B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Flow Mediated Dilation in Cirrhosis: A Pilot Study in Different Stages of the Disease.

INTRODUCTION: Cirrhosis is associated with changes in the cardiovascular system, where the circulatory dysfunction is compensated by the development of a hyperdynamic circulation. Endothelial function can be understood as the endothelium capability to release Nitric Oxide (NO) where an impairment in the normal development of this process constitutes a main step in the genesis and progression of atherosclerosis, a major cause of cardiovascular events. In recent years, non-invasive measurements have gained attention, due to the potential complications associated to invasive procedures. OBJECTIVE: To evaluate endothelial function (EF) in patients with cirrhosis, in different stages of the disease, complemented with hemodynamic measurements. METHODS: Individuals were divided in three age groups, according to the severity of their disease. EF was assessed by using the flow mediated dilation technique (FMD), jointly with noninvasive determination of cardiac output (CO), total peripheral resistance (TPR) and arterial compliance (AC). RESULTS: TPR showed a decrease in advanced severity while AC had an increase. Particularly, EF was found to be higher in CHC group, decreasing in CHB and more pronounceably in CHA. Concomitantly, an inverse behavior was observed regarding CO evolution. CONCLUSION: EF was noninvasively evaluated in cirrhosis, in terms of the progression of the disease. Hyperdynamic states in the more advanced condition were accompanied by a higher vascular reactivity, probably associated with higher peripheral NO release and increased AC.

Towards a paradigm shift in the treatment of chronic Chagas disease.

Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.

Prevención de la transmisión congénita de la enfermedad de Chagas / Prevention of congenital transmission of chagas disease

INTRODUCCIÓN La enfermedad de Chagas transmitida por vía congénita ha adquirido mayor importancia a partir del descenso de la infección por insecto/vector y es la principal forma de transmisión en países no endémicos. El tratamiento con benznidazol reduce significativamente las parasitemias, un factor importante ligado a la transmisión vertical. OBJETIVOS Evaluar si el tratamiento con benznidazol indicado a mujeres en edad fértil puede prevenir o reducir la incidencia de nuevos casos de Chagas congénito. MÉTODOS Se diseñó un estudio de cohorte histórico, que incluyó a todas las mujeres en edad fértil (15-45 años) asistidas en el Hospital Eva Perón, a partir de la información obtenida de la base de datos general del centro. Se incluyó a 67 madres con enfermedad de Chagas crónica, 156 binomios (madre-hijo), 114 hijos sin tratamiento previo y 42 previamente tratados con benznidazol. RESULTADOS Ocho madres gestaron 16 hijos con Chagas congénito (8/67, 12%). La prevalencia de Chagas congénito fue de 16/114 (14%) en binomios no tratados frente a 0/42 (0%) en binomios tratados, p=0,01. No se observaron diferencias significativas en las variables clínicas, serológicas, epidemiológicas y socioeconómicas entre madres con o sin hijos nacidos con Chagas congénito. La tasa de seroconversión negativa de las 67 madres tratadas en el seguimiento alejado fue del 30%. DISCUSIÓN El presente estudio confirma que es posible prevenir la enfermedad de Chagas congénita mediante el tratamiento antiparasitario previo de las mujeres en edad fértil.

Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study.

OBJECTIVES: Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. PATIENTS AND METHODS: Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. RESULTS: The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. CONCLUSIONS: This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease.

Seronegative conversion after incomplete benznidazole treatment in chronic Chagas disease.

In 12-18% of adult patients, treatment with benznidazole for chronic Chagas disease has to be discontinued because of side-effects. We identified and analysed a cohort of 81 adult patients with three positive tests for Trypanosoma cruzi infection and serological monitoring following incomplete treatment with benznidazole for a median of 10 days. Twenty percent of these patients (16/81) met the criteria of cure, showing that the optimal schedule of benznidazole administration remains to be determined.

Is manual dexterity essential in the selection of dental students?

OBJECTIVE: The purpose of this study was to determine whether basic manual dexterity (BMD) could be an important parameter in selecting students for the Degree in Dentistry (CLOPD) and to assess whether initial manual dexterity in students admitted to the CLOPD can improve with training in pre-clinical and clinical practice. DESIGN: Observational study. SETTING: The study was carried out at the Catholic University of Rome, in five consecutive academic years. SUBJECTS AND METHODS: Four hundred and thirty-three subjects (262 males and 171 females) were tested (10 different exercises) in five consecutive years. Two retests were performed after three and five years respectively from the beginning of the experimentation. MAIN OUTCOME MEASURES: The scores of individual exercises were averaged for each candidate, assessing the mean value of basic manual dexterity score (BMDS). RESULTS: It was possible to observe some differences among candidates coming from different types of high schools, since those having a prior university degree or a scientific high school degree proved better than those with classical or vocational high school qualifications (p < 0.05). A statistically significant improvement of BMDS has been observed in students who attended the CLOPD for at least 32 months. CONCLUSIONS: Data obtained revealed that basic manual dexterity is not essential in the selection of dental students. Students who could follow training significantly improved in their manual ability.

Value of echocardiography for diagnosis and prognosis of chronic Chagas disease cardiomyopathy without heart failure.

