Browsing by Autor "Cristina Alonso‐Vega"

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Achievements and Challenges upon the Implementation of a Program for National Control of Congenital Chagas in Bolivia: Results 2004–2009
(Public Library of Science, 2013) Cristina Alonso‐Vega; Claire Billot; Faustino Torrico
Bolivia is one of the most endemic countries for Chagas disease. Data of 2005 shows that incidence is around 1.09‰ inhabitants and seroprevalence in children under 15 ranged from 10% in urban areas to 40% in rural areas. In this article, we report results obtained during the implementation of the congenital Chagas program, one of the biggest casuistry in congenital Chagas disease, led by National Program of Chagas and Belgian cooperation from 2004 to 2009. The program strategy was based on serological results during pregnancy and on the follow up of children born from positive mothers until one year old; if positive, treatment was done with Benznidazole, 10 mg/Kg/day/30 days with one post treatment control 6 months later. Throughout the length of the program, a total of 318,479 pregnant women were screened and 23.31% were detected positive. 42,538 children born from positive mothers were analyzed at birth by micromethod, of which 1.43% read positive. 10,120 children returned for their second micromethod control of which 2.29% read positive, 7,650 children returned for the serological control, of which 3.32% turned out positive. From the 1,093 positive children, 70% completed the 30 day-treatment and 122 returned for post treatment control with 96% showing a negative result. It has been seen that maternal-fetal transmission rates vary between 2% and 4%, with an average of 2.6% (about half of previously reported studies that reached 5%). In this work, we show that it is possible to implement, with limited resources, a National Congenital Chagas Program and to integrate it into the Bolivian health system. Keys of success are population awareness, health personnel motivation, and political commitment at all levels.
AMNIOTIC FLUID IS NOT USEFUL FOR DIAGNOSIS OF CONGENITAL TRYPANOSOMA CRUZI INFECTION
(American Society of Tropical Medicine and Hygiene, 2006) Myrna Virreira; Sabrina Sales Martínez; Cristina Alonso‐Vega; Faustino Torrico; Marco Solano; Mary Cruz Torrico; Rudy Parrado; Carine Truyens; Yves Carlier; Michal Svoboda
Although Trypanosoma cruzi can be transmitted transplacentally and induce congenital infection, no data are available about the presence of this parasite in human amniotic fluid. We examined 8, 19, and 4 amniotic fluid samples (collected at delivery or by aspiration of gastric content of neonates) from control uninfected mothers (M−B−), infected mothers delivering uninfected newborns (M+B−), and mothers of confirmed congenital cases (M+B+), respectively. Polymerase chain reaction (PCR), using nuclear and kinetoplastic DNA primers (Tcz1-Tcz2 and 121–122), were negative for all control M−B− samples, but positive for 5 of 19 M+B− and 2 of 4 M+B+ samples. To determine the number of parasites in the positive samples, real-time PCR using S35/S36 kinetoplastic DNA was performed. Only one M+B+ sample presented a high parasitic DNA amount, whereas the other six PCR-positive samples displayed traces of T. cruzi DNA. In conclusion, the release of parasites in amniotic fluid is probably a rare event that cannot be helpful for the routine diagnosis of congenital Chagas disease.
