Estudio de la toxicidad del tratamiento antiparasitario en la enfermedad de Chagas

La enfermedad de Chagas es una parasitosis endémica en regiones del centro y el sur del continente americano y está considerada una enfermedad desatendida por la Organización Mundial de la Salud. Gracias a los movimientos poblacionales en un mundo cada vez más globalizado, presenta cada vez mayor impacto en otros continentes, como en Europa donde tiene su mayor prevalencia en España. A pesar de haber sido descrita hace más de 100 años, existen importantes limitaciones respecto a su diagnóstico, al seguimiento de los pacientes y al tratamiento, especialmente en aquellos con infección crónica. En el presente trabajo nos hemos centrado en el estudio de su tratamiento, poniendo el foco de atención en su tolerancia. El tratamiento de la enfermedad de Chagas se limita en la actualidad a dos únicos fármacos: benznidazol y nifutimox. Ambos presentan alta frecuencia de efectos secundarios que obliga en muchos casos a los pacientes a suspender el tratamiento de manera precoz. Así en nuestro primer trabajo nos propusimos cuantificar de manera global la toxicidad del benznidazol, dado que en nuestro medio es el fármaco más utilizado. Realizamos una revisión sistemática y metaanálisis añadiendo además la experiencia con nuestra cohorte de pacientes. Seguidamente, describimos un caso excepcional y grave de toxicidad, como es la trombocitopenia inmune inducida por benznidazol. Posteriormente analizamos la tolerancia secuencial de los dos fármacos, estudiando la tolerabilidad del nifurtimox en segunda línea, tras la suspensión del benznidazol por toxicidad. A lo largo de los últimos años se ha extendido el uso de distintas pautas de tratamiento con benznidazol en un intento de mejorar su tolerancia. Así, realizamos una comparativa entre dos cohortes de pacientes con enfermedad de Chagas tratados con distintas pautas: a dosis estándar y con pauta ascendente progresiva con un máximo de 300 mg diarios. Por último, realizamos una revisión literaria aglutinando toda la evidencia recientemente publicada y ensayos clínicos en marcha en la actualidad, con el objetivo de ofrecer una visión global y actualizada del tratamiento de la enfermedad de Chagas

Risk of Trypanosoma cruzi infection among travellers visiting friends and relatives to continental Latin America

Factors de risc mèdic; Serologia; Malaltia de ChagasFactores de riesgo médicos; Serología; Enfermedad de ChagasMedical risk factors; Serology; Chagas diseaseBackground Chagas disease (CD) is regarded as a possible risk for travellers to endemic areas of continental Latin America (LA). The aim of the study is to determine the risk of Trypanosoma cruzi (TC) infection among travellers to CD endemic areas and to identify risk factors for acquiring TC infection. Methods/Principal finding We designed a multicenter cross-sectional study among travellers in Spain (Badalona, Barcelona and Madrid). All available adults with laboratory confirmed proof of absence of TC infection from January 2012 to December 2015 were contacted. Participants referring a trip to LA after the negative TC screening were offered to participate. We performed a standardized questionnaire of travel related factors and measurement of TC antibodies in serum. A total of 971 participants with baseline negative TC serology were selected from the microbiology records. After excluding participants not meeting inclusion criteria, eighty participants were selected. Sixty three (78.8%) were female, and the median age was 38 (IQR 34–47) years. The reason to travel was visiting friends and relatives in 98.8% of the participants. The median duration of travel was 40 (IQR 30–60) days, with 4911 participants-day of exposure. Seventy seven cases (96.25%) participants had two negative TC serology tests after the travel, two cases (2.5%) had discordant serology results (considered false positive results) and one case was infected before travelling to LA. According to our data, the upper limit of the 95% confidence interval of the incidence rate of TC acquisition in travellers is 0.8 per 1000 participant-days. Conclusions/Significance Among 79 non-CD travellers to TC endemic areas, we found no cases of newly acquired TC infection. The incidence rate of TC acquisition in travellers to endemic countries is less than or equal to 0.8 per 1000 traveller-days.ASM was supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from the Instituto de Salud Carlos III (www.isciii.es) through the Spanish Ministry of economy and competitiveness. The funders had no role in study design data collection and analysis, decision to publish, or preparation of the manuscript

Risk of Trypanosoma cruzi infection among travellers visiting friends and relatives to continental Latin America

Chagas disease (CD) is regarded as a possible risk for travellers to endemic areas of continental Latin America (LA). The aim of the study is to determine the risk of Trypanosoma cruzi (TC) infection among travellers to CD endemic areas and to identify risk factors for acquiring TC infection. We designed a multicenter cross-sectional study among travellers in Spain (Badalona, Barcelona and Madrid). All available adults with laboratory confirmed proof of absence of TC infection from January 2012 to December 2015 were contacted. Participants referring a trip to LA after the negative TC screening were offered to participate. We performed a standardized questionnaire of travel related factors and measurement of TC antibodies in serum. A total of 971 participants with baseline negative TC serology were selected from the microbiology records. After excluding participants not meeting inclusion criteria, eighty participants were selected. Sixty three (78.8%) were female, and the median age was 38 (IQR 34-47) years. The reason to travel was visiting friends and relatives in 98.8% of the participants. The median duration of travel was 40 (IQR 30-60) days, with 4911 participants-day of exposure. Seventy seven cases (96.25%) participants had two negative TC serology tests after the travel, two cases (2.5%) had discordant serology results (considered false positive results) and one case was infected before travelling to LA. According to our data, the upper limit of the 95% confidence interval of the incidence rate of TC acquisition in travellers is 0.8 per 1000 participant-days. Among 79 non-CD travellers to TC endemic areas, we found no cases of newly acquired TC infection. The incidence rate of TC acquisition in travellers to endemic countries is less than or equal to 0.8 per 1000 traveller-days. Chagas disease is caused by the protozoan parasite T. cruzi. It is endemic in certain areas of continental Latin America. Few cases of T. cruzi infection have been described in travellers. However, there is little information regarding the incidence rate of T. cruzi infection during a trip to continental Latin America. In this study we aim to study the incidence of T. cruzi infection among migrants from Latin America living in Spain travelling to visit friends and relatives. In this study we found no cases of newly acquired T. cruzi infection among 79 previously uninfected travellers and calculate that the upper limit of the 95% CI of the incidence rate of T. cruzi acquisition in travellers is 0.8 per 1000 participants-da

Use of benznidazole to treat chronic Chagas disease: An updated systematic review with a meta-analysis.

BackgroundApproximately 6 million people worldwide are affected by Chagas disease, with many in the chronic phase of the disease (CCD). It is crucial to evaluate the effectiveness of benznidazole for CCD treatment.Methods/principal findingsWe updated a meta-analysis published in 2009 up to February 2021, including controlled trials (RCT) and prospective observational studies (OBS) that compared benznidazole vs placebo/no-treatment (P/nT). Main outcomes evaluated were clinical progression (CP) and seroreversion with subgroup analysis performed according to study design and participants' age. Parasitological response and safety were also described. We identified 879 articles and selected nine for inclusion (corresponding to eight studies). After adding the nine articles from the previous meta-analysis, 17 studies were analyzed corresponding to 6640 patients. The odds ratio (OR) for seroreversion in children treated with benznidazole vs P/nT was 38.3 (95%CI: 10.7-137) and 34.9 (95%CI: 1.96-624.09) in RCT and OBS, respectively. In adults the OR for seroreversion in OBS was 17.1 (95%CI: 2.3-129.1). CP was only evaluated in adults, where benznidazole did not demonstrate a beneficial effect: OR 0.93 (95%CI: 0.8-1.1) and OR 0.49 (95%CI:0.2-1.2) for RCT and OBS, respectively. Most outcomes were deemed to have a low level of certainty, except for the beneficial effect in children and the low efficacy in adults (moderate certainty).ConclusionsBenznidazole should be recommended for CCD in children, though this is only based on serological response and a moderate grade of evidence, while in adults benznidazole efficacy remains uncertain. More data on clinical efficacy of benznidazole in CCD is needed in both children and adults

Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection:A Systematic Review and Meta-Analysis

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or &gt;200 CD4/μL) or VL (≤ or &gt;100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 &lt;200 cells/μL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.</p

J Travel Med

Background: International travel has increased in the past few decades, placing more travellers at risk of acquiring systemic endemic mycoses. There are limited published data on systemic endemic mycoses among international travellers. We report epidemiological characteristics of non-migrant, international travellers who acquired systemic endemic mycoses during travel. Methods: We analysed records of non-migrant international travellers with a confirmed diagnosis of histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis or talaromycosis reported from 1997 through 2017 to GeoSentinel, a global surveillance network now consisting of 70 travel or tropical medicine centres in 31 countries. Results: Sixty-nine records met the inclusion criteria. Histoplasmosis was most frequently reported; the 51 travellers with histoplasmosis had the lowest median age (30 years; range: 8-85) and shortest median duration of travel (12 days; range: 5-154). Coccidioidomycosis was reported in 14 travellers; travellers with coccidioidomycosis were older (median 62 years; range: 22-78) and had the longest median number of days between return from travel and presentation to a GeoSentinel site (55 days; range: 17-273). Almost all travellers with coccidioidomycosis were exposed in the USA. Other systemic endemic mycoses were less frequently reported, including blastomycosis (three travellers) and talaromycosis (one traveller). Conclusions: Although relatively rare, systemic endemic mycoses should be considered as potential travel-related infections in non-migrant international travellers. Epidemiological exposures should be used to guide diagnostic evaluations and treatment