Prevalence and Risk Factors for Colonization by Multidrug-Resistant Microorganisms among Long-Term Travelers and Recently Arrived Migrants.

Multidrug-resistant (MDR) bacteria have become one of the most important health problems. We aimed to assess whether international travel may facilitate their spread through the colonization of asymptomatic travelers. A cross-sectional study was conducted (November 2018 to February 2022). Pharyngeal and rectal swabs were obtained from long-term travelers and recently arrived migrants from non-European countries, and an epidemiological survey was performed. Colonization by Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) was determined by chromogenic media and MALDI-TOF-MS. Resistance mechanisms were determined by the biochip-based molecular biology technique. Risk factors for colonization were assessed by logistic regression. In total, 122 participants were included: 59 (48.4%) recently arrived migrants and 63 (51.6%) long-term travelers. After their trip, 14 (11.5%) participants-5 (8.5%) migrants and 9 (14.3%) travelers-had rectal colonization by one MDR bacterium. Escherichia coli carrying the extended-spectrum beta-lactamase (ESBL) CTX-M-15 was the most frequent. No participants were colonized by MRSA or carbapenemase-producing Enterobacteriaceae. The only risk factor independently associated with MDR bacterial colonization was previous hospital attention [OR, 95% CI: 10.16 (2.06-50.06)]. The risk of colonization by MDR bacteria among recently arrived migrants and long-term travelers is similar in both groups and independently associated with previous hospital attention.

Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations.

BACKGROUND: We aimed to evaluate the performance of a novel multiplex serological assay, able to simultaneously detect IgG of six infections, as a screening tool for imported diseases in migrants. METHODS: Six panels of 40 (n = 240) anonymized serum samples with confirmed infections were used as positive controls to assess the multiplex assay's sensitivity. One panel of 40 sera from non-infected subjects was used to estimate the seropositivity cutoffs, and 32 non-infected sera were used as negative controls to estimate each serology's sensitivity and specificity. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas. The sensitivity of the Luminex assay was calculated as the proportion of positive results over all positive samples identified by reference tests. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95 % confidence intervals using receiver operating characteristic analyses. RESULTS: The sensitivity/specificity were 100 %/100 % for HIV (gp41 antigen), 97.5 %/100 % for Hepatitis B virus (HBV-core antigen), 100 %/100 % for Hepatitis C virus (HCV-core antigen), 92.5 %/90.6 % for strongyloidiasis [31-kDa recombinant antigen (NIE)], 97.5 %/100 % for schistosomiasis (combined serpin Schistosoma mansoni and S.haematobium antigens) and 95 %/90.6 % for Chagas disease [combined Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP11) and paraflagellar rod proteins 2 (PFR2) antigens]. In the migrant cohort, antibody response to the combination of the T.cruzi antigens correctly identified 100 % individuals, whereas HBV-core antigen correctly identified 91.7 % and Strongyloides-NIE antigen 86.4 %. CONCLUSIONS: We developed a new, robust and accurate 8-plex Luminex assay that could facilitate the implementation of screening programmes targeting migrant populations.

Prognostic factors in Spanish COVID-19 patients: A case series from Barcelona.

BACKGROUND: In addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community. AIM: To determine clinical factors of a poor prognosis in patients with COVID-19 infection. DESIGN AND SETTING: Descriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000. METHOD: Examination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Logistic multivariate regression models adjusted for age and sex were constructed to analyse independent predictive factors associated with death, ICU admission and hospitalization. RESULTS: We included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged ≥ 65 years): 123 (38.2) were health workers (doctors, nurses, auxiliaries). Predictors of ICU admission or death were greater age (OR = 1.05; 95%CI = 1.03 to 1.07), male sex (OR = 2.94; 95%CI = 1.55 to 5.82), autoimmune disease (OR = 2.82; 95%CI = 1.00 to 7.84), bilateral pulmonary infiltrates (OR = 2.86; 95%CI = 1.41 to 6.13), elevated lactate-dehydrogenase (OR = 2.85; 95%CI = 1.28 to 6.90), elevated D-dimer (OR = 2.85; 95%CI = 1.22 to 6.98) and elevated C-reactive protein (OR = 2.38; 95%CI = 1.22 to 4.68). Myalgia or arthralgia (OR = 0.31; 95%CI = 0.12 to 0.70) was protective factor against ICU admission and death. Predictors of hospitalization were chills (OR = 5.66; 95%CI = 1.68 to 23.49), fever (OR = 3.33; 95%CI = 1.89 to 5.96), dyspnoea (OR = 2.92; 95%CI = 1.62 to 5.42), depression (OR = 6.06; 95%CI = 1.54 to 40.42), lymphopenia (OR = 3.48; 95%CI = 1.67 to 7.40) and elevated C-reactive protein (OR = 3.27; 95%CI = 1.59 to 7.18). Anosmia (OR = 0.42; 95%CI = 0.19 to 0.90) was the only significant protective factor for hospitalization after adjusting for age and sex. CONCLUSION: Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.

