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E L Segura

Publications and source records attributed to E L Segura.

At least 19 recordsLinked to original sources

alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation.

We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease.

Adult↗

Molecular and biologic characterization of Leishmania parasites implicated in an epidemic outbreak in northwestern Argentina.

Leishmania (Viannia) braziliensis and its variants were implicated in the epidemic outbreak of mucocutaneous leishmaniasis that occurred in Salta, northwestern Argentina, in 1985. A total of 24 suspected, untreated cases were evaluated clinically and parasitologically. Four of five stable isolates were consistent with the reference strain of L. (V.) braziliensis as determined by monoclonal antibodies and indirect immunofluorescence or radioimmunobinding assays. Zymodeme analysis in agarose gels showed a close relationship with L. (V.) guyanensis and L. (V.) panamensis. All zymograms obtained with polyacrylamide gels belonged to the subgenus Viannia; the patterns were different from, but very closely related to, the reference strains of L. (V.) braziliensis as determined by dendrogram analysis. Hamsters infected with two isolates showed a pattern consistent with L. (V.) braziliensis. The pattern of development in the gut of Lutzomyia longipalpis was consistent with members of Viannia.

Adult↗

Congenital transmission of Trypanosoma cruzi: an operational outline for detecting and treating infected infants in north-western Argentina.

We designed a set of procedures for first-line local health services to detect and treat the congenital transmission of Trypanosoma cruzi at a province-wide scale, and field-tested the programme in the province of Tucumán, northwestern Argentina, from 1992 to 1994. The programme consists of routine screening of pregnant women for seroreactivity to T. cruzi, serological and parasitological follow-up of the newborn at least twice during the first year of age, treatment of the infected infants, and evaluation of the outcome. 927 (5.5%) of 16 842 pregnant women were seroreactive to T. cruzi by indirect haemagglutination assay and ELISA. Twenty-one (6.7%) of 315 newborns to seroreactive mothers were diagnosed as infected with T. cruzi parasites microhaematocrit concentration before 30 days of age. Five newborns who initially tested negative had a T. cruzi infection detected by microhaematocrit and/or serological techniques at 3 or 6 months of age. Thus, congenital infection was diagnosed in 26 (7.1%) infants born to seroreactive women and residing in houses free of triatomine bugs. Four of 6 infants born to seroreactive mothers died during the first year of age and had some evidence of T. cruzi infection; one of the deaths was attributed to T. cruzi based on clinical evidence. After specific treatment with nifurtimox or benznidazole, 30 of 32 infants remained parasitologically and serologically negative. This study shows the feasibility of controlling the incidence of congenitally acquired T. cruzi infections at a province-wide scale by means of a specific screening programme at first-line health services level.

Adult↗

Transfusion-transmitted infectious diseases in Argentina, 1995 through 1997.

BACKGROUND: Assessment of the safety of the blood supply, the quality of screening procedures, and the risk of transfusion transmission of infectious diseases in any country can be estimated by reviewing the records of blood donations and screening procedures and the prevalence of serologic markers of infectious diseases. STUDY DESIGN AND METHODS: Information on blood donors, particularly the number of screened donors, and on the prevalence of serologic markers of infectious diseases was available from Argentina for 1995 through 1997. This information permitted the estimation of the risks and costs of preventing transfusion transmission of infectious diseases within the country during this period. RESULTS: Screening coverage was higher in the private sector. The proportion of donors screened for HIV increased from 84.52 percent in 1995 to 97.97 percent in 1997; in the same period, serologic screening for HbsAg increased from 83.71 percent to 98.48 percent; that for HCV from 69. 92 percent to 97.83 percent; and that for syphilis from 87.94 percent to 98.71 percent. One hundred percent of donors were screened for Trypanosoma cruzi throughout the period. The overall prevalence of HIV per year varied from 2.42 to 3.36 per 1,000 donors; that of HBV, from 5.80 to 9.76 per 1,000; of HCV, from 7.39 to 16.61 per 1,000; and of syphilis, from 5.25 to 7.65 per 1,000. The overall prevalence of antibodies to T. cruzi ranged from 36.53 to 49.20 per 1,000 donors. The overall index of the spread of infectious viral disease through blood transfusion decreased from 47. 74 per 10,000 donations in 1995 to 4.75 per 10,000 in 1997. The ratio of acquired infections to donations improved from 1:209 to 1:2, 102 during the same period. The risk of T. cruzi infection from 1995 through 1997 was, in theory, nil, given the 100-percent screening. The greatest threat to the quality of the blood supply throughout the period studied was HCV. CONCLUSION: The status of the blood supply in Argentina improved steadily from 1995 to 1997, as shown by the increase in screening coverage.

