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The genetic diversity of Echinococcus multilocularis (E. multilocularis) specimens isolated from patients with alveolar echinococcosis (AE), is a major field of investigation to correlate with sources of infection, clinical manifestations and prognosis of the disease. Molecular markers able to distinguish samples are commonly used worldwide, including the EmsB microsatellite. Here, we report the use of the EmsB microsatellite polymorphism data mining for the retrospective typing of Belgian specimens of E. multilocularis infecting humans. A total of 18 samples from 16 AE patients treated between 2006 and 2021 were analyzed through the EmsB polymorphism. Classification of specimens was performed through a dendrogram construction in order to compare the similarity among Belgian samples, some human referenced specimens on the EWET database (EmsB Website for the Echinococcus Typing) and previously published EmsB profiles from red foxes circulating in/near Belgium. According to a comparison with human European specimens previously genotyped in profiles, the 18 Belgian ones were classified into three EmsB profiles. Four specimens could not be assigned to an already known profile but some are near to EWET referenced samples. This study also highlights that some specimens share the same EmsB profile with profiles characterized in red foxes from north Belgium, the Netherlands, Luxembourg and French department near to the Belgian border. Furthermore, Belgian specimens present a genetic diversity and include one profile that don't share similarities with the ones referenced in the EWET database. However, at this geographical scale, there is no clear correlation between EmsB profiles and geographical location. Further studies including additional clinical samples and isolates from foxes and rodents of south Belgium are necessary to better understand the spatial and temporal circumstances of human infections but also a potential correlation between EmsB profiles and parasite virulence.
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Echinococcus multilocularis , Animales , Humanos , Bélgica/epidemiología , Echinococcus multilocularis/genética , Zorros/parasitología , Estudios Retrospectivos , Variación Genética , Repeticiones de MicrosatéliteRESUMEN
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.
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We previously identified the recombinant (r) macrophage (M) infectivity (I) potentiator (P) of the protozoan parasite Trypanosoma cruzi (Tc) (rTcMIP) as an immuno-stimulatory protein that induces the release of IFN-γ, CCL2 and CCL3 by human cord blood cells. These cytokines and chemokines are important to direct a type 1 adaptive immune response. rTcMIP also increased the Ab response and favored the production of the Th1-related isotype IgG2a in mouse models of neonatal vaccination, indicating that rTcMIP could be used as a vaccine adjuvant to enhance T and B cell responses. In the present study, we used cord and adult blood cells, and isolated NK cells and human monocytes to investigate the pathways and to decipher the mechanism of action of the recombinant rTcMIP. We found that rTcMIP engaged TLR1/2 and TLR4 independently of CD14 and activated the MyD88, but not the TRIF, pathway to induce IFN-γ production by IL-15-primed NK cells, and TNF-α secretion by monocytes and myeloid dendritic cells. Our results also indicated that TNF-α boosted IFN-γ expression. Though cord blood cells displayed lower responses than adult cells, our results allow to consider rTcMIP as a potential pro-type 1 adjuvant that might be associated to vaccines administered in early life or later.
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Receptor Toll-Like 2 , Trypanosoma cruzi , Animales , Ratones , Recién Nacido , Humanos , Adulto , Receptor Toll-Like 4 , Factor de Necrosis Tumoral alfa , Macrófagos , Interferón gamma , Células Asesinas NaturalesRESUMEN
This work identifies the protein "macrophage infectivity potentiator" of Trypanosoma cruzi trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h in vitro culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18. rTcMIP activity is totally abolished by protease treatment and is not associated with its peptidyl-prolyl cis-trans isomerase enzymatic activity. The ability of rTcMIP to act as adjuvant was studied in vivo in neonatal mouse immunization models, using acellular diphtheria-tetanus-pertussis-vaccine (DTPa) or ovalbumin, and compared to the classical alum adjuvant. As compared to the latter, rTcMIP increases the IgG antibody response towards several antigens meanwhile skewing antibody production towards the Th-1 dependent IgG2a isotype. The amplitude of the rTcMIP adjuvant effect varied depending on the antigen and the co-presence of alum. rTcMIP did by contrast not increase the IgE response to OVA combined with alum. The discovery of the rTcMIP immunostimulatory effect on neonatal cells opens new possibilities for potential use as pro-type 1 adjuvant for neonatal vaccines. This, in turn, may facilitate the development of more efficient vaccines that can be given at birth, reducing infection associated morbidity and mortality which are the highest in the first weeks after birth.
