Itraconazole or allopurinol in the treatment of chronic American trypanosomiasis: the results of clinical and parasitological examinations 11 years post-treatment.

Eleven years after they had been given itraconazole or allopurinol for the treatment of chronic American trypanosomiasis, 109 adult patients were checked for electrocardiographic abnormalities and evidence of Trypanosoma cruzi infection. The parasitological investigations included xenodiagnosis, in which the faeces of Triatoma infestans that had fed on the patients were checked under the microscope for flagellates. In addition, a PCR-based assay and a hybridization assay were used to test blood samples from the patients, and faeces from the Tri. infestans that had fed on the patients, for Try. cruzi DNA. For the data analysis, the patients were divided into four groups known as normal/normal, abnormal/normal, normal/abnormal and abnormal/abnormal, according to whether the patients had been found to have normal or abnormal electrocardiograms (ECG) shortly before the first treatment and to have normal or abnormal ECG when checked at the 11-year follow-up. The 51 normal/normal and 24 normal/abnormal patients were assumed to have been in the 'indeterminate' phase of the disease when they were treated, whereas the 16 abnormal/normal and 18 abnormal/abnormal patients all had evidence of chagasic cardiopathy at that time. When checked 11 years post-treatment, 40 (78.4%), 17 (70.8%), 14 (87.5%) and 17 (94.4%) of these patients, respectively, were each found positive for Try. cruzi in at least one of the parasitological tests. The hybridization assay, whether applied to human blood or bug faeces, appeared a significantly more sensitive test than the PCR-based assays or microscopically assessed xenodiagnosis (P<0.05). Only the 21 patients who appeared to be negative for Try. cruzi could be considered parasitologically cured (although all still appeared to have anti-Try. cruzi antibodies in their blood). Only 13 of these parasitologically cured patients (seven of those treated with itraconazole and six of those given allopurinol) had normal ECG at the 11-year follow-up. In Chile at least, itraconazole, which caused fewer adverse effects than the allopurinol while being no less effective at preventing cardiopathy, appears to be the drug of choice to treat chronic American trypanosomiasis in adults.

Monitoring the efficacy of specific treatment in chronic Chagas disease by polymerase chain reaction and flow cytometry analysis.

PCR and FC-ALTA were used to monitor parasite clearance in 54 chronic chagasic patients who had completed therapy with allopurinol (ALLO, n = 31) or itraconazole (ITRA, n = 23) ten years earlier. All patients maintained positive conventional serology. 25 of them showed positive XD (ALLO, n = 11 and ITRA, n = 14) and 29 negative XD (ALLO, n = 20 and ITRA, n = 9). 43 patients were positive by both techniques (ALLO, n = 23 and ITRA, n = 20). Seven of 54 patients were negative by PCR and positive by FC-ALTA and three of 54 were positive by PCR and negative by FC-ALTA. Only one case with both tests negative should be considered cured. Of 29 patients with negative XD, 14 treated ALLO (70 %) and nine with ITRA (77.8 %) showed positive PCR and FC-ALTA. These results do not show differences of efficacy among the drugs, and reinforce the relevance of using sensitive tools such as PCR and FC-ALTA for the follow-up of patients with chronic Chagas disease.

Itraconazole or allopurinol in the treatment of chronic American trypanosomiasis: the regression and prevention of electrocardiographic abnormalities during 9 years of follow-up.

Several drugs are now known to have useful activity against Trypanosoma cruzi, the causative agent of human American trypanosomiasis (Chagas disease). However, the long-term effects of chemotherapy on the electrocardiographic (ECG) abnormalities associated with this disease have only been assessed for benznidiazole. In the present study, the ECG changes in 299 cases of chronic Chagas disease were followed for 9 years after treatment with itraconazole (N = 136) or allopurinol (N = 163). Among the 97 cases who were found to have ECG abnormalities immediately prior to their treatment, the two drugs appeared equally effective, such abnormalities being corrected in 23 (50%) of the 46 cardiopathy cases given itraconazole and 25 (49%) of the 51 given allopurinol (P > 0.05). Both of these 'cure rates' are much higher than the 8.1% frequency of abnormal-normal conversion observed among 198 'historical controls' (i.e. cases of chronic Chagas disease who had been left untreated; P < 0.05). Itraconazole appeared better than allopurinol at preventing the development of cardiopathy in the cases who appeared electrocardiographically normal at baseline. Among 202 such cases, only two (2.2%) of the 90 treated with itraconazole but 28 (25.0%) of the 112 given allopurinol were found to have developed ECG abnormalities during follow-up (P < 0.05). Therefore, although itraconazole and allopurinol are equally effective at reversing ECG alterations, itraconazole offers better protection against the development of new ECG abnormalities among those with chronic Chagas disease.

Cystic echinococcosis of the tongue leading to diagnosis of multiple localizations.

The tongue is a rare site of localization of cystic echinococcosis. We report a 3-year-old patient with cystic echinococcosis of the tongue demonstrated by histopathology. The cyst of the tongue was surgically removed. The tongue lesion led us to find additional liver and lung cystic lesions that were successfully treated with albendazole therapy.

