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Background Rickettsioses are emerging zoonotic diseases with worldwide prevalence, recognized as a cause of imported fever in travellers and migrants. Our objective is to describe the microbiological, clinical and epidemiological characteristics of imported rickettsioses in travellers and migrants included in a Spanish collaborative network database. Methods This multicentre retrospective observational study was nested in +Redivi, the Cooperative Network for the Study of Infections Imported by Immigrants and Travellers. We asked collaborating centres for microbiological, clinical and epidemiological data on the rickettsiosis cases from the inception of the network in 2009 to December 2020. Results Fifty-four cases of imported rickettsioses were included; 35 (64.8%) patients were men, and the median age was 37 years (interquartile range 26, 51.2). Only 7.4% of patients were travellers visiting friends and relatives, and 5.6% were migrants. The most frequent travel destination (38.9%) was South Africa, and 90.7% engaged in a high-risk activity. Twenty-seven patients (50.0%) started presenting symptoms after their return to Spain. The most frequent symptoms were febrile syndrome (55.6%) and cutaneous manifestations (27.8%). Most diagnoses (63.0%) were confirmed by serology. Only a few cases (9.3%) required hospitalization. All participants had a full recovery. Conclusions Clinicians should suspect rickettsial diseases in travellers coming from high-risk areas, especially Southern Africa, who have engaged in activities in rural areas and natural parks. Doxycycline should be considered in the empiric treatment of imported fever of travellers coming from those areas or who have engaged in high-risk activities. There is a need to improve access to molecular diagnosis of rickettsiosis in Spain.

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.

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.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.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).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.

OBJECTIVES: To describe and compare the main clinical characteristics and outcome measures in hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) according to geographical area of origin. METHODS: A retrospective analysis of patients hospitalized with confirmed COVID-19 at a referral centre in Madrid, Spain, during March-May 2020 was performed. Recorded variables (age, gender, intensive care unit (ICU) admission, outcome), and geographical area of origin were compared for Europeans and non-Europeans (Latin Americans, Asians and Africans). RESULTS: In total, 2345 patients with confirmed COVID-19 hospitalized during the study period were included in the study. Of these, 1956 (83.4%) were European and 389 (16.6%) were non-European (of whom over 90%, 354/389, were Latin American). Non-Europeans were significantly younger than Europeans (mean 54 (SD 13.5) versus 70.4 (SD 15.1) years, p

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.

A questionnaire survey of animal and human health authorities in Europe revealed that leishmaniases are not notifiable in all countries with autochthonous cases. Few countries implement surveillance and control targeting both animal and human infections. Leishmaniases are considered emergent diseases in most countries, and lack of resources is a challenge for control. publishersversion published

A review on the current evidence of the efficacy and security of liposomal amphotericinB (L-AmB) for the treatment of visceral leishmaniasis (VL) has been performed. In the Indian subcontinent, a single dose of 10mg/kg has shown effectiveness in the treatment of VL due to Leishmania donovani. In contrast, higher doses of L-AmB (up to 30mg/kg) are required in Africa to treat a VL of the same etiology. When treating VL by Leishmania infantum acquired in the Americas and Europe the usual dose of L-AmB is 20-21mg/kg. In HIV co-infected patients the required doses are usually higher, up to 60mg/kg, and if it is administered in a prophylactic schedule after the treatment of VL relapses are reduced. L-AmB has shown synergism with other antiparasitic drugs, especially with paromomycin in the Indian subcontinent and with miltefosin in patients coinfected with HIV in East Africa. Due to its efficacy and safety profile, L-AmB is the first therapeutic option for VL.

Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.