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Trypanosoma cruzi , Vacunas , Humanos , Ratones , Recién Nacido , Animales , Adyuvantes Inmunológicos/farmacología , Antígenos , Inmunoglobulina G , MacrófagosRESUMEN
Aims: To assess the epigenetic effects of in utero exposure to maternal Trypanosoma cruzi infection. Methods: We performed an epigenome-wide association study to compare the DNA methylation patterns of umbilical cord blood cells from uninfected babies from chagasic and uninfected mothers. DNA methylation was measured using Infinium EPIC arrays. Results: We identified a differential DNA methylation signature of fetal exposure to maternal T. cruzi infection, in the absence of parasite transmission, with 12 differentially methylated sites in B cells and CD4+ T cells, including eight protein-coding genes. Conclusion: These genes participate in hematopoietic cell differentiation and the immune response and may be involved in immune disorders. They also have been associated with several developmental disorders and syndromes.
Maternal infection with Trypanosoma cruzi, the parasite that causes Chagas disease, may influence fetal development, even in the absence of parasite transmission. Thus we investigated how exposure to maternal infection might lead to changes in gene expression in the infant, by examining changes in DNA methylation in the umbilical cord blood. We found that exposure to maternal infection alters DNA methylation of at least 12 sites, including eight genes. Expression of these genes may be altered, which may affect blood cell function, the immune response and newborn development later in life. Further studies should monitor newborns from infected mothers to better assess their health and possible longer term effects.
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Enfermedad de Chagas , Sangre Fetal , Enfermedad de Chagas/genética , Enfermedad de Chagas/metabolismo , Metilación de ADN , Epigénesis Genética , Epigenómica , Femenino , Sangre Fetal/metabolismo , Humanos , Lactante , Recién Nacido , Exposición Materna , Linfocitos TRESUMEN
BACKGROUND: Benznidazole is an effective drug in the trypanocidal treatment of acute and chronic indeterminate Chagas' disease (CD). However, adverse drug reactions (ADR) are common and frequently cause patients to discontinue treatment. OBJECTIVES: We hypothesized that antioxidant supplementation could mitigate benznidazole-induced toxicity. METHODS: We co-supplemented an adult traveller with chronic indeterminate CD who experienced benznidazole ADR with ascorbic acid (AA), 1000â mg/day. We measured selected serum biomarkers of oxidative stress [total antioxidant status (TAS), total oxidative status (TOS), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), extracellular glutathione peroxidase (GPX3), catalase (CAT) and total superoxide dismutase (T-SOD)] at timepoints before and throughout benznidazole treatment and after AA co-supplementation. RESULTS: AA co-supplementation effectively mitigated benznidazole-induced ADR during the aetiological treatment of chronic indeterminate CD. The kinetics of serum biomarkers of oxidative stress suggested significantly decreased oxidative insult in our patient. CONCLUSIONS: We hypothesize that the key pathophysiological mechanism of benznidazole-associated toxicity is oxidative stress, rather than hypersensitivity. AA co-supplementation may improve adherence to benznidazole treatment of chronic indeterminate (or acute) CD. Oxidative stress biomarkers have the potential to guide the clinical management of CD. Prospective studies are needed to establish the benefit of antioxidant co-supplementation to benznidazole treatment of CD in reducing benznidazole toxicity, parasite clearance and the prevention of end-organ damage.
