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

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.

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.

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

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

There are few reports of imported fascioliasis in Spain. This study aimed to describe the characteristics of cases registered in +REDIVI network.Observational, retrospective, descriptive study of imported fascioliasis cases registered in the +REDIVI, a multicenter collaborative network collecting information on imported infectious diseases in Spain, from October 2009 to May 2019.Of 25,203 cases of imported disease registered over the study period, 16 (0.063%) were fascioliasis, acquired mainly in Pakistan, Morocco, Bolivia, and Peru. Clinical, analytical, and therapeutic data were available for 12 cases (6 immigrants, 4 people visiting friends and relatives, 2 travelers). Eleven (91.6%) had eosinophilia. The most frequent symptoms were abdominal pain (n = 5) and cough (n = 5). Two cases (16.66%) were acute and 10 (83.33%) chronic. Two patients presented lung involvement, and four had other parasitic co-infections. Twelve cases (100%) were seropositive for Fasciola hepatica. Ten patients underwent a coproparasitological study, none of which detected Fasciola spp. eggs. The probable food origin (watercress) was confirmed in 3 cases (25%). Nine of the 10 patients treated with triclabendazole (90%) and one patient treated with praziquantel were considered to meet the criteria for cure. One patient was lost to follow-up.Fascioliasis is a rare imported parasitosis in Spain. Eosinophilia, along with geographical origin, is the main clue for diagnosis.

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

Introduction International travellers contribute to the rapid spread of Zika virus (ZIKV) and its sentinel identification globally. We describe ZIKV infections among international travellers seen at GeoSentinel sites with a focus on ZIKV acquired in the Americas and the Caribbean, describe countries of exposure and traveller characteristics, and assess ZIKV diagnostic testing by site. Methods Records with an international travel-related diagnosis of confirmed or probable ZIKV from January 2012 through December 2019 reported to GeoSentinel with a recorded illness onset date were included to show reported cases over time. Records from March 2016 through December 2019 with an exposure region of the Americas or the Caribbean were included in the descriptive analysis. A survey was conducted to assess the availability, accessibility and utilization of ZIKV diagnostic tests at GeoSentinel sites. Results GeoSentinel sites reported 525 ZIKV cases from 2012 through 2019. Between 2012 and 2014, eight cases were reported, and all were acquired in Asia or Oceania. After 2014, most cases were acquired in the Americas or the Caribbean, a large decline in ZIKV cases occurred in 2018–19. Between March 2016 and December 2019, 423 patients acquired ZIKV in the Americas or the Caribbean, peak reporting to these regions occurred in 2016 [330 cases (78%)]. The median age was 36 years (range: 3–92); 63% were female. The most frequent region of exposure was the Caribbean (60%). Thirteen travellers were pregnant during or after travel; one had a sexually acquired ZIKV infection. There was one case of fetal anomaly and two travellers with Guillain-Barré syndrome. GeoSentinel sites reported various challenges to diagnose ZIKV effectively. Conclusion ZIKV should remain a consideration for travellers returning from areas with risk of ZIKV transmission. Travellers should discuss their travel plans with their healthcare providers to ensure ZIKV prevention measures are taken.

Travel-related infections with prolonged incubation periods should be considered in febrile patients despite the current epidemiological situation, especially if alternative more frequent diagnoses, such as COVID-19, are not confirmed.

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.

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.

