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Chagas disease is a neglected parasitosis caused by the protozoan parasite Trypanosoma cruzi. This infection is present in most Latin American countries, although, due to migratory movements, it is a growing cause for concern in non-endemic countries. The only two drugs currently available for its treatment-benznidazole and nifurtimox-were marketed 50 years ago. While they are very effective for acute and recent infection, and for the prevention of maternofoetal transmission, their efficacy declines in people who have chronic infection, especially those older than 18 years of age. In the presence of visceral involvement, parasiticidal treatment is of little or no value. The safety profile of both drugs is far from ideal, with frequent adverse events and high rates of drug discontinuation, mainly in adults. So far, new drugs and new strategies have not been shown to improve the results of the current nitroimidazoles, although the results are promising. In this review, we focus on the aspects that allow clinicians to make the best use of currently available drugs. In addition, we discuss new therapeutic options and ongoing research in the field.

Background The study aimed to analyse the likelihood of imported malaria in people with a suggestive clinical picture and its distinctive characteristics in a hospital in the south of Madrid, Spain. Methods Observational retrospective study that consisted of a review of all medical files of patients with any malaria test registered at Móstoles University Hospital between April 2013 and April 2018. All suspected malaria cases were confirmed by Plasmodium spp. polymerase chain reaction (PCR). Results Of the 328 patients with suspected malaria (53.7% migrant-travellers; 38.7% visitors; 7.6% travellers), 108 cases were confirmed (101 by Plasmodium falciparum), accounting for a 33% positive sample rate. Sixteen cases were diagnosed only by PCR. Patients with malaria, compared to those without, presented predominantly with fever (84% vs. 65%), were older (34 vs. 24 years), sought medical attention earlier (17d vs. 32d), had a greater number of previous malaria episodes (74% vs. 60%), lower levels of platelets (110,500µL vs. 250,000µL), and higher of bilirubin (0.6 mg/dL vs. 0.5 mg/dL). Severe malaria was present in 13 cases; no deaths were recorded. Malaria diagnosis showed a bimodal distribution with two peaks: June to September and November to January. Conclusions Malaria is still a common diagnosis among febrile patients coming from the tropics specially among migrant travellers. Fever, thrombocytopenia, and/or high bilirubin levels should raise suspicion for this parasitic infection. Prompt diagnosis is crucial to avoid severe cases and deaths.

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.

Summary Background Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. Methods In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramon y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. Findings 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3–2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per μL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. Interpretation HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. Funding None.

Helminth infections cause considerable morbidity worldwide and may be frequently underdiagnosed especially in areas of lower endemicity. Patients may harbor latent infections that may become symptomatic years or decades after the initial exposure and timely diagnosis may be critical to prevent complications and improve outcomes. In this context, disease in special populations, such as immunosuppressed patients, may be of particular concern. Heightened awareness and recent diagnostic developments may contribute to the correct management of helminth infections in nonendemic regions. A review of the main helminth infections in travelers and migrants (strongyloidiasis, taeniasis-neurocysticercosis and schistosomiasis) is presented, focusing on epidemiology, developments in diagnosis, treatment and prevention.

Post-kala-azar dermal leishmaniasis due to Leishmania infantum in an HIV-negative patient is very infrequent and this case highlights how it can be associated to other types of immunosuppression. Moreover, this case reports an effective therapeutic option with miltefosine, which can be very useful due to the scarce experience reported.

Recently arrived migrants may be oligosymptomatic and bear a burden of infectious/non-infectious diseases. A patient with no past medical history was diagnosed with non-typhoidal Salmonella osteomyelitis, sickle cell anemia, chronic hepatitis B infection, strongyloidiasis and schistosomiasis. Establishing diagnoses in vulnerable populations may not imply successful linkage to health care.

Strongyloides stercoralis; Immunosupressió; Ivermectina Strongyloides stercoralis; Inmunosupresión; Ivermectina Strongyloides stercoralis; Immunosuppression; Ivermectin Strongyloidiasis affects an estimated 600 million people worldwide, especially in tropical and subtropical areas. Single-dose ivermectin treatment has shown to be effective among immunocompetent patients with uncomplicated strongyloidiasis. Here, we present the protocol of the ImmunoStrong study, a prospective observational study aiming to evaluate the effectiveness and safety of a single-dose ivermectin for treatment of uncomplicated strongyloidiasis in immunosuppressed patients. The secondary objectives are to assess accuracy of molecular techniques for the follow-up of these patients and to determine the population pharmacokinetics of ivermectin. The information retrieved by this study will cover relevant information gaps in the strongyloidiasis management among immunosuppressed patients. The present work was supported by the 2020 Research Grant from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

BackgroundWhile there are no treatments with proven efficacy for patients with severe coronavirus disease 2019 (COVID-19), tocilizumab has been proposed as a candidate therapy, especially among patients with higher systemic inflammation.MethodsWe conducted a cohort study of patients hospitalized with COVID-19 in Spain. The primary outcome was time to death and the secondary outcome time to intensive care unit admission (ICU) or death. We used inverse-probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between tocilizumab use and the outcomes.ResultsA total of 1,229 and 10,673 person/days were analyzed. In the adjusted marginal structural models, a significant interaction between tocilizumab use and high C- reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (aHR 0.34, 95% CI 0.16–0.72, p=0.005) and ICU admission or death (aHR 0.38, 95% CI 0.19–0.81, p=0.011) among patients with baseline CRP >150 mg/L, but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings.ConclusionsIn this large observational study, tocilizumab was associated with a lower risk of death or ICU or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials and support the use of tocilizumab among subjects with higher CRP levels.

