Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment

BACKGROUND The current chemotherapy for Chagas disease is based on monopharmacology with low efficacy and drug tolerance. Polypharmacology is one of the strategies to overcome these limitations. OBJECTIVES Study the anti-Trypanosoma cruzi activity of associations of benznidazole (Bnz) with three new synthetic T. cruzi-triosephosphate isomerase inhibitors, 2, 3, and 4, in order to potentiate their actions. METHODS The in vitro effect of the drug combinations were determined constructing the corresponding isobolograms. In vivo activities were assessed using an acute murine model of Chagas disease evaluating parasitaemias, mortalities and IgG anti-T. cruzi antibodies. FINDINGS The effect of Bnz combined with each of these compounds, on the growth of epimastigotes, indicated an additive action or a synergic action, when combining it with 2 or 3, respectively, and an antagonic action when combining it with 4. In vivo studies, for the two chosen combinations, 2 or 3 plus one fifth equivalent of Bnz, showed that Bnz can also potentiate the in vivo therapeutic effects. For both combinations a decrease in the number of trypomastigote and lower levels of anti-T. cruzi IgG-antibodies were detected, as well clear protection against death. MAIN CONCLUSIONS These results suggest the studied combinations could be used in the treatment of Chagas disease.

Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination

Abstract INTRODUCTION: Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination. METHODS: T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data. RESULTS: On the 4th day, no parasites were observed in any of the treated cultures. CONCLUSIONS: Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.

Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations

Eukaryotic initiation factor 5A (eIF5A) is a conserved protein with an essential role in translation elongation. Using one and two-dimensional western blotting, we showed that the eIF5A protein level was 2-fold lower in benznidazole (BZ)-resistant (BZR and 17LER) Trypanosoma cruzi populations than in their respective susceptible counterparts (BZS and 17WTS). To confirm the role of eIF5A in BZ resistance, we transfected BZS and 17WTS with the wild-type eIF5A or mutant eIF5A-S2A (in which serine 2 was replaced by alanine). Upon overexpressing eIF5A, both susceptible lines became approximately 3- and 5-fold more sensitive to BZ. In contrast, the eIF5A-S2A mutant did not alter its susceptibility to BZ. These data suggest that BZ resistance might arise from either decreasing the translation of proteins that require eIF5A, or as a consequence of differential levels of precursors for the hypusination reactions (e.g., spermidine and trypanothione), both of which alter BZ's effects in the parasite.

Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease

PA-824 is a novel bicyclic nitroimidazole anti-tuberculosis (TB) drug. Cordyceps sinensis (Berk.) Sacc. (CS) was proven to be a good immunomodulatory compound. This research aimed to investigate the effect of CS on PA-824 in Mycobacterium tuberculosis (M.tb) infected mice (female CBA/J mice, 6 to 8 weeks of age and 20±2 g of weight). Mice were randomly assigned to 4 groups: PA-824, CS, PA-824+CS, and control. To verify the effect of PA-824 and CS on M.tb, after drug administration, mice lungs were harvested and bacterial colony formations were measured. Cells were isolated from infected lungs and spleens to analyze the percentage of CD4+ T cells (CD11a positive). Lung cells were cultured to detect the secretion of interferon-γ (IFN-γ) and interleukin-10 (IL-10) by ELISA. IFN-γ and IL-10 double-positive CD4+ cells in peripheral blood were measured by flow cytometry. The expression levels of IL-2 and IL-10 in mice lungs were analyzed by real-time PCR and western blot. Results showed that PA-824 combined with CS led to the lowest lung colony-forming units (CFU) counts among treated groups. Furthermore, this beneficial outcome might be associated with the decreased CD11a on CD4+ cells in mice lungs and spleens. Moreover, the suppressed secretion of IFN-γ and IL-10, and IL-10 expressions, as well as the decreased IFN-γ and IL-10 double-positive CD4+ cells in blood, could also be associated with the positive effect. However, no significant effect on IL-2 production was found. The combination of PA-824 and CS had more effective bacteriostatic and immunomodulatory effects on M.tb infected mice than PA-824 alone. In conclusion, CS has the potential to be an effective adjuvant in TB treatment.

A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole

Benznidazole (BZ) is one of the two drugs used for Chagas disease treatment. Nevertheless therapeutic failures of BZ have been reported, which were mostly attributed to variable drug susceptibility among Trypanosoma cruzi strains. ATP-binding cassette (ABC) transporters are involved in a variety of translocation processes and some members have been implicated in drug resistance. Here we report the characterisation of the first T. cruzi ABCG transporter gene, named TcABCG1, which is over-expressed in parasite strains naturally resistant to BZ. Comparison of TcABCG1 gene sequence of two TcI BZ-resistant strains with CL Brener BZ-susceptible strain showed several single nucleotide polymorphisms, which determined 11 amino acid changes. CL Brener transfected with TcI transporter genes showed 40-47% increased resistance to BZ, whereas no statistical significant increment in drug resistance was observed when CL Brener was transfected with the homologous gene. Only in the parasites transfected with TcI genes there was 2-2.6-fold increased abundance of TcABCG1 transporter protein. The analysis in wild type strains also suggests that the level of TcABCG1 transporter is related to BZ natural resistance. The characteristics of untranslated regions of TcABCG1 genes of BZ-susceptible and resistant strains were investigated by computational tools.

New Therapeutic Strategies against Helicobacter pylori / 대한소화기학회지

The standard therapy for Helicobacter pylori infection in Korea is a triple-drug regimen consisting of a proton pump inhibitor with two antibiotics such as clarithromycin, amoxicillin, and metronidazole. However, as the eradication rate of this regimen has declined over the past decade, this prompted the formulation of new therapeutic regimens. New therapeutic strategies against H. pylori infection that had been tried all over the world include sequential therapy, concomitant therapy, and tailored therapy This article will review the basic concepts and the results of previous clinical trials on the aforementioned new therapeutic regiments.

A Comparative Study for Efficacy and Tolerability of Satranidazole Plus Ofloxacin Versus Ornidazole Plus Ofloxacin in Periodontal Infections.

Periodontal infections and related conditions like Chronic Gingivitis, Chronic Periodontitis, Pericoronitis, Peridontal & Periapical Abscess are common clinical problems, but sometimes Gingivitis and Periodontitis can be acute also. These all are generally treated by scaling and root planning, but studies have reported that despite conventional periodontal therapy certain sites continue to show periodontal tissue destruction. These periodontal infections can be controlled by antibiotics which are effective against Gram-negative aerobic and anaerobic bacteria and has good penetration in periodontal tissues. Objective: The purpose of the present study was to compare the efficacy and tolerability of a fixed dose combination of Satranidazole (300 mg) plus Ofloxacin (200 mg) versus fixed dose combination of Ornidazole (500 mg) plus Ofloxacin (200 mg) for the treatment of periodontal infections. Methods : One hundred and twelve adult patients (59 females and 53 males) with moderate to advanced periodontitis were enrolled and given fixed dose combination of Satranidazole (300 mg) plus Ofloxacin (200 mg) or Ornidazole (500 mg) plus Ofloxacin (200 mg) orally two times daily. Clinical assessment like Gingival Index, Periodontal Index, Mobility Index and VAS Score were done before and after the treatment. Clinical evaluation was performed on 3rd and 5th day after treatment. Results : At the baseline the values for Gingival Index, Periodontal Index, Mobility Index and VAS Score were comparable in both the groups. Both the treatment group have shown attenuation of Gingival Index, Periodontal Index, Mobility Index and VAS Score. However, treatment with Satranidazole plus Ofloxacin showed significantly (p< 0.05) better improvement in all clinical parameters compared to Ornidazole plus Ofloxacin treatment. Treatment with Satranidazole plus Ofloxacin was well tolerated and no serious adverse event was observed. 6 patients (15%) with Ornidazole plus Ofloxacin have shown side effects, which resulted in discontinuation of therapy. These side effects include allergy, nausea, vomiting & acidity. Conclusion : This study concludes that efficacy and tolerability of fixed dose combination of Satranidazole (300 mg) plus Ofloxacin (200 mg) is better than fixed dose combination of Ornidazole (500 mg) plus Ofloxacin (200 mg) in treatment of periodontal infections.

The level of ascorbate peroxidase is enhanced in benznidazole-resistant populations of Trypanosoma cruzi and its expression is modulated by stress generated by hydrogen peroxide

Ascorbate peroxidases (APX) are class I heme-containing enzymes that convert hydrogen peroxide into water molecules. The gene encoding APX has been characterized in 11 strains of Trypanosoma cruzi that are sensitive or resistant to benznidazole (BZ). Bioinformatic analysis revealed the presence of two complete copies of the T. cruzi APX (TcAPX) gene in the genome of the parasite, while karyotype analysis showed that the gene was present in the 2.000-kb chromosome of all of the strains analyzed. The sequence of TcAPX exhibited greater levels of similarity to those of orthologous enzymes from Leishmania spp than to APXs from the higher plant Arabidopsis thaliana. Northern blot and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed no significant differences in TcAPX mRNA levels between the T. cruzi strains analyzed. On the other hand, Western blots showed that the expression levels of TcAPX protein were, respectively, two and three-fold higher in T. cruzi populations with in vitro induced (17 LER) and in vivo selected (BZR) resistance to BZ, in comparison with their corresponding susceptible counterparts. Moreover, the two BZ-resistant populations exhibited higher tolerances to exogenous hydrogen peroxide than their susceptible counterparts and showed TcAPX levels that increased in a dose-dependent manner following exposure to 100 and 200 µM hydrogen peroxide.

Sensibilidad al benzonidazol de cepas de Trypanosoma cruzi sugiere la circulación de cepas naturalmente resistentes en Colombia / Trypanosoma cruzi strains resistant to benznidazole occurring in Colombia

Introducción. La enfermedad de Chagas, causada por Trypanosoma cruzi, es uno de los problemas más graves de salud pública en el continente americano. El benzonidazol es uno de los dos medicamentos utilizados para tratar la enfermedad de Chagas. Sin embargo, la variación de la sensibilidad del parásito a este medicamento es una de las principales causas del fracaso del tratamiento. Objetivo. Evaluar la sensibilidad in vitro al benzonidazol de cepas colombianas de T. cruzi de diferentes orígenes y procedencia geográfica. Materiales y métodos. Treinta y tres cepas colombianas de T. cruzi aisladas de humanos, vectores y mamíferos, se analizaron in vitro mediante el micrométodo enzimático de MTT para determinar la concentración inhibitoria 50 (CI50) al benzonidazol. Se estudió la correlación entre la sensibilidad in vitro al medicamento y diferentes parámetros biológicos y eco-epidemiológicos. Resultados. El análisis de sensibilidad al medicamento indicó que el 36 % de las cepas eran sensibles, el 48 %, parcialmente resistentes y, el 16 %, resistentes al benzonidazol. Los análisis de correlación entre las CI50 con algunos parámetros biológicos y eco-epidemiológicos, mostraron diferencias en cuanto a la sensibilidad según el origen biológico y el área geográfica de procedencia de la cepa. Conclusiones. Existe una gran variabilidad en cuanto a la sensibilidad al benzonidazol de las cepas circulantes de T. cruzi en Colombia, lo cual sugiere la presencia de cepas naturalmente resistentes en el país.

Introduction. Chagas disease caused by Trypanosoma cruzi is one of the most serious public health problems in the Americas. Benznidazole is one of two drugs used to treat Chagas´ disease. However, the variation in susceptibility of the parasite to this drug is one of the main causes of treatment failure. Objective. The in vitro susceptibility to benznidazole was assessed in Colombian strains of T. cruzi from several sources and geographical regions. Materials and methods. Thirty-three Colombian T. cruzi strains were isolated from humans, vectors and mammals. These were analyzed in vitro by the MTT enzymatic micromethod to determine the IC50 to benznidazole. Additionally, the in vitro susceptibility was correlated with several biological and ecoepidemiological parameters. Results. Thirty-six percent of the strains were considered to be sensitive, 48% partially resistant, and 16% were resistant. Correlations between the IC50 and several biological and eco-epidemiological parameters indicated that differences in susceptibility depended on the biological source and geographical origin of the strain. Conclusions. A high degree of variability exists in the susceptibility to benznidazole of T. cruzi strains in Colombia. The distribution data indicate the presence and circulation of naturally resistant strains.

Evaluación de ELISA F29 como marcador de eficacia del tratamiento etiológico en la enfermedad de Chagas / Assessment of ELISA F29 as a marker of etiological treatment efficacy for Chagas disease