Animals↗

Development and evaluation of a solid-phase enzyme immunoassay based on Andes hantavirus recombinant nucleoprotein.

Hantavirus pulmonary syndrome (HPS) with high mortality rate has been reported in five countries in South America. Rapid accurate methods are important both for monitoring acute infections and for epidemiological studies. The Andes virus nucleoprotein amino acid sequence has a high identity percentage compared with other sequences of this region and has been chosen for the development of diagnostic reagents. Andes nucleoprotein expressed in Escherichia coli was applied as antigen in IgG, IgA and mu-capture IgM enzyme-linked inmunosorbent assays (ELISAs). An evaluation of this reagent was conducted to establish its usefulness for differential diagnosis of HPS and seroprevalence studies. Samples from 135 reverse transcription (RT)-PCR-confirmed HPS cases, 77 individuals with other respiratory infections and 957 healthy inhabitants from endemic and non-endemic areas were analysed. The hantavirus-infected patients had an early and strong IgM, IgG and IgA serum antibody response, in most of the cases as early as 1, 7 and 1 days following onset of symptoms, respectively. IgM and IgG detection showed a specificity and sensitivity of 100%. Andes-specific IgM antibodies were found in all patients in the first available sample, which remained detectable for at least 43 days. Specific IgA antibodies were also detected in saliva of patients with acute HPS. The short duration of the disease and the risk for contacts due to person-to-person transmission of Andes virus necessitate the use of highly sensitive tests which might lead to earlier detection of infected people and improve the treatment and management of patients with HPS.

Adult↗

Long-term effects of a nationwide control program on the seropositivity for Trypanosoma cruzi infection in young men from Argentina.

Unselected nationwide cohorts of Argentine men 18 years of age summoned for military service were tested for antibodies to Trypanosoma cruzi each year from 1981 to 1993. After an initial screening using indirect hemagglutination test, the positive sera were retested by titrated indirect hemagglutination and immunofluorescence antibody tests at 39 laboratories or at the national reference center in Buenos Aires. Nearly 1.8 million men were examined for T. cruzi antibodies using the same standardized procedures under a quality assurance program. The prevalence of seropositivity for T. cruzi decreased significantly from 5.8% in 1981 to 1.9% in 1993, but the decrease was not homogeneous among provinces within each region or constant over time. Prior to the nationwide control campaign initiated in 1961-1962, 15 provinces had high (> 20%) percentages of houses with domiciliary infestation by Triatoma infestans bugs, which decreased to nine provinces in 1982, and four provinces in 1992. The observed decrease in the prevalence of seropositivity for T. cruzi may be mostly attributed to the spraying with insecticides to eliminate the domiciliary populations of Triatoma infestans. The lack of a sustainable triatomine surveillance program set a limit to the decrease of seropositivity rates and prompted a revised strategy based on community participation.

Adolescent↗

The cytostome of Trypanosoma cruzi epimastigotes is associated with the flagellar complex.

