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Possible routes of maternal-fetal transmission of T. cruzi. According to Carlier and Truyens (2010).
Source publication
The aim of this paper is to discuss the main ecological interactions between the parasite Trypanosoma cruzi and its hosts, the mother and the fetus, leading to the transmission and development of congenital Chagas disease. One or several infecting strains of T. cruzi (with specific features) interact with: (i) the immune system of a pregnant woman...
Contexts in source publication
Context 1
... and Truyens, 2010;Martins et al., 2011;Cencig et al., 2013;Norman and López-Vélez, 2013). Placenta is therefore the key fetal organ facing the parasites present into the intervillous blood space (their amount resulting from the systemic immune control exerted by the pregnant woman, see Section 5.1) and from which transmission depends (Fig. 3). Besides the physical barrier formed by the syncytiotrophoblast that forgoes intercellular junctions, the placenta is an active immuno- logical organ also able to initiate an innate immune response. It can release pro-inflammatory cytokines, chemokines, reactive oxygen- and nitrogen-intermediates and anti-microbial peptides, through ...
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Herein we characterize Trypanosoma cruzi infections from blood and CSF samples in a case series of people with HIV and Chagas disease. We identify different infecting T. cruzi populations highlighting qPCR usefulness for Chagas disease reactivation diagnosis and evaluation of treatment response.
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Trypanosoma cruzi is the etiological agent of Chagas disease. The life cycle of this protozoan parasite is digenetic because it alternates its different developmental forms through two hosts, a vector insect and a vertebrate host. As a result, the parasites are exposed to sudden and drastic environmental changes causing cellular stress. The stress...
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Citations
... Otra vía de transmisión de gran relevancia es la transferencia vertical de madre a hijo durante el embarazo o parto. La transmisión connatal o congénita ( Fig. 1) es responsable del 22% de nuevas infecciones en países endémicos con programas activos de control vectorial, y la principal vía de transmisión en zonas no endémicas [11]. Dependiendo de la zona geográfica, la tasa de transmisión vertical oscila entre un 1% a un 12% [12], indicando que la infección por T. cruzi es y será un tema central de Salud Pública durante los próximos años. ...
... El Grupo 2 comprende 31 niños (7 meses a 3 años de edad; mediana = 1 año) mientras que el grupo 3 está conformado por 26 pacientes (3 a 16 años de edad; mediana = 8,4 años). La estratificación del Grupo 1 fue establecida a priori, debido a la posible presencia de anticuerpos maternos transferidos durante la gestación[11]. La estratificación del resto de los pacientes en los Grupos 2 y 3 fue establecida a posteriori, en base a la eficacia diferencial entre ambos grupos para negativizar en el ELISA convencional (tELISA) (ver debajo). ...
Evaluación del antígeno α-Gal como biomarcador de eficacia terapéutica en pacientes pediátricos con enfermedad de Chagas
... 5,6 The prevalence of Chagas in pregnant women in South America ranges from 4% to 52%, of whom only 0.1% to 7% transmits the infection to their offspring. 7 Transplacental transmission of T. cruzi constitutes an increasing public health problem worldwide. 8,9 A transcriptomic study in placentas from T. cruzi infected pregnant women demonstrated an increase in the expression of an important number of genes of innate immunity. ...
Problem
Congenital Trypanosoma cruzi ( T. cruzi ) infection has been associated with changes in the levels of TNF‐α and IFN‐γ during the pregnancy. Therefore, we propose to study the participation and dynamics of proinflammatory cytokines in the infection process of placental explants infected by T. cruzi in vitro.
Method of Study
Chorionic villous explants (CVE) obtained of human term placentas ( n = 8) from normal pregnancies were cultured with 10 ⁵ trypomastigotes/mL of Tulahuen strain DTU VI for 0, 2, 4, 16, 24, 48 and 72 h. Explants were treated with sulfasalazine (SULF) (5 mM) and N ‐acetyl‐cysteine (NAC) (15 mM), as inhibitors molecules of NF‐κB pathway, or LPS (1 μg/mL) for 24 and 72 h p.i. Motile trypomastigotes were counted in culture supernatants. Immunohistochemistry and ELISA for TNF‐α, IFN‐γ, IL‐1β, IL‐4, and IL‐10 were performed in CVE and culture supernatants respectively. The parasite load was measured by RT‐qPCR.