COMPARISON OF POLYMERASE CHAIN REACTION METHODS FOR RELIABLE AND EASY DETECTION OF CONGENITAL TRYPANOSOMA CRUZI INFECTION
(American Society of Tropical Medicine and Hygiene, 2003) Myrna Virreira; Faustino Torrico; Carine Truyens; Cristina Alonso‐Vega; Marco Solano; Yves Carlier; Michal Svoboda
The polymerase chain reaction (PCR) is a potentially interesting diagnostic tool for detecting congenital Trypanosoma cruzi infection at birth. We have compared the sensitivity and capacity of a group of T. cruzi PCR primers in detecting the complete spectrum of known T. cruzi lineages, and to improve and simplify the detection of infection in neonatal blood. We found that the two primers, Tcz1/Tcz2 and Diaz1/Diaz2, which target the 195-basepair satellite repeat, detected all parasitic lineages with the same sensitivity. However, the intensity of the amplicon was somewhat higher with Tcz1/Tcz2. For other tested primers (nuclear DNA primers BP1/BP2, O1/O2, Pon1/Pon2, and Tca1/Tca2 and kinetoplast DNA primers S35'/S36' and 121/122), either the intensity of amplicons varied according to T. cruzi lineages or the PCR assay was less sensitive. The use of the Tcz1/Tcz2 primers, which target a tandem repetitive sequence, requires a careful determination of the appropriate amount of Taq polymerase to avoid the formation of smears and multiple amplicon bands. The Tcz1/Tcz2 primers resulted in an intense 200-basepair amplicon with DNA extracted from blood equivalent to 0.02 parasites per assay when used with a simple DNA extraction method and of a low amount of Taq polymerase from a standard PCR kit. To better assess such PCR protocol, we assayed 311 samples of neonatal blood previously tested by parasitologic methods. The reliability of our PCR test was demonstrated, since all the 18 blood samples from newborns with congenital T. cruzi infection were positive, whereas the remaining samples (30 from control newborns of uninfected mothers and 262 of 263 from babies born to infected mothers) were negative. Since our PCR method is simple, reliable, robust, and inexpensive, it appears suitable for the detection of T. cruzi infection in neonatal blood, even in laboratories that are not equipped for performing the PCR.
CONGENITAL CHAGAS DISEASE IN BOLIVIA IS NOT ASSOCIATED WITH DNA POLYMORPHISM OF TRYPANOSOMA CRUZI
(American Society of Tropical Medicine and Hygiene, 2006) Myrna Virreira; Cristina Alonso‐Vega; Marco Solano; Juan Jijena; Laurent Brutus; Zulema Bustamante; Carine Truyens; Dominique Schneider; Faustino Torrico; Yves Carlier
This study aims to typify the Trypanosoma cruzi (sub)lineage(s) in umbilical cord blood of congenitally infected Bolivian newborns, using PCR amplifications of "Region Markers", mini-exon or kDNA fragments followed by hybridization or sequencing. New probes were also designed to distinguish three variants within the TcIId sublineage. The IIb, IId, or IIe T. cruzi sublineages, as well as different variants of the IId sublineage, were detected in infected neonates, whereas mixed infections were not found. The frequencies of the IId sublineage were similar in neonates (95.1%) and adults of the same area (94.1%). The IId-infected newborns displayed either asymptomatic, or severe and fatal clinical forms of congenital Chagas disease, as well as low or high parasitemia. Altogether these data show that T. cruzi DNA polymorphism, based on the presently available markers, is not associated with the occurrence of congenital infection or the development of severe clinical forms of congenital Chagas disease.
Congenital Transmission ofTrypanosoma cruziIs Associated with Maternal Enhanced Parasitemia and Decreased Production of Interferon‐γ in Response to Parasite Antigens
(Oxford University Press, 2004) Emmanuel Hermann; Carine Truyens; Cristina Alonso‐Vega; Patricia Rodríguez; Aurélie Berthe; Faustino Torrico; Yves Carlier
The conditions and mechanisms of congenital transmission of Trypanosoma cruzi remain largely unknown. In the present study, we compared the parasitic loads and the immune responses of pregnant T. cruzi-infected women who transmitted parasites to their fetus ("M+B+ mothers") with those of such women who did not transmit parasites to their fetus ("M+B- mothers"). M+B+ mothers had a higher frequency of positive results of hemoculture for T. cruzi than did M+B- mothers, in association with depressed production of parasite-specific interferon- gamma by blood cells that persisted after delivery. In contrast, the production of interleukin (IL)-2, IL-4, and IL-10 and transforming growth factor- beta 1 was similar between both groups of infected mothers, after stimulation with T. cruzi lysate. Flow cytometric analysis showed that T cells and monocytes of M+B+ mothers were less activated than were those of M+B- mothers. Altogether, these results indicate that congenital transmission of T. cruzi is associated with high parasitic loads and peripheral deficient immunological responses in mothers.
[Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia].
(National Institutes of Health, 2005) Faustino Torrico; Cristina Alonso‐Vega; Eduardo Suárez; Patricia Rodríguez; Mary‐Cruz Torrico; M. Dramaix; Carine Truyens; Yves Carlier
In Bolivia, the prevalence of infection by T. cruzi in women in fertile age can vary between 20 and 60%. The present study made in the Maternity Germin Urquidi of Cochabamba - Bolivia, it has demonstrated, that 19.9% of the mothers who go to this hospitable center to be taken care of in the childbirth, they are carrying of the infection and that 4,6% of them, they are going to transmit, by transplacentaria route, the infection to its babies. Of the 71 children born with congenital Chagas, only 47,8 % present/display some type of alteration or of development(Apgar to 1 minute low, BPN, prematuridad, pathological dismadurez) or signs (SDR, hepatomegalia, esplenomegalia, neurological signs, cardiomegalia, anasarca, petequias). When investigating the effect of the differences in the vectorial density (low, medium and high) of the zone of maternal residence, on the transmission of the infection of the mother infected to the fetus, we concluded that the rate of transmission of the congenital infection of T. cruzi is not modified by the level of endemicidad of the zone of maternal residence. By another infected new born sides whose mothers reside in zones of high endemicidad present/display, most frequently and of significant way, Apgar to 1 minute < to 7, low weight when being born and prematuridad or an association of these alterations with respiratory syndrome of distress or anasarca, when one compares them with new born of resident mothers in the zones of loss or medium endemicidad, mortality in this group is greater. These results suggest calls to account it of the mothers, in areas of high endemicidad, she is associate with a serious increase in the risk of Disease of newborn severe and mortal congenital Chagas in.
Estatus inmunológico de las madres infectadas por T. cruzi.
(Université Libre de Bruxelles, 2005) Cristina Alonso‐Vega; Emmanuel Hermann; Carine Truyens; Patricia Rodríguez; Mary Cruz Torrico; Faustino Torrico; Yves Carlier
The mechanisms of congenital transmission of Chagas disease remain largely unknown. To better understand the role of maternal immunology during pregnancy in congenital Chagas transmission, we studied the cytokine production and the parasitic load in three groups of mothers: infected mothers who transmitted the disease to their babies (M+B+-), infected mothers who did not transmit the disease to their babies (M+B-) and not infected mothers as a control group (M-B-). M+B+ mothers produced less IFNgamma and more IL-10 than the M+B- mothers, and they are not able to produce IL-2. M+B+ mothers showed a higher parasitic load. These results, indicated that the congenital Chagas transmission is associated with an immunological imbalance and a high parasitic load in the M+B+ mothers.