Background Testing used in screening, diagnosis and follow-up of COVID-19 has been a subject of debate. Several organisations have developed formal advice about testing for COVID-19 to assist in the control of the disease. We collated, delineated and appraised current worldwide recommendations about the role and applications of tests to control SARS-CoV- 2/COVID-19. Methods We searched for documents providing recommendations for COVID-19 testing in PubMed, EMBASE, LILACS, the Coronavirus Open Access Project living evidence database and relevant websites such as TRIP database, ECRI Guidelines Trust, the GIN database, from inception to 21 September 2020. Two reviewers applied the eligibility criteria to potentially relevant citations without language or geographical restrictions. We extracted data in duplicate, including assessment of methodological quality using the Appraisal of Guidelines for Research and Evaluation-II tool. Results We included 47 relevant documents and 327 recommendations about testing. Regarding the quality of the documents, we found that the domains with the lowest scores were ‘Editorial independence’ (Median=4%) and ‘Applicability’ (Median=6%). Only six documents obtained at least 50% score for the ‘Rigour of development’ domain. An important number of recommendations focused on the diagnosis of suspected cases (48%) and deisolation measures (11%). The most frequently recommended test was the reverse transcription-PCR (RT-PCR) assay (87 recommendations) and the chest CT (38 recommendations). There were 22 areas of agreement among guidance developers, including the use of RT-PCR for SARS-Cov- 2 confirmation, the limited role of bronchoscopy, the use chest CT and chest X-rays for grading severity and the co-assessment for other respiratory pathogens. Conclusion This first scoping review of recommendations for COVID-19 testing showed many limitations in the methodological quality of included guidance documents that could affect the confidence of clinicians in their implementation. Future guidance documents should incorporate a minimum set of key methodological characteristics to enhance their applicability for decision making., Instituto de Salud Carlos III 2017/CD17/00219, European Social Fund 2014-2020, 'Investing in your future', Spanish Government

Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio, This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016, project PI18/00154, a Gilead Fellowship (GLD16-00030), the SPANISH AIDS Research Network RD16/0025/0001project), and co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (ERDF). The present investigation was also funded by the Instituto de Salud Carlos III and the Fundación Asociación Española contra el Cáncer within the ERANET TRANSCAN-2 program, grant number AC17/00022, a crowdfunding project from the precipita platform of the Fundación Española para la Ciencia y la Tecnología (FECYT) and a restricted grant from Finch Therapeutics. The SEIMC-GESIDA Foundation supported this study with safety and data monitoring (GESIDA 9116).

Background While the microbiota has been associated with human papillomavirus malignant transformation, it is unclear whether anal bacteria could improve the low specificity of anal cytology for the screening of high-grade intraepithelial squamous neoplasia (HSIL) Methods We recruited men who have sex with men undergoing anal cytology and high-resolution anoscopy. We assessed the microbiota composition from fecal samples and cytobrush anal samples using 16S ribosomal DNA sequencing in participants with or without biopsy-proven HSIL (bHSIL). We selected bacterial biomarkers based on their linear discriminant analysis. We assessed their predictive performance using logistic regression and bootstrap resampling. Results We included 128 individuals, 47 (36.7%) with bHSIL and 99 (77.3%) with human immunodeficiency virus. We detected 40 potential predictors of bHSIL. Ruminococcaceae NK4A214 group, Alloprevotella genus, Prevotella melanonigenica, and Ruminococcaceae UCG-014 were the most predictive of bHSIL. From 35 false-positive cytologic results, the combination of these 4 biomarkers with the anal cytology reclassified to true-negative 33 individuals (94%) and showed good diagnostic performance (area under the receiver operating characteristic curve, 0.805; 95% confidence interval, .728–.882). Conclusions We found anal-associated bacteria indicative of a higher risk of precancerous anal lesions, which combination was highly specific. The microbiota could be developed as a complementary diagnostic tool to overcome the limitations of the current screening strategy for anal cancer.

BackgroundA false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.MethodsWe searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results with the corresponding 95% CI using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false- negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.ResultsWe included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared= 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low, due to the risk of bias, indirectness, and inconsistency issues.ConclusionsThere is a substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-CoV-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (certainty of evidence: very low). An update of this review when additional studies become available is warranted.Systematic review registrationProtocol available on the OSF website:https://osf.io/gp38w/

Background The lack of evidence-based recommendations for therapeutic decisions during the early weeks of the COVID-19 pandemic creates a unique scenario of clinical decision making which is worth to analyze. We aim to identify the drivers of therapeutic aggressiveness during the first weeks of the COVID-19 pandemic. Methods This cross-sectional worldwide survey (conducted April 12 to 19, 2020) was aimed at physicians who managed patients diagnosed with COVID-19. Treatment preferences were collected in five different clinical scenarios. We used multilevel mixed-effects ordered logistic regression to identify variables that were associated with the use of more aggressive therapies. Findings The survey was completed by 852 physicians from 44 different specialties and 29 countries. The heterogeneity of therapeutic decisions increased as the clinical scenario worsened. Factors associated with aggressive therapeutic decisions were higher self-perceived expertise (high vs. null, OR 1.95, 95%CI 1.31–2.89), perceived quality of COVID-19 publications (high vs. null, OR 1.92, 95%CI 1.17–3.16), and female sex (OR 1.17, 95%CI 1.02–1.33). Conversely, Infectious Diseases specialty, Latin American and North American origin, lower confidence in the treatments chosen, and having published articles indexed in PubMed as the first-author were associated with the use of less aggressive therapies. Interpretation Our study provides insight into the drivers of the decision-making process during a new and extreme health emergency. Different factors including the perceived expertise and quality of publications, gender, geographic origin, medical specialty and implication in medical research influenced this process. The clinical severity attenuated the physician's tolerance for uncertainty. Funding No funding was required.

