nifurtimox and Chagas-Cardiomyopathy

People with Chagas disease may develop progressive and lethal heart conditions. Drugs to eliminate the parasite Trypanosoma cruzi (T cruzi) currently carry limited therapeutic value and are used in the early stages of the disease. Extending the use of these drugs to treat chronic chagasic cardiomyopathy (CCC) has also been proposed.. To assess the benefits and harms of nitrofurans and trypanocidal drugs for treating late-stage, symptomatic Chagas disease and CCC in terms of blood parasite reduction or clearance, mortality, adverse effects, and quality of life.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS databases on 12 November 2019. We also searched two clinical trials registers, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), on 3 December 2019.. We included randomised controlled trials (RCTs) assessing trypanocidal drugs versus placebo or no treatment for late-stage, symptomatic Chagas disease and CCC.. We conducted the reporting of the review according the standard Cochrane methods. Two review authors independently retrieved articles, performed data extraction, and assessed risk of bias. Any disagreements were resolved by a third review author. We contacted study authors for additional information.. We included two studies in this review update. One RCT randomly assigned 26 participants to benznidazole 5 mg/kg/day; 27 participants to nifurtimox 5 mg/kg/day; and 24 participants to placebo for 30 days. The second RCT, newly included in this update, randomised 1431 participants to benznidazole 300 mg/day for 40 to 80 days and 1423 participants to placebo. We also identified one ongoing study. Benznidazole compared to placebo At five-year follow-up, low quality of the evidence suggests that there may be a benefit of benznidazole when compared to placebo for clearance or reduction of antibody titres (risk ratio (RR) 1.25, 95% confidence interval (CI) 1.14 to 1.37; 1 trial; 1896 participants). We are uncertain about the effects of benznidazole for the clearance of parasitaemia demonstrated by negative xenodiagnosis, blood culture, and/or molecular assays due to very limited evidence. Low quality of the evidence suggests that when compared to placebo, benznidazole may make little to no difference in the risk of heart failure (RR 0.89, 95% CI 0.69 to 1.14; 1 trial; 2854 participants) and ventricular tachycardia (RR 0.80, 95% CI 0.51 to 1.26; 1 trial; 2854 participants). We found moderate quality of the evidence that adverse events increase with benznidazole when compared to placebo (RR 2.52, 95% CI 2.09 to 3.03; 1 trial; 2854 participants). Adverse effects were observed in 23.9% of patients in the benznidazole group compared to 9.5% in the placebo group. The most frequent adverse effects were: cutaneous rash, gastrointestinal symptoms, and peripheral polyneuropathy. No data were available for the outcomes of pathological demonstration of tissue parasites and quality of life. Nifurtimox compared to placebo Data were only available for this comparison for the outcome clearance or reduction of antibody titres, and we are uncertain about the effect due to very limited evidence. Regarding adverse events, one RCT mentioned in a general manner that nifurtimox caused intense adverse events, without any quantification.. There is insufficient evidence to support the efficacy of the trypanocidal drugs benznidazole and nifurtimox for late-stage, symptomatic Chagas disease and CCC.

Topics: Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Humans; Nifurtimox; Nitroimidazoles; Parasitemia; Placebos; Randomized Controlled Trials as Topic; Trypanocidal Agents; Trypanosoma cruzi

Although Chagas disease is a rare entity in North America, it is associated with significant cardiac morbidity. It is estimated that 20-30% of those who are infected will eventually develop cardiovascular disease secondary to Chagas disease. We review the literature and share our experience on the surgical management of this challenging patient population.

Topics: Cardiac Surgical Procedures; Chagas Cardiomyopathy; Echocardiography; Female; Heart Aneurysm; Heart Ventricles; Humans; Magnetic Resonance Imaging; Middle Aged; Nifurtimox; Nitroimidazoles; Serologic Tests; Stroke Volume; Treatment Outcome; Trypanocidal Agents

A conservative estimation indicates that more than 400 000 Latin American immigrants are living in Italy. Several studies have shown that among these, the prevalence of Chagas disease is between 3.9% and 17%, so it is not unlikely to find a patient with this disease during a cardiology visit. How many patients from Latin America are diagnosed with heart failure in Italy and no one has ever thought about a possible Chagas disease? This brief review describes the situation of the disease in Italy, its characteristics, the etiology of this disease and its treatment. The latter aspect will be discussed considering the recent published results of the BENEFIT study, where it was found that treatment with benznidazole in patients with Chagas' cardiomyopathy is able to reduce significantly the detection of parasites in the blood, but it is not able to prevent clinical deterioration during 5 years of follow-up. The possible implications of these results will be discussed.

