RESUMEN
Chagas disease (ChD), caused by Trypanosoma cruzi, has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF. Treatment response was evaluated by clinical, parasitological, and serological after-treatment evaluation. A total of 289 patients were enrolled, of which 199 were children and 90 adults. At diagnosis, 89.6% of patients were asymptomatic. Overall, all symptomatic patients showed clinical improvement. At baseline, parasitemia was positive in 130 of 260 (50%) patients. All but one adult patient had cleared their parasitemia by the end of treatment. That patient was considered a treatment failure. Median follow-up time for children was 37.7 months, with an interquartile range of (IQR25-75 12.2 to 85.3), and for adults was 14.2 months (IQR25-75, 1.9 to 33.8). After treatment, a decrease of T. cruzi antibodies and seroconversion were observed in 34.6% of patients. The seroconversion profile showed that, the younger the patient, the higher the rate of seroconversion (log rank test; P value, <0.01). At least 20% seroreduction at 1 year follow-up was observed in 33.2% of patients. Nifurtimox was highly effective for ChD treatment. Patients had excellent treatment responses with fully resolved symptoms related to acute T. cruzi infection. Clearance of parasitemia and a decrease in T. cruzi antibodies were observed as markers of treatment response. This study reinforces the importance of treating patients during childhood since the treatment response was more marked in younger subjects. (This protocol was registered at ClinicalTrials.gov under registration number NCT04274101).
Asunto(s)
Enfermedad de Chagas , Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Adulto , Anticuerpos Antiprotozoarios , Enfermedad de Chagas/tratamiento farmacológico , Niño , Estudios de Cohortes , Humanos , Nifurtimox/uso terapéutico , Nitroimidazoles/uso terapéutico , Parasitemia/tratamiento farmacológico , Estudios Retrospectivos , Tripanocidas/uso terapéuticoRESUMEN
Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, data on NF safety are scarce, and many physicians defer or refuse NF treatment because of concerns about drug tolerance. In a retrospective study of adverse drug reactions (ADRs) associated with NF treatment of ChD, children received NF doses of 10 to 15 mg/kg/day for 60 to 90 days, and adults received 8 to 10 mg/kg/day for 30 days. A total of 215 children (median age, 2.6 years; range, 0 to 17 years) and 105 adults (median age, 34 years; range, 18 to 57 years) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 adults and 63/215 children (odds ratio [OR] = 3.7; 95% confidence interval [CI], 2.2 to 6.3). We observed 215 ADRs, 131 in adults (median, 2 events/patient; interquartile range for the 25th to 75th percentiles [IQR25-75], 1 to 3) and 84 in children (median, 1 event/patient; IQR25-75 = 1 to 1.5) (Padjusted < 0.001). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous, and digestive systems were the most frequently affected, without differences between groups. Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95% CI = 1.5 to 24). Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence. (This study has been registered in ClinicalTrials.gov under identifier NCT04274101.).
Asunto(s)
Enfermedad de Chagas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adulto , Enfermedad de Chagas/tratamiento farmacológico , Niño , Preescolar , Tolerancia a Medicamentos , Humanos , Nifurtimox/efectos adversos , Estudios RetrospectivosRESUMEN
INTRODUCTION: The clinical and laboratory data of immunocompetent patients with acute toxoplasmosis (AT) are described. PATIENTS AND METHODS: We performed a retrospective study of patients with AT attended between 1996 and 2004. Diagnostic criteria consisted of compatible clinical findings (generalized and cervical lymphadenopathies) and specific serology against Toxoplasma gondii (high IgG and IgM and/or reactive IgA). IgG and IgM determinations were performed by ELFA and IgA determinations by ELISA. IgM-CMV, heterophil antibodies, hemogram, hepatic chemistry were also determined and funduscopic examination was performed. RESULTS: Eleven immunocompetent patients with AT were evaluated. The mean age was 8.8 years (95 % CI: 3.6-12.9). The patients were evaluated between the first and the third month after symptom onset. Of the 11 patients, hard elastic lymphadenopathies were found in 10, single cervical lymphadenectomy in three and generalized lymphadenectomy in seven. One patient showed no symptoms. In one patient, nodal histology showed the Piringer-Kuchinka triad. None of the patients showed alterations in the hemogram, hepatic chemistry or funduscopic examination. The mean IgG value was 4.143 UI/ml (95 % CI: 2.570 and 5.717). IgM was reactive in nine of the 11 patients (81.8 %) and IgA in seven out of 10 patients (70 %). In all patients, at least one of these two immunoglobulins was reactive. In all patients, clinical outcome was favorable without parasiticide treatment. CONCLUSION: Except for one asymptomatic patient, all the patients had generalized lymphadenopathies and only 27.2 % showed cervical lymphadenopathies. A negative IgM or IgA result does not rule out a diagnosis of AT. Parasiticide treatment is unnecessary in this entity. Acute toxoplasmosis should be considered early in children with lymphadenopathies to avoid invasive procedures.