Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

BACKGROUND: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. METHODS: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FINDINGS: From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69-2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61-2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04-0·95; p=0·044). INTERPRETATION: Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FUNDING: European Community's 7th Framework Programme.

Chagas Disease in Europe.

Chagas disease is currently present in many non-endemic countries and remains a neglected tropical disease globally. A review of the literature identified significant gaps and scarcity of updated information from European countries, with most studies reporting data from Spain and Italy. The index of underdiagnosis may be as high as 70%, affecting mainly females of child-bearing age. Standardized screening of fertile, non-pregnant, women from endemic countries and subsequent treatment is considered an essential strategy to control transmission and prevent new cases, yet no uniform legislation for screening risk groups exists. There is heterogeneity in Europe in terms of preventive strategies to avoid transfusion-related transmission of Chagas disease, not necessarily in line with the European directives, with some countries conducting systematic screening for T. cruzi infection in blood donors, whilst others rely on pre-transfusion questionnaires. The growing burden of the infection in resource-rich areas may provide an opportunity for progress in certain aspects of control and prevention. Options for improving screening strategies, management and linkage to care are reviewed.

Executive summary consensus statement of imported diseases group (GEPI) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SETMSI), on the diagnostic and treatment of imported schistosomiasis / Resumen ejecutivo del documento de consenso del Grupo de Patología Importada (GEPI) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y la Sociedad Española de Medicina Tropical y Salud Internacional (SEMTSI), sobre el diagnóstico y tratamiento de la esquistosomiasis importada

Schistosomiasis is a highly prevalent disease, especially in immigrant populations, and is associated with significant morbidity and diagnostic delays outside endemic areas. For these reasons, the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SEMTSI) have developed a joint consensus document to serve as a guide for the screening, diagnosis and treatment of this disease outside endemic areas. A panel of experts from both societies identified the main questions to be answered and developed recommendations based on the scientific evidence available at the time. The document was reviewed by the members from both societies for final approval (AU)

La esquistosomiasis es una enfermedad de elevada prevalencia, especialmente en población inmigrante, asociada a importante morbilidad y retraso diagnóstico fuera de zona endémica. Por estas razones, la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y la Sociedad Española de Medicina Tropical y Salud Internacional (SEMTSI) han elaborado un documento conjunto de consenso que sirva de guía para el cribado, diagnóstico y tratamiento de esta patología en zonas no endémicas. Un panel de expertos de ambas sociedades identificó las principales preguntas a responder y elaboró las recomendaciones siguiendo la evidencia científica disponible en el momento. El documento fue revisado por los miembros de ambas sociedades para su aprobación final (AU)

Executive summary consensus statement of imported diseases group (GEPI) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SETMSI), on the diagnostic and treatment of imported schistosomiasis.

Schistosomiasis is a highly prevalent disease, especially in immigrant populations, and is associated with significant morbidity and diagnostic delays outside endemic areas. For these reasons, the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Tropical Medicine and International Health (SEMTSI) have developed a joint consensus document to serve as a guide for the screening, diagnosis and treatment of this disease outside endemic areas. A panel of experts from both societies identified the main questions to be answered and developed recommendations based on the scientific evidence available at the time. The document was reviewed by the members from both societies for final approval.

Screening of imported malaria infection in asymptomatic migrants from Sub-Saharan Africa: A retrospective analysis of a 2010-2019 cohort.

BACKGROUND: Up to 40% of cases of imported malaria in Europe are diagnosed in recently arrived migrants, who generally exhibit asymptomatic or mild symptoms and show low parasitaemia (submicroscopic). The study describes the prevalence of malaria infection among asymptomatic Sub-Saharan African migrants (ASSAM) and compares asymptomatic malaria-infected (AMI) vs non-malaria infected patients. METHODS: An observational, comparative, retrospective study was carried out in ASSAM who underwent a medical examination, between 2010 and 2019 at the National Reference Unit for Tropical Diseases (NRU-Trop) in Madrid, Spain. Medical examination and systematic screening protocol for infectious diseases, including screening for malaria infection by Polymerase Chain Reaction (PCR) was performed. RESULTS: During the study period, 632 out of 1061 ASSAM were screened for malaria, median age: 24 years (IQR:1-5); median time from arrival to diagnosis: 2 months (IQR:1-5). P. falciparum was the most frequent species: 61 patients (67.8%). Compared to non-malaria infected, AMI subjects had: higher rate of co-infection with S. stercoralis (41.1%VS 22.9%;p < 0.001) and filariae (8.9% VS 2.4%;p = 0.006), lower erythrocyte corpuscular volume (83.6 VS 84.4;p = 0.008) and lower levels of cholesterol (151.0 VS 167.3;p < 0.001). CONCLUSIONS: We observed a high prevalence of AMI among ASSAM. This highlights the need to consider routing screening of migrants from endemic areas and to study if such screening could avoid the potential morbidities associated with chronic infection, reduce morbi-mortality of acute malaria and the risk of transmission in host communities.

Epidemiological and clinical profile of immunosuppressed patients with imported strongyloidiasis: a substudy from a larger cohort of the +REDIVI Spanish Collaborative Network.

The aim of this study was to describe the clinical and epidemiological profile of immunosuppressed patients with imported strongyloidiasis in a non-endemic setting, and to compare these results with non-immunosuppressed patients. This is a case-control substudy from a larger observational retrospective study that included all patients with strongyloidiasis registered in the +REDIVI Spanish Collaborative Network. Overall, 1245 patients with imported strongyloidiasis were included. From these, 80 (6.4%) patients had some kind of immunosuppression. Three (3.8%) patients had a hyperinfection syndrome, and 34 (52.3%) patients had eosinophilia. The percentages of positive results of the formalin-ether technique, the fecal culture and serology were 12.3%, 21.1% and 95.4%, respectively. When comparing the main characteristics, immunosuppressed patients had higher proportion of severe clinical manifestations and lower proportion of eosinophilia. No differences were found regarding yield of microbiological techniques and treatment response. These results stress the importance of strongyloidiasis screening among immunosuppressed patients coming from endemic areas. Serological tests have an acceptable sensitivity to be used as a screening tool.

Use of methotrexate for leprosy reactions. Experience of a referral center and systematic review of the literature.

BACKGROUND: Patients with leprosy can present with systemic inflammatory complications called leprosy reactions (LR), which can be severe and cause a loss of nerve function. The treatment of choice is prolonged corticosteroid therapy, frequently associated with severe side effects. We have used methotrexate as a corticosteroid-sparing regimen with good results. METHODS: To evaluate the role of methotrexate in managing LR, we performed a systematic review of the literature including our cases. We evaluated studies, prospective and retrospective, in both adults and children, which included any dose/regimen of methotrexate for the treatment of LR type 1 or 2. RESULTS: The systematic search revealed 261 records that yield 21 patients including our 3 cases (19 adults/two children), who were treated with methotrexate for LR type 1 and 2. There were 14 males. Median age was 35 years (P25-P75 28 to 52). Patients showed lepromatous (7), borderline lepromatous (9) or borderline tuberculoid (3) leprosy, among the 19 cases in which the type of leprosy was specified. As for the type of LR, 15 patients showed erythema nodosum leprosum (ENL), five showed LR type 1 and one showed polyarthritis and previous ENL. Methotrexate at weekly doses ranging from 7.5 mg to 20 mg (median 15 mg per week), typically administered with low-dose corticosteroids, was effective and safe as a corticosteroid-sparing agent. CONCLUSIONS: Methotrexate could be a suitable ancillary treatment or alternative to corticosteroids, especially in populations who are more prone to its adverse events. However, this evidence is based only on case reports and short clinical series.

Imported strongyloidiasis: Data from 1245 cases registered in the +REDIVI Spanish Collaborative Network (2009-2017).

BACKGROUND: Imported strongyloidiasis is increasingly being diagnosed in non-endemic areas. The aim of this study was to describe the epidemiological, clinical and microbiological characteristics of patients with imported strongyloidiasis in Spain. METHODOLOGY: This is an observational retrospective study that included all patients diagnosed of strongyloidiasis registered in the +REDIVI Collaborative Network from 2009 to 2017. Demographic, epidemiological and clinical information was collected from the +REDIVI database, and extra information regarding microbiological techniques, treatment and follow-up was requested to participant centers. FINDINGS: Overall, 1245 cases were included. Most of them were immigrants (66.9%), and South America was the most frequent area of origin. Detection of larvae in stool samples was observed in 21.9% of the patients, and serological tests allowed making the diagnosis in the rest of the cases. Eosinophilia was present in 82.2% of cases. Treatment with ivermectin (compared with albendazole) was the most strongly associated factor to achieve the cure (OR 2.34). CONCLUSIONS: Given the long latency of the infection and the risk of developing a severe presentation, screening of S. stercoralis infection should be mandatory in patients coming from or had traveling to endemic areas, especially in those with immunosuppressant conditions.

Zika virus: An emerging player in the global scenario / Virus Zika: un jugador emergente en el escenario global

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Management of osseous cystic echinococcosis.

INTRODUCTION: Osseous cystic echinococcosis (CE) is one of the most complicated and devastating conditions caused by Echinococcus granulosus. Its management is difficult and there is scant literature about it. Areas covered: A literature review was performed to provide an update on its diagnosis, treatment and follow-up. Expert commentary: In most cases diagnosis of osseous CE can only be confirmed by surgery. Osseous CE should be managed by experienced physicians and addressed as a chronic disease with therapies must be aimed at controlling the disease and its sequels or complications, rather than with a curative intent.

Imported brucellosis: A case series and literature review.

BACKGROUND: Brucellosis is one of the main neglected zoonotic diseases. Several factors may contribute to the epidemiology of brucellosis. Imported cases, mainly in travellers but also in recently arrived immigrants, and cases associated with imported products, appear to be infrequently reported. METHODS: Cases of brucellosis diagnosed at a referral unit for imported diseases in Europe were described and a review of the literature on imported cases and cases associated with contaminated imported products was performed. RESULTS: Most imported cases were associated with traditional risk factors such as travel/consumption of unpasteurized dairy products in endemic countries. Cases associated with importation of food products or infected animals also occurred. Although a lower disease incidence of brucellosis has been reported in developed countries, a higher incidence may still occur in specific populations, as illustrated by cases in Hispanic patients in the USA and in Turkish immigrants in Germany. Imported brucellosis appears to present with similar protean manifestations and both classical and infrequent modes of acquisition are described, leading on occasions to mis-diagnoses and diagnostic delays. CONCLUSIONS: Importation of Brucella spp. especially into non-endemic areas, or areas which have achieved recent control of both animal and human brucellosis, may have public health repercussions and timely recognition is essential.