[Echinococcosis/hydatidosis in the VII Region of Chile: diagnosis and educational intervention]. / Equinococosis/hidatidosis en la VII Región de Chile: diagnóstico e intervención educativa.

This study was designed to embrace three areas: a) serologic and radiologic diagnosis and surgical treatment of hydatidosis in an asymptomatic human population, b) animal diagnosis and the treatment of dogs, and c) evaluation of extent of knowledge and performance of educational interventions among rural families and health, livestock, and education professionals and technicians, in order to help control the disease transmission cycle. Indirect hemagglutination and ELISA tests were performed on 5,556 apparently healthy people. Of these, 42 (0.8%) had positive results on both tests, for a seroprevalence of 754.6 per 100,000. These 42 subjects were scheduled for liver ultrasonography and a chest x-ray; of the 26 who complied, 16 showed images compatible with a hydatid cyst. Those 16 cases were sent to the hospital for surgery. In 9 of the cases the diagnosis was confirmed surgically, for a prevalence of 161.7 per 100,000. Arecoline hydrobromide was administered as a laxative to 2,358 dogs to detect the strobilar form of Echinococcus granulosus, and positive results were found in 11% of the dogs. Official data for slaughterhouses indicated the presence of hydatid cysts in 13% of the cattle, 4.4% of the sleep, and 4.2% of the pigs slaughtered in the region. The educational program included an evaluation of the extent of knowledge by surveying heads of household; an educational intervention among families through an informal active participatory process using educational games, in which 1,082 families participated; and an educational intervention with professionals and technicians using distance and in-person approaches. To evaluate the program, the results of knowledge tests before and after educational interventions with 200 families (cases) were compared with those from 95 families who did not participate (controls). Of the 1,423 heads of household initially surveyed about their knowledge of echinococcosis/hydatidosis, 783 of them (55%) said they knew nothing about the infection. It was found that the participatory educational games were well adapted to the lifestyle of people from rural areas and made change possible. Training was provided to 276 health professionals, 201 technical assistants, and 453 rural teachers. The program reached 100% of the staff members of the area's rural primary health care services.

[Serologic evaluation of treatment of chronic Chagas disease with allopurinol and itraconazole]. / Evaluación serológica del tratamiento de la enfermedad de Chagas crónica con alopurinol e itraconazol.

BACKGROUND: 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. AIM: To evaluate the chemotherapeutic effects of allopurinol and itraconazole using conventional and non conventional serologic tests. PATIENTS AND METHODS: 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. RESULTS: 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 allopurinol or itraconazole that had a negative xenodiagnosis before drug treatment (35.8 and 61.6%, respectively). CONCLUSIONS: There is a reversion of lytic activity in sera of patients with negative xenodiagnosis before treatment, suggesting the parasitemia could be an important parameter to be considered in the chemotherapy of Chagas disease.

Treatment of chronic Chagas' disease with itraconazole and allopurinol.

Four hundred four patients with chronic Chagas' disease were treated with itraconazole (6 mg/kg of body weight/day for 120 days), allopurinol (8.5 mg/kg of body weight/day for 60 days), or with a placebo of pure starch. Patients were monitored over a period of four years by clinical examination, serology, xenodiagnosis, hemoculture, and electrocardiogram. Drug tolerance was good, with only four treatments discontinued due to side effects that subsided after suspension of treatment. Parasitologic cure was evident in 44% of the those treated with allopurinol and 53% of those treated with itraconazole, and the electrocardiographic evaluation showed normalization in 36.5% and 48.2%, respectively, of patients with chronic or recent cardiopathy.

[Non conventional treatment of human hydatidosis]. / Tratamiento no convencional de la hidatidosis humana.

Treatment of human hydatidosis is surgical. Lately, however, surgical indications have decreased, due to pharmacological therapy and ultrasound-guided percutaneous cyst puncture, aspiration of its contents, instillation of medications and respiration. As a general rule, surgical treatment is indicated in cysts larger than 10 cm phi and located in extra abdominal sites, such as thorax, brain or bone. The drug of choice is albendazole, in doses of 10 to 15 mg/kg/day for one month. Three cures with intervals of 15 to 30 days in between, are generally used. Thirty percent of cysts disappear, 30 to 50% experience degenerative changes and 30 to 40% do not change. Aspirative needle puncture is used, after four days of albendazole treatment, in those cysts that can be reached percutaneously.

[Evaluation of ELISA and counterimmunoelectrophoresis in diagnosis of human neurocysticercosis in Chile]. / Evaluación de ELISA y contrainmunoelectroforesis en el diagnóstico de la neurocisticercosis humana en Chile.

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 sought paralelly in serum and cerebrospinal fluid using ELISA and counterimmunoelectrophoresis.

[Treatment of chronic human Chagas disease with itraconazole and allopurinol. Preliminary report]. / Tratamiento de la enfermedad de Chagas humana crónica con itraconazol y alopurinol. Informe preliminar.