Okuda, K., Esteva, M., Segura, E. L., and Bijovsky, A. T. 1999. The cytostome of Trypanosoma cruzi epimastigotes is associated with the flagellar complex. Experimental Parasitology 92, 223-231. Proliferative forms of Trypanosoma cruzi, amastigotes and epimastigotes, have a cytostome, a specialized structure formed by an invagination of the flagellar pocket's membrane surrounded by microtubules and frequently followed by a row of vesicles. All this assemblage penetrates deeply into the cytoplasm overpassing the nucleus. This structure, together with the flagellar pocket, appears to play an important role in the nutrition of the parasite. We demonstrated that the monoclonal antibody 2C4, made-up against isolated flagellar complex of T. cruzi epimastigotes, recognizes a protein doublet of 76 and 87 kDa in total epimastigotes homogenate. The 76-kDa polypeptide is enriched in the detergent-soluble fraction whereas the 87-kDa polypeptide is highly represented in the insoluble fractions and the purified flagella. Immuno-fluorescence assays show the antigen as a small spot at the flagellar pocket region. Immunogold labeling of ultrathin sections of epimastigote forms reveals gold particles at the opening of flagellar pocket, concentrated in the cytostome region. Immunocytochemistry of epimastigote whole-mount cytoskeletons reveals the labeling on an array of three to four microtubules that appears attached to flagellum, running in the direction of the nucleus. Ultrastructural observations have shown that the posterior region of isolated flagella, corresponding to the level of the flagellar pocket, possesses a microtubular structure compatible with that from the cytostome. The relationship between the cytostome, an endocytic organelle, and the flagellum is here described for the first time.

Animals↗

Soluble platelet selectin (sP-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease during therapy with benznidazole in children with indeterminate form of Chagas' disease.

The immune response against Trypanosoma cruzi infection has been associated with both protection and pathogenesis. Central events in host defence system- and immune-mediated damage are tightly regulated by cell adhesion molecules (CAM). Levels of sP-selectin and sVCAM-1 were measured in sera from 41 children with the indeterminate phase of Chagas' disease. Simultaneously, levels of soluble adhesion molecule were also quantified in Chagas' disease children undergoing specific chemotherapy with benznidazole. Levels of sP-selectin and sVCAM-1 were found to be elevated in children with indeterminate Chagas' disease before aetiologic therapy was started. However, a small group of patients showed sP-selectin and sVCAM-1 levels comparable to those of non-infected children. A positive correlation between levels of sVCAM-1 and sP-selectin in sera from Chagas' disease patients was found. There was a significantly greater decrease in the titres of sP-selectin and sVCAM-1 in those children receiving benznidazole therapy compared with those children receiving placebo. Measurement of soluble adhesion molecules revealed differences in the activation of the immune system in children with the indeterminate form of Chagas' disease. The early decrease of sP-selectin and sVCAM-1 levels after anti-parasitic treatment suggests that these molecules might be valuable indicators of effective parasitologic clearance.

Chagas Disease↗

Chagas' disease in patients with kidney transplants: 7 years of experience 1989-1996.

Chagas' disease was present in 17.22% of persons undergoing kidney transplantation in an Argentine Hospital. The criterion for attributing reactivation of chronic Chagas' disease and transmission of Trypanosoma cruzi to grafts was detection of parasites in blood (patent parasitemia) or tissues. Reactivation was diagnosed in 5 (21.7%) of 23 recipients. Ten (43.4%) of 23 chagasic recipients without reactivation of chronic Chagas' disease had abrogation of serological reactivity. T. cruzi infection was transmitted to 3 (18.7%) of 16 non-chagasic recipients. Reactivation and infection were diagnosed by patent parasitemia or cutaneous panniculitis. For diagnosis, detection of parasites in blood and tissues had more relevance than serology. Sequential monitoring detected early reactivation and infection, permitting application of preemptive or therapeutic therapy with benznidazole, thus inhibiting, in all patients, severe clinical disease produced by a progressive and systemic replication of the parasite.

Adolescent↗

Identification of immunodominant antigens in Mexican strains of Trypanosoma cruzi.