First external quality assurance program for bloodstream Real-Time PCR monitoring of treatment response in clinical trials of Chagas disease
(Public Library of Science, 2017) Juan Carlos Ramı́rez; Rudy Parrado; Elena Sulleiro; Anabelle de la Barra; Marcelo Rodríguez; Sandro Villarroel; Lucía Irazú; Cristina Alonso‐Vega; Fabiana Alves; María Á. Curto
Real-Time PCR (qPCR) testing is recommended as both a diagnostic and outcome measurement of etiological treatment in clinical practice and clinical trials of Chagas disease (CD), but no external quality assurance (EQA) program provides performance assessment of the assays in use. We implemented an EQA system to evaluate the performance of molecular biology laboratories involved in qPCR based follow-up in clinical trials of CD. An EQA program was devised for three clinical trials of CD: the E1224 (NCT01489228), a pro-drug of ravuconazole; the Sampling Study (NCT01678599), that used benznidazole, both conducted in Bolivia; and the CHAGASAZOL (NCT01162967), that tested posaconazole, conducted in Spain. Four proficiency testing panels containing negative controls and seronegative blood samples spiked with 1, 10 and 100 parasite equivalents (par. eq.)/mL of four Trypanosoma cruzi stocks, were sent from the Core Lab in Argentina to the participating laboratories located in Bolivia and Spain. Panels were analyzed simultaneously, blinded to sample allocation, at 4-month intervals. In addition, 302 random blood samples from both trials carried out in Bolivia were sent to Core Lab for retesting analysis. The analysis of proficiency testing panels gave 100% of accordance (within laboratory agreement) and concordance (between laboratory agreement) for all T. cruzi stocks at 100 par. eq./mL; whereas their values ranged from 71 to 100% and from 62 to 100% at 1 and 10 par. eq./mL, respectively, depending on the T. cruzi stock. The results obtained after twelve months of preparation confirmed the stability of blood samples in guanidine-EDTA buffer. No significant differences were found between qPCR results from Bolivian laboratory and Core Lab for retested clinical samples. This EQA program for qPCR analysis of CD patient samples may significantly contribute to ensuring the quality of laboratory data generated in clinical trials and molecular diagnostics laboratories of CD.
Human Congenital Infection With Trypanosoma cruzi Induces Phenotypic and Functional Modifications of Cord Blood NK Cells
(Springer Nature, 2006) Emmanuel Hermann; Cristina Alonso‐Vega; Aurélie Berthe; Carine Truyens; Amilcar Flores; Marisol Córdova; Lorenzo Moretta; Faustino Torrico; Véronique M. Braud; Yves Carlier
[Immunological status of mothers infected with Trypanosoma cruzi].
(National Institutes of Health, 2005) Cristina Alonso‐Vega; Emmanuel Hermann; Carine Truyens; Patricia Rodríguez; Mary Cruz Torrico; Faustino Torrico; Yves Carlier
The mechanisms of congenital transmission of Chagas disease remain largely unknown. To better understand the role of maternal immunology during pregnancy in congenital Chagas transmission, we studied the cytokine production and the parasitic load in three groups of mothers: infected mothers who transmitted the disease to their babies (M+B+-), infected mothers who did not transmit the disease to their babies (M+B-) and not infected mothers as a control group (M-B-). M+B+ mothers produced less IFNgamma and more IL-10 than the M+B- mothers, and they are not able to produce IL-2. M+B+ mothers showed a higher parasitic load. These results, indicated that the congenital Chagas transmission is associated with an immunological imbalance and a high parasitic load in the M+B+ mothers.
[Integral treatment of congenital Chagas disease: the Bolivian experience ].
(National Institutes of Health, 2005) Eduardo Suárez; Cristina Alonso‐Vega; Faustino Torrico; Marisol Córdova
We have analyzed the response to the treatment with benznidazol in newborns and nurslings in the Hospital Materno Infantil Germán Urquidi of Cochabamba, Bolivia, between 1999 and 2002. It is important an integral treatment of the nursling with a subsequent information directed to the family. The response was close to 100% when the treatment was correctly administrated. They were not adverse effects and the detected biochemical alterations did not present clinical significance.