Topics: Chagas Cardiomyopathy; Chagas Disease; Emigrants and Immigrants; Humans; Italy; Neglected Diseases; Nifurtimox; Nitroimidazoles; Prevalence; South America; Treatment Outcome; Trypanocidal Agents; Trypanosoma cruzi

Topics: Adult; Animals; Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Disease Progression; Electrocardiography; Female; Humans; Life Cycle Stages; Nifurtimox; Nitroimidazoles; Practice Guidelines as Topic; Trypanocidal Agents; Trypanosoma cruzi

There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

Topics: Acute Disease; Animals; Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Cyclooxygenase 1; Cyclooxygenase 2; Humans; Mice; Nifurtimox; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi

Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.

Topics: Argentina; Chagas Cardiomyopathy; Chagas Disease; Child; Drug Administration Schedule; Humans; Nifurtimox; Nitroimidazoles; Trypanocidal Agents

People with Chagas disease (American Trypanosomiasis) may develop progressive and potentially lethal heart conditions. Drugs to eliminate the causative parasite, Trypanosoma cruzi, currently in use have limited therapeutic value and are used in early stages of the disease. Extending the use of these drugs to treat symptomatic chronic parasitism with chronic Chagasic cardiopathy (CCC) and progressive dilated cardiomyopathy has been proposed.. To assess the effects (harms and benefits) of nitrofurans and imidazolic trypanocidal drugs for treating late stage chronic Chagas disease and CCC.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 3, 2004), MEDLINE (1985-2004), EMBASE (1985-2004), BIREME (1985-2004), LILACS (1985-2004), ARTEMISA (1985-2004), SCIELO (1985-2004). Indexing terms in English and Spanish were used. References obtained were assessed for relevance by two reviewers independently.. We included randomized controlled clinical trials (RCTs), single or double blind using trypanocidal drugs versus placebo or no treatment in CCC.. All articles retrieved were assessed using a predefined check list to determine if they met the inclusion criteria. Two independent reviewers collected data using a pre-designed form piloted on three articles before the review process started. Disagreements were resolved by a third reviewer. If the information was unavailable the articles were excluded. We planned a quantitative analysis of reduction of parasite load whether recorded as a categorical variable or the reduction of specific antibody titers. However insufficient data were available for quantitative analysis. We prepared a qualitative description of data identified.. We found only one randomized double blind placebo controlled trial. We also found six uncontrolled or non-randomized studies which were of some relevance and were therefore described. We found insufficient evidence to define the effects of drug treatment for people with CCC.. There is insufficient evidence to support the efficacy of nitrofurans or imidazolic drugs as recommended treatment in CCC and chronic T.cruzi infections, specifically if overt heart disease is present. A well designed randomized controlled trial is necessary to establish if new drugs are suitable for treatment of cardiac patients with CCC.

Topics: Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Clinical Trials as Topic; Humans; Imidazoles; Nifurtimox; Nitroimidazoles; Trypanocidal Agents

We present 2 patients who underwent orthotopic heart transplantation for end-stage Chagas' cardiomyopathy. Despite immunosuppressive therapy, postoperative prophylaxis with nifurtimox appeared to prevent Trypanosoma cruzi reactivation. Neither patient has shown signs of Chagas' myocarditis, and both are clinically well 12 and 72 months after transplantation. The successful outcome of our patients suggests that heart transplantation is a reasonable therapeutic option in patients with end-stage Chagas' cardiomyopathy.

Topics: Adult; Antiparasitic Agents; Chagas Cardiomyopathy; Female; Follow-Up Studies; Heart Transplantation; Humans; Immunosuppression Therapy; Middle Aged; Nifurtimox; Postoperative Care; Recurrence