Chagas disease represents an important public health problem. In Mexico most studies have been performed using Trypanosoma cruzi' antigens extracted from strains of other geographical origins. This work was aimed at developing a reactive antigen to perform serological diagnosis of Chagas' disease, using Mexican T. cruzi strains. We prepared antigenic extracts from epimastigotes, trypomastigotes and sphaeromastigotes of three Mexican strains. Parasites homogenate was obtained by lysis and sonication, solubilized proteins were analyzed by SDS-PAGE, Western-blot assays, and ELISA to determine the reactivity against sera from chagasic reference serum and chagasic and leishmaniasic patients and healthy donors. Western Blot profiles revealed, with the reference serum, eleven main components between 212 to 25 kDa; however, five bands corresponding to 74, 44, 31, 25 and 18 kDa antigens were recognized by the T. cruzi reactive sera from Mexican chagasic patients, which did not cross-react with Leishmania mexicana. Antigens from the Tequesquitengo strain yielded the best reactivity in the enzymatic immunoassay, thus enabling us to propose their use for serodiagnoses of Chagas' disease in Mexico.

Animals↗

[Control of the transmission of Trypanosoma cruzi in Argentina 1999].

Approximately 2 million people in Argentina are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease, thereby constituting the major tropical disease in the country. As in other six Southern Cone countries, Triatoma infestans is the only or major vector of T. cruzi among human and domestic animals. In Argentina, a vertically structured National Chagas Control Program was established in 1962. Such a program pursued the elimination of domestic and peri-domestic populations of T. infestans through insecticidal spraying, and the serological control of blood donors to prevent transfusion-related infections. This program strongly reduced the nation-wide serological prevalence of T. cruzi in the population. For example, in 18 or 20 year-old men drafted into military service, the seroprevalence decreased from 10.1% in 1964 for those who had been born in 1944 to 1.9% in 1993 for those born in 1975. However, the vertical strategy failed to reach and sustain the surveillance phase in widespread rural areas with disperse populations due to its intrinsic limitations and the reduced priority level assigned to rural health programs. An alternative, horizontally-structured control strategy of T. infestans was developed and assayed in the Province of Santiago del Estero between 1985-1989, and 1991-1992. The projects demonstrated that insecticidal spraying carried out with community participation combined effectiveness and commitment in such a way as to produce a strong impact on house reinfestation and the extension of the area under entomological surveillance. This experience has been transferred in a chain of responsibilities to the personnel of the National Chagas Control Program, using participating workshops, procedural guidelines, and practical training. This personnel transferred the strategy using similar methods to the field health care agents and volunteers chosen by their own communities (community leaders). After the workshops, the leaders received all the materials needed to install and develop the ongoing surveillance activities: third generation pyrethroid insecticides, manuals, hand-operated sprayers, and sensor boxes to detect domiciliary infestations. From 1993 to 1998, a total of 15,000 health care agents or community leaders were trained. A total of 675,000 houses were sprayed with residual insecticides in the attack phase, and 850,000 houses entered the surveillance phase. This is the first time that such large coverage has been accomplished in Argentina. The network of laboratories installed a quality assurance program to current serological procedures applied to blood donors, organ transplant, and the detection and treatment of newborns to women sero-reactive for T. cruzi in Argentina. We expect to interrupt the vector-mediated transmission of T. cruzi in the next 18 months, but the sustainability of such a program depends on, at least, additional work with the community to achieve a change of attitudes and practices related to house infestation for the next 10 years. A social effort will be needed to cover those expenses, but the expected economic returns exceed largely the cost of any such program, as suggested by cost-benefit studies. To illustrate, the annual treatment costs of one Chagas patient can help maintain 25 households free from triatomine bugs in Argentina.

Adult↗

[Control of congenital transmission of Trypanosoma cruzi in Argentina].