Killer cell immunoglobulin‐like receptor expression induction on neonatal CD8+ T cells in vitro and following congenital infection with Trypanosoma cruzi
(Wiley, 2009) Emmanuel Hermann; Aurélie Berthe; Carine Truyens; Cristina Alonso‐Vega; Rudy Parrado; Faustino Torrico; Yves Carlier; Véronique M. Braud
Major histocompatibility complex (MHC) class I-specific inhibitory natural killer receptors (iNKRs) are expressed by subsets of T cells but the mechanisms inducing their expression are poorly understood, particularly for killer-cell immunoglobulin-like receptors (KIRs). The iNKRs are virtually absent from the surface of cord blood T cells but we found that KIR expression could be induced upon interleukin-2 stimulation in vitro. In addition, KIR expression was enhanced after treatment with 5-aza-2'-deoxycytidine, suggesting a role for DNA methylation. In vivo induction of KIR expression on cord blood T cells was also observed during a human congenital infection with Trypanosoma cruzi which triggers activation of fetal CD8(+) T cells. These KIR(+) T cells had an effector and effector/memory phenotype suggesting that KIR expression was consecutive to the antigenic stimulation; however, KIR was not preferentially found on parasite-specific CD8(+) T cells secreting interferon-gamma upon in vitro restimulation with live T. cruzi. These findings show that KIR expression is likely regulated by epigenetic mechanisms that occur during the maturation process of cord blood T cells. Our data provide a molecular basis for the appearance of KIRs on T cells with age and they have implications for T-cell homeostasis and the regulation of T-cell-mediated immune responses.
Lessons from community engagement to improve COVID-19 diagnosis and treatment in Cochabamba, Bolivia
(Taylor & Francis, 2024) Elizabeth Posada; Nilce Mendoza; Cristina Alonso‐Vega; Claire Billot; Beatriz Mallén Muñoz; Leonardo de la Torre; Adalid Paiva; Luís Villarroel; Regina Rabinovich
Through a stepped and multi-pronged approach, incorporating co-creation and community listening, the engagement could respond to emerging local challenges during the pandemic. The project created spaces for dialogue and opportunities for collaboration that strengthened links between the community and the health services.
Maternal Infection with Trypanosoma cruzi and Congenital Chagas Disease Induce a Trend to a Type 1 Polarization of Infant Immune Responses to Vaccines
(Public Library of Science, 2009) Nicolás Dauby; Cristina Alonso‐Vega; Eduardo Suárez; Amilcar Flores; Emmanuel Hermann; Marisol Córdova; Tatiana Tellez; Faustino Torrico; Carine Truyens; Yves Carlier
These results show that: i) both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period, and ii) the overcoming of immunological immaturity by T. cruzi infection in early life is not limited to the development of parasite-specific immune responses, but also tends to favour type 1 immune responses to vaccinal antigens.
MATERNAL TRYPANOSOMA CRUZI INFECTION, PREGNANCY OUTCOME, MORBIDITY, AND MORTALITY OF CONGENITALLY INFECTED AND NON-INFECTED NEWBORNS IN BOLIVIA
(American Society of Tropical Medicine and Hygiene, 2004) Faustino Torrico; Cristina Alonso‐Vega; Eduardo Suárez; Patricia J Rodriguez; Mary‐Cruz Torrico; Michèle Dramaix; Carine Truyens; Yves Carlier
This work compares the results of two epidemiologic and clinical surveys on the consequences of maternal chronic Trypanosoma cruzi infection. They were conducted in 1992-1994 and 1999-2001 in the same maternity clinic in Bolivia, a country highly endemic for infection with this parasite. In both surveys, the materno-fetal transmission of parasites occurred in 5-6% of the infected mothers. Maternal chronic T. cruzi infection had no effect on pregnancy outcome and health of newborns when there was no materno-fetal transmission of parasites. Comparisons between the older and the more recent surveys highlighted significant reductions in frequencies of symptomatic cases (from 54% to 45%), Apgar scores < 7, and low birth weights and prematurity (from 32-50% to 6-16%) among congenitally infected babies. Neonatal mortality related to congenital Chagas disease also decreased from 13% to 2% in the interval between both studies. These results suggest that the decrease in poverty that has occurred in Bolivia between both surveys might have contributed to reduce the morbidity and mortality, but not the transmission rate of T. cruzi congenital infection, which remains a serious public health problem in this country.
MaternalTrypanosoma cruziInfection Upregulates Capacity of Uninfected Neonate Cells To Produce Pro- and Anti-Inflammatory Cytokines
(American Society for Microbiology, 2000) Johan Vekemans; Carine Truyens; Faustino Torrico; Marco Solano; Mary‐Cruz Torrico; Patricia Rodríguez; Cristina Alonso‐Vega; Yves Carlier
The possibility of maternal in utero modulation of the innate and/or adaptive immune responses of uninfected newborns from Trypanosoma cruzi-infected mothers was investigated by studying the capacity of their whole blood cells to produce cytokines in response to T. cruzi lysate or lipopolysaccharide-plus-phytohemagglutinin (LPS-PHA) stimulation. Cells of such newborns occasionally released gamma interferon (IFN-gamma) and no interleukin-2 (IL-2) and IL-4 upon specific stimulation, while their mothers responded by the production of IFN-gamma, IL-2, and IL-4. Infection in mothers was also associated with a hyperactivation of maternal cells and also, strikingly, of cells of their uninfected neonates, since their release of proinflammatory (IL-1beta, IL-6, and tumor necrosis factor alpha [TNF-alpha]) as well as of anti-inflammatory (IL-10 and soluble TNF receptor) cytokines or factors was upregulated in the presence of LPS-PHA and/or parasite lysate. These results show that T. cruzi infection in mothers induces profound perturbations in the cytokine response of their uninfected neonates. Such maternal influence on neonatal innate immunity might contribute to limit the occurrence and severity of congenital infection.
Monocytes from Uninfected Neonates Born to Trypanosoma cruzi-Infected Mothers Display Upregulated Capacity to Produce TNF-α and to Control Infection in Association with Maternally Transferred Antibodies
(Multidisciplinary Digital Publishing Institute, 2023) Amilcar Flores; Cristina Alonso‐Vega; Emmanuel Hermann; Mary‐Cruz Torrico; Nair Alaide Montaño Villarroel; Faustino Torrico; Yves Carlier; Carine Truyens
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.
New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia
(BMJ, 2021) Cristina Alonso‐Vega; Julio A. Urbina; Sergi Sanz; María‐Jesús Pinazo; Jimy Pinto; Virginia Gonzalez; Gimena Rojas; Lourdes Ortiz; Wilson García; Daniel Lozano
NCT03981523.
New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial
(Elsevier BV, 2021) Faustino Torrico; Joaquím Gascón; Fabiana Barreira; Bethania Blum; Igor C. Almeida; Cristina Alonso‐Vega; Tayná Barboza; Graeme Bilbe; Erika Correia; Wilson García
For the Spanish translation of the abstract see Supplementary Materials section.
Real Time PCR for the Evaluation of Treatment Response in Clinical Trials of Adult Chronic Chagas Disease: Usefulness of Serial Blood Sampling and qPCR Replicates
(2018) Rudy Parrado; Ramírez Jc; Anabelle de la Barra; Cristina Alonso‐Vega; Natalia Juiz; Lourdes Ortiz; Daniel Illanes; Faustino Torrico; Joaquím Gascón; Fabiana Alves
Abstract This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real time PCR (qPCR) for baseline detection and quantification of parasitic loads and post-treatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely DNDi-CH-E1224-001 ( NCT01489228 ) and MSF-DNDi PCR sampling optimization study ( NCT01678599 ). Patients from Cochabamba (N= 294), Tarija (N = 257), and Aiquile (N= 220) were enrolled. Three serial blood samples were collected at each time-point, and qPCR triplicates were tested per sample. The first two samples were collected during the same day and the third one seven days later. A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pre-treatment sample positivity from 54.8 to 76.2%, 59.5 to 77.8%, and 73.5 to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively and increased cumulative detection of treatment failure from 72.9 to 91.7%, 77.8 to 88.9%, and 42.9 to 69.1% for E1224 low, short, and high dosage regimes, respectively; and from 4.6 to 15.9% and 9.5 to 32.1% for the benznidazole (BZN) arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasional non-detectable results. This serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials which require an initial positive qPCR result for patient admission.