Epidemiology of Chagas' disease in northern Chile: isozyme profiles of Trypanosoma cruzi from domestic and sylvatic transmission cycles and their association with cardiopathy.

Trypanosoma cruzi was isolated from 98 patients, 59 Triatoma infestans, 51 Triatoma spinolai, and 1 Octodon degus from northern Chile. With few exceptions, stocks originating from domestic hosts were classified, based on their isozyme profile, as principal zymodeme (Z)2, while sylvatic stocks from T. spinolai and the rodent O. degus showed Z1 profiles. These results indicate the existence of separate domestic and sylvatic transmission cycles. Clinical data and T. cruzi isozyme profiles from 107 chronic Chagas' disease patients showed no association between infecting T. cruzi zymodeme and the prevalence of chagasic cardiopathy. However, the age distributions of two groups of patients carrying different zymodemes were significantly different.

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.

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.

Parasitic cardiomyopathies.

Fifty-one parasitic cardiomyopathies studied for periods ranging from 1 to 14 years were analyzed. In 32 cases chagasic etiology was demonstrated and in 19 cases toxoplasmic etiology. In the chagasic cases the diagnosis was confirmed by serological study and/or xenodiagnosis. In one of these patients an aneurysmatic dilatation of the left ventricular cavity was found. The clinic picture showed cardiac insufficiency and deleterous arrhythmias in 18 of the 32 cases. The rest of the patients had precordial pains. The mortality of the group was 12.5%. In toxoplasmic patients the diagnosis was made by periodical serological study, considering only those cases where concomitant clinical activity and pathological antibody response was demonstrated. In three cases the parasite was recovered from the myocardium and in another from a peripheral gland. The clinical picture in these groups consisted of precordial pain and arrhythmias in 14 cases, and cardiac failure in 13 cases. The mortality rate for the group was 42%.

[Chagas cardiopathy in the first region of Chile. Clinical, epidemiologic, and parasitologic study]. / Cardiopatía chagásica en la primera región de Chile. Estudio clínico, epidemiológico y parasitológico.

705 inhabitants of rural towns in northern Chile were surveyed to study chagasic infection and cardiac involvement. Clinical evaluation, electrocardiogram, indirect hemagglutination test and xenodiagnosis for reactors were employed. Culture of positive xenodiagnosis was done to identify different zymodemes and schizodemes of T cruzi, T spinolai was not found in this area implying the absence of a wild cycle. Triotomines were not found over 3000 m high. Four cases of Z2b T cruzi strains were found. Simultaneous infection by Z1 and Z2b strains was found in the same bug obtained from houses. Overall human infection rate was 10%, and 69% of them showed altered electrocardiograms. Therefore, a lower infection rate but greater evidence of cardiac involvement is found in northern Chile compared to other areas in the country.

[Transesophageal atrial stimulation in 168 patients]. / Estimulacion auricular transesofagica. Experiencia en 168 pacientes.

Transesophageal atrial stimulation was performed in 168 patients, 95 males and 73 males, 20 to 81 years of age. The indication for atrial stimulation was the study of some bradyarrhythmia in 109 and ischemic heart disease in 59. An esophageal catheter was introduced through the nose and placed at a spot where a bimodal P wave was obtained. Stimulation was performed using a baby Medtronic stimulator coupled to a Vygon amplifier delivering an output of 30 volt. Sinus node recovery time was measured after 2 to 3 min of stimulation at different rates. Wenckebach and 2:1 A-V block as well as ST deviation were determined. Sick sinus syndrome was diagnosed in 41 cases through altered sinus node recovery time and/or secondary pauses; 35 patients showed Wenckebach rhythm at a stimulation rate over 120 per min; 2: 1 A-V block appeared in 22. Ischemic ST-T changes were produced in 20 subjects. No complications were observed, confirming this approach as a simple and effective way to achieve atrial stimulation for diagnostic purposes.

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.

[Electrocardiographic abnormalities in cocaine base paste consumers of the metropolitan area]. / Alteraciones electrocardiográficas en consumidores de pasta base de cocaína del Area Metropolitana.

BACKGROUND: The adverse effects of cocaine use mainly occur in the heart and central nervous system. AIM: To study the effects of cocaine base paste consumption on the cardiovascular system. SUBJECTS AND METHODS: Thirty five chronic cocaine base paste consumers, 26 male, aged 15 to 43 years old, were studied. A clinical assessment and a resting EKG were performed. Results were compared with those of 82 healthy controls. RESULTS: Sixty percent of cocaine consumers had EKG abnormalities, compared with 43% of controls. Forty one percent of cocaine users and 33% of controls had a prolonged QTc. Likewise, 36% of cocaine users and 46% of controls had an incomplete right bundle branch block. Among cocaine users, an active nodal rhythm, an ischemic and a QS anteroseptal image were observed. CONCLUSIONS: A slightly higher frequency of EKG abnormalities were observed in chronic cocaine users, when compared with healthy controls.

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.

[HLA antigens in Chagas cardiomyopathy: new evidence based on a case-control study]. / Antígenos HLA en cardiopatas chagásicos: nueva evidencia basada en un análisis de casos y controles.

We studied the distribution of HLA, B and C antigens in 73 Chagasic subjects with and without heart disease. Both groups were matched for age, sex, birth place and history of family residence. Thirty two subjects without evidence of Chagasic infection, with and without heart disease and matched for the same variables were also studied. Compared to all other groups, a significant increase in the level of the B40 Cw3 antigen combination was found in Chagasic subjects without evidence of heart disease.

[Genetic evidence corroborates Negme's hypothesis about the greater mildness of American trypanosomiasis in Chile]. / Evidencias genéticas corroboran la hipótesis de Neghme sobre la mayor benignidad de la tripanosomiasis Americana en Chile.

Chagas disease is present in northern and central Chile. Not more than 25% of infected individuals have had a pathologic condition presumably due to Trypanosoma cruzi. The majority of individuals with chronic infectious Chagas disease in Chile are asymptomatic in contrast to what has been observed in other South American countries. Historic and paleopathologic evidences suggest that this particular behavior could be explained by a genetic adaptation of Chilean aborigines to T cruzi. Associations between ethnic admixture, presence of Chagas disease, associated cardiac pathology and 4 blood groups (ABO, MNSs, Rh and Duffy) were investigated among inhabitants of San Pedro de Atacama in northern Chile. Cardiac pathology was determined by positive serologic reactions in individuals with abnormal electrocardiographic findings. Individuals with negative serologic results had a significantly greater aboriginal admixture (88%) compared to those with positive serology (66%). This findings supports the hypothesis of genetic adaptation explaining mildness of Chagas disease in Chile.

[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.