Results
T. cruzi invades the chorionic villi from 4 h p.i. increasing significantly its DNA at 48 and 72 h p.i. of culture (parasite multiplication phase). They were detected in stromal cells, which was related to elevation of TNF‐α, IL‐1β, IFN‐γ, and IL‐10. The inhibition of NF‐κB activity in the explants decreased the production of the analyzed cytokines, showing elevated levels of T. cruzi DNA during the multiplication phase of the parasite.
Conclusions
Placental tissue modifies the secretion of pro‐inflammatory cytokines during the phase of parasite multiplication, but not during the invasion phase, which in turns modifies the level of infection via the signaling pathway NF‐κB.
... National control programs of vectorial and transfusional transmission in various South American countries have reduced the prevalence to around 6-8 million infected people, and the number of exposed individuals to around 60 million [2]. Subsequently, the maternal-fetal transmission of T. cruzi became an increasingly important mode of infection, which is susceptible to be repeated to several siblings and from one generation to another [3,4]. Chagas disease has extended to non-endemic countries owing to the migrations of individuals from endemic countries to North America, Europe, Japan, and Australia. ...
... Except for infected women of reproductive age who are treated with trypanocidal drugs before pregnancy, it is impossible to prevent congenital transmission in pregnant women, as they may not be treated during pregnancy and no biomarkers of transmission are identified. The mechanisms of maternal-fetal transmission are still under study [3,6,8]. The parasite lineage does not seem to be a determinant of congenital transmission, although some haplotypes may be preferentially transmitted [9,10]. ...
... The parasite lineage does not seem to be a determinant of congenital transmission, although some haplotypes may be preferentially transmitted [9,10]. However, a high parasite burden associated with a deficient specific immune response during pregnancy are maternal risk factors for in utero transmission [3,6,11]. The familial clustering of congenital cases (transmission repeated in each pregnancy and/or transgenerational) suggests the existence of maternal genetic or epigenetic risk factors of vertical transmission [3,6,12]. ...
Activated monocytes/macrophages that produce inflammatory cytokines and nitric oxide are crucial for controlling Trypanosoma cruzi infection. We previously showed that uninfected newborns from T. cruzi infected mothers (M+B- newborns) were sensitized to produce higher levels of inflammatory cytokines than newborns from uninfected mothers (M-B- newborns), suggesting that their monocytes were more activated. Thus, we wondered whether these cells might help limit congenital infection. We investigated this possibility by studying the activation status of M+B- cord blood monocytes and their ability to control T. cruzi in vitro infection. We showed that M+B- monocytes have an upregulated capacity to produce the inflammatory cytokine TNF-α and a better ability to control T. cruzi infection than M-B- monocytes. Our study also showed that T. cruzi-specific Abs transferred from the mother play a dual role by favoring trypomastigote entry into M+B- monocytes and inhibiting intracellular amastigote multiplication. These results support the possibility that some M+B- fetuses may eliminate the parasite transmitted in utero from their mothers, thus being uninfected at birth.
... CCD is transmitted through the transplacental hematogenous route, causing placentitis with subsequent placental necrosis, resulting in miscarriage, stillbirth, or preterm delivery. 15 Unfortunately, given the potential teratogenicity of drugs, congenital transmission cannot be prevented by treating the mother during pregnancy. ...
... 14 If the diagnosis was not made at birth, it is essential to monitor the newborn of a mother with CD Once a pregnant woman is diagnosed with having CD, screening should be performed in other siblings and her mother. 12,15 To determine the presence of infection in the newborn of a mother with CD, it is recommended to take a sample of peripheral Abbreviation: CD, Chagas disease. ...