OBJECTIVES: To establish the usefulness of echocardiography for the clinical classification of patients with Chagas disease and to determine the predictors of mortality and clinical events. METHODS: 849 patients with chronic Chagas disease with a mean follow up of 9.9 years were studied. On admission, ECG, chest radiograph, and two dimensional echocardiogram were obtained from all patients. Clinical events were defined as new ECG abnormalities, change in clinical status resulting in transfer to another group, and death. Morphologically characterised segmental lesions were also seen in 12 patients on a second harmonic echocardiogram with intravenous contrast agent. Univariate and multivariate analysis for clinical events and mortality were performed. SETTING: Community of San Martín, Buenos Aires, Argentina. RESULTS: Change in clinical group (68 of 833 survivors v 15 of 16 who died, p < 0.001), left ventricular systolic dimension (mean (SD) 3.06 (0.72) cm v 4.71 (0.90) cm, p < 0.0001), and ejection fraction (mean (SD) 0.67 (0.11)% v 0.42 (0.17)%, p < 0.0001) were found to be the only predictors of mortality. ECG abnormalities related to the disease (in 220 of 699 patients with no clinical event v 98 of 150 patients with a clinical event, p < 0.0001), left ventricular diastolic dimension (mean (SD) 4.88 (0.54) cm v 5.44 (0.83) cm, p < 0.0001), left ventricular systolic dimension (mean (SD) 2.98 (0.62) cm v 3.64 (1.03) cm, p < 0.0001), and ejection fraction (mean (SD) 0.68 (0.10)% v 0.60 (0.16)%, p < 0.0001) were predictors of clinical events. Segmental lesions were observed in 211 of 849 patients (25%). Segmental lesions were seen in 66 (13%) and systolic dysfunction was seen in four of 505 (0.8%) patients with normal ECG. Significant differences were found between the groups of patients (group 0: reactive serology and normal ECG and chest radiography without cardiac enlargement and no signs of heart failure; group 1: reactive serology and abnormal ECG and chest radiography without cardiac enlargement; group 2: reactive serology and abnormal ECG and chest radiography with cardiac enlargement and no signs of heart failure). CONCLUSION: Echocardiography was useful both to characterise and to determine the prognosis of patients with chronic Chagas disease without heart failure.

[Structure of dental services in a social security system: Córdoba, Argentina]. / Estructura de las prestaciones odontológicas en un efector del sistema de la seguridad social: Córdoba, Argentina.

We describe here the results of a survey carried out to determine the nature, extent and distribution of the dental service provided by the Board of the University Personnel Social Assistance (Dirección de Asistencia Social del Personal Universitario [DASPU] From 1988 to 1990. Such survey was performed on the bases of a representative sample of assistance recipients. The greatest dental service demand was registered among the group of persons of 25-44 years-old (40.3% of the total), although the rendered services per person/years increased with the member's ages. Restorative Dental and Prosthesis registered the highest occurrence (50.2% of the total). Preventive Odontology practices were infrequent (1.2%) while Odontopediatric was the less demanded (0.3%). 31.8% of the assistance was provided by DASPU own services, Prothesis being the most predominant kind. As for external effectors (62.3%), the most frequent were those of Dental Operating. It is concluded that the demanded dental services were mainly curative and reparative. The reorganization of the Odontology Service may increase the system' performance efficiency and effectiveness.

Treatment of chronic Chagas' disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up.

Prescribing etiologic treatment for chronic Chagas' disease is highly controversial because of the difficulties involved in assessing its therapeutic efficacy--the low degree of parasitemia, the persistence of positive immunologic reactions, the lack of clinical findings to support each type of treatment, and the necessarily prolonged follow-up of the patient. An 8-year average follow-up was performed on 131 patients treated with benznidazole (5 mg/kg/day for 30 days) (TP) and 70 untreated patients (UTP) by serial electrocardiograms and analysis of the cardiomyopathic progress of the clinical groups, and by immunologic tests at both the beginning and end of the study. TPs presented less electrocardiographic changes during the follow-up period (4.2% vs 30%) and a lower frequency of deterioration in their clinical condition (2.1% vs 17%). The percentage of TPs who were serologically negative was 19.1% whereas 6% of the UTPs became serologically negative, a result that correlated with a lack of progress in the cardiomyopathy. Benznidazole treatment significantly decreased serologic titers, signifying parasitologic cure in two patients.

Estructura de las prestaciones odontológicas en un efector del sistema de la seguridad social: Córdoba, Argentina. / [Structure of dental services in a social security system: Córdoba, Argentina]

We describe here the results of a survey carried out to determine the nature, extent and distribution of the dental service provided by the Board of the University Personnel Social Assistance (Dirección de Asistencia Social del Personal Universitario [DASPU] From 1988 to 1990. Such survey was performed on the bases of a representative sample of assistance recipients. The greatest dental service demand was registered among the group of persons of 25-44 years-old (40.3

of the total), although the rendered services per person/years increased with the members ages. Restorative Dental and Prosthesis registered the highest occurrence (50.2

of the total). Preventive Odontology practices were infrequent (1.2

) while Odontopediatric was the less demanded (0.3

). 31.8

of the assistance was provided by DASPU own services, Prothesis being the most predominant kind. As for external effectors (62.3

), the most frequent were those of Dental Operating. It is concluded that the demanded dental services were mainly curative and reparative. The reorganization of the Odontology Service may increase the system performance efficiency and effectiveness.