Chagas disease, a vector-borne parasitosis caused by Trypanosoma cruzi, is endemic to Latin America and has spread to other countries due to immigration of infected persons. It is estimated that 160,000 people are infected in Chile, most of them in the chronic phase and without etiological treatment. The infection is confirmed by conventional serological methods while molecular methods have become in valuable tools to evaluate parasitemia in treated and non-treated chronic Chagas disease patients. The objective of this study was to determine, by conventional Polymerase Chain Reaction, the presence of T. cruzi kinetoplastid DNA in peripheral blood samples from 114 adult individuals with confirmed chronic Chagas disease, before and 6.6 years (average) after treatment with nifurtimox. The samples were received and preserved in guanidine-EDTA until DNA purification. Conventional PCR assays were performed in triplicate with T. cruzi kinetoplastid DNA primers 121 and 122. The amplified products were fractionated by electrophoresis in 2% agarose gels. A 330 bp product represented a positive assay. 84.2% (96 cases) and 6.1% (7 cases) of the samples taken before and after the treatment, respectively, were positive. The McNemar test showed a statistically significant difference between the groups of samples (p<0.001). Since serological negativization (the current cure criterion) delay many years after therapy and positive parasitological results represent a treatment failure, the conversion of pre-therapy positive conventional PCR is a qualitative and complementary tool that could be included in protocols of prolonged follow-up.

Topics: Adolescent; Adult; Aged; Chagas Cardiomyopathy; Chile; Chronic Disease; DNA, Protozoan; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nifurtimox; Polymerase Chain Reaction; Treatment Failure; Trypanosoma cruzi

Topics: Allopurinol; Chagas Cardiomyopathy; Chagas Disease; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Nifurtimox; Nitroimidazoles; Trypanocidal Agents

Parasite persistence after acute infection with Trypanosoma cruzi is an important factor in the development of Chagas disease (CD) cardiomyopathy. Few studies have investigated the clinical effectiveness of CD treatment through the evaluation of cardiological events by long term follow-up of treated children. Cardiological evaluation in children is challenging since features that would be diagnosed as abnormal in an adult's ECG may be normal, age-related findings in a pediatric ECG trace. The objective was to evaluate cardiac involvement in patients with Chagas disease with a minimum follow-up of 6 years post-treatment.. A descriptive study of a cohort of pediatric patients with CD treated with benznidazole (Bz) or nifurtimox (Nf) was conducted. Children (N = 234) with at least 6 years post CD treatment followed at the Parasitology and Chagas Service, Buenos Aires Children's Hospital (Argentina) were enrolled. By convenience sampling, children who attended a clinical visit between August 2015 and November 2019 were also invited to participate for additional cardiovascular studies like 24-hour Holter monitoring and speckle-tracking 2D echocardiogram (STE). Benznidazole was prescribed in 171 patients and nifurtimox in 63 patients. Baseline parasitemia data was available for 168/234 patients. During the follow-up period, alterations in routine ECG were observed in 11/234 (4.7%, 95% CI [2-7.4%]) patients. In only four patients, with complete right bundle branch block (cRBBB) and left anterior fascicular block (LAFB), ECG alterations were considered probably related to CD. During follow-up, 129/130 (99%) treated patients achieved persistent negative parasitemia by qPCR. Also decrease in T.cruzi antibodies titers was observed in all patients and negative seroconversion occurred in 123/234 (52%) patients.. A low incidence of cardiological lesions related to CD was observed in patients treated early for pediatric CD. This suggests a protective effect of parasiticidal treatment on the development of cardiological lesions and highlights the importance of early treatment of infected children.. ClinicalTrials.gov NCT04090489.

Topics: Adult; Cardiology; Chagas Cardiomyopathy; Chagas Disease; Child; Humans; Nifurtimox; Nitroimidazoles; Parasitemia; Trypanocidal Agents; Trypanosoma cruzi

This study aimed to describe the electrocardiographic and echocardiographic status of chronic Chagas disease (cChD) patients treated with nifurtimox.. An observational study was performed in 146 cChD patients followed over a mean of 7.9 years.. Of the 146 patients, 41 (28.1%) with normal electrocardiogram (ECG) at baseline maintained this condition, 34 (23.3%) with altered ECG at baseline normalised the alterations, and 46 (31.5%) with ECG abnormalities at baseline maintained this condition [23 (15.8%) with small alterations]. Finally, 25 cases (17.1%) in indeterminate phase altered the ECG. Differences before and after follow-up (P < 0.001) were found. The percentage of beneficial treatment was different than expected by chance (Z = 4.8; P < 0.001) and the annual percentage of cases that developed ECG alterations was lower than that of a historical cohort of untreated patients (P < 0.001). An echocardiogram was performed in 68 patients with baseline ECG alterations. The ejection fraction (EF) was normal in 57 (83.8%) and abnormal in 11 (16.2%). In 38 patients with ECG abnormalities that did not progress after treatment, EF and segmental motility (SM) were normal in 31 (81.6%) and 26 (68.4%), respectively. In 17 patients with ECG abnormalities, EF and SM were normal in 15 (88.2%) and 14 (82.4%) cases, respectively.. Less progression to cardiomyopathy compared with a historical untreated cohort as well as the EF/SM results in patients with abnormal ECG that did not progress and in indeterminate cChD that altered the ECG suggests a beneficial effect of nifurtimox.

