to be useful to track a parasite-specific response. We also demonstrated that the agnostic activation is mediated by different T. cruzi strains, such as Dm28c, CL Brener or Sylvio. Additionally, we successfully used this approach to identify the phenotype of activated T lymphocytes based on the expression of CD45RA and CCR7. Overall, our results show that different combinations of AIM markers represent an effective and simple tool for the detection of T. cruzi-specific CD4+ and CD8+ T cells.

Prevalence of Chagas disease in Latin American pregnant women in Madrid, Spain: A multicentre cross-sectional study from 2011 to 2016.

OBJECTIVE: The aim of this study is to assess Trypanosoma cruzi infection prevalence among pregnant migrants living in Madrid according to the country of origin and to assess screening coverage in this at-risk population. METHODS: Retrospective multicentre cross-sectional study conducted from January 2011 to December 2016 in eight Madrid hospitals. Each hospital reviewed their microbiology data records to assess the screening coverage and serological diagnosis in all pregnant women coming from endemic areas. RESULTS: From 2011 to 2016, 149,470 deliveries were attended at the eight hospitals, and 11,048 pregnant women were screened for Chagas disease. Most cases (93.5%) were in women from Bolivia, who also showed the highest prevalence (12.4%, 95% confidence interval: 9.9-15.0). Pooled prevalence amongst the screened women was 2.9% (95% CI: 1.8-4.1). Chagas disease screening coverage varied greatly between centres, with a pooled mean coverage of 47% (95% CI: 37%-57%; 73% [95% CI: 63%-82%] for those centres with universal screening vs. 10% [95% CI: 6%-15%] for those with a selective screening approach; p < 0.001). CONCLUSION: Our study provides useful data for policy makers and epidemiologists in a non-endemic area without congenital Chagas screening programmes.

Pfizer-BioNTech vaccine induces the production of cross-reactive antibodies against Trypanosoma cruzi proteins: A preliminary study.

OBJECTIVE: To evaluate the presence of cross-reactivity by anti-severe acute respiratory syndrome coronavirus 2 antibodies induced by the Pfizer-BioNTech vaccine against Trypanosoma cruzi proteins in a screening test. METHODS: Forty-three serum samples were obtained from personnel at the Hospital General Naval de Alta Especialidad in Mexico City who received one or two doses of the vaccine and were tested for T. cruzi infection using four tests: two 'in house' enzyme-linked immunosorbent assays (ELISAs), a commercial ELISA diagnostic kit and an immunoblot test. RESULTS: IgG antibodies against the T. cruzi proteins were present in the serum of unvaccinated subjects and subjects who had received one or two doses of the vaccine. The positivity of the samples against T. cruzi was ruled out by means of a Western Blot assay, where all samples were negative for T. cruzi. CONCLUSION: The data suggest that people convalescing from coronavirus disease 2019 and those who received the Pfizer-BioNTech vaccine exhibit cross-reactive antibodies against T. cruzi antigens in ELISA assays.