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Enfermedad de Chagas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Nitroimidazoles , Adulto , Antioxidantes/uso terapéutico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Biomarcadores , Enfermedad de Chagas/tratamiento farmacológico , Suplementos Dietéticos , Humanos , Nitroimidazoles/efectos adversos , Estrés OxidativoRESUMEN
BACKGROUND: Trichinellosis is a parasitic infection caused by nematodes of the genus Trichinella, and its principal mode of transmission is the consumption of raw or undercooked contaminated meat. Cardiac involvement in trichinellosis is unusual, yet it represents the most frequent cause of death. Here, we report a case in which Trichinella spiralis-associated myocarditis simulated a myocardial infarction. CASE PRESENTATION: A 35-year-old African man with no previous medical history was admitted to the emergency department for acute substernal discomfort at rest described as a pressure with no radiation. The electrocardiogram performed upon admission showed non-specific alterations of repolarization. Blood biology revealed high levels of troponin T and predominant eosinophilic leukocytosis. A transthoracic echocardiography was carried out and found a significant left ventricular concentric hypertrophy with a preserved ejection fraction. The septal and inferior walls, as well as the endocardium were hyperechogenic. The patient was hospitalized for eosinophilic myocarditis. The cause of hypereosinophilia was investigated, and a Trichinella spiralis serology came back strongly positive. A diagnosis of Trichinella spiralis associated-myocarditis was made.The patient was treated with albendazole-prednisolone dual therapy with favorable clinical and biological outcomes. CONCLUSION: The clinical suspicion of trichinellosis is based on suggestive epidemiology associated with the typical clinical presentation and the presence of eosinophilia. Eosinophilic myocarditis is a severe complication of trichinellosis which can result in death due to rhythm disorders. Chest pain, increase in troponins, and electrocardiographic abnormalities are all elements that can mimic a myocardial infarction and mislead clinicians.Abbreviations: ANCA: Anti-Neutrophil Cytoplasmic Antibodies; ANA: Anti-Nuclear Antibodies; ECDC: European Centre for Disease Prevention and Control; ECG: Electrocardiogram; ELISA: Enzyme-Linked ImmunoSorbent Assay; EMF: Endomyocardial Fibrosis; ES: Excretory-Secretory; ICT: International Commission on Trichinellosis; MRI: Magnetic Resonance Imaging.
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Infarto del Miocardio , Miocarditis , Trichinella spiralis , Triquinelosis , Adulto , Animales , Anticuerpos Antihelmínticos , Antígenos Helmínticos , Ensayo de Inmunoadsorción Enzimática , Proteínas del Helminto , Humanos , Masculino , Miocarditis/diagnóstico , Triquinelosis/diagnósticoRESUMEN
Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi-infected women to evaluate the reactivity of two rapid diagnostic tests and one enzyme-linked immunosorbent assay (ELISA). Our cohort was derived from a previous study on congenital transmission of T. cruzi and consisted of 481 blood/plasma samples from Argentina (n = 149), Honduras (n = 228), and Mexico (n = 104), with at least one positive T. cruzi PCR. Reactivity of the three tests ranged from 70.5% for the Wiener ELISA to 81.0% for the T-Detect and 90.4% for the Stat-Pak rapid tests. Test reactivity varied significantly among countries and was highest in Argentina and lowest in Mexico. When considering at least two reactive serological tests to confirm seropositivity, over 12% of T. cruzi infection cases from Argentina were missed by serological tests, over 21% in Honduras, and an alarming 72% in Mexico. Differences in test performance among countries were not due to differences in parasitemia, but differences in antibody levels against ELISA antigens were observed. Geographic differences in T. cruzi parasite strains as well as genetic differences among human populations both may contribute to the discrepancies in serological testing. Improvements in serological diagnostics for T. cruzi infections are critically needed to ensure an optimum identification of cases.
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Enfermedad de Chagas , Trypanosoma cruzi , Anticuerpos Antiprotozoarios , Enfermedad de Chagas/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Pruebas SerológicasRESUMEN
The newborns of women infected with the parasite Trypanosoma cruzi (the agent of Chagas disease) can be infected either before birth (congenitally), or after birth (as e.g., by vector route). Congenital Chagas disease can induce high levels of neonatal morbidity and mortality. Parasite-infected pregnant women transmit antibodies to their fetus. Antibodies, by opsonizing parasites, can promote phagocytosis and killing of T. cruzi by cells expressing FcγR, on the mandatory condition that such cells are sufficiently activated in an inflammatory context. Antibody-dependent enhancement (ADE) is a mechanism well described in viral infections, by which antibodies enhance entry of infectious agents into host cells by exploiting the phagocytic FcγR pathway. Previously reported Chagas disease studies highlighted a severe reduction of the maternal-fetal/neonatal inflammatory context in parasite-transmitting pregnant women and their congenitally infected newborns. Otherwise, experimental observations brought to light ADE of T. cruzi infection (involving FcγR) in mouse pups displaying maternally transferred antibodies, out of an inflammatory context. Herein, based on such data, we discuss the previously unconsidered possibility of a role of ADE in the trans-placental parasite transmission, and/or the development of severe and mortal clinical forms of congenital/neonatal Chagas disease in newborns of T. cruzi-infected mothers.