Topics: Chagas Cardiomyopathy; Chagas Disease; Chile; Echocardiography; Electrocardiography; Follow-Up Studies; Humans; Nifurtimox

This study compared the serological and electrocardiographic evolution among patients with chronic T. cruzi infection treated during childhood or left untreated. A retrospective cohort study was conducted during a mean follow-up period of 25 years in 82 patients: half of them underwent treatment (nifurtimox 8, benznidazole 33) before being 15 years old, whereas the other half remained untreated. During the follow-up, negative seroconversion occurred in 92.7% of the treated children, while all the untreated ones remained positive for conventional serology. At baseline, 2 patients from each group had electrocardiographic abnormalities. During the study period, 4/41 (9.75%) and 9/41 (21.95%) of treated and untreated patients displayed an altered electrocardiogram, respectively. In multivariate analyses, the probability of developing electrocardiographic abnormalities was significantly reduced among treated patients (OR = 0.18, 95% CI = 0.04-0.79; p = 0.023). Electrocardiographic abnormalities attributable to Chagas cardiomyopathy were seen in 3 patients from the untreated group (complete right bundle branch block + left anterior fascicular block, frequent ventricular extrasystole, and left anterior fascicular block). The remarkable seronegativization seen in Benznidazole and Nifurtimox recipients underlines the parasiticidal effect of both compounds. Such demonstration along with the fact that CCC-related alterations were only present in the untreated group, reinforces the view of trypanocidal treatment in chronically T. cruzi-infected children as decreasing the risk for cardiomyopathy development.

Topics: Adolescent; Chagas Cardiomyopathy; Chagas Disease; Child; Follow-Up Studies; Humans; Nifurtimox; Nitroimidazoles; Retrospective Studies; Trypanocidal Agents; Trypanosoma cruzi

As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy.. To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease.. NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods.. In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved.. DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.

Topics: Acute Disease; Animals; Chagas Cardiomyopathy; Dipyridamole; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Male; Mice; Nifurtimox; Trypanocidal Agents

Trypanosoma cruzi, causative agent of Chagas disease, displays high intraspecific genetic diversity: six genetic lineages or discrete typing units (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a particular distribution pattern across the Americas, and is loosely associated with different transmission cycles and hosts. Several DTUs are known to circulate in Central America. It has been previously suggested that TcI infection is benign and does not lead to chronic chagasic cardiomyopathy (CCC).. In this study, we genotyped T. cruzi parasites circulating in the blood and from explanted cardiac tissue of an El Salvadorian patient who developed reactivation Chagas disease while on immunosuppressive medications after undergoing heart transplant in the U.S. as treatment for end-stage CCC. Parasite typing was performed through molecular methods (restriction fragment length polymorphism of polymerase reaction chain amplified products, microsatellite typing, maxicircle sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as lineage-specific serology. We show that the parasites infecting the patient belong to the TcI DTU exclusively. Our data indicate that the parasites isolated from the patient belong to a genotype frequently associated with human infection throughout the Americas (TcIDOM).. Our results constitute compelling evidence in support of TcI DTU's ability to cause end-stage CCC and help dispel any residual bias that infection with this lineage is benign, pointing to the need for increased surveillance for dissemination of this genotype in endemic regions, the USA and globally.

Topics: Adult; Chagas Cardiomyopathy; DNA, Protozoan; Heart Transplantation; Humans; Male; Nifurtimox; Nitroimidazoles; Phylogeny; Recurrence; Trypanocidal Agents; Trypanosoma cruzi

Topics: Animals; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Chagas Disease; Death, Sudden, Cardiac; Defibrillators, Implantable; Disease Management; Heart Failure; Humans; Insect Control; Insect Vectors; Nifurtimox; Nitroimidazoles; Thromboembolism; Treatment Outcome; Trypanocidal Agents; Trypanosoma cruzi

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.