A transversal study was performed on sera from chronic chagas ic patients treated with nifurtimox (Nx) or benznidazole (Bz), in order to evaluate the Trypanosoma cruzi flagellar calcium-binding protein (F29) as a marker for therapeutic effectiveness. An ELISA was used with these F29 recombinant antigen, and its relation to conventional serology (CS) and parasitological and clinical evolution was analysed. Sera from 118 patients with retrospective, serological, parasitological and clinical information was available, were analyzed. Patients were grouped into: A) 30 treated patients whose CS became negative after treatment; B) 34 treated patients whose CS remained positive; C) 54 untreated patients. A double-blind trial was conducted simultaneously in all serum samples, by means ofCS (indirect hemagglutination, direct agglutination and indirect immunofluorescence) and ELISA F29. The ELISA F29 test was non reactive in: 100 percent of group A, 82.4 percent of group B and 13 percent> of group C. The infected patients who presented electrocardiographic alterations compatible with chronic chagasic myocardiopathy (n = 11) were reactive for ELISA F29. All patients whose parasitological studies (xenodiagnosis and/or strout method) were positive presented a high reactivity to the ELISA F29 test. The correlation between ELISA F29 and CS was statistically significant (p < 005) in the treated group whose CS was non reactive (group A) and the untreated group (group C). As opposed to this, in the group of treated patients whose CS remained positive (group B), the ELISA F29 test was reactive only in a 17.6 percent>. These results suggest that the fast and user-friendly ELISA F29 test could be useful to monitor changes after trypanocidal treatment.

La proteína flagelar F29 es una proteína ligadora de calcio del Trypanosoma cruzi. En el presente trabajo se realizó un estudio transversal en sueros de pacientes con infección crónica por T. cruzi tratados con nifurtimox (Nx) o benznidazol (Bz) y no tratados, para evaluar el antígeno F29 como marcador de eficacia terapéutica. Se utilizó un ensayo inmuno-enzimático con la proteína recombinante F29 (ELISA F29) y se analizó su relación con la serología convencional (SC) y la evolución parasitológica y clínica en esos pacientes. Se estudiaron 118 sueros de pacientes que formaban parte de una cohorte, de los cuales se disponía de información retrospectiva, serológica, parasitológica y clínica. Los pacientes se dividieron en 3 grupos: A) 30 tratados negativizaron SC post-tratamiento; B) 34 tratados permanecieron con SC reactiva; C) 54 no tratados. Las muestras de suero se procesaron a doble ciego en forma simultánea mediante serología convencional (hemoaglutinación indirecta, aglutinación directa e inmunofluorescencia indirecta) y ELISA F29. El test ELISA F29 resultó no reactivo en: 100 por ciento del grupo A, 82,4 por ciento del grupo B y 13 por ciento del grupo C. Los infectados con alteraciones electrocardiográficas compatibles con miocardiopatía chagásica crónica (n = 11) fueron reactivos al ELISA F29. Los pacientes en quienes los estudios parasitológicos (xenodiagnóstico y/o strout) fueron (+) presentaron elevada reactividad al ELISA F29. La correlación entre ELISA F29 y SC en los pacientes tratados con SC no reactiva (grupo A) y no tratados (grupo C), fue significativa (p < 0,05). En cambio, en pacientes tratados que mantuvieron la SC reactiva (grupo B) el test de ELISA F29 fue reactivo sólo en 17,6 por ciento. Estos resultados sugieren que el test ELISA F29, rápido y sencillo, podría ser útil para monitorear cambios post-tratamiento tripanocida.

Anticonvulsant activities of new 1,4-dihydropyridine derivatives containing 4-nitroimidazolyl substituents

Anticonvulsant activity of Alkyl, cycloalkyl and arylalkyl ester analogues of nifedipine in which the ortho-nitro phenyl group at position 4 is replaced by 1-methyl-4-nitro-5-imidazolyl substituent, were determined against pentylenetetrazole-induced seizures in mice. The anticonvulsant effects of the compounds were evaluated by the measurement of seizure latency and duration. Significant differences were observed between treated animals with control group and nifedipine in seizure duration. Our results show that most of the compounds had similar activity to the reference drug nifedipine. In addition, compounds 6a, 6b, 6f, 6g, 6h, 8e, 8f, 8g, 8h and 8i were more active than the reference drug nifedipine

Trypanosoma cruzi: susceptibility to chemotherapy with benznidazole of clones isolated from the highly resistant Colombian strain

The present investigation was performed to evaluate the susceptibility of seven clones isolated from the highly resistant Colombian strains, prototype of Biodeme Type III. Seven clones previously obtained, showed a phenotypic homogeneity and high similarity with the parental strain. Eight groups of 30 mice were inoculated with one of seven clones or the parental strain; 20 were treated with benznidazole (100mg/kg/day) and 10 were untreated controls. Cure evaluations were done by parasitological and serological tests and PCR. Cure rates varied from 0 percent (null) to 16.7 percent. Correlation between positivity of parasitological and serological tests with positive PCR reached 37 percent. The results demonstrated the high resistance of the clones, suggesting the predominance of a highly resistant principal clone in this strain. The findings apparently indicate that the possibility of cure is minimal for patients infected with this biodeme; a fact that could affect the control of Chagas' disease through treatment of chronically infected people