Background Updated seroprevalence studies of infections in migrants may aid the design of tailored vaccination and prevention programmes. The objective of this study was to describe the seroprevalence rates for potentially transmissible viral infections in migrants attended at a referral centre in a major European city. Methods Descriptive analysis of seroprevalence of vaccine-preventable and non-vaccine-preventable infections in migrants attended at a centre in Madrid, Spain (2018–19). Recorded variables included age, gender, country of birth/continent of origin, time from arrival to Spain until first clinic visit, rubella, measles, mumps, varicella (VZV), hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis C virus (HCV) and HIV serology. Results In total, 468 patients were included, 135 females (28.8%) and 333 males (71.2%), mean age 30.4 years. The majority of patients were from Africa (52.5%, of which 88.2% from sub-Saharan Africa), followed by Latin America (38.5%) and other areas (9%). Seroprevalence for tested migrants for rubella, measles and mumps was 20 years (compared with those ≤ 20 years). Over 10% of females were potentially susceptible (negative/indeterminate serology) to rubella (11.4%), measles (12.7%) or mumps (10.3%). Lowest rates of rubella seropositivity were in Latin American migrants (over 12% potentially susceptible); measles and mumps seropositivity was lowest in migrants from areas other than Africa/Latin America (74% and 68%, respectively). Seroprevalence rates were 91% for VZV, 90% overall for HAV, ~6% for HBV chronic infection (~50% of migrants tested susceptible), 2% for HCV and 6% for HIV. Conclusions Differences in seroprevalence for vaccine-preventable and transmissible infections according to gender, age range and area of origin were observed. Tailored screening, vaccination and prevention strategies in potentially vulnerable migrant groups should be designed.

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.

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.

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.

[ES] Algunas enfermedades infecciosas han adquirido más relevancia por el aumento de los movimientos poblacionales. La eosinofilia es un hallazgo frecuente en inmigrantes y en viajeros. Una de las causas más frecuentes de eosinofilia es la infección por helmintos y algunos protozoos intestinales. El objetivo de este trabajo es describir las características epidemiológicas de los casos con eosinofilia y su asociación con la presencia de parásitos en la red de datos REDIVI. Se trata de un estudio observacional multicéntrico prospectivo, donde se incluyen los casos diagnosticados de eosinofilia registrados en la Red cooperativa para el estudio de las infecciones importadas por viajeros e inmigrantes (+REDIVI) desde enero de 2009 hasta diciembre de 2012. Se registraron en la red un total de 5.255 episodios durante el periodo de estudio, y la eosinofilia fue un hallazgo en el 8,1 al 31,3% de los casos (dependiendo del tipo migratorio). Fueron hombres el 60,2%, con una mediana de 31,0 años, inmigrantes el 72,4% y asintomáticos el 81,2%. Los parásitos más frecuentemente identificados fueron S. stercoralis (34,4%), Schistosoma sp. (11,0%) y uncinarias (8,6%). Existía asociación entre eosinofilia y presencia de parásitos para todos los helmintos (excepto para larva migrans cutánea). La sintomatología y la duración del viaje no determinaron significativamente la presencia de eosinofilia. Ante una eosinofilia en una persona que ha vivido en zonas endémicas de helmintiasis es aconsejable realizar estudios dirigidos para su diagnóstico, independientemente del tipo migratorio, la duración de la estancia o la presencia de sintomatología., [EN] 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 31 years. 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.

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.

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.

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.

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.

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.

Immigrants coming from endemic Strongyloides stercoralis countries have been described as having high prevalence rates of chronic infection. Most published data are regarding immigrants coming from sub-Saharan Africa and South East Asia. In this manuscript we describe a communitarian screening campaign for Strongyloides stercoralis amongst Latin American immigrants in Spain. This study dose not only provide information about Strongyloides stercoralis prevalence, but it also shows how communitarian targeted screening campaigns for Latin American immigrants could be an effective measure to improve Strongyloides stercoralis diagnosis and treatment avoiding potential fatal hyperinfection syndrome in immunosuppressed individuals and potential local transmission.