The number of migrants and travellers has grown in recent decades. This phenomenon is also true of people living with HIV, given their much-improved life expectancy and quality of life. A significant number of travellers with HIV are migrants returning to their home countries to visit friends and relatives (VFRs). This population constitutes a high-risk group because they travel for longer and often to rural and remote areas and have closer contact with the local population. In this review we discuss the sociodemographic characteristics of travellers with HIV, the differences between conventional travellers and VFRs, and the risks of HIV acquisition and transmission during travel. We also present the most relevant travel-associated illnesses and highlight the particularities of pre-travel advice given to this population, including immunosuppression, responses to vaccines, high incidence of comorbidities, drug interactions, legal and language barriers. The need to integrate these factors based on far less evidence than that available for the general population makes pre-travel advice for travellers with HIV genuinely challenging.

Globalization has contributed to the emergence of specific parasitic diseases in novel geographical areas, and in these regions, these infections in travelers and immigrants may cause a considerable burden of disease. Timely diagnosis and treatment of protozoan infections to decrease mortality and prevent associated complications are essential. In this respect, the increased availability of specific DNA-detection procedures has improved the diagnosis of many imported parasitic infections. Travelers and immigrants with associated comorbidities or immunosuppression may pose a special challenge regarding management. An updated review of the main protozoan infections in mobile populations (malaria, Chagas disease, leishmaniasis, enteric protozoan infections) is provided, focusing on the changing epidemiology of these diseases, recent developments in diagnosis and management and the possibility of local transmission of imported infections.

Background Chagas disease has spread beyond its original borders on the American continent with migration. It can be transmitted from mother to child, through organ transplantation and transfusion of blood and blood products. It is necessary to determine when to screen for this infection. Aim Our objective was to evaluate the appropriateness of screening for Trypanosoma cruzi infection in Latin American migrants and their descendants. Methods We reviewed the literature using rigorous criteria. The quality of evidence was ranked according to the GRADE classification. An evidence to decision framework was adopted to provide information on the most relevant aspects necessary to formulate recommendations. Results The 33 studies evaluated revealed a prevalence of T. cruzi infection among Latin American migrants in Europe of 6.08% (95% confidence interval (CI): 3.24–9.69; 28 studies). Vertical transmission occurred in three of 100 live births (95% CI: 1–6; 13 studies). The prevalence of cardiovascular disease was 19% (95% CI: 13–27; nine studies), including only 1% severe cardiac events (95% CI: 0–2; 11 studies). The overall quality of evidence was low because of risk of bias in the studies and considerable heterogeneity of the evaluated populations. The recommendations took into account economic studies on the value of screening strategies and studies on acceptability of screening and knowledge of the disease in the affected population. Conclusions We identified five situations in which screening for T. cruzi infection is indicated. We recommend screening persons from endemic areas and children of mothers from these areas.

To determine the epidemiologic and clinical characteristics of patients in Spain with imported arbovirus infections, we analyzed 22,655 records from a collaborative network for January 2009–December 2018. Among 861 arbovirus infections, 845 were monoinfections (456 [53%] dengue, 280 [32.5%] chikungunya, 109 [12.7%] Zika) and 16 (1.8%) were co-infections. Most patients were travelers (56.3%) or immigrants returning to Spain after visiting friends or relatives (31.3%). Median patient age was 37 years; most (62.3%) were women and some (28.6%) had received pretravel advice. Only 12 patients were immunosuppressed. Six cases (all dengue monoinfections, none in immunosuppressed patients) were severe. Since 2014, nondengue arbovirus infections increased; until 2016, chikungunya and Zika were most common. Imported arbovirus infections (mostly dengue) were frequently diagnosed, although increased chikungunya and Zika virus infections coincided with their introduction and spread in the Americas. A large proportion of cases occurred in women of childbearing age, some despite receipt of pretravel advice.

Benznidazole is the preferred drug for treatment of Chagas disease. However, it is toxic and of limited value in chronic infection. We aimed to estimate the rates of and factors related to adverse reactions (ARs) to benznidazole and treatment discontinuations (TDs). A meta-analysis was performed using an electronic search of the published literature with no language restrictions until June 2017. Prospective studies were included of chronically infected patients in which at least one treatment arm included benznidazole. Data were added from a prospective cohort of patients with Chagas disease at our centre (January 2007–June 2017). Weighted rates of ARs and TDs were estimated, and potentially related factors were analysed. Some 413 studies were found, from which we chose 42 (nine clinical trials and 33 observational studies, including ours), comprising data for 7822 patients. The weighted rate of ARs to benznidazole was 44.1% (95% confidence interval [CI] 37.2–51.2). ARs were more frequent in adults than in children (51.6 vs. 24.5%), with the most common being skin reactions (34%), gastrointestinal complaints (12.6%) and neurological symptoms (11.5%). Grade 4 ARs were recorded in 3% of cases. The weighted rate of TDs was 11.4% (95% CI 8.5–14.5); TDs were more frequent in adults than in children (14.2 vs. 3.8%). In our cohort, only female sex was related to an increased rate of ARs but not to TDs. Benznidazole had a poor tolerability profile, with a high incidence of TDs, especially in adult patients and women. Optimised dosing schedules and/or new drugs are urgently needed.

Background Post-artesunate delayed haemolysis is described as hemolytic anemia presenting days after malaria treatment in hyperparasitemic patients. Physiopathological mechanisms and clinical manifestations have not been thoroughly characterised. Methods We conducted a retrospective study of hospitalised malaria patients who received artemisinin derivatives from January 1, 2010 to December 31, 2015. Results 21 patients were included in the study: 11 travellers, 8 travellers visiting friends and relatives and 2 immigrants. Median age was 35.5 years (IQR: 25.7–44.8) and 11 were men. Eight patients received oral and 13 received intravenous (IV) artemisinin-based drugs. Follow-up after the malaria episode was available for 15 patients (12 with IV treatment). Four patients presented with delayed haemolysis 9–14 days after artesunate treatment; all had been admitted with severe malaria, were treated IV and had hyperparasitaemia (17%–33%). Other than hyperparasitaemia, no other factors were associated with artesunate haemolysis. Patients' outcomes were favourable and the only additional therapeutic measure needed was a blood transfusion. Conclusions Delayed haemolysis is a frequent complication in hyperparasitemic malaria treated with IV artesunate. Follow-up is mandatory for at least 2 weeks after treatment initiation. This condition is potentially severe but does not appear to be life threatening.