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 From the first Zika virus (ZIKV) description, it has progressively widespread worldwide. We analyzed demographic, clinical, microbiologic and travel-related characteristic from returned patients from a ZIKV endemic country in a referral Tropical Medicine Unit. Method A prospective cohort study performed in a Spanish referral center with the aim of determining the significant factors associated with confirmed Zika virus (ZIKV) infection. Results 817 patients, (56% women, median age 36 [IQR, Interquartile Range: 32–42]) were enrolled. Most had returned from Latin America (n = 486; 59.4%), travelled for tourism (n = 404; 49.4%) and stayed a median of 18 days (IQR: 10–30). 602 (73.6%) presented symptoms, but only 25 (4%) were finally diagnosed with confirmed ZIKV infection (including two pregnant women, without adverse fetal outcomes), 88% (n:22) presented with fever and 92% (n:23) with rash. 56% (n:14) arthralgia and/or myalgia and 28% (n:7) conjunctivitis. The presence of conjunctivitis, fever and rash were associated with an 8.9 (95% CI: 2.2–34.9), 6.4 (95% CI: 1.2–33.3) and 72.3 (95% CI: 9.2–563.5) times greater probability of confirmed ZIKV infection, respectively. Conclusion Travel characteristics and clinical presentation may help clinicians to optimize requests for microbiological testing. Diagnosis of arboviriasis in travellers arriving form endemic areas remains a challenge for clinicians, but must be detected for the possible transmission outside endemic areas, where the vector is present.

Background Rabies represents a major public health issue for travellers because pretravel preexposure (PrEP) rabies vaccination is not routinely indicated. For those unvaccinated, adequate postexposure prophylaxis (PEP), including rabies immunoglobulin (RIG) if needed, is the only effective method to prevent this fatal disease. Methods Descriptive retrospective study at a National Referral Unit for Tropical and Travel Medicine in Madrid, Spain, among travellers treated with PEP for rabies (January 2012–December 2017). Demographic, clinical and management data were reviewed. Results 168 patients were treated for possible rabies exposure (53% females, median age 35 years; IQR: 31–42). Southeast Asia accounted for more than half of the cases (N = 86, 57.3%; CI 95% 49–65%). Dogs were the primary animal involved (n = 67, 44.9%; CI 37–53%). After the bite, in half of the cases (n = 88, 52.4%; CI 44–60%) PEP rabies vaccine was started abroad, and the vaccine plus RIG in about 10% (n = 22, 13.1%; CI: 8–19%). Most of patients classified as category III did not received RIG at all (n = 88, 69.3% CI: 60–77%). Conclusions Although indicated, most travellers did not receive RIG abroad, nor appropriate first doses of PEP. Clinicians should be aware of the importance of appropriate PrEP in selected individuals.

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.

Initial research on Zika disease defined infected mosquito bite as the only possible route of infection. Subsequent studies, most of which developed during the current epidemic, have opened the range to other mechanisms of transmission: vertical, sexual, laboratory exposition, through blood transfusion products or after monkey bite. Currently, other probable routes that need more research to be settled (breast milk, saliva or organ transplantation) have already been reported as potentially infective, but they have not been definitely documented. International heath authorities have published specific guidelines with recommendations to prevent or minimize transmission through these routes. Table 5.1 highlights the most important items in each route and summarizes the scientific evidence, with a specific link to the chapter in which more detailed information is provided.

Risk of dissemination of ZIKV disease is based on multiple factors, including environmental (climate, socioeconomically, deforestation or industrialization) and travel/traveller factors. Both the disease (viremic travellers) and vector movement to mosquito-free area contributes to the introduction and establishment of autochthonous ZIKV transmission. Mass gathering events can contribute to magnify transmission due to close crowd life in a confined area. Also, multitudinary events can promote the introduction of an infectious disease to a previously naive area when returning home. Although mathematical models estimate a low risk for introduction of ZIKV in Europe, specific European regions (mainly Portuguese Island of Madeira) account with suitable and efficient vector and opportune climate conditions to harbour the disease. Clinicians should be aware to enable early detection of autochthonous ZIKV cases. International and local guidelines can help clinicians on how to handle suspicious cases, how to confirm the infection and how to report suspected and confirmed cases. In case of autochthonous ZIKV detection, public authorities should perform surveillance and provide adequate resources to sustain enhanced mosquito control.

Knowing the mode of transmission of a disease can affect its control and prevention. Here, we identify 5 protozoan parasites with demonstrated presence in seminal fluid, only 1 of which has been identified as a sexually transmitted disease among humans.