All persons with symptomatic visceral leishmaniasis (VL) should be treated with antileishmanial drugs. The therapeutic options for VL are diverse and depend on different factors, such as geographical area of the infection; the Leishmania species involved, the development of failure to habitual treatment, the evidence of HIV co-infection or other infections and the presence of malnourishment. The traditional treatment of VL used to be pentavalent antimonials, but the development of resistance, as their potential toxicity, made necessary new treatment options such as amphotericin B deoxycholate or lipid formulations of amphotericin B which due to their efficacy and lower toxicity have become the first-choice treatment in different world areas. In countries of fewer resources, studies have been carried out demonstrating the efficacy of parenteral paromomycin. Within the range of oral treatments, miltefosine had demonstrated very good cure rates; however, currently, also a high rate of clinical failures has been reported. In this chapter we provide a review on the treatment of VL and give therapeutic options with the grade of recommendation according to the Leishmania implicated and the geographical location of the infection.

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.

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

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.

Background Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. Objectives To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. Search methods We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. Selection criteria Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. Main results We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly. Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle. In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results. When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results. Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. Authors' conclusions There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome. We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful. It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.

Estimated worldwide incidence of tegumentary leishmaniasis (cutaneous leishmaniasis [CL] and mucocutaneous leishmaniasis [MCL]) is over 1.5 million cases per year in 82 countries, with 90 % of cases occurring in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria. Current treatments of CL are poorly justified and have sub-optimal effectiveness. Treatment can be based on topical or systemic regimens. These different options must be based on Leishmania species, geographic regions, and clinical presentations. In certain cases of Old World CL (OWCL), lesions can spontaneously heal without any need for therapeutic intervention. Local therapies (thermotherapy, cryotherapy, paromomycin ointment, local infiltration with antimonials) are good options with less systemic toxicity, reserving systemic treatments (azole drugs, miltefosine, antimonials, amphotericin B formulations) mainly for complex cases. The majority of New World CL (NWCL) types require systemic treatment (mainly with pentavalent antimonials), either to speed the healing or to prevent dissemination to oral-nasal mucosa as MCL (NWMCL). These types of lesions are potentially serious and always require systemic-based regimens, mainly antimonials and pentamidine; however, the associated immunotherapy is promising. This paper is an exhaustive review of the published literature on the treatment of OWCL, NWCL and NWMCL, and provides treatment recommendations stratified according to their level of evidence regarding the species of Leishmania implicated and the geographical location of the infection.

Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.

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.

Leishmania and HIV coinfection is a major health problem in more than 35 countries worldwide. The impaired immune function of visceral leishmaniasis/HIV-coinfected patients may: (i) favor the reactivation of latent Leishmania infection; (ii) induce a more severe presentation of visceral leishmaniasis; (iii) cause a poorer therapeutic response; and (iv) increase the risk of relapse after treatment. One of the major challenges in the management of visceral leishmaniasis/HIV coinfection is developing an effective drug therapy that not only resolves the first episode of visceral leishmaniasis but also prevents relapse. However, scarce evidence and data are available on the optimal therapy for visceral leishmaniasis/HIV coinfection. In our study we reviewed the efficacy of several drugs currently employed for visceral leishmaniasis in HIV patients and current knowledge of secondary prophylaxis. Additionally, we reviewed a set of ongoing clinical trials that are being performed to evaluate the efficacy of new therapeutic regimens for visceral leishmaniasis in patients with and without HIV. Finally, other therapeutic strategies based on immunotherapy, vaccination, or screening for latent leishmaniasis infection in HIV patients are reviewed. Apart from being potentially useful in clinical practice, the results obtained in our study highlight the need for further research on the management of visceral leishmaniasis/HIV coinfection.

Zika virus (ZIKV) and chikungunya virus (CHIKV) are currently circulating in overlapping areas in the American continents and may both be transmitted by Aedes spp. mosquitoes. The first documented case, to the authors' knowledge, of sequential CHIKV and ZIKV infections diagnosed in a nonendemic area in a returning traveler is reported. The implications for heightened clinical surveillance for these infections and specific patient recommendations are emphasized.