The aim of this work was to assess the efficacy of itraconazole and allopurinol in chronic Chagas disease. Two hundred two subjects (137 infected, 59 with Chagas cardiopathy and 6 with non chagasic cardiopathy) were randomly assigned to be treated with itraconazole (87 subjects receiving 6 mg/kg/day for 120 days), allopurinol (68 subjects receiving 8.5 mg/kg/day for 60 days) or placebo (47 subjects during 60 days). Medications were well tolerated. Indirect hemagglutination test was modified in 5 subjects (3.2%) after treatment. Initially positive xenodiagnosis became negative in 34 of 36 subjects (94.4%) treated with itraconazole and 8 of 10 subjects (80%) treated with allopurinol. Initially normal EKG was not modified in 100% of patients receiving placebo, 84.9% receiving itraconazole and 86.7% receiving allopurinol. Initially abnormal EKG became normal in 10 of 31 subjects (32%) receiving itraconazole, 8 of 20 (40%) receiving allopurinol and none of 8 receiving placebo. It is concluded that xenodiagnosis and EKG improvements indicate that itraconazole and allopurinol have a role in the treatment of chronic Chagas disease. A 36 months follow up of these patients will help to confirm this conclusion.

Characterization of Chilean, Bolivian, and Argentinian Trypanosoma cruzi populations by restriction endonuclease and isoenzyme analysis.

Ninety-one Chilean, 15 Bolivian, and 9 Argentinian Trypanosoma cruzi stocks, isolated from various hosts and vectors, were characterized by schizodeme analysis with EcoRI and MspI endonucleases. The three major similar pattern groups that emerged from this sample correlated with results of isoenzyme analysis. This result confirms previous work and supports the hypothesis of the clonal structure of natural populations of T. cruzi, fully defined at the level of isoenzyme analysis, quantitative kinetoplast DNA restriction fragment length polymorphism, and kinetoplast DNA hybridization analysis. In Chile, sylvatic and domestic cycles of T. cruzi transmission appear to be mainly independent: genetically different families of natural clones are specific to these cycles. Nevertheless, the possibility of overlap remains unclear. Results described here indicate that natural clones inhabiting Chilean regions appear genetically related to the natural clones identified in neighboring countries. In Chile the more frequently sampled parasite types are natural clone 39 and a genetically closely related clone NP13. In this work an evaluation of T. cruzi natural clone mixtures in T. cruzi stocks from Chile was performed for the first time by schizodeme analysis before and after serial transfer in mouse maintenance. The results indicate that six of nine stocks are composed of two or more natural clones. This observation raises the relevant question of whether specific T. cruzi natural clones generate different clinical features of Chagas' disease.

[Tungiasis. A clinical case]. / Tungiasis. Caso clinico.

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.

[New anthelmintic drugs]. / Nuevos medicamentos antihelmínticos.

New anti-helminthic drugs have appeared lately: benzimidazoles (mebendazole, flubendazol, and abendazole), praziquantel and ivermectin. Mebendazol and flubendazol are poorly absorbed and are effective for ascaris, oxyuriasis and trycocephalus both in adults and children. Abendazole is well absorbed and may be considered the drug of choice for ascaris and oxyuriasis at a single 400 mg dose. This drug may also be used for hydatid cyst when surgery is not possible and for cysticercosis of the nervous system. Praziquantel is useful for treatment of tenia infections and ivermectin is useful for strongyloides and trichostrongyloides. Detailed dose schedules for different parasitic diseases are given in the text.

[Multiple hydatid cysts and generalized cysticercosis]. / Hidatidosis múltiple y cisticercosis generalizada.

A 64 year old male presented with parotid gland swelling and neck and pulmonary nodules. Contrast and scintigraphic studies ruled out a primary process of the gland. Other nodules were detected in the abdomen and upper limbs. Biopsy of one of these showed C cellulosae and a positive serologic test followed. On the other hand echographic findings support the diagnosis of lung hydatid disease.

Natural history of chagasic cardiopathy in Chile. Follow-up of 71 cases after 4 years.

As part of study of Chagasic cardiopathy in Chile we report a follow-up study of 100 cardiopathic patients from two endemic areas who had been diagnosed 4 years earlier during an epidemiological and clinical survey. The follow-up consisted of a clinical, serological and electrocardiographic examination, and a continuous ECG recording for 60 min to detect possible arrhythmias. From the original 100 cases, three had died: one of a gastric cancer and the other two due to probable chagasic cardiopathy. Twenty-six had migrated to other areas and were lost to our study. From the remaining 71 patients, 48 were asymptomatic and 23 had complaints including palpitations, dyspnoea and Stokes-Adams crisis. In most cases, seropositivity by indirect haemagglutination did not change, but in six cases the titres decreased, becoming negative in three of them. Xeno-diagnosis was positive in 19.3% of seropositive patients. The ECG had returned to normal in 18 cases (17%) but showed a higher degree of blockades in others, three of which reached complete A-V block. The 60 min ECG was very important as it showed alterations in 93% of the cases, revealing arrhythmias that the ECG alone did not show. This work demonstrates that chagasic cardiopathy in Chile is a slow, progressive disease, that attacks the heart as a whole, but with special damage to the conducting tissues.