Biological characterization of Trypanosoma cruzi strains

Biological parameters of five Trypanosoma cruzi strains from different sources were determined in order to know the laboratory behaviour of natural populations. The parameters evaluated were growth kinetics of epimastigotes, differentiation into metacyclic forms, infectivity in mammalian cells grown in vitro and parasite susceptibility to nifurtimox, benznidazole and gentian violet. Differences in transformation to metacyclic, in the percentage of infected cells as well as in the number of amastigotes per cell were observed among the strains. Regarding to pharmacological assays, Y strain was the most sensitive to the three assayed compounds. These data demonstrate the heterogeneity of natural populations of T. cruzi, the only responsible of infection in humans

Avaliaçäo do tratamento especifíco para Trypanosoma cruzi em crianças, na evoluçäo da fase indeterminada / Specific treatment evaluation for Trypanosoma cruzi in children, in the evolution of the indeterminate phase

Doze pacientes com idades entre 7 a 12 anos, na forma indeterminada da doença de Chagas, com sorologia e xenodiagnóstico positivos, receberam tratamento específico. Dois pacientes tomaram 7mg/kg de nifurtimox durante 60 e 90 dias e 10 usaram 5-7mg/kg de benznidazol durante 60 dias. A evoluçäo clínica foi verificada através de exame clínico, eletrocardiograma, exame radiológico contrastado do esôfago. Após o tratamento somente uma (8,3 por cento) paciente apresentou todos os exames negativos. Oito deles foram avaliados após oito anos do tratamento e 4 acompanhados durante 20 anos. Sete (58,4 por cento) permaneceram na forma indeterminada e 4 (33,3 por cento) chagásicos progrediram clinicamente para cardiopatia grau II e/ou esofagopatia, apesar do tratamento precoce. Säo necessários estudos com maior número de crianças na fase indeterminada e acompanhamento a longo prazo para se estabelecer a influência do tratamento específico na evoluçäo da doença de Chagas

Reativaçäo da infecçäo por Trypanosoma cruzi em paciente com síndrome de imunodeficiência adquirida / Reactivation of Trypanosoma cruzi ifection in a patient with acquired immunodeficiency syndrome

Uma paciente com síndrome de imunodeficiência adquirida (SIDA) e doença de Chagas, com xenodiagnóstico positivo, estava em uso prolongado de cetoconazol com o objetivo de suprimir a parasitemia e prevenir a reativaçäo da doença de Chagas. O cetoconazol foi suspenso inadvertidamente após 6 meses de uso. Um mês após, a paciente foi internada com febre, cefaléia, vomitos, taquicardia e hepatoesplenomegalia. Tanto o xenodiagnóstico como o exame de sangue a fresco demonstraram a presença de Trypanosoma cruzi. O tratamento com benzonidarol foi instituído, com supressäo da parasitemia. A paciente desenvolveu concomitantemente uma provável neurotoxopiasmose, evoluindo para o óbito em septcemia. A necropsia, näo foram encontrados parasitas

Nova rota de síntese do megazol [1-metil-2-(5-amino-1,3,4-tiadiazol-2-il)-5-nitroimidazol], um antiparasitário ativo contra o Trypanosoma cruzi / A new synthetic route of megazol [1-methyl-2-(5-amino-1,3,4-thiadiazol-2-yl)-5-nitroimidazol], an anti-Trypanosoma cruzi agent

Em 1968, um composto do tipo 5-nitroimidazol, o megazol, foi sintetizado por Berkelhammer e Asato e demonstrou largo espectro de ação biológica. Em 1980, pesquisadores brasileiros determinaram excelente atividade desta molécula contra o Trypanosoma cruzi em ratos. Constam da literatura somente três rotas para obtenção deste fármaco, que podem ser otimizadas no tocante ao aumento da produtividade e minimizacao dos riscos. A nova rota, ora proposta, é uma alternativa para a síntese do megazol e abre caminhos para obtenção de seus análogos estruturais

Comparative study of the efficacy and tolerability of Secnidazole suspension (single dose) and Tinidazole suspension (two days dosage) in the treatment of amebiasis in children