Clinical Features Associated with Strongyloidiasis in Migrants and the Potential Impact of Immunosuppression: A Case Control Study.

Strongyloides stercoralis is a widely distributed nematode more frequent in tropical areas and particularly severe in immunosuppressed patients. The aim of this study was to determine factors associated with strongyloidiasis in migrants living in a non-endemic area and to assess the response to treatment and follow-up in those diagnosed with the infection. We performed a multicenter case-control study with 158 cases and 294 controls matched 1:2 by a department service. Participants were recruited simultaneously at six hospitals or clinics in Spain. A paired-match analysis was then performed looking for associations and odds ratios in sociodemographic characteristics, pathological background, clinical presentation and analytical details. Cases outcomes after a six-month follow-up visit were also registered and their particularities described. Most cases and controls came from Latin America (63%-47%) or sub-Saharan Africa (26%-35%). The number of years residing in Spain (9.9 vs. 9.8, p = 0.9) and immunosuppression status (30% vs. 36.3%, p = 0.2) were also similar in both groups. Clinical symptoms such as diffuse abdominal pain (21% vs. 13%, p = 0.02), and epigastralgia (29% vs. 18%, p < 0.001); along with a higher eosinophil count (483 vs. 224 cells/mL in cases and controls, p < 0.001) and the mean total Immunoglobulin E (IgE) (354 U/L vs. 157.9 U/L; p < 0.001) were associated with having strongyloidiasis. Finally, 98.2% percent of the cases were treated with ivermectin in different schedules, and 94.5% met the cure criteria at least six months after their first consultation. Abdominal pain, epigastralgia, eosinophilia, increased levels of IgE and Latin American origin remain the main features associated with S. stercoralis infection, although this association is less evident in immunosuppressed patients. The appropriate follow-up time to evaluate treatment response based on serology titers should be extended beyond 6 months if the cure criteria are not achieved.

Management of severe strongyloidiasis attended at reference centers in Spain.

INTRODUCTION: Strongyloides stercoralis is a globally distributed nematode that causes diverse clinical symptoms in humans. Spain, once considered an endemic country, has experienced a recent increase in imported cases. The introduction of serology helps diagnosis and is currently replacing microbiological techniques in some settings, but its sensitivity is variable and can be low in immunocompromised patients. Diagnosis can only be confirmed by identification of larvae. Often, this "gold standard" can only be achieved in severe cases, such as disseminated S.stercoralis infection, or S.stercoralis hyperinfection syndrome, where parasite load is high. In addition, these clinical presentations are not well-defined. Our aim is to describe severe cases of S.stercoralis, their epidemiological profile, and their clinical details. METHODS: An observational retrospective study of disseminated S.stercoralis infection, or hyperinfection syndrome. Inclusion criteria: aged over 18, with a diagnosis of disseminated S.stercoralis infection, or hyperinfection syndrome, confirmed by visualization of larvae. Patients were identified through revision of clinical records for the period 2000-2015, in collaboration with eight reference centers throughout Spain. RESULTS: From the period 2000-2015, eighteen cases were identified, 66.7% of which were male, with a median age of 40 (range 21-70). Most of them were foreigners (94.4%), mainly from Latin America (82.3%) or Western Africa (17.6%). Only one autochthonous case was identified, from 2006. Immunosuppressive conditions were present in fourteen (77%) patients, mainly due steroids use and to retroviral coinfections (four HIV, two HTLV). Transplant preceded the clinical presentation in four of them. Other comorbidities were coinfection with HBV, Trypanosoma cruzi, Mycobacterium leprae or Aspergillus spp. All presented with digestive disorders, with 55.6% also presenting malaise. 44.4% of cases had fever, 27.8% skin complaints, and 16.7% respiratory or neurological disorders. One patient presented anemia, and one other nephrotic syndrome. Diagnosis was confirmed by identification of larvae in fresh stool samples (n = 16; 88.9%), concentration techniques (n = 6; 33.3%), larval culture (n = 5; 29.4%), or digestive biopsies (n = 8; 44%). S.stercoralis forms were identified during necropsy in one case. In addition, ten (55%) had a positive serