An international study was performed by 26 experienced PCR laboratories from 14 countries to asse... more An international study was performed by 26 experienced PCR laboratories from 14 countries to assess the performance of duplex quantitative real-time PCR (qPCR) strategies on the basis of TaqMan probes for detection and quantification of parasitic loads in peripheral blood samples from Chagas disease patients. Two methods were studied: Satellite DNA (SatDNA) qPCR and kinetoplastid DNA (kDNA) qPCR. Both methods included an internal amplification control. Reportable range, analytical sensitivity, limits of detection and quantification, and precision were estimated according to international guidelines. In addition, inclusivity and exclusivity were estimated with DNA from stocks representing the different Trypanosoma cruzi discrete typing units and Trypanosoma rangeli and Leishmania spp. Both methods were challenged against 156 blood samples provided by the participant laboratories, including samples from acute and chronic patients with varied clinical findings, infected by oral route or vectorial transmission. kDNA qPCR showed better analytical sensitivity than SatDNA qPCR with limits of detection
Efficient drugs against Chagas' disease must have an effect on the amastigote forms or intrac... more Efficient drugs against Chagas' disease must have an effect on the amastigote forms or intracellular reproduction elements of Trypanosoma cruzi (T. cruzi). Trypomastigote and epimastigote forms derive from the former and their response to medications is less marked. The only drugs used in humans are nifurtimox (NF) and benznidazole (BNZ). Other useful medications are allopurinol and itraconazole. NF acts producing free radicals and BNZ inhibits the synthesis of macromolecules. There is consensus that Chagas' disease must be treated in all its periods, since T.cruzi DNA is detected by polymerase chain reaction in chronic cases, even when microscopy is negative. The pharmacological treatment modifies the natural evolution of the disease. It also helps to solve a public health problem, considering that there is a high number of subjects with Chagas' disease. Subjects with chronic chagasic cardiomyopathy with terminal heart failure are the only cases without indication for t...
The American journal of tropical medicine and hygiene
Fecal samples were obtained from 722 of 820 children attending 7 nursery schools and 1 primary sc... more Fecal samples were obtained from 722 of 820 children attending 7 nursery schools and 1 primary school in the city of Santiago, Chile. Microscopy of formol-ether concentrates showed that 33% of the children were infected with Giardia lamblia. Prevalences among primary school students (5-10 years of age) of G. lamblia (38%), Endolimax nana (43%), and Entamoeba coli (25%) were overall higher than among nursery school students (3 months-5 years of age; prevalences 29%, 21%, and 16%, respectively). There was no apparent association between socio-economic intake and levels of G. lamblia infection: the private nursery school had the highest recorded level of infection (40%). One hundred sixty-two triplicate stool specimens were used to compare microscopy with an enzyme-linked immunosorbent assay (ELISA) for the detection of Giardia fecal antigens. The ELISA was highly sensitive and specific either visually (95% and 97%, respectively) or by optical density determination (99% and 96%, respec...
The aim of this study was to assess the efficacy of Chagas disease vector control in Chile, using... more The aim of this study was to assess the efficacy of Chagas disease vector control in Chile, using human disease as an index. After a twelve years control program using insecticides, dwelling infection in the IV region fell from 49 to 4%. In Combarbalá (a community of the IV region) the infection rate, detected by indirect hemagglutination, immunofluorescence and ELISA tests, decreased from 21.8% in 1986 to 8.2% in 1992 in primary school students (p < 0.001) and from 7.5 to 5% in high school students. Besides the vector control program, no other important epidemiological changes occurred in this period, excepting some ecological changes.
Between January 1986 and December 1990 the prevalence of F. hepatica infection was studied in 586... more Between January 1986 and December 1990 the prevalence of F. hepatica infection was studied in 5861 rural inhabitants of the provinces of Curico, Talca and Linares, VII Region, an hyperendemic zone of animal fascioliasis. Every one was screened by intradermal (IDR), complement fixation (CF), double diffusion (DD) counterelectrophoresis (CIEF), immunoelectrophoresis (IEP) and enzyme-linked immunoabsorbent assay (ELISA) tests. 366/1881 (9.3%) had positive IDR; 61 (1.04%) positive CF; 14 (0.24%) positive DD and 105/3838 (2.73%) positive ELISA and thus considered under suspicion to be infected. F. hepatica eggs were searched in stool in 241 of these persons. 37 cases were thus confirmed. Another 4 individuals with positive immunobiological tests and absence of the parasite eggs in stools were confirmed by duodenal intubation. 21 of the confirmed cases (51.2%) had less than 15 years of age. Women were more frequently infected than men (73.2% vs 26.8%). The 41 cases represent 0.7% of the s...
A 22 year old Chilean male presented with necrotic lesions of the 5 toes of the right foot and th... more A 22 year old Chilean male presented with necrotic lesions of the 5 toes of the right foot and the heal of the left foot. He had spent 7 months traveling in the Amazona region of Brazil. Surgery was performed to clean the areas where eggs of Tunga penetrans were identified.
Boletín de la Oficina Sanitaria Panamericana. Pan American Sanitary Bureau
This study sought to estimate for the first time the prevalence of fascioliasis among the rural p... more This study sought to estimate for the first time the prevalence of fascioliasis among the rural population in the Chilean provinces of Curico, Talca, and Linares, while also determining the disease's prevalence among horses and wild rabbits in Curico and Talca and among pigs in Talca. From January 1986 to December 1990 a randomly selected sample of 5,861 persons in the three provinces was given intradermal, complement-fixation, double-diffusion, and immunoelectrophoresis tests to detect antibody to Fasciola hepatica. In addition, the ELISA test was used in Talca and Linares. Fecal specimens from horses and pigs were inspected for eggs, and the liver and bile ducts of rabbits were examined histopathologically. The overall prevalence of infection among the human subjects was 0.70%, with rates of 0.6% in Curico, 0.75% in Talca, and 0.71% in Linares. The prevalences of infection in horses, rabbits, and pigs were 13.5%, 6.1%, and 20.6%, respectively. It is estimated that some 2,000 p...
There are currently no biomarkers to assess which patients with chronic indeterminate Chagas dise... more There are currently no biomarkers to assess which patients with chronic indeterminate Chagas disease will develop heart disease and which will spend their entire life in this state. We hypothetize that the parasite burden and Trypanosoma cruzi genotypes are related to the presence of heart disease in patients with Chagas disease. This study is aimed to investigate the parasite burden and T. cruzi genotypes in chagasic cardiopaths versus chagasic individuals without cardiac involvement according to the New York Heart Association. Patients with chronic Chagas disease, 50 with and 50 without cardiopathy (controls), groups A and B, respectively, were submitted to anamnesis, physical examination, and electrocardiogram. Echo-Doppler was performed for group A; all important known causes of cardiopathy were discarded. Xenodiagnosis, conventional PCR, and quantitative PCR were performed on patients of both groups. T. cruzi genotyping was done for 25 patients of group A and 20 of group B. The 50 cardiopaths had 80 electrocardiographic alterations, most of them in grade II of the New York Heart Association classification; 49 were classified in grade I by Echo-Doppler, and only one patient was in grade III. The difference in average parasitemia in patients of groups A and B was not significant. The most frequent T. cruzi DTU found was TcV. The parasite burden and genotype of the groups with and without cardiopathy were similar.Figure 2 Chronic Chagas cardiopathy microaneurism of left ventricle. Cineangiography.
... Destacamos los estudios pioneros de Amador Negh-me, Roberto Gajardo Tobar, Mafalda Rubio, Jor... more ... Destacamos los estudios pioneros de Amador Negh-me, Roberto Gajardo Tobar, Mafalda Rubio, Jorge Howard, Tulio Pizzi, Moisés Agosín, Gustavo Hoec-ker, Gabriel Gasic y Hugo Schenone. ... Werner Apt B1, Arturo Arribada C2, Inés Zu-lantay A1. ...
Chagas disease is endemic in Chile. Allopurinol and itraconazole have activity against Trypanosom... more Chagas disease is endemic in Chile. Allopurinol and itraconazole have activity against Trypanosoma cruzi and are recommended for the treatment of chronic disease in adults. To evaluate the chemotherapeutic effects of allopurinol and itraconazole using conventional and non conventional serologic tests. Sera of 90 patients with chronic Chagas disease were studied before and after 9 to 11 months of treatment with allopurinol or itraconazole and after two months of treatment with placebo. Indirect immunofluorescence, ELISA and Western Blot analysis were the conventional serologic tests used and antibody dependent complement mediated lysis (CoML) the non conventional test. There were no differences in ELISA and indirect immunofluorescence tests before and after therapy. Antigenic recognition profiles by Western Blot showed qualitative and quantitative differences in a small number of cases. CoML showed that the greater negativity was achieved in the Chagasic group treated with allopurino...
The aim of this work was to assess the diagnostic accuracy for neurocysticercosis, of ELISA and c... more The aim of this work was to assess the diagnostic accuracy for neurocysticercosis, of ELISA and counterimmunoelectrophoresis techniques, in sera and cerebrospinal fluid. Two hundred eight serum samples (47 coming from patients with confirmed cysticercosis) and 87 cerebrospinal fluid samples (27 coming from patients with confirmed cysticercosis) were analyzed. A crude and standardized extract of swine muscle cysticercus cellulose was used as antigen. ELISA and counter immunoelectrophoresis had a 100% specificity in cerebrospinal fluid. In sera, counterimmunoelectrophoresis had a 94.1% specificity. In sera and cerebrospinal fluid, ELISA had a 85.1% sensitivity. Cross reactions were observed in sera of patients with confirmed hydatidosis. Thus, the high specificity of both techniques in cerebrospinal fluid is probably due to the low incidence of cerebral hydatidosis in Chile. It is concluded that for the diagnosis of neurocysticercosis, antibodies against cysticercus cellulosae must be...
The American journal of tropical medicine and hygiene, 1995
Between November 1990 and March 1992, 24 asymptomatic individuals in Chile with chronic hepatic f... more Between November 1990 and March 1992, 24 asymptomatic individuals in Chile with chronic hepatic fascioliasis confirmed by the presence of Fasciola hepatica eggs in feces were treated with a single oral dose of triclabendazole (10 mg/kg of body weight) after an overnight fast. Nineteen (79.2%) of 24 patients were egg-negative two months after treatment. Three of five cases with F. hepatica in feces after the first treatment were retreated and parasitologic cure was achieved. Tolerance to the drug was excellent; none of the patients had either secondary symptoms or important alterations in levels of aspartate and amino transferases, alkaline phosphatase, or bilirubin during or after treatment. Mild eosinophilia, present in 70% of the cases, persisted at least until 60 days after treatment. An enzyme-linked immunosorbent assay (ELISA) was highly effective in diagnosis and post-treatment monitoring. Before treatment, 20 (83.3%) of 24 confirmed cases had positive test results. The test r...
We report the chemotherapeutic effect of itraconazole in chronic chagasic patients. The efficacy ... more We report the chemotherapeutic effect of itraconazole in chronic chagasic patients. The efficacy of treatment was analyzed by xenodiagnosis (XD), conventional serology (CS) and antibody dependent-complement mediated lysis test (CoML). Twenty chronic chagasic persons from endemic areas of Chile were grouped according to the results of xenodiagnosis (XD) performed before therapy. The follow-up of patients was performed at an average time of 42 months after treatment. No significative statistical differences were observed in the result of ELISA and Indirect Immunofluorescence test performed on serq before and after therapy with itraconazole. In the group of patients with positive XD before therapy, sera from six of them displayed lytic activity against Trypanosoma cruzi. The lytic activity of only one of these sera became negative after therapy. In relation to XD, five of those patients showed a positive tests at least once during the follow-up period. In the group of ten patients with negative XD before therapy, sera from eight of them displayed lytic activity. At the end of the follow-up period seven of them became negative. Nine of the ten patients maintained their original condition with respect to XD. These results suggests that parasitaemia level before therapy condition could be an important parameter to consider in the chemotherapy of chronic Chagas disease.
... 1999. BERNARDO LOPEZ*, LEONARDO LIDID*, EVELYN SANCHEZ*, INES ZULANTAY** y WERNER APT*. ... p... more ... 1999. BERNARDO LOPEZ*, LEONARDO LIDID*, EVELYN SANCHEZ*, INES ZULANTAY** y WERNER APT*. ... positivo. 1 El tratamiento de elección del megacolon chagásico es la operación de Duhamel-Haddad modificada. ...
An international study was performed by 26 experienced PCR laboratories from 14 countries to asse... more An international study was performed by 26 experienced PCR laboratories from 14 countries to assess the performance of duplex quantitative real-time PCR (qPCR) strategies on the basis of TaqMan probes for detection and quantification of parasitic loads in peripheral blood samples from Chagas disease patients. Two methods were studied: Satellite DNA (SatDNA) qPCR and kinetoplastid DNA (kDNA) qPCR. Both methods included an internal amplification control. Reportable range, analytical sensitivity, limits of detection and quantification, and precision were estimated according to international guidelines. In addition, inclusivity and exclusivity were estimated with DNA from stocks representing the different Trypanosoma cruzi discrete typing units and Trypanosoma rangeli and Leishmania spp. Both methods were challenged against 156 blood samples provided by the participant laboratories, including samples from acute and chronic patients with varied clinical findings, infected by oral route or vectorial transmission. kDNA qPCR showed better analytical sensitivity than SatDNA qPCR with limits of detection
Efficient drugs against Chagas' disease must have an effect on the amastigote forms or intrac... more Efficient drugs against Chagas' disease must have an effect on the amastigote forms or intracellular reproduction elements of Trypanosoma cruzi (T. cruzi). Trypomastigote and epimastigote forms derive from the former and their response to medications is less marked. The only drugs used in humans are nifurtimox (NF) and benznidazole (BNZ). Other useful medications are allopurinol and itraconazole. NF acts producing free radicals and BNZ inhibits the synthesis of macromolecules. There is consensus that Chagas' disease must be treated in all its periods, since T.cruzi DNA is detected by polymerase chain reaction in chronic cases, even when microscopy is negative. The pharmacological treatment modifies the natural evolution of the disease. It also helps to solve a public health problem, considering that there is a high number of subjects with Chagas' disease. Subjects with chronic chagasic cardiomyopathy with terminal heart failure are the only cases without indication for t...
The American journal of tropical medicine and hygiene
Fecal samples were obtained from 722 of 820 children attending 7 nursery schools and 1 primary sc... more Fecal samples were obtained from 722 of 820 children attending 7 nursery schools and 1 primary school in the city of Santiago, Chile. Microscopy of formol-ether concentrates showed that 33% of the children were infected with Giardia lamblia. Prevalences among primary school students (5-10 years of age) of G. lamblia (38%), Endolimax nana (43%), and Entamoeba coli (25%) were overall higher than among nursery school students (3 months-5 years of age; prevalences 29%, 21%, and 16%, respectively). There was no apparent association between socio-economic intake and levels of G. lamblia infection: the private nursery school had the highest recorded level of infection (40%). One hundred sixty-two triplicate stool specimens were used to compare microscopy with an enzyme-linked immunosorbent assay (ELISA) for the detection of Giardia fecal antigens. The ELISA was highly sensitive and specific either visually (95% and 97%, respectively) or by optical density determination (99% and 96%, respec...
The aim of this study was to assess the efficacy of Chagas disease vector control in Chile, using... more The aim of this study was to assess the efficacy of Chagas disease vector control in Chile, using human disease as an index. After a twelve years control program using insecticides, dwelling infection in the IV region fell from 49 to 4%. In Combarbalá (a community of the IV region) the infection rate, detected by indirect hemagglutination, immunofluorescence and ELISA tests, decreased from 21.8% in 1986 to 8.2% in 1992 in primary school students (p < 0.001) and from 7.5 to 5% in high school students. Besides the vector control program, no other important epidemiological changes occurred in this period, excepting some ecological changes.
Between January 1986 and December 1990 the prevalence of F. hepatica infection was studied in 586... more Between January 1986 and December 1990 the prevalence of F. hepatica infection was studied in 5861 rural inhabitants of the provinces of Curico, Talca and Linares, VII Region, an hyperendemic zone of animal fascioliasis. Every one was screened by intradermal (IDR), complement fixation (CF), double diffusion (DD) counterelectrophoresis (CIEF), immunoelectrophoresis (IEP) and enzyme-linked immunoabsorbent assay (ELISA) tests. 366/1881 (9.3%) had positive IDR; 61 (1.04%) positive CF; 14 (0.24%) positive DD and 105/3838 (2.73%) positive ELISA and thus considered under suspicion to be infected. F. hepatica eggs were searched in stool in 241 of these persons. 37 cases were thus confirmed. Another 4 individuals with positive immunobiological tests and absence of the parasite eggs in stools were confirmed by duodenal intubation. 21 of the confirmed cases (51.2%) had less than 15 years of age. Women were more frequently infected than men (73.2% vs 26.8%). The 41 cases represent 0.7% of the s...
A 22 year old Chilean male presented with necrotic lesions of the 5 toes of the right foot and th... more A 22 year old Chilean male presented with necrotic lesions of the 5 toes of the right foot and the heal of the left foot. He had spent 7 months traveling in the Amazona region of Brazil. Surgery was performed to clean the areas where eggs of Tunga penetrans were identified.
Boletín de la Oficina Sanitaria Panamericana. Pan American Sanitary Bureau
This study sought to estimate for the first time the prevalence of fascioliasis among the rural p... more This study sought to estimate for the first time the prevalence of fascioliasis among the rural population in the Chilean provinces of Curico, Talca, and Linares, while also determining the disease's prevalence among horses and wild rabbits in Curico and Talca and among pigs in Talca. From January 1986 to December 1990 a randomly selected sample of 5,861 persons in the three provinces was given intradermal, complement-fixation, double-diffusion, and immunoelectrophoresis tests to detect antibody to Fasciola hepatica. In addition, the ELISA test was used in Talca and Linares. Fecal specimens from horses and pigs were inspected for eggs, and the liver and bile ducts of rabbits were examined histopathologically. The overall prevalence of infection among the human subjects was 0.70%, with rates of 0.6% in Curico, 0.75% in Talca, and 0.71% in Linares. The prevalences of infection in horses, rabbits, and pigs were 13.5%, 6.1%, and 20.6%, respectively. It is estimated that some 2,000 p...
There are currently no biomarkers to assess which patients with chronic indeterminate Chagas dise... more There are currently no biomarkers to assess which patients with chronic indeterminate Chagas disease will develop heart disease and which will spend their entire life in this state. We hypothetize that the parasite burden and Trypanosoma cruzi genotypes are related to the presence of heart disease in patients with Chagas disease. This study is aimed to investigate the parasite burden and T. cruzi genotypes in chagasic cardiopaths versus chagasic individuals without cardiac involvement according to the New York Heart Association. Patients with chronic Chagas disease, 50 with and 50 without cardiopathy (controls), groups A and B, respectively, were submitted to anamnesis, physical examination, and electrocardiogram. Echo-Doppler was performed for group A; all important known causes of cardiopathy were discarded. Xenodiagnosis, conventional PCR, and quantitative PCR were performed on patients of both groups. T. cruzi genotyping was done for 25 patients of group A and 20 of group B. The 50 cardiopaths had 80 electrocardiographic alterations, most of them in grade II of the New York Heart Association classification; 49 were classified in grade I by Echo-Doppler, and only one patient was in grade III. The difference in average parasitemia in patients of groups A and B was not significant. The most frequent T. cruzi DTU found was TcV. The parasite burden and genotype of the groups with and without cardiopathy were similar.Figure 2 Chronic Chagas cardiopathy microaneurism of left ventricle. Cineangiography.
... Destacamos los estudios pioneros de Amador Negh-me, Roberto Gajardo Tobar, Mafalda Rubio, Jor... more ... Destacamos los estudios pioneros de Amador Negh-me, Roberto Gajardo Tobar, Mafalda Rubio, Jorge Howard, Tulio Pizzi, Moisés Agosín, Gustavo Hoec-ker, Gabriel Gasic y Hugo Schenone. ... Werner Apt B1, Arturo Arribada C2, Inés Zu-lantay A1. ...
Chagas disease is endemic in Chile. Allopurinol and itraconazole have activity against Trypanosom... more Chagas disease is endemic in Chile. Allopurinol and itraconazole have activity against Trypanosoma cruzi and are recommended for the treatment of chronic disease in adults. To evaluate the chemotherapeutic effects of allopurinol and itraconazole using conventional and non conventional serologic tests. Sera of 90 patients with chronic Chagas disease were studied before and after 9 to 11 months of treatment with allopurinol or itraconazole and after two months of treatment with placebo. Indirect immunofluorescence, ELISA and Western Blot analysis were the conventional serologic tests used and antibody dependent complement mediated lysis (CoML) the non conventional test. There were no differences in ELISA and indirect immunofluorescence tests before and after therapy. Antigenic recognition profiles by Western Blot showed qualitative and quantitative differences in a small number of cases. CoML showed that the greater negativity was achieved in the Chagasic group treated with allopurino...
The aim of this work was to assess the diagnostic accuracy for neurocysticercosis, of ELISA and c... more The aim of this work was to assess the diagnostic accuracy for neurocysticercosis, of ELISA and counterimmunoelectrophoresis techniques, in sera and cerebrospinal fluid. Two hundred eight serum samples (47 coming from patients with confirmed cysticercosis) and 87 cerebrospinal fluid samples (27 coming from patients with confirmed cysticercosis) were analyzed. A crude and standardized extract of swine muscle cysticercus cellulose was used as antigen. ELISA and counter immunoelectrophoresis had a 100% specificity in cerebrospinal fluid. In sera, counterimmunoelectrophoresis had a 94.1% specificity. In sera and cerebrospinal fluid, ELISA had a 85.1% sensitivity. Cross reactions were observed in sera of patients with confirmed hydatidosis. Thus, the high specificity of both techniques in cerebrospinal fluid is probably due to the low incidence of cerebral hydatidosis in Chile. It is concluded that for the diagnosis of neurocysticercosis, antibodies against cysticercus cellulosae must be...
The American journal of tropical medicine and hygiene, 1995
Between November 1990 and March 1992, 24 asymptomatic individuals in Chile with chronic hepatic f... more Between November 1990 and March 1992, 24 asymptomatic individuals in Chile with chronic hepatic fascioliasis confirmed by the presence of Fasciola hepatica eggs in feces were treated with a single oral dose of triclabendazole (10 mg/kg of body weight) after an overnight fast. Nineteen (79.2%) of 24 patients were egg-negative two months after treatment. Three of five cases with F. hepatica in feces after the first treatment were retreated and parasitologic cure was achieved. Tolerance to the drug was excellent; none of the patients had either secondary symptoms or important alterations in levels of aspartate and amino transferases, alkaline phosphatase, or bilirubin during or after treatment. Mild eosinophilia, present in 70% of the cases, persisted at least until 60 days after treatment. An enzyme-linked immunosorbent assay (ELISA) was highly effective in diagnosis and post-treatment monitoring. Before treatment, 20 (83.3%) of 24 confirmed cases had positive test results. The test r...
We report the chemotherapeutic effect of itraconazole in chronic chagasic patients. The efficacy ... more We report the chemotherapeutic effect of itraconazole in chronic chagasic patients. The efficacy of treatment was analyzed by xenodiagnosis (XD), conventional serology (CS) and antibody dependent-complement mediated lysis test (CoML). Twenty chronic chagasic persons from endemic areas of Chile were grouped according to the results of xenodiagnosis (XD) performed before therapy. The follow-up of patients was performed at an average time of 42 months after treatment. No significative statistical differences were observed in the result of ELISA and Indirect Immunofluorescence test performed on serq before and after therapy with itraconazole. In the group of patients with positive XD before therapy, sera from six of them displayed lytic activity against Trypanosoma cruzi. The lytic activity of only one of these sera became negative after therapy. In relation to XD, five of those patients showed a positive tests at least once during the follow-up period. In the group of ten patients with negative XD before therapy, sera from eight of them displayed lytic activity. At the end of the follow-up period seven of them became negative. Nine of the ten patients maintained their original condition with respect to XD. These results suggests that parasitaemia level before therapy condition could be an important parameter to consider in the chemotherapy of chronic Chagas disease.
... 1999. BERNARDO LOPEZ*, LEONARDO LIDID*, EVELYN SANCHEZ*, INES ZULANTAY** y WERNER APT*. ... p... more ... 1999. BERNARDO LOPEZ*, LEONARDO LIDID*, EVELYN SANCHEZ*, INES ZULANTAY** y WERNER APT*. ... positivo. 1 El tratamiento de elección del megacolon chagásico es la operación de Duhamel-Haddad modificada. ...
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