Congenital Chagas Disease.
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ABSTRACT:
SUBMITTER: Chancey RJ
PROVIDER: S-EPMC10313159 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Publications
Congenital Chagas Disease.
Chancey Rebecca J RJ Edwards Morven S MS Montgomery Susan P SP
Pediatrics in review 20230401 4
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Project description:BackgroundDetection of congenital T. cruzi transmission is considered one of the pillars of control programs of Chagas disease. Congenital transmission accounts for 25% of new infections with an estimated 15,000 infected infants per year. Current programs to detect congenital Chagas disease in Latin America utilize microscopy early in life and serology after 6 months. These programs suffer from low sensitivity by microscopy and high loss to follow-up later in infancy. We developed a Chagas urine nanoparticle test (Chunap) to concentrate, preserve and detect T. cruzi antigens in urine for early, non-invasive diagnosis of congenital Chagas disease.Methodology/principal findingsThis is a proof-of-concept study of Chunap for the early diagnosis of congenital Chagas disease. Poly N-isopropylacrylamide nano-particles functionalized with trypan blue were synthesized by precipitation polymerization and characterized with photon correlation spectroscopy. We evaluated the ability of the nanoparticles to capture, concentrate and preserve T. cruzi antigens. Urine samples from congenitally infected and uninfected infants were then concentrated using these nanoparticles. The antigens were eluted and detected by Western Blot using a monoclonal antibody against T. cruzi lipophosphoglycan. The nanoparticles concentrate T. cruzi antigens by 100 fold (western blot detection limit decreased from 50 ng/ml to 0.5 ng/ml). The sensitivity of Chunap in a single specimen at one month of age was 91.3% (21/23, 95% CI: 71.92%-98.68%), comparable to PCR in two specimens at 0 and 1 month (91.3%) and significantly higher than microscopy in two specimens (34.8%, 95% CI: 16.42%-57.26%). Chunap specificity was 96.5% (71/74 endemic, 12/12 non-endemic specimens). Particle-sequestered T. cruzi antigens were protected from trypsin digestion.Conclusion/significanceChunap has the potential to be developed into a simple and sensitive test for the early diagnosis of congenital Chagas disease.
| S-EPMC4183489 | biostudies-literature
Project description:BackgroundTrypanosoma cruzi is a protozoan parasite which causes Chagas disease. Mother-to-child transmission is the main route of transmission in vector-free areas. Congenital Chagas disease refers specifically to cases arising from this route of transmission. This work evaluates the clinical sensitivity of two qPCR techniques for diagnosis of congenital Chagas disease.MethodsThe study was developed in the National Institute of parasitology (NIP), Argentina, and Pan-American Health Organization/ Word Health Organization Collaborating Center for Chagas Disease. Between July 2014 and May 2018, a prospective cohort study was carried out with 499 children born to seropositive for T. cruzi infection included. The performance of qPCR techniques was compared with the gold standard diagnostic algorithm for Congenital Chagas disease (CCD-GS), which comprises performing more than one parasitological test on children from birth until nine months of age, and serology from ten months of age.FindingsOf the 961 babies born to women seropositive for Chagas disease who were attended at the NIP laboratory, 462 did not meet the study inclusion criteria; 22 cases were diagnosed with congenital Chagas disease. qPCR showed 100% clinical sensitivity and 98 to 100% clinical specificity for the diagnosis of congenital Chagas disease compared with CCD-GS algorithm.InterpretationThe results obtained in this study demonstrate the clinical accuracy and effectiveness of qPCR SatDNA and qPCR kDNA for diagnosis of congenital Chagas disease. It could be a powerful tool for chagas test and treat strategies to reduce late complications of the disease.FundingThis work was financed by the INP Dr. Mario Fatala Chaben, ANLIS Dr. Carlos G. Malbran.
| S-EPMC11825091 | biostudies-literature
Project description:Chagas disease, caused by Trypanosoma cruzi, is a parasitic zoonosis with significant health impacts, particularly in Latin America. While traditionally associated with vector-borne transmission, increased migration has expanded its reach into urban and non-endemic regions. Congenital transmission has become a critical route of infection, involving intricate maternal-fetal immune interactions that challenge diagnosis and treatment. This review synthesizes findings from three RNA-seq studies that explore the molecular underpinnings of congenital Chagas disease, emphasizing differentially expressed genes (DEGs) implicated in host-pathogen interactions. The DAVID tool analysis highlighted the overexpression of genes associated with the innate immune response, including pro-inflammatory cytokines that drive chemotaxis and neutrophil activation. Additionally, calcium-dependent pathways critical for parasite invasion were modulated. T. cruzi exploits the maternal-fetal immune axis to establish a tolerogenic environment conducive to congenital transmission. Alterations in placental angiogenesis, cellular regeneration, and metabolic processes further demonstrate the parasite's ability to manipulate host responses for its survival and persistence. These findings underscore the complex interplay between the host and pathogen that facilitates disease progression. Future research integrating transcriptomic, proteomic, and metabolomic approaches is essential to unravel the molecular mechanisms underlying congenital Chagas disease, with a particular focus on the contributions of genetic diversity and non-coding RNAs in immune evasion and disease pathogenesis.
| S-EPMC11858232 | biostudies-literature
Project description:Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.
| S-EPMC6086189 | biostudies-literature
Project description:Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities. From December 2015 to April 2016, we jointly developed a strategy to illustratively advertise newborn screening at the Health Center. The strategy included socioculturally appropriate promotional and educational material, in collaboration with midwives, nurses and nongovernmental organizations. By March 2016, eight of 228 (3.9%) pregnant women had been diagnosed with T. cruzi at the Health Center. Up to this date, no neonatal screening had been performed. By August 2016, seven of eight newborns born to Chagas seropositive women had been parasitologically screened at the Health Center, according to international standards. Thus, we implemented a successful community-based neonatal screening strategy to promote congenital Chagas disease healthcare in a rural setting. The success of the health promotion strategies developed will depend on local access to maternal-infant services, integration with detection of other congenital diseases and reliance on community participation in problem and solution definition.
| S-EPMC5634652 | biostudies-literature
Project description:BackgroundCongenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low.MethodsWomen who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months.ResultsAmong 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod.ConclusionsThe proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.
| S-EPMC5848221 | biostudies-literature
Project description:Chagas disease, also known as American trypanosomiasis, is caused by a protozoan blood-borne pathogen called Trypanosoma cruzi. The World Health Organization (WHO) has classified Chagas as one of 21 neglected tropical diseases present in the world and estimates that 6-7 million people are currently infected with Chagas. Congenital transmission of Chagas disease contributes to a significant amount of new infections, especially in endemic areas where 22.5% of new infections are due to congenital transmission. In this paper, we investigate congenital transmission's impact on Chagas disease dynamics through a mathematical model. Specifically, we examine how treating a proportion of infants born to infected individuals impacts the progression and spread of Chagas disease. The influence of newborn therapy on the dynamics of the model is thoroughly investigated, both theoretically and numerically. The results illustrate the importance of treating a high proportion of newborns to reduce the number of infected cases of the disease. The findings show that the therapy given to newborns is necessary but not sufficient to curb the transmission of Chagas disease, and a comprehensive approach that includes vector and vertical transmission control strategies is essential for eradicating Chagas disease. We also observed that if vector transmission can be controlled, then at least 55% of the newborns need to be treated to eliminate the disease.
| S-EPMC11412536 | biostudies-literature
Project description:BackgroundChagas disease (CD) is an emergent disease in Europe, due to immigration. The aims of this study are to describe the epidemiological characteristics of a cohort of Chagas infected pregnant women in Spain, to assess the vertical transmission (VT) rate and evaluate the usefulness of the PCR in the diagnosis of congenital infection in the first months of life.MethodsA descriptive, retrospective study including Chagas seropositive pregnant women who were attended at three tertiary hospitals in Madrid, from January 2012 to September 2016. Infants were examined by PCR at birth and 1 month later and serologically studied at 9 months or later. Children were considered infected when the parasite was detected by PCR at any age or when serology remained positive without decline over the age of 9 months.ResultsWe included 122 seropositive-infected pregnant women, 81% were from Bolivia and only 8.2% had been treated before. 125 newborns were studied and finally 109 were included (12.8% lost the follow-up before performing the last serology). The VT rate was 2.75% (95% CI: 0,57-8,8%). Infected infants had positive PCR at birth and 1 month later. All of them were treated successfully with benznidazole (PCR and serology became negative later on). All non-infected children presented negative PCR. The mean age at which uninfected patients had negative serology was 10.5 months.ConclusionsThe VT rate is in keeping with literature and confirms the need to carry out a screening in pregnant women coming from endemic areas. PCR seems to be a useful tool to provide early diagnosis of congenital CD.
| S-EPMC6619651 | biostudies-literature
Project description:Congenital transmission is a key route of Trypanosoma cruzi infection in Latin America and globally, contributing significantly to the burden of Chagas disease. The interruption of transmission from mother to child has recently become a focus issue. However, the research landscape on congenital Chagas disease remains largely unexplored. The purpose of this scoping review is to assess the production of knowledge on congenital Chagas disease (CCD), aiming to identify research trends and potential gaps. Our initial hypothesis was that the CCD literature overly represents the medical sciences and that there is a need for socio-cultural research on the subject. We conducted a systematic search of publications focusing on congenital Chagas disease in six languages (English, Spanish, Portuguese, French, German and Italian). This comprehensive literature search identified 876 studies that met the inclusion criteria, out of a total of 8893 sources. The relevant literature was analyzed by language, year of publication, discipline, source type and research location. The main outcome of this study has been to prove our hypothesis that there is a scarcity of knowledge produced within the non-biomedical sciences on CCD. This underscores the need for further exploration into the social and structural issues surrounding this disease. Visually clear data concerning congenital Chagas disease produced by this study can contribute to hone in future research efforts and support funding applications. Additionally, this article provides a reference list that other researchers can consult for their own studies.
| S-EPMC10536740 | biostudies-literature
Project description:Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi-infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite-induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.
| S-EPMC2653922 | biostudies-literature