Objectives International health agencies have promoted nontargeted universal (opt-out) HIV screening tests in different settings, including emergency departments (EDs). We performed a systematic review and meta-analysis to assess the testing uptake of strategies (opt-in targeted, opt-in nontargeted and opt-out) to detect new cases of HIV infection in EDs. Methods We searched the Pubmed and Embase databases, from 1984 to April 2015, for opt-in and opt-out HIV diagnostic strategies used in EDs. Randomized controlled or quasi experimental studies were included. We assessed the percentage of positive individuals tested for HIV infection in each programme (opt-in and opt-out strategies). The mean percentage was estimated by combining studies in a random-effect meta-analysis. The percentages of individuals tested in the programmes were compared in a random-effect meta-regression model. Data were analysed using stata version 12. Quality assessments were performed using the Newcastle−Ottawa Scale. Results Of the 90 papers identified, 28 were eligible for inclusion. Eight trials used opt-out, 18 trials used opt-in, and two trials used both to detect new cases of HIV infection. The test was accepted and taken by 75 155 of 172 237 patients (44%) in the opt-out strategy, and 73 581 of 382 992 patients (19%) in the opt-in strategy. The prevalence of HIV infection detected by the opt-out strategy was 0.40% (373 cases), that detected by the opt-in nontargeted strategy was 0.52% (419 cases), and that detected by the opt-in targeted strategy was 1.06% (52 cases). Conclusions In this meta-analysis, the testing uptake of the opt-out strategy was not different from that of the opt-in strategy to detect new cases of HIV infection in EDs.

Symptomatic chronic Chagas disease affects up to 40% of patients infected with Trypanosoma cruzi. The lack of reliable early markers of cure after therapy hinders disease management and clinical trials with new drugs. We performed a study with 18 months of follow-up to compare changes in immune parameters and T. cruzi-specific immune responses as surrogate markers of response to therapy between patients treated with benznidazole and untreated patients. This was a pilot, open-label, randomised clinical trial of treatment with benznidazole versus no treatment in patients with indeterminate chronic T. cruzi infection. In both groups we investigated changes in T-cell activation, T-cell subpopulations, regulatory T-cell counts, IL6, and sCD14 levels, and T. cruzi-specific immune responses (Th1, Th2, and Th17 responses). Fourteen patients were included in the study (seven in each group). Median age was 35 years (P25-75 31-43), 57% were female, and 93% were Bolivian. Benznidazole was administered at 5mg/kg/day for 60days. Three patients discontinued benznidazole owing to adverse reactions and were not evaluated. At the end of the follow-up period, treated patients showed significantly less immune activation and lower regulatory T-cell counts, with an increased Th17 and Th1 response. This randomised pilot clinical trial administering benznidazole to patients with indeterminate chronic Chagas disease brings about changes in the adaptive immunity, leading to a general decrease in inflammatory status. This apparently beneficial response could act as the basis for monitoring new antiparasitic drugs.

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.

Chagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole.This was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)).471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08).The use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.

[EN] This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.1 The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisions. The main difference with respect to the previous document concerns recommended initial ART regimens, only three of which are maintained as preferential. All three include dolutegravir or raltegravir, together with emtricitabine/tenofovir alafenamide or abacavir/lamivudine. Other differences concern the section on switching ART in patients with suppressed viral replication, which now includes new two- and three-drug regimens, and the antiretroviral drugs recommended for pregnant women and patients with tuberculosis. A recommendation has also been added for patients who present with acute HIV infection after pre-exposure prophylaxis., [ES] Esta actualización del documento sobre el tratamiento antirretroviral (TAR) en adultos que GeSIDA y el PNS elaboran desde hace 2 décadas, reemplaza a la de 20171. Su objetivo es proporcionar a los clínicos que tratan a adultos con infección por el VIH-1 recomendaciones basadas en evidencias científicas para guiar sus decisiones terapéuticas. El principal cambio respecto al documento previo incumbe a los regímenes recomendados para el TAR de inicio, solo 3 de los cuales se mantienen como preferentes, incluyendo todos ellos dolutegravir o raltegravir junto con emtricitabina/tenofovir alafenamida o abacavir/lamivudina. Otros cambios conciernen al apartado de cambio del TAR en pacientes con replicación viral suprimida, en el que se han incluido nuevos regímenes de 2 y 3 fármacos, y a los antirretrovirales recomendados en embarazadas o en pacientes con tuberculosis. Se ha añadido también una recomendación para personas que habiendo realizado profilaxis pre-exposición al VIH presentan una infección aguda por dicho virus.