Amebiasis caused by Entamoeba histolytica may be considered the most aggressive parasitic disease affecting human intestine, causing acute amoebic colitis and extra-intestinal diseases of high morbidity and mortality. 5-nitroimidazoles are the drugs of choice. In this multicenter, open and randon clinical trial, the efficacy and tolerability of secnidazole suspension in a single oral dose of 1ml/kg was compared with 0.5ml/kg doses of tinidazole suspension given for 2 consecutive days to 303 Entamoeba histolytica-positive children aged 2 to 13. Patients with extra-intestinal complications were excluded from the study. Clinical and parasitological follow-up using the Faus and Kato-Katz method were carried out 7, 14, and 21 days after treatment. Clinical improvement/cure was observed in 93 percent of the patients in the secnidazole group and 91 percent in the tinidaloze group. Parasitological sucess was reported for 77 percent and 63 percent of the secnidazole and tinidazole patients, respectively, showing a significant statistical difference between the two groups (p=0.007). Both drugs were well tolerated, and the adverse effects reported were mild, consisting mainly of digestive disturbances. This comparative study showed that a single oral dose of 1ml/kg of secnidazole produced a significantly higher parasitological cure rate than 2 doses of tinidazole. Secnidazole is a safe and effective drug for the treatment of uncomplicated intestinal amebiasis.

Antibacterianos de acción sistémica, parte II: otros grupos de antibióticos / Systemic antibacterial drugs, part II: other groups of antibiotics

Se presenta la segunda parte de una revisión bibliográfica sobre los antibacterianos de acción sistémica, la cual incluye grupos de antibióticos tan importantes como aminociclitoles, aminoglucósidos, diaminopirimidinas, estreptograminas, fosfomicinas, fusidanos, glicopéptidos, lincosamidas, macrólidos, nitrofuranos, nitroimidazoles, polipéptios, quinolonas y rifamicinas

Enfermedad de Chagas crónica: efectos del tratamiento en los niveles de anticuerpos hacia antígenos crudos y semipurificados del trypanosoma cruzi / Chagas chronic disease: effects of treatment in antibodies levels to crude and partially purified trypanosoma cruzi antigens

The specific therapy in chagas' disease is useful in acute and neonatal infection and in children under three years old. The results of antiparasitic treatment during chronic infection are still controversial. It will be interesting to analyze the serological behavior in patients treated during chronic infection, to advance in the search of evolutive markers and markers of therapeutic efficacy. In the present work we have measured the antibody response by conventional serology and the response to partially purified T. cruzi antigens in chagasic patients who received nifurtimox or benznidazol 2 to 20 years before. The results showed that, by indirect immunofluorescence in 20 percent of treated patients the antibody levels were below the established cut off (1:32). By indirect hemagglutination 55 percent of treated patients showed this serological behavior. In this group a high number of discordant results was observed. By immunoenzimatic assay it was possible to detect a significative decrease of serologic reactivity to a partially purified acidic antigen (F IV) and to exoantigen of T. cruzi. It will be interesting to perform longitudinal surveys employing these antigens, to go further in the knowledge of possible immunological evolutive markers in Chagasïdisease

Evaluation of secnidazole gel and tinidazole suspension in the treatment of giardiasis in children

Giardiasis is a cosmopolitan parasitosis. Diarrhea, abdominal colic, and flatulence are the main clinical symptoms, however, malabsorption, and impairment of growth of children may occur. The 5-nitroimidazoles are drugs of choice in the treatment of giardiasis. Methods: The efficacy and tolerability of secnidazole and tinidazole were evaluated in a randomized, open-label clinical trial performed with 267 Giardia lamblia-positive children. Secnidazole , in a new gel formulation, and tinidazole suspension were prescribed as single oral doses of 30mg/kg and 50mg/kg, respectively. Clinical and parasitological follow-up was carried out before, and at 7, 14, and 21 days after treatment. Results: Clinical cure was observed in 77,3 percent and 75,7 percent of the patients in the secnidazole and tinidazole groups, respectively. Parasitological cure was obtained in the 91,3 percent and 89,6 percent in the secnidazole and tinidazole groups, respectively. A metallic taste after drug ingestion was more commonly reported in the tinidazole group than in the secnidazole group (p<0.05). Conclusions: The authors conclude that both secnidazole gel and tinidazole administered as a single oral dose are effective treatments for children with giardiasis since both high cure rates and good tolerability were observed