... Although side effects have also been reported (Table 6), 8 it is better tolerated in children than in adults. 15,25 Benznidazole is not contraindicated in mothers with CD during breastfeeding, because of the low transmission of the drug in breast milk and the low potential of exposure to the newborn. 16 In the acute phase, treatment is effective in 80% of cases, reach- treatment, but evidence suggests that it could have a potential benefit especially in young adults and in women of childbearing age. ...
Chagas disease (CD) is caused by the parasite Trypanosoma cruzi. Although it is endemic in many Latin American (LA) countries, mother‐to‐child transmission has caused it to expand to other countries and continents. In places where vector transmission is controlled or absent, the epidemiological importance of T. cruzi transmission of the infected mother to her child during pregnancy or childbirth (i.e., perinatal CD) increases. In countries where CD is not endemic, CD screening should be performed in pregnant or fertile women who are native to LA countries or whose mothers are native to LA countries. Diagnosis is established by detecting anti–T. cruzi IgG antibodies in a serum or plasma sample. Antiparasitic treatment cannot be offered during pregnancy, and since the majority of infected newborns are asymptomatic at birth, a diagnosis is made by direct observation or concentration (microhematocrit) or by using molecular testing techniques. Once the infected child receives a diagnosis, it is essential to offer treatment (benznidazole/nifurtimox) as soon as possible, with good tolerance and effectiveness in the first year of life. Even if the diagnosis is negative at birth, the newborn must be followed up for at least the first 9 months of life.
... 902 A transmissão congênita do T. cruzi é processo complexo, resultante da interação de múltiplos fatores relacionados ao parasita, à placenta e à resposta imune do feto e da mãe. 903 A carga parasitária de mulheres infectadas durante a gravidez é fator fundamental para a transmissão congênita. 904 A parasitemia pode reaparecer com a RDC geralmente associada à imunossupressão fisiológica transiente que ocorre durante a gravidez. ...
... 902 A transmissão congênita do T. cruzi é processo complexo, resultante da interação de múltiplos fatores relacionados ao parasita, à placenta e à resposta imune do feto e da mãe. 903 A carga parasitária de mulheres infectadas durante a gravidez é fator fundamental para a transmissão congênita. 904 A parasitemia pode reaparecer com a RDC geralmente associada à imunossupressão fisiológica transiente que ocorre durante a gravidez. ...
... The Republic of El Salvador has historically experienced the highest incidence of acute and chronic Chagas disease in Central America, and TcI discrete typing unit is predominant in this country [8,[11][12][13][14][15]. Despite great strides toward vector control with the removal of Rhodnius prolixus from El Salvador in 2009 [16], vector transmission continues to occur and efforts to reduce human-vector contact in parts of the region have proven difficult. ...
... This study was limited by sample size (n = 198 participants) and geographically limited to two western departments. Though these departments both fall under a high index of multidimensional poverty [33], future works should encompass further departments with low socioeconomic status and substandard housing, both being well-established risk factors for Chagas disease infection [14,42,43]. Infant testing results were unavailable for the current study, limiting our knowledge of vertical transmission in this cohort; however, the Ministry of Health is actively performing this testing, ensuring proper treatment of both mothers and any subsequently infected infants. ...
Congenital Chagas disease is a growing concern, prioritized by the World Health Organization for public health action. El Salvador is home to some of the highest Chagas disease (Trypanosoma cruzi infection) burdens in the Americas, yet pregnancy screening remains neglected. This pilot investigation performed a maternal T. cruzi surveillance study in Western El Salvador among women presenting for labor and delivery. From 198 consented and enrolled pregnant women, 6% were T. cruzi positive by serology or molecular diagnosis. Half of the infants born to T. cruzi-positive women were admitted to the NICU for neonatal complications. Geospatial statistical clustering of cases was noted in the municipality of Jujutla. Older women and those knowing an infected relative or close friend were significantly more likely to test positive for T. cruzi infection at the time of parturition. In closing, maternal T. cruzi infections were significantly higher than national HIV or syphilis maternal rates, creating an urgent need to add T. cruzi to mandatory pregnancy screening programs.