Background Cystic echinococcosis (CE) is present in all continents, except for the Antarctica. Characteristically, CE lesions are found in the liver and the lungs, but virtually any part of the body may be affected (the spleen, kidneys, heart, central nervous system, bones, among others). It is estimated that the incidence of bone involvement in CE is 0.5% to 4%. Methodology A retrospective study was performed of patients with osseous CE treated at the National Reference Unit of Tropical Diseases of the Ramon y Cajal Hospital, Madrid, Spain, between 1989 and December 2017. Epidemiological, clinical, diagnostic and therapeutic data of patients with long-term follow-up were collected. Main findings During the study period, of the 104 patients with CE, 27 exhibited bone involvement (26%). The bones most frequently affected were the spine, followed by the ribs, pelvis, femur, tibia and the scapula. The most common symptom was pain followed by medullar syndrome and pathologic fracture. In total, 81.5% of patients underwent surgery for osseous CE at least once. As many as 96% received albendazol either in (mostly long-term) monotherapy or in combination with praziquantel. Conclusions The diagnosis and management of osseous CE is challenging. In many cases osseous CE should be considered a chronic disease and should be managed on a case-by-case basis. Lifelong follow-up should be performed for potential recurrence and sequels., Author summary Echinococcosis occurs in humans as a result of infection by a cestodes of the genus Echinococcus. One of the species, E. granulosus, causes cystic echinococcosis (CE) in humans worldwide. In the lifecycle there is a definitive host (generally dogs) which host this parasites at the small bowel. From there, ground is shed with the eggs of the parasite through feces and the intermediate host (usually a sheep or other herbivores get infected). Humans act as an incidental intermediate host when they become infected through the consumption of water or food contaminated with Echinococcus eggs. Once the egg has been ingested, it penetrates the intestinal mucosa and through the circulatory system finds an anatomical site forming a cystic lesion (hydatid or hydatid cyst). Characteristically, CE are found in the liver and the lungs, but virtually any part of the body may be affected. Incidence of osseous CE is low, its diagnosis and management is challenging and there is little information published. In this study we report our experience at a referral unit during nearly 30 years in the management of a series of patients with osseous CE. Such information may be useful for other physicians when treating osseous CE.

[Background]: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. [Methods]: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load

Leprosy remains infrequent in non-endemic areas. The objective of this study was to describe the cases of leprosy reviewed at a referral unit for imported diseases in Europe and to compare these findings with published data on imported leprosy.Cases of leprosy evaluated at a referral centre are described and salient features of autochthonous and imported cases are compared. A review of the literature on imported leprosy was performed.During the study period, 25 patients with leprosy were followed-up (10 were autochthonous cases and 15 were considered to be imported). Regarding imported cases, the majority were diagnosed in Latin American immigrants (10/15, 67%), mean age was 42 years, there were no differences in gender distribution, estimated average time from arrival in Spain to first visit at the unit was 3 years and from symptom onset to diagnosis was 2 years. Over 80% of imported cases had multibacillary disease and over one third of patients had been previously diagnosed with leprosy. One third had received alternate incorrect diagnoses initially,50% of patients with imported leprosy completed standard therapy and were considered cured and over one third were lost to follow-up.Leprosy remains a complex disease for healthcare professionals unfamiliar with this infection. Manifestations are polymorphic so misdiagnoses and consequent delays in diagnosis are not infrequent and may lead to resulting disabilities. Early diagnosis and management are essential to prevent sequelae and possible transmission. Improving access to health care, especially for vulnerable groups, would be necessary to advance in the control of this disease.

Background Continuous growth of mobile populations has influenced the global epidemiology of infectious diseases, including chronic and acute viral hepatitis. Method A prospective observational multicentre study was performed in a Spanish network of imported infections. Viral hepatitis cases from January 2009 to September 2017 were included. Results Of 14,546 records, 723 (4.97%) had imported viral hepatitis, including 48 (6.64%) acute cases and 675 (93.36%) chronic cases. Of the 48 acute cases, 31 were travellers and immigrants returning from visiting friends or relatives (VFR), while 19 (61%) were acute Hepatitis A or Hepatitis B. Only 18.2% of VFR immigrants and 35% of travellers received pre-travel advice. Acute hepatitis was more frequent in VFR immigrants (AOR 2.59, CI95% 1.20–5.60) and travellers (AOR 2.83, CI95% 1.46–5.50) than immigrants. Of the 675 Chronic cases, 570 were immigrants, and 439 (77%) had chronic Hepatitis B. Chronic hepatitis was more frequent in immigrants (AOR 20.22, CI95% 11.64–35.13) and VFR immigrants (AOR 11.12, CI95% 6.20–19.94) than travellers. Conclusions Chronic viral hepatitis was typical of immigrants, acute viral hepatitis was common among travellers, and VFR immigrants had mixed risk. Improving pre-travel consultation and screening of immigrants may contribute to preventing new cases of viral hepatitis and avoiding community transmission.

Background Tuberculosis (TB) is the leading cause of infectious disease mortality worldwide. We analysed active and latent TB infections (LTBI) from the Spanish Network for the Study of Imported Infectious Diseases by Travellers and Immigrants (+REDIVI). Methods Observational, retrospective, multicentre study of TB and LTBI registered in the +REDIVI network from October 2009 to December 2016. Results Of 1008 cases of LTBI, 884 (87.7%) were immigrants; 93 (4.5%), immigrants visiting friends and relatives (VFR); 2 (0.9%), VFR-travellers; and 29 (1.1%), travellers. Absolute (N = 157 vs. N = 75) and relative (12.5% vs. 5.9%) frequency decreased over the study period (p = 0.003). Median time to diagnosis was 24.6 months (females 50.3 vs males 11.9; p Of 448 TB cases, 405 (90.4%) were in immigrants; 30 (6.7%), VFR-immigrants; 6 (1.3%), VFR-travellers; and 7 (1.6%), travellers. Median time to diagnosis was 62.5 months (females 86.6 vs males 70.1; p = 0.0075). There were 8 multidrug resistant TB cases and 1 extensively drug resistant case of TB, all in immigrants. Conclusion TB was frequently diagnosed more than 5 years after arrival in Spain. Screening programmes for TB and LTBI in immigrants should be considered beyond this time point. Women showed a higher diagnostic delay for both latent and active TB.

