Caryn Bern

We describe a case of autochthonous acute Chagas disease in an infant with fulminant myocarditis requiring aggressive support. Peridomestic investigation revealed Trypanosoma cruzi-infected vectors and animals. This highlights the importance of (1) early diagnosis and treatment and (2) understanding the epidemiological risk factors for Chagas disease in the United States.

Background: Particulate air pollution (specifically <2·5µm diameter [PM2·5]), temperature, and Trypanosoma cruzi (Tc) each are deleterious to pregnancy. PM2·5 crosses the placenta, weakening the trophoblastic layer through inflammation. Sustained exposure to high heat causes chronic intrauterine inflammation, affecting placental formation. Tc parasitemia increases during pregnancy, causing placental degradation through inflammation and resulting in congenital Chagas disease (cCD) in approximately one-in-twenty Tc(+) pregnancies. The interaction of PM2·5 and temperature during pregnancy with cCD is unstudied.Methods: We analyzed a Bolivian pregnancy cohort (2006-2014) including 581 Tc(+) pregnancies with 46 congenitally infected infants. European Space Agency-Copernicus estimates of monthly mean wet-bulb temperature and PM2·5 were used to create individual monthly pregnancy exposures for 12-months prior-to-birth. Lagged-Weighted Quantile Sum regression analysis was conducted to determine the time-varying association of these exposures with cCD.Findings: cCD was significantly associated with exposure to higher temperatures and PM2·5 pre-conception and high PM2·5 in the last three months of pregnancy.Interpretation: Systemic inflammation from PM2·5 and high temperatures likely depress the already modulated maternal immune system allowing higher parasitemia during pregnancy. Inflammatory responses to PM2·5, temperature, and Tc may weaken the placental barrier, allowing the parasite to more easily cross the marginal sinus and the trophoblastic layer of the intervillous space and infect the fetus. In urban areas, vector-bone Tc transmission is now uncommon; however, there is still a significant incidence of cCD. Mitigating the effects exposure to high PM2·5 and temperatures during pregnancy is an important component to preventing cCD.

BACKGROUND: Infection by Trypanosoma cruzi , the agent of Chagas disease, is endemic to the Americas and can irreparably damage the cardiac and gastrointestinal systems during decades of parasite persistence. Diagnosis of chronic infection requires confirmation by multiple serological assays due to the imperfect performance of existing tests. Current serology tests were developed using small specimen sets predominantly from South America, and lower performance has been observed in patients who acquired infection in Central America and Mexico. METHODS: To improve Chagas disease serology, we evaluated antibody responses against the entire T . cruzi proteome with phage display immunoprecipitation sequencing and further evaluated high-prevalence antigens by immunoassay. We utilized specimen sets representing Mexico, Central America, and South America and varying cardiac disease presentations, from 185 cases and 143 controls. RESULTS: We identified over 1,300 antigenic T . cruzi peptides. A trans-sialidase antigen demonstrated high seroprevalence across all regions and has not previously been described as a diagnostic target to our knowledge. Orthogonal validation of this peptide demonstrated increased antibody reactivity for infections originating from Central America. CONCLUSION: This study provides proteome-wide identification of seroreactive T . cruzi peptides across a range of endemic populations not previously represented in antigen discovery and identifies a trans-sialidase peptide antigen (TS23) with potential for translation into diagnostic serological assays. FUNDING: Chan Zuckerberg Biohub, the Chan Zuckerberg Biohub Physician-Scientist Fellowship Program, the NIH National Heart Lung and Blood Institute award K38HL154203, and the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development award F30HD117526.

Background: Chagas disease (ChD), a neglected tropical disease caused by Trypanosoma cruzi, affects around 7.5 to 10 million people globally, primarily in Latin America. Chronic Chagas cardiomyopathy (CCM) is the most severe clinical form, leading to substantial cardiovascular morbidity and mortality. Despite existing guidelines, fragmented health systems, low provider awareness, and limited access to care hinder effective disease management. Objectives: We aimed to define the key components of the CCM quality of care (structure, process, and outcomes) for main clinical activities at the three levels of care. Methods: We applied the Donabedian model to define essential components of ChD care at primary, secondary, and tertiary levels. Key recommendations from the World Heart Federation (WHF) roadmap and evidence-based guidelines were used to identify core services at each level. We also examined two case studies that demonstrate successful implementation of innovative screening and management models. Results: Essential components of ChD care were identified at all levels. Primary care plays a central role in early diagnosis and timely treatment. Secondary care addresses complications through imaging and targeted therapy, while tertiary care provides advanced interventions and rehabilitation. Although structural gaps persist, the implementation of systematic processes and clearly defined outcomes is key to strengthening the quality, continuity, and equity of care. Conclusions: A comprehensive, structured approach to ChD care is essential to improving outcomes. Successful models illustrate that scalable, resource-appropriate interventions can enhance diagnosis and treatment. Integration into routine health systems, supported by universal health coverage, improved data systems, and implementation research, is critical to closing the care gap and advancing equity in cardiovascular health.