Topics: Adolescent; Adult; Antibodies, Protozoan; Chagas Cardiomyopathy; Child; Chronic Disease; Disease Management; Drug Administration Schedule; Humans; Nifurtimox; Nitroimidazoles; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Trypanocidal Agents; Trypanosoma cruzi

Nifurtimox is one of the two molecules used for treatment of Chagas disease. Although posology has not yet been clearly defined, nifurtimox is increasingly used, especially in combination with eflonithin. Nifurtimox is perfectly suited to the WHO's Chagas disease eradication program.

Topics: Chagas Cardiomyopathy; Chagas Disease; Drug Therapy, Combination; Eflornithine; Humans; Nifurtimox; Treatment Outcome; Trypanocidal Agents; Trypanosoma cruzi

Cardiomyopathy is the most common clinical form of Chagas' disease in Colombia, and one treatment option is a heart transplant. Tracking the behavior of the Chagas' parasite, Trypanosoma cruzi, is a priority due to the risk of post-transplant reactivation of the infection.. A case is presented of a patient who had suffered from dilated chagasic cardiopathy and cardiac failure, and had subsequently undergone heart transplant. The case was monitored by PCR, histopathological and echocardiographic examinations.. Blood samples were drawn before and after the transplant, and post-transplant endomyocardial biopsies were taken. The extracted DNA was amplified with the TcH2AF-R and S35-S36 primers. Parasitemia was examined by the microhematocrit test. In addition, histopathological studies determined the parasite presence and transplant rejection status. Echocardiograms were administered to evaluate cardiac function.. Of the blood samples taken 83 and 48 days pre-transplant, the latter was positive by the S35-S36 PCR test. PCR tests in blood with both primers were negative up to the second month post-transplant. However, both PCR tests were positive by the third month post-transplant. Thereupon, the patient was treated with nifurtimox. Both tests presented negative results in blood 35 days after treatment was started and remained negative thereafter at 0, 3, 10 and 12 months post-treatment. The pathology, microhematocrit, and PCR test results from biopsies were negative on all the specified dates.. PCR tests were used as indicators of a reactivation of trypanosomid infection in the patient. After treatment administration, PCR tests became negative. The patient's clinical evolution was favorable.

Topics: Animals; Chagas Cardiomyopathy; Colombia; DNA Primers; Female; Follow-Up Studies; Heart; Heart Transplantation; Humans; Middle Aged; Nifurtimox; Polymerase Chain Reaction; Trypanocidal Agents; Trypanosoma cruzi

Topics: Abdominal Pain; Chagas Cardiomyopathy; Chagas Disease; Diagnosis, Differential; Flank Pain; Heart Aneurysm; Humans; Infarction; Kidney; Magnetic Resonance Imaging; Male; Middle Aged; Nifurtimox; Radiography, Abdominal; Tomography, X-Ray Computed; Trypanocidal Agents; Ultrasonography

Topics: Chagas Cardiomyopathy; Chagas Disease; Clinical Trials as Topic; Drug Administration Schedule; Drug Eruptions; Humans; Meta-Analysis as Topic; Nifurtimox; Nitroimidazoles; Polyneuropathies; Trypanocidal Agents; Trypanosoma cruzi; United States

In this study is presented the comparative therapeutical experience comparing the Allopurinol, Benznidazol y Nifurtimox, in a prospective following in a long term, considering the responses to the parasitemia, specific serology and evolution of the clinic manifestations and complementaries in the 535 chronic chagasic cases (44.5%), instead of 668 patients who did not get any treatment (1203 chagasic cases followed for more than 5 years average). This study was done between April 1984 and April 1994 in patients with and without cardiopathy, in the Córdoba Hospital and the Salud Estudiantil Direccion, Universidad Nacional de Córdoba (U.N.C.); from them, 309 patients were given Allopurinol, 130 were given Benznidazol, and 96 were given Nifurtimox, with usual doses of Benznidazol and Nifurtimox, but with Allopurinol it was made an study evaluating the answering-doses, with a following time of post-therapeutic average of 55.6 months (D.S. = + -57 m.) The comparative parameters were the starting clinic characteristics, the qualitative and quantitative for Chagas, the pre-treatment xerodiagnostic, the treatment fulfillment, the treatment duration, the adverse effects, the treatment abandon, the time of postreatment longitudinal following till the last clinic-complementary evaluation, the clinic characteristics at the end of the following period; quantitative and qualitative serology for Chagas after the treatment, and post-treatment xerodiagnostic. It was observe a prevalence of Electrocardiographic Changes in the ECG in rest, in the first complementary evaluation in 76 of the 535 "Treated" and in the 225 "No-treated" patients, being Electrocardiographic abnormality proportion much more in the "No-treated" patients (P = 0.000000). After the end of the following period it was thought to have been found Miocardic Damage Progression in 120 patients "No-treated" and in 31 "Treated" patients (17.9% and 5.8% respectively) (P = 0.0000000). The complications in the evolution course were proved in 113 of the "No-treated" and in 19 of the "Treated" patients (16.9% and 3.5%, being this a statistically significant difference (P = 0.0000000). The mortality along the evolution was proved in 37 of the "No-Treated:" patients and in 7 of the "Treated" patients (5.5% and 1.3%), being this a statistically significant difference (P = 0.00019). The most tolerated drug and the one with the least incidence of therapeutic abandons was the Allopurinol. The xerodiagnostic negativization

Topics: Adolescent; Adult; Aged; Allopurinol; Antiprotozoal Agents; Chagas Cardiomyopathy; Chagas Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nifurtimox; Nitroimidazoles; Prospective Studies; Retrospective Studies; Time Factors; Treatment Outcome; Trypanocidal Agents

Reactivation of Chagas' disease in immuno-compromised hosts may represent a recognizable clinical syndrome that can be diagnosed by examination of skin biopsy specimens of characteristic lesions resembling ordinary bacterial cellulitis. This syndrome appears to result in significant morbidity, which can be avoided with the institution of prophylactic therapy for Chagas' disease. An awareness of this complication of immunosuppression is of paramount importance for the thousands of asymptomatic persons infected with Chagas' disease currently living in the United States and abroad.

Topics: Adult; Antiparasitic Agents; Biopsy; Cellulitis; Chagas Cardiomyopathy; Chagas Disease; Diagnosis, Differential; Heart Transplantation; Humans; Leg Dermatoses; Male; Nifurtimox; Recurrence; Skin Diseases, Parasitic

Topics: Animals; Chagas Cardiomyopathy; Chagas Disease; Nifurtimox; Nitroimidazoles; Rabbits; Trypanocidal Agents

Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi-infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma.

Topics: Animals; Chagas Cardiomyopathy; Female; Injections, Intraperitoneal; Lymphoma, Non-Hodgkin; Male; Myocarditis; Myositis; Nifurtimox; Nitrofurans; Nitroimidazoles; Rabbits; Trypanosoma cruzi

Topics: Animals; Antibodies, Protozoan; Betamethasone; Chagas Cardiomyopathy; Cyclophosphamide; Drug Therapy, Combination; Electrocardiography; Female; Mice; Mice, Inbred BALB C; Nifurtimox; Nitrofurans; Random Allocation; Recurrence; Trypanosoma cruzi

Topics: Acute Disease; Chagas Cardiomyopathy; Chagas Disease; Diet, Sodium-Restricted; Furosemide; Humans; Isosorbide Dinitrate; Male; Middle Aged; Nifurtimox

Topics: Animals; Chagas Cardiomyopathy; Chagas Disease; Female; Intestinal Diseases, Parasitic; Mice; Mice, Inbred Strains; Myositis; Nifurtimox; Nitroimidazoles; Trypanocidal Agents

After the successful struggle against malaria, smallpox and tuberculosis, Chagas' disease must be considered the commonest and most serious scourge of the American continent. Experts assess the number of persons suffering from Chagas' disease at about 7 millions with about 35 millions at risk. The acute infection with Trypanosoma cruzi in the blood stream is found chiefly in children in the first few years of life but rarely in adults. Mortality in the acute phase is about 10%. The disease tends to run a chronic course. After an asymptomatic phase (usually 10--12 years), chronic Chagas' myocarditis dominates the chronic form. A great therapeutic advance has been achieved with the nitrofurfurylidene preparation Lampit. For the first time it has become possible to eliminate trypanosomes found in both blood and tissues. Success is particularly to be expected in the treatment of the acute infection.

Topics: Animals; Central America; Chagas Cardiomyopathy; Chagas Disease; Disease Vectors; Hemiptera; Humans; Infant; Nifurtimox; South America; Trypanosoma cruzi