The vertical transmission of Trypanosoma cruzi has been augmenting its relative importance as vector and transfusion-mediated transmission routes have been, and continue to be, increasingly controlled. The vertical transmission of T. cruzi cannot be prevented; but early detection and treatment of congenital infection achieve cure rates close to 100%. In Argentina, the Subprogram of Control of Pregnant Women examined 58,196 women from 13 provinces in 1997 and found a 9% seropositivity to T. cruzi. In spite of such high maternal prevalence rates of T. cruzi, only a small proportion of live newborns to infected mothers acquires the infection. The probability of vertical transmission was 1.9% (range: 0.1% to 3.5%) in surveys carried out in the '70s, and 2.5% (range: 0.7% to 10.4%) in others conducted in the '70-'80s. Other more recent studies in Argentina estimated the probability of transmission in 2.6%-6.7%, but studies from Paraguay estimated 10.5% by PCR or serodiagnosis. The microhematocrit technique is the recommended parasitologic method to detect congenital infection. Routine serodiagnosis that detects IgG against T. cruzi is only helpful after the newborn reaches 6 months of age. Detection of specific IgM using recombinant antigens and PCR constitute excellent alternatives, but their feasibility from operational and cost-effective viewpoints in affected endemic areas remains to be considered. In a longitudinal project carried out in Maternidad Nuestra Señora de la Merced in the city of Tucumán between 1992-1994, the majority of congenital cases were asymptomatic. They were diagnosed through the microhematocrit technique, but a number of cases could only be detected later as a result of the parasitological and/or serological follow-up. Of a total of 32 newborns infected with T. cruzi who were treated with nifurtimox or benznidazole, 30 had a negative microhematocrit and serodiagnosis between 6 months and 2 years post-treatment. The magnitude of congenital transmission, and its associated morbidity and mortalidad, largely justify the efforts needed to detect T. cruzi infection in the mothers and newborns. This project demonstrated that the transmission of T. cruzi can be successfully controlled at a provincial scale through a specific program inserted in the primary health care system or at the first level of attention. The congenital transmission of T. cruzi clearly represents a public health problem in areas that in the past were of active transmission, even years after being under entomologic surveillance.

Argentina↗

[Treatment of Trypanosoma cruzi infection in the indeterminate phase: experience and current guidelines in Argentina].

An effective treatment for Trypanosoma cruzi infection has been investigated, since the 30s. The goals of the specific treatment against T. cruzi infection are, at the individual level, to eliminate the parasite, and to reduce the probability of developing Chagas disease. At the end of the 60s and at the beginning of the 70s, two compounds were clinically investigated in Argentina: Nifurtimox and Benznidazole. After the approval by the Ministry of Health, in 1983 the first guidelines for the treatment of T. cruzi infection were proposed and approved. These guidelines recommended the treatment of cases in the acute phase. Due to the publication of new information in support of the utility of these drugs for treating cases in the indeterminate phase of Chagas disease, in 1997 the original guidelines were revised and new procedures were approved. At present, the treatment is recommended for: 1) all patients undergoing the acute phase; 2) children and young people undergoing the indeterminate phase; 3) adult patients undergoing the indeterminate phase or with incipient heart lesions; 4) laboratory accidents and during surgery, and 5) organ transplant recipients or donors. The general clinical laboratory control is needed for the intra-treatment monitoring of the patient. Titration of specific antibodies with monospecific antigens has been shown to be an adequate marker of therapeutic efficacy.

Adult↗

Quality assurance of the serologic diagnosis of Chagas' disease.

A quality assurance program of the Chagas' disease laboratory network of Argentina has been conducted by the National Reference Center since 1988, with the aim of assessing the reliability of serologic test results. Chagas' disease is endemic in Argentina, but the prevalence of seropositivity for Trypanosoma cruzi among 18- to 20-year-old men decreased from 5.8% in 1981 to 1.8% in 1994. About 600 laboratories form the Chagas' disease laboratory network, with main central laboratories in each of the 24 provinces in Argentina. The quality assurance program promotes regular use of good laboratory practice and internal and external quality control to improve performance of the participants; it also provides technical assistance and guidelines. Eventual corrective measures are discussed in workshops. Results of the first external evaluation by proficiency testing of serum panels and confirmation of results for 58 of the main laboratories reveal that from 1988 to 1994 the rate of agreement has increased.