... Mientras que la transmisión vectorial es la principal en zonas endémicas, otros modos documentados en el humano incluyen la transfusión de sangre y/o el trasplante de órganos provenientes de dadores infectados, y la ingesta de comidas y/o bebidas contaminadas con el parásito (transmisión oral) 1 . La ruta congénita de infección también es un punto importante a considerar, y representa el 22% de las nuevas infecciones en zonas con políticas activas de control vectorial 4 . En este contexto, el desarrollo e implementación de nuevas herramientas tendientes a optimizar el diagnóstico y tratamiento de pacientes constituye uno de los pilares de las políticas para un efectivo control de la transmisión de este parásito 5 . ...
Trypanosoma cruzi es el parásito protozoario causante de la enfermedad de Chagas, de gran relevancia sanitaria y socio-económica en la región. Este patógeno presenta una estructura poblacional muy compleja, compuesta por múltiples aislamientos o cepas genéticamente divergentes. El consenso actual sugiere que éstas pueden agruparse en al menos 6 linajes evolutivos, llamados TcI a TcVI, los que tienen distinta distribución eco-epidemiológica y significativas diferencias geno- y fenotípicas. La superficie celular de T. cruzi se compone de una densa capa de glicoconjugados, usualmente codificados por familias multigénicas complejas, que presentan variaciones entre cepas del parásito. Esta variabilidad, que resulta en general subvalorada debido a dificultades asociadas al ensamblaje y anotación del genoma de T. cruzi, es de carácter cuantitativo (dosaje génico) y cualitativo (organización genómica, polimorfismos de secuencia), y se traduce incluso en eventos de pseudogenización y de quimerización entre miembros de diferentes familias multigénicas. Una de las familias multigénicas más representada en el
genoma de T. cruzi corresponde a las MASP (Mucin Associated-Surface Proteins), factores de virulencia expresados en la superficie de los estadios infectivos del parásito, que contribuyen a su capacidad para invadir distintos tipos celulares y/o a evadir el sistema inmune. En este trabajo realizamos un exhaustivo análisis y curado de las bases de datos de MASP de dos cepas pertenecientes a linajes divergentes de T. cruzi: Brazil A4 (TcI) y TCC (TcVI). En ese proceso encontramos secuencias truncas, pseudogénicas y con errores de predicción, atribuibles a los esquemas actuales de anotación genómica en T.cruzi. Asimismo, identificamos secuencias MASP quiméricas con genes de trans-sialidasa y mucinas y, como consecuencia, abordamos también el curado de estas dos familias multigénicas. La búsqueda de secuencias conservadas en todas estas bases de datos nos permitió identificar 19 firmas moleculares, las cuales fueron incorporadas como expresiones regulares en un algoritmo de clasificación diseñado para la identificación y clasificación de miembros de la familia MASP. Nuestro algoritmo fue capaz de identificar y diferenciar desde sets de datos complejos y con una performance excepcional tanto
proteínas MASP canónicas como quiméricas. Más aún, el empleo de una estrategia
masiva, basada en la predicción de ORFs de novo acoplada a nuestro algoritmo, nos
permitió identificar no sólo nuevos miembros de esta familia sino también nuevos
eventos de quimerización. En conjunto, estos hallazgos y las herramientas aquí
generadas sientan las bases para futuros estudios tanto funcionales como evolutivos de las proteínas MASP de T. cruzi.
... The rates of T. cruzi vertical transmission range from 1% to 12%, depending on the area (6), with an average rate of 5% (7). CCD often presents as an acute infection, and although 60% of infected babies are born asymptomatic, they usually exhibit detectable levels of parasitemia and display higher frequencies of low weight, prematurity and lower APGAR scores (aspect, pulse, grimace, activity, and respiration) than noninfected babies (8)(9)(10). Although rarely lethal, untreated CCD can lead to hepatosplenomegaly, meningoencephalitis, and myocarditis (11); however, when detected and treated early, parasitic clearance is more than 90% effective (12,13). ...