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Acrecentamiento Dependiente de Anticuerpo , Enfermedad de Chagas/inmunología , Transmisión Vertical de Enfermedad Infecciosa , Placenta/parasitología , Trypanosoma cruzi/inmunología , Animales , Enfermedad de Chagas/congénito , Enfermedad de Chagas/parasitología , Femenino , Humanos , Recién Nacido , Ratones , Placenta/inmunología , Embarazo , Complicaciones Parasitarias del Embarazo/inmunología , Mujeres Embarazadas , Trypanosoma cruzi/parasitologíaRESUMEN
BACKGROUND: IgE characterizes the humoral response of allergic sensitization but less is known about what modulates its function and why some patients present clinical symptoms for a given IgE level and others do not. An IgE response also occurs during helminth diseases, independently of allergic symptoms. This response could be a model of non-functional IgE. OBJECTIVE: To study the IgE response against environmental allergens induced during natural helminth infection. METHODS: In 28 non allergic subjects from the periphery of Ho Chi Minh city with (H+, n = 18) and without helminth infection (H-, n = 10), we measured IgE and IgG4 against several components of Dermatophagoïdes pteronyssinus (Dpt) and Ascaris (a marker of immunization against nematodes), and determined the IgE component sensitization profile using microarray ISAC biochips. The functional ability of IgE to induce degranulation of cultured mast cells was evaluated in the presence of Dpt. RESULTS: Non allergic H+ subjects exhibited higher levels of IgE against Dpt compared to H- subjects. Dpt IgE were not functional in vitro and did not recognize usual Dpt major allergens. IgE recognized other component allergens that belong to different protein families, and most were glycosylated. Depletion of IgE recognizing carbohydrate cross-reactive determinant (CCD) did not induce a reduction in Dpt IgE. The Dpt IgG4 were not significantly different. CONCLUSION: Helminth infections induced IgE against allergens such as Dpt and molecular components that belong to different sources as well as against CCD (such as ß-1,2-xylose and/or âº-1,3-fucose substituted N-glycans). Dpt IgE were not able to induce degranulation of mast cells and were not explained by sensitization to usual major allergens or N-glycans.
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Alérgenos/inmunología , Dermatophagoides pteronyssinus/inmunología , Inmunoglobulina E/inmunología , Infecciones por Nematodos/inmunología , Adolescente , Adulto , Anciano , Ancylostomatoidea/inmunología , Animales , Antígenos Dermatofagoides/inmunología , Ascaris/inmunología , Estudios de Casos y Controles , Células Cultivadas , Reacciones Cruzadas , Femenino , Voluntarios Sanos , Humanos , Inmunoglobulina E/sangre , Masculino , Mastocitos , Persona de Mediana Edad , Infecciones por Nematodos/sangre , Infecciones por Nematodos/parasitología , Cultivo Primario de Células , Vietnam , Adulto JovenRESUMEN
BACKGROUND: Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment. METHODOLOGY: Twenty hookworm infected (HW+) and 14 non-infected subjects HW-from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1ß, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFß. RESULTS: HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP3lo resting Treg (rTreg). CD45RA-FoxP3lo non-suppressive Treg cells were also increased. No preferential Th1/Th2 orientation was observed, nor difference for IL-10 between two groups. After treatment, Treg, TregICOS+, TregCD62L+, Treg PD1- and rTreg decreased while IL-4 and IL-6 cytokines increased. CONCLUSION: During HW infection, Treg are increased and characterized by a heterogeneous population: a highly suppressive as well as a non-suppressive T cells phenotype. After treatment, Treg with immune-suppressive phenotype exhibited a decrease parallel to an inflammatory Th2 response.
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Albendazol/administración & dosificación , Ancylostomatoidea/inmunología , Antihelmínticos/administración & dosificación , Infecciones por Uncinaria/tratamiento farmacológico , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Adulto , Albendazol/farmacología , Animales , Antihelmínticos/farmacología , Sangre/parasitología , Estudios de Casos y Controles , Citocinas/metabolismo , Heces/parasitología , Regulación de la Expresión Génica/efectos de los fármacos , Infecciones por Uncinaria/inmunología , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is considered a neglected tropical disease by the World Health Organization. Congenital transmission of CD is an increasingly relevant public health problem. It progressively becomes the main transmission route over others and can occur in both endemic and non-endemic countries. Though most congenitally infected newborns are asymptomatic at birth, they display higher frequencies of prematurity, low birth weight, and lower Apgar scores compared to uninfected ones, and some suffer from severe symptoms. If not diagnosed and treated, infected newborns are at risk of developing disabling and life-threatening chronic pathologies later in life. The success or failure of congenital transmission depends on interactions between the parasite, the placenta, the mother, and the fetus. We review and discuss here the current knowledge about these parameters, including parasite virulence factors such as exovesicles, placental tropism, potential placental defense mechanisms, the placental transcriptome of infected women, gene polymorphism, and the maternal and fetal/neonatal immune responses, that might modulate the risk of T. cruzi congenital transmission.