Chagas disease is a parasitic disease that mostly affects Latin American countries, but it has currently become a worldwide epidemic due to migration. Both drugs marketed for its treatment (benznidazole and nifurtimox) are associated with a high rate of adverse reactions. Benznidazole is preferred initially because of its more favourable toxicity profile and perceived greater efficacy. Hypersensitivity dermatological reactions, gastrointestinal and neurological disturbances represent the most common drug-related adverse events. General symptoms such as fever, arthralgia, myalgia or bone marrow depression (leucopaenia) are seen less frequently. We describe the case of a 33-year-old woman with chronic Chagas disease who presented with acute gingival bleeding and severe thrombocytopaenia, probably related to benznidazole treatment. Temporal association with drug initiation and recovery after treatment withdrawal were demonstrated. Clinicians should be aware of the possible association between immune thrombocytopaenia and benznidazole, even though the pathogenesis remains unclear at present.

A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 ratio normalization with efavirenz, which was driven by a greater CD8 + T-cell decline.

Summary Chagas disease, caused by the parasite Trypanosoma cruzi , is a neglected disease, which can lead to cardiomyopathy, arrhythmias, megaviscera, and more rarely, polyneuropathy in up to 30–40% of patients around 20 to 30 years after acute infection. Although it is endemic in the Americas, global population movements mean that it can be located wherever migrants from endemic areas settle. The disease was first described 100 years ago and still challenges clinicians worldwide, since diagnostic, therapeutic, and prognostic methods remain insufficient. Furthermore, factors such as HIV co-infection, immunosuppressive drugs, transplantation, and neoplastic disease can alter the natural course of the infection. We present the case of a Bolivian woman with chronic T cruzi infection diagnosed at our clinic in Madrid, Spain, who subsequently developed non-Hodgkin lymphoma. Our report illustrates the challenges of an increasingly common infection seen in non-endemic countries, and highlights both daily management dilemmas and associated difficulties that arise.

Malaria is a common parasitic disease diagnosed in the returned traveler. Mortality in travelers with imported malaria is around 2-3%, and one of the main factors associated with poor prognosis is the delay in the diagnosis and treatment. Imported malaria cases usually present with fever, headache and myalgia, but other symptoms may appear. The diagnosis should be performed as soon as possible, using thick smear or rapid diagnostic tests, and a blood smear. Treatment should be initiated urgently. In cases of severe malaria, the use of intravenous artemisinins has proved to be superior to intravenous quinine. This document reviews the recommendations of the expert group of the Spanish Society of Tropical Medicine and International Health (SEMTSI) for the diagnosis and treatment of imported malaria in Spain.

The growth in international commerce, travel and migration contribute to the global emergence of certain parasitic infections. Importation of vectors and food products may contribute to the emergence of protozoan infections in nonendemic countries. Infections such as malaria are potentially fatal, especially in nonimmune patients, and outcome depends largely on timely diagnosis and treatment. Diagnosis/management of imported parasitic infections may be complex especially as some patients may have underlying immunosuppressive conditions such as HIV infection. Major challenges concern the development of improved diagnostic techniques, safer/more effective drug therapies and identification of biological markers of progression and response to treatment. Imported parasitic diseases which may be transmitted vertically or through blood transfusion/organ donation could become a public health priority in the near future. Climate change may affect arthropod distribution and facilitate the spread of protozoan vector-borne diseases. The first part of this review focuses on protozoan infections in travelers and immigrants. The ongoing growth in international commerce, travel and migration contributes to the global emergence of certain pathogens which may be imported into nonendemic areas. According to the UN World Tourism Organization, the number of international tourist arrivals increased from 25 million in 1950 to 1035 million in 2012. The strongest growth in arrivals was recorded in Asia and the Pacific (+7%) followed by Africa (+6%) and the Americas (+5%). In recent years, tour - ism has experienced continued growth and diversification, despite the global economic crisis, and between 2010 and 2030 arrivals in emerging destinations are expected to increase at double the rate of that in advanced economies (1). In 2012, the number of international migrants worldwide was estimated to be 214 million (approximately 3% of the global population) and this figure could rise to 405 million by the year 2050 (2). Other mobile populations which may contribute to change the epidemiology of infectious diseases include travelers visiting friends and relatives (VFRs), refugees, international adoptees and asylum seekers. Parasitic diseases are a heterogeneous group of infections which may be caused by protozoa, hel- minths or ectoparasites. A recent estimation of the global burden of the most important neglected tropical diseases caused by helminths and protozoa reported over 5400 million persons may be at risk and over 1200 million may be infected (3). Some parasitic infections, such as toxoplasmosis and giardiasis, have a worldwide distribution, whereas others such as trypanosomiasis and filariasis remain geographically restricted to certain areas. This geographical restriction may be determined by environmental factors such as climate, the presence of a competent vector or the presence of a

Background Understanding and detecting imported diseases is a priority in the prevention and management of prevalent and emergent infectious diseases acquired abroad. The +Redivi network measures the burden of imported infections in Spain and is essential for closing the gap in travel medicine. Methods Demographic characteristics, travel information, syndromes and confirmed travel-related diagnoses were registered in a standardised online database. Results A total of 10 767 cases of imported infectious diseases were registered between October 2009 and December 2015. Of these, 60.8% of cases were immigrants seen for the first time after arrival, 20.6% were travellers, and 18.4% were individuals visiting friends and relatives (VFR [immigrants and travellers]). The median time between arrival and medical consultation was 5.5 years for immigrants, 2.0 weeks for travellers, 3.1 weeks for VFR-travellers and 11.4 for VFR-immigrants. The most prevalent diagnoses were Chagas disease in immigrants and nonspecific acute diarrhoea in travellers. Malaria by P. falciparum was one of the most prevalent diagnoses among VFR. More than half the travellers saw a physician before travelling, although one-third of those for whom antimalarial medication was indicated did not take their medication correctly. As for VFR, only 10.4% of VFR-immigrants and 32.5% of VFR-travellers sought pre-travel advice. Only 23 and 21%, respectively, of those for whom antimalarial prophylaxis was indicated took the medication properly. Conclusions +Redivi provides a clear picture of the prevalence of imported infectious diseases among travellers and immigrants in Spain. The data collected could be used to improve everyday health care provided to travellers and immigrants after travel, to guide pre-travel consultations and to monitor the potential occurrence of tropical or exotic infectious diseases.