Adolescent↗

Influence of humans and domestic animals on the household prevalence of Trypanosoma cruzi in Triatoma infestans populations in northwest Argentina.

In three rural villages of northwest Argentina, the overall proportion of domiciliary Triatoma infestans infected with Trypanosoma cruzi was 49% among 1,316 bugs individually examined for infection in March and October 1992). Most of the variation among individual households in the proportion of infected triatomines was explained by variations among houses in the proportion of bugs that fed on dogs or cats, the prevalence of infected dogs or cats, and the proportion of bugs that fed on humans, according to a logistic multiple regression analysis. The effects of human infection rates on bug infection rates were not statistically significant. After adjusting for the effects of other predictors, the presence of chickens in bedroom areas had negative and significant effects on the proportion of infected Triatoma infestans, and positive and significant effects on the number of T. cruzi-infected triatomines collected per person-hr per house. Dog or cat infection rates and the proportion of bugs that fed on dogs or cats and on chickens explained 80% of the total variance of infected-bug numbers in a linear multiple regression model. This is the first study to use detailed field data to show that variations in triatomine infection rates depend on bug host feeding patterns and dog or cat infection rates, while the presence of chickens in bedroom areas exerts opposite effects on the proportion and number of infected triatomines. Domestic animals play a crucial role in the domiciliary transmission of T. cruzi.

Animals↗

Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease.

A double-blind, randomized, clinical field trial was designed to test the efficacy and tolerance of a specific drug treatment in children in the indeterminate phase of infection by Trypanosoma cruzi. Children were treated with benznidazole at a dose of 5 mg/kg/day for 60 days or placebo and followed-up for 48 months. The treated children showed a significant decrease in geometric mean titers of antibodies against T. cruzi measured by indirect hemagglutination, indirect immunofluorescence, and ELISA. After a four year follow-up, 62% of the benznidazole-treated children and no placebo-treated child were seronegative for T. cruzi when tested by an ELISA using a T. cruzi flagellar calcium-binding protein (F29). Xenodiagnosis carried out after 48 months of follow-up was positive in 4.7% of the benznidazole-treated children and in 51.2% of the placebo-treated children. These results show the tolerance to and efficacy of benznidazole against T. cruzi in seropositive children six to 12 years of age. We used an early serologic marker of cure after treatment, consisting of a recombinant antigen implemented in a rapid, conventional serologic procedure.

Chagas Disease↗

Household prevalence of seropositivity for Trypanosoma cruzi in three rural villages in northwest Argentina: environmental, demographic, and entomologic associations.

Environmental, demographic, and entomologic variables were analyzed by logistic multiple regression analysis for their association with the likelihood of being seropositive for Trypanosoma cruzi in three highly infested rural villages of northwest Argentina. The prevalence of seropositivity for T. cruzi, as determined by the composite results of three serologic tests, was 34% among 338 persons in 1992. The strongest positive predictors of the adjusted odds of being infected were the household number of dogs, the density of T. cruzi-infected Triatoma infestans in bedroom areas, and each person's age. Dwellers from houses with roofs made completely or partly with a grass called simbol, or which used insecticides rudimentarily and nonsystematically, had a significantly lower odds of being seropositive for T. cruzi than residents from other types of dwellings. The adjusted odds of infection also increased with the number of T. cruzi-infected dogs or cats and the presence of chickens in bedroom areas. No significant effects on the adjusted odds of infection of a community-wide deltamethrin spraying carried out in one of the villages seven years before were detected. Socioeconomic indicators, such as domiciliary area, and numbers of corrals and livestock, were inversely related to being infected. Our study identified several manageable variables suitable for control actions, most of them not examined before in univariate or multivariate analyses. Environmental management based on low-cost housing with appropriate local materials and removal of domestic animals from domiciliary areas have a crucial role to play in the control of Chagas' disease in rural areas.

Adolescent↗