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Trypanosoma cruzi, the causative agent of Chagas disease, exhibits a high genetic variability and has been classified into six discrete typing units (DTUs) named TcI through TcVI. This genetic diversity is believed to be associated with clinical characteristics and outcomes, but evidence supporting such associations has been limited. Herein, we performed a phylogenetic analysis of T. cruzi sequences of the mini-exon intergenic region obtained from a large cohort of pregnant women and newborns from Argentina, Honduras, and Mexico, to assess parasite genetic diversity and possible associations with congenital transmission. Analysis of 105 samples (including five paired samples) from maternal and umbilical cord blood indicated that T. cruzi DTU distribution was similar among pregnant women and newborns from these three countries, with a high frequency of TcII-TcV-TcVI DTUs, including mixed infections with TcI. However, phylogenetic analysis revealed that although the same parasite haplotypes circulated in these three countries, they were present at different frequencies, leading to significant geographic differences. Of importance, a strong association was observed between parasite haplotypes and congenital infection of newborns. Thus, the identification of parasite haplotypes in pregnant women, but not of parasite DTUs, may help predict congenital transmission of T. cruzi.
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Enfermedad de Chagas/parasitología , Filogenia , Complicaciones Parasitarias del Embarazo/parasitología , Trypanosoma cruzi/genética , Argentina , Enfermedad de Chagas/transmisión , Exones , Femenino , Técnicas de Genotipaje , Haplotipos , Honduras , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , México , Reacción en Cadena de la Polimerasa , EmbarazoRESUMEN
INTRODUCTION: The microscopic examination of microhematocrit tubes (mHCT) has been proposed as the gold standard for acute and congenital Chagas disease diagnosis. We compared different mHCT methodologies detecting T. cruzi parasites in the blood. METHODS: The rotating method, water mount, and immersion oil methods were compared for their suitability, sensitivity, and specificity. RESULTS: The rotating method was easier, faster, and more sensitive than the others with 100% specificity. CONCLUSIONS: The rotating method is feasible for laboratory technicians with standard training in microscopic techniques and is recommended for the diagnosis of acute Chagas disease in primary health care facilities.
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Tubo Capilar , Centrifugación/métodos , Enfermedad de Chagas/diagnóstico , Hematócrito/métodos , Parasitemia/diagnóstico , Trypanosoma cruzi/aislamiento & purificación , Animales , Enfermedad de Chagas/sangre , Enfermedad de Chagas/parasitología , Servicios de Laboratorio Clínico , Humanos , Parasitemia/parasitología , Sensibilidad y EspecificidadRESUMEN
Abstract INTRODUCTION: The microscopic examination of microhematocrit tubes (mHCT) has been proposed as the gold standard for acute and congenital Chagas disease diagnosis. We compared different mHCT methodologies detecting T. cruzi parasites in the blood. METHODS: The rotating method, water mount, and immersion oil methods were compared for their suitability, sensitivity, and specificity. RESULTS: The rotating method was easier, faster, and more sensitive than the others with 100% specificity. CONCLUSIONS: The rotating method is feasible for laboratory technicians with standard training in microscopic techniques and is recommended for the diagnosis of acute Chagas disease in primary health care facilities.