Chagas disease is mainly transmitted by vertical transmission (VT) in nonendemic areas and in endemic areas where vector control programs have been successful. For the present study, we isolated natural Trypanosoma cruzi strains vertically transmitted through three generations and proceeded to study their molecular mechanism of VT using mice. No parasitemia was detected in immunocompetent mice, but the parasites were able to induce an immune response and colonize different organs. VT experiments revealed that infection with different strains did not affect mating, pregnancy, or resorption, but despite low parasitemia, VT strains reached the placenta and resulted in higher vertical transmission rates than strains of either moderate or high virulence. While the virulent strain modulated more than 2,500 placental genes, VT strains modulated 150, and only 29 genes are shared between them. VT strains downregulated genes associated with cell division and replication and upregulated immunomodulatory genes, leading to anti-inflammatory responses and tolerance. The virulent strain stimulated a strong proinflammatory immune response, and this molecular footprint correlated with histopathological analyses. We describe a unique placental response regarding the passage of T. cruzi VT isolates across the maternal-fetal interphase, challenging the current knowledge derived mainly from studies of laboratory-adapted or highly virulent strains. IMPORTANCE The main findings of this study are that we determined that there are Trypanosoma cruzi strains adapted to transplacental transmission and completely different from the commonly used laboratory reference strains. This implies a specific strategy for the vertical transmission of Chagas disease. It is impressive that the strains specialized for vertical transmission modify the gene expression of the placenta in a totally different way than the reference strains. In addition, we describe isolates of T. cruzi that cannot be transmitted transplacentally. Taken together, these results open up new insights into the molecular mechanisms of this insect vector-independent transmission form.
... T. cruzi parasite has a highly complex plastic genome and is organized into seven sub-clades or DTU from TcI-TcVI, with six infecting humans and mammals (DTU TcI-TcVI) and a seventh distinct TcBat that circulates within Chiropteran populations [45,[47][48][49]. Differential distributions of parasite DTU occur geographically, with the most common DTU, TcI, predominating from North America to the northern region of South America [50]. TCV and TcVI dominate within human Chagas disease transmission cycles in South American southern cone countries [47]. ...
... Similar to other protozoans, T. cruzi is able to evade host immune response and cross the placental barrier; however, the distinct mechanisms of congenital transmission have yet to be clarified [46]. Susceptibility for vertical transmission depends upon virulence factors of the T. cruzi strain, level of parasitemia, ability of the parasite to evade immune response, and maternal and fetal immune responses to the pathogen [44,50]. High parasitemia is thought to contribute to destruction of the placental trophoblast layer, for differentiation within the basal laminae and stromal cells [46]. ...
... High parasitemia is thought to contribute to destruction of the placental trophoblast layer, for differentiation within the basal laminae and stromal cells [46]. Therefore, vertical transmission is more likely to occur during acute or reactivated infection during pregnancy or when maternal parasitemia is significantly elevated in chronically infected mothers [50]. When parasitemia is lower, placental breaches or tears are thought to contribute to parasite passage of the placental barrier [50]. ...
TORCH pathogens are a group of globally prevalent infectious agents that may cross the placental barrier, causing severe negative sequalae in neonates, including fetal death and lifelong morbidity. TORCH infections are classically defined by Toxoplasma gondii, other infectious causes of concern (e.g., syphilis, Zika virus, malaria, human immunodeficiency virus), rubella virus, cytomegalovirus, and herpes simplex viruses. Neonatal disorders and congenital birth defects are the leading causes of neonatal mortality in Central America’s Northern Triangle, yet little is known about TORCH congenital syndrome in this region. This review synthesizes the little that is known regarding the most salient TORCH infections among pregnant women and neonates in Central America’s Northern Triangle and highlights gaps in the literature that warrant further research. Due to the limited publicly available information, this review includes both peer-reviewed published literature and university professional degree theses. Further large-scale studies should be conducted to clarify the public health impact these infections in this world region.