Introducción: El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP), pautas alternativas (PA) y otras pautas (OP) para el tratamiento antirretroviral (TARV) como terapia de inicio en pacientes infectados por VIH para 2016. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con estas pautas. Métodos: Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.

PURPOSE OF THE REVIEW Chagas disease has spread beyond the geographical barriers of the American continent in the past decade. Consequently, physicians treating HIV-infected patients in nonendemic countries have to face an opportunistic infection they have little experience with. This review examines the literature on Chagas disease in HIV-infected patients, with special emphasis on recent findings. RECENT FINDINGS Although infection by Trypanosoma cruzi is a severe opportunistic infection in HIV-infected patients, awareness of this parasitosis in nonendemic countries remains low. Deeply immunosuppressed patients with chronic infection can develop reactivations, which can be very severe and are associated with high mortality. Reactivations mostly affect the central nervous system, followed by the heart, and diagnosis is based on the direct detection of the parasite or histology. There is no reliable method of predicting reactivations. Treatment is based on benzimidazoles, although neither the appropriate treatment schedule nor the need for secondary prophylaxis has been clearly established. Antiretroviral therapy seems to play a fundamental role in the prevention of reactivations and control of relapses; however, more information is needed. SUMMARY Many aspects of T. cruzi-HIV coinfection remain uncertain. Until new data covering the current gaps become available, early diagnosis and prompt antiretroviral therapy seem to be fundamental for avoiding reactivations and improving late visceral involvement.

Currently, only two drugs are approved for treating Trypanosoma cruzi infection: benznidazole and nifurtimox. Adverse reactions are frequent with both drugs: they have chemical similarities and common metabolic pathways making cross reactions a possibility. Our objective was to describe the safety/tolerability profile of nifurtimox in patients who had previously discontinued benznidazole due to hypersensitivity reactions. We performed a prospective observational study from September 2009 to December 2011. Patients who discontinued benznidazole therapy due to hypersensitivity reactions (HR) and were later treated with nifurtimox were included. HR to benznidazole were defined as presence of a rash with or without mucosal involvement, fever or laboratory abnormalities (such as eosinophilia, leucopaenia or impaired liver function tests). The drugs were prescribed for 60 days (benznidazole) or 60-90 days (nifurtimox). The National Cancer Institute criteria (CTCAE, 2006, Version 3.0) were used for grading and reporting of adverse reactions (AR). Eighteen patients (16 females, two males, median age 35.5 years, range 15-50 years) with asymptomatic late chronic infection, were included. Median time between benznidazole interruption and start of therapy with nifurtimox was 121.5 days (IQR 72-223 days). Fifteen patients (83.3%) developed an AR to nifurtimox, gastrointestinal complaints and anorexia being the most common, and 13 patients (72%) completed the treatment schedule. Five patients interrupted therapy (27.8%) mainly because of gastrointestinal intolerance and/or nervous system toxicity. Only one patient developed skin lesions, a mild maculopapular rash not requiring specific therapy or treatment withdrawal. There was no severe AR. Nifurtimox as second line therapy in patients who discontinued benznidazole specifically due to HR appears to be safe and does not seem to be associated with a higher incidence of AR.

Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence). In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials). Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Authors' conclusions Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole.

Resumen Introduccion Las enfermedades importadas por viajeros e inmigrantes son un objeto prioritario en la prevencion de la emergencia de las enfermedades infecciosas en el siglo xxi . Existen registros internacionales sobre patologia importada, pero en Espana no hay un sistema similar. Material y metodos En 2009 se crea la red cooperativa +Redivi, formada por 14 centros sanitarios nacionales. +Redivi recoge datos demograficos, relativos al viaje/inmigracion y al proceso infeccioso en formularios informatizados. Resultados Desde enero de 2009 a octubre de 2011 se registran 4.570 pacientes y se describen los principales datos demograficos (edad, sexo, presencia de inmunosupresion), relativos al viaje (destino, duracion, tiempo en acudir a consulta desde la llegada del viaje) o al proceso migratorio (pais de procedencia, tiempo en acudir a consulta desde la llegada a Espana), medidas preventivas realizadas (solicitud de consejo previaje, indicacion de quimioprofilaxis antimalarica, farmaco utilizado y si se hizo correctamente), motivo de consulta y diagnosticos finales de viajeros, inmigrantes e inmigrantes que viajan. Asi mismo, se describen en los 3 grupos los diagnosticos mas frecuentes en los pacientes asintomaticos que acudieron a realizarse un examen de salud. Conclusiones La red +Redivi permite conocer y cuantificar las infecciones importadas por inmigrantes y viajeros, su origen geografico, el tipo de paciente que las padece y su patron temporal. Los datos preliminares de la red muestran la presencia significativa de enfermedades transmisibles y con potencial reintroduccion en nuestro medio, asi como la importancia del cribado sistematico en sujetos que proceden de zonas tropicales. El objetivo de +Redivi es el de evaluar el impacto de la patologia importada en Espana con el fin de contribuir a la mejora en la asistencia a los pacientes e incidir en la prevencion y el tratamiento de las enfermedades importadas mas prevalentes, y detectar la posible existencia de brotes epidemicos.

The immigrant population in Spain, whether legal or not, has been entitled to healthcare under the same conditions as the Spanish population since the year 2000. The entry into vigour of the Royal Decree-Law 12/2012 of 20 April has significantly restricted this right, so that unauthorized or non-resident foreigners may now only receive emergency care, if they are under 18 or pregnant women. Out of an estimated 459,909 illegal immigrants in our country, 2,700 to 4,600 are probably infected with HIV; 1,800 to 3,220 know that they are infected, and 80% of the latter could receive antiretroviral treatment. The Royal Decree-Law is likely to cause many undesirable consequences in this population infected with HIV: increasing mortality, promoting the emergence of opportunistic diseases, increasing hospital admissions, increasing infections in the population (by HIV and other pathogens), or contributing to mother to child transmission of HIV. The expected increase in morbidity and mortality will be a greater cost in patient care, a cost which will be significantly higher in the more immunosuppressed patients. Therefore, the enforcement of the Royal Decree-Law will be much less cost-effective in the short term than was expected, and will negatively affect our country's public health, especially for those patients infected with HIV who will not be covered, thus increasing healthcare medium to long term costs, and moving away from the international health goals that were established.

The population movements during the last decades have resulted in a progressively increasing interest in certain infectious diseases. Eosinophilia is a common finding in immigrants and travellers. One of the most common causes of eosinophilia is helminth infection, and some intestinal protozoa. The aim of this paper is to describe the epidemiological characteristics of cases with eosinophilia and its association with the presence of parasites in the REDIVI data network. This is a multicentre prospective observational study that includes patients diagnosed with eosinophilia registered in the cooperative network for the study of infectious diseases in travellers and immigrants (+REDIVI) from January 2009 to December 2012. A total of 5,255 episodes were recorded in the network during the study period, and eosinophilia was observed in 8.1-31.3% of cases (depending on the immigration group). There were 60.2% men, with a median age of 31years. There were 72.4% immigrants, and 81.2% were asymptomatic. The most commonly identified parasites were S.stercoralis (34.4%), Schistosoma sp. (11.0%), and hookworm (8.6%). The relationship between eosinophilia and parasite infection was significant for all helminths (except for cutaneous larva migrans). The symptoms and duration of the journey did not significantly determine the presence of eosinophilia. In the case of eosinophilia in a person who has lived in helminth endemic areas, it is advisable to carry out targeted studies to diagnose the infection, regardless of immigration type, length of stay, or the presence of symptoms.

Filariases are infections caused by distinct species of nematodes. These infections are transmitted through insect bites and primarily affect lymph nodes and skin. Filariases are classified as neglected diseases and affect millions, producing severe disability and social stigma. This type of infection is rarely diagnosed in travellers, as prolonged stays in endemic areas are usually required acquire infection. Infections may be asymptomatic, and clinical manifestations depend on the host immune response to the infection and the parasite burden. Diagnosis is based on the demonstration of microfilariae in blood or skin, but there are other methods that support the diagnosis. Individual treatment is effective, but community interventions, mostly mass drug administration, have helped to diminish the incidence of filariases.

Chagas’ disease affects millions in Latin America and is the leading cause of cardiomyopathy and death due to cardiovascular disease in patients aged 30–50 years. As a consequence of immigration it has settled in several European countries, where besides imported cases, autochthonous infections arise through vertical transmission and blood/organ donation. All Latin American immigrants who attended our Unit were screened for T. cruzi infection (ELISA and IFAT ± PCR). An ECG and echocardiogram were requested for all positive patients, and oesophageal manometry, barium swallow and barium enema were requested according to patient symptoms. All patients under 50 years without severe cardiac involvement and who had not received correct treatment previously were treated with benznidazole 5 mg/kg/day for 60 days. Patients were followed-up with serology and PCR 1 month after treatment ended and every 6 months thereafter. A total of 1146 Latin Americans were screened for T. cruzi (357 positive serology results). The typical patient profile was a Bolivian female, of rural origin, in her fourth decade of life, without evidence of visceral involvement. Treatment tolerance was poor, with 29.7% discontinuing treatment due to adverse reactions. Among those with adverse reactions (52%), the most frequent were cutaneous hypersensitivity (68.7%), gastrointestinal upset (20%) and nervous system disturbances (16.2%). T. cruzi infection is no longer limited to Latin America. Poor treatment tolerance can limit current treatment options. More epidemiological data are necessary to estimate the magnitude of a problem of great relevance for public health and health resource planning.

We aimed to evaluate the effectiveness of nitazoxanide in disseminated cystic echinococcosis (DCE) that failed to respond to surgical and antiparasitic therapy. We report on seven patients (five of them with bony involvement): two cases from the literature and five patients who were included in a compassionate trial of nitazoxanide therapy in our hospital. Median follow-up time until nitazoxanide therapy was 12 years and all patients had received prior medical treatment and extensive surgery. Nitazoxanide (500 mg/12 h) in combination with albendazole, with/without praziquantel, was administered for 3-24 months. Three patients improved: one with muscle involvement (clinico-radiological response), one with lung involvement (radiological response), and another with soft tissue and bony involvement (clinico-radiological response of soft tissue cysts). There was one discontinuation after 15 days of starting therapy. Nitazoxanide combination therapy could have a role in the treatment of DCE when there is no bony involvement. Long-term safety profile seems to be favorable.

This study investigates the reasons why sub-Saharan African migrants (SSAM) living in Spain may be unwilling to have their blood tested. A qualitative study was developed for 3 years (2006-2009) with the participation of 1338 SSAM. Cultural differences along with lack of information about Spanish health care system and health-related rights produced a feeling of mistrust towards medical staff. Reluctance to do blood testing may prevent SSAM from having a prompt HIV diagnosis and an appropriate health care. Linguistically and culturally adapted information is essential to overcome these barriers and achieve an equal access to health care services and HIV testing.