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Humanos , Animales , Trypanosoma cruzi/aislamiento & purificación , Centrifugación/métodos , Enfermedad de Chagas/diagnóstico , Parasitemia/diagnóstico , Tubo Capilar , Hematócrito/métodos , Sensibilidad y Especificidad , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/sangre , Parasitemia/parasitología , Servicios de Laboratorio ClínicoRESUMEN
Compared with South America, there is a lack of epidemiologic studies about the risk of congenital transmission of Trypanosoma cruzi in Central America and Mexico. It has been suggested that T. cruzi genotypes might differ by region and that congenital transmission might vary according to the parasite's genotype. Our objective was to compare T. cruzi congenital transmission rates in three countries. We performed an observational prospective study in 2011-2014 enrolling women at delivery in one hospital in Argentina, two hospitals in Honduras, and two hospitals in Mexico. Congenital T. cruzi infection was defined as the presence of one or more of the following criteria: presence of parasites in cord blood (direct parasitological microscopic examination) with positive polymerase chain reaction (PCR) in cord blood, presence of parasites in infant's blood at 4-8 weeks (direct parasitological microscopic examination), and persistence of T. cruzi-specific antibodies at 10 months, as measured by at least two tests. Among 28,145 enrolled women, 347 had at least one antibody rapid test positive in cord blood and a positive enzyme-linked immunosorbent assay in maternal blood. PCR in maternal blood was positive in 73.2% of the cases, and genotyping identified a majority of non-TcI in the three countries. We found no (0.0%; 95% confidence interval [CI]: 0.0, 2.0) confirmed congenital case in Honduras. Congenital transmission was 6.6% (95% CI: 3.1, 12.2) in Argentina and 6.3% (95% CI: 0.8, 20.8) in Mexico. Trypanosoma cruzi non-TcI predominated and risks of congenital transmission were similar in Argentina and Mexico.
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Enfermedad de Chagas/transmisión , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Adulto , Enfermedad de Chagas/epidemiología , Femenino , Sangre Fetal/parasitología , Honduras/epidemiología , Humanos , Recién Nacido , México/epidemiología , Embarazo , Estudios Prospectivos , Estadísticas no Paramétricas , Trypanosoma cruzi/patogenicidadRESUMEN
This study develops an original co-infection model in mice using Brucella melitensis, the most frequent cause of human brucellosis, and Trypanosoma brucei, the agent of African trypanosomiasis. Although the immunosuppressive effects of T. brucei in natural hosts and mice models are well established, we observed that the injection of T. brucei in mice chronically infected with B. melitensis induces a drastic reduction in the number of B. melitensis in the spleen, the main reservoir of the infection. Similar results are obtained with Brucella abortus- and Brucella suis-infected mice and B. melitensis-infected mice co-infected with Trypanosoma cruzi, demonstrating that this phenomenon is not due to antigenic cross-reactivity. Comparison of co-infected wild-type and genetically deficient mice showed that Brucella elimination required functional IL-12p35/IFNγ signaling pathways and the presence of CD4+ T cells. However, the impact of wild type and an attenuated mutant of T. brucei on B. melitensis were similar, suggesting that a chronic intense inflammatory reaction is not required to eliminate B. melitensis. Finally, we also tested the impact of T. brucei infection on the course of Mycobacterium tuberculosis infection. Although T. brucei strongly increases the frequency of IFNγ+CD4+ T cells, it does not ameliorate the control of M. tuberculosis infection, suggesting that it is not controlled by the same effector mechanisms as Brucella. Thus, whereas T. brucei infections are commonly viewed as immunosuppressive and pathogenic, our data suggest that these parasites can specifically affect the immune control of Brucella infection, with benefits for the host.
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The protozoan parasite Trypanosoma cruzi circulates in the blood upon infection and invades various cells. Parasites intensively multiply during the acute phase of infection and persist lifelong at low levels in tissues and blood during the chronic phase. Natural killer (NK) and NKT cells play an important role in the immune control of T. cruzi infection, mainly by releasing the cytokine IFN-γ that activates the microbicidal action of macrophages and other cells and shapes a protective type 1 immune response. The mechanisms by which immune cells are regulated to produce IFN-γ during T. cruzi infection are still incompletely understood. Here, we show that urokinase plasminogen activator (uPA) is induced early upon T. cruzi infection and remains elevated until day 20 post-infection. We previously demonstrated that the inhibitory receptor Ly49E, which is expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we compared wild type (WT) to Ly49E knockout (KO) mice for their control of experimental T. cruzi infection. Our results show that young, i.e., 4- and 6-week-old, Ly49E KO mice control the infection better than WT mice, indicated by a lower parasite load and less cachexia. The beneficial effect of Ly49E depletion is more obvious in 4-week-old male than in female mice and weakens in 8-week-old mice. In young mice, the lower T. cruzi parasitemia in Ly49E KO mice is paralleled by higher IFN-γ production compared to their WT controls. Our data indicate that Ly49E receptor expression inhibits the immune control of T. cruzi infection. This is the first demonstration that the inhibitory Ly49E receptor can interfere with the immune response to a pathogen in vivo.