Background: India is transitioning to the visceral leishmaniasis (VL) post-elimination phase where robust surveillance is critical to sustaining elimination. We conducted a targeted longitudinal study combining epidemiological, serological, and entomological data in endemic villages in Bihar and Jharkhand states to assess active VL transmission levels. Methods: Our investigation was conducted in the villages of Rahar Diyara, Bihar, and Murbhanga, Jharkhand, based on spatial distribution of recently reported VL cases. Samples were collected quarterly from December 2021 to September 2022 in Rahar Diyara, and April 2022 to May 2023 in Murbhanga, to determine seroprevalence against Leishmania rK39 antigen. Sand flies were collected bi-weekly in Rahar Diyara (February to December, 2022) and Murbhanga (April to December, 2022) from different microhabitats and analyzed by qPCR targeting Leishmania kDNA. Results: rK39 Leishmania seroprevalence ranged from 20% to 30% in both villages. Murbhanga, an outbreak village, exhibited higher antibody levels in 9–23% of subjects compared with the low incidence village, Rahar Diyara (3–6%), reflecting a higher intensity of transmission in Murbhanga. Despite implementation of indoor residual spraying, Leishmania-infected sand flies were found in both villages, with 1.4% (4/285) and 1.2% (5/431) positive pools in Rahar Diyara and Murbhanga, respectively. Infected sand fly pools were collected from diverse microhabitats, predominantly from vegetation in Rahar Diyara and cattle enclosures in Murbhanga, indicative of focal and distinct patterns of transmission. Conclusions: Low-level Leishmania transmission persists in India highlighting criticality of continued surveillance. Combining epidemiological, serological, and entomological surveys improves rapid outbreak assessment and intervention, and enhances efficacy of surveillance to sustain VL elimination.

: Understanding the at-risk population’s perception of Chagas disease is essential for its effective prevention and control. A cross-sectional survey of knowledge, attitudes, and practices toward Chagas disease was conducted with Bolivians in a highly endemic region of Bolivia and Latin American migrants in London. In total, 175 participants completed the survey: 100 Bolivians in a highly endemic village in Santa Cruz, Bolivia and 75 Latin American migrants in London (of whom 31 were from Bolivia). All participants from the endemic village and all Bolivian migrants in London knew of Chagas disease, whereas only 25% of other Latin American migrants had heard of it (P <0.001). In London, Bolivians had more knowledge of Chagas disease than those from other Chagas-endemic countries. In Bolivia only, better understanding of Chagas disease was associated with educational attainment. Only 4% of participants overall were aware of the risk of vertical transmission. Few Latin American migrants in London had previously been tested for Chagas disease, and most were not aware of how to access testing. Migration and level of endemicity may shape individuals’ understanding of as well as attitudes and practices toward Chagas disease. A better understanding of these factors can guide effective prevention and control program development in both endemic and non-endemic settings.

Background: Trypanosoma cruzi causes Chagas disease, a poorly understood and clinically heterogeneous disease. Recent work has demonstrated that parasites adapted to laboratory conditions are genomically variable, but little is known of the extent of genomic diversity from clinically isolated specimens. Methods: In this retrospective observational genomic study, we isolated 15 T. cruzi specimens from three clinical studies of Chagas disease, representing different clinical contexts. We sequenced the genome of each strain and used single nucleotide variant (SNV) based analyses to estimate parasite genetic lineage, genomic population structure, regions of copy number plasticity, and to identify gene conversion events. In addition, we generated and annotated whole genome assemblies of each isolate. From these assemblies, we compared the repertoires of genes encoding for highly virulent and variable proteins that have been implicated in disease pathogenesis. Findings: We identified parasites from two genetic lineages in this collection of clinical isolates. Our analysis revealed evidence of genomic instability. Diversity-generating copy number variation was statistically enriched in regions encoding the virulence-associated multigene families, while diversity-eliminating gene conversion events were enriched in regions depleted of multigene family members. We also discovered a set of multigene family members that is present in all of the clinically isolated parasite genomes and absent from all of the lab adapted strains, regardless of parasite lineage. Multigene family repertoires were more conserved among field isolated specimens of the same genetic lineage than among culture adapted strains of the same genetic type. Interpretation: This study provides whole genome sequencing data for TcV parasites isolated from naturally infected human patients with Chagas disease for the first time. Our analysis of these genomes revealed substantial genomic instability, suggesting the parasite undergoes genomic change in response to the pressures imposed by the host environment. Moreover, we observed a set of virulence-associated genes that are present exclusively within clinical isolates and absent from lab-adapted strains, indicating a potential role for these genes in parasite survival in natural hosts. These findings highlight the limitations of genetic studies focused exclusively on lab-adapted parasite strains and provide insight into the genomic features of T. cruzi that are likely to be important for clinical infection.

Infection by Trypanosoma cruzi , the agent of Chagas disease, can irreparably damage the cardiac and gastrointestinal systems during decades of parasite persistence and related inflammation in these tissues. Diagnosis of chronic disease requires confirmation by multiple serological assays due to the imperfect performance of existing clinical tests. Current serology tests utilize antigens discovered over three decades ago with small specimen sets predominantly from South America, and lower test performance has been observed in patients who acquired T. cruzi infection in Central America and Mexico. Here, we attempt to address this gap by evaluating antibody responses against the entire T. cruzi proteome with phage display immunoprecipitation sequencing comprised of 228,127 47-amino acid peptides. We utilized diverse specimen sets from Mexico, Central America and South America, as well as different stages of cardiac disease severity, from 185 cases and 143 controls. We identified over 1,300 antigenic T. cruzi peptides derived from 961 proteins between specimen sets. A total of 67 peptides were reactive in 70% of samples across all regions, and 3 peptide epitopes were enriched in ≥90% of seropositive samples. Of these three, only one antigen, belonging to the trans-sialidase family, has not previously been described as a diagnostic target. Orthogonal validation of this peptide demonstrated increased antibody reactivity for infections originating from Central America. Overall, this study provides proteome-wide identification of seroreactive T. cruzi peptides across a large cohort spanning multiple endemic areas and identified a novel trans-sialidase peptide antigen (TS-2.23) with significant potential for translation into diagnostic serological assays. One Sentence Summary: Phage display immunoprecipitation sequencing (PhIP-seq) designed with a T. cruzi whole proteome library reveals a trans-sialidase peptide antigen (TS-2.23) with antibody responses highly prevalent across endemic regions of Latin America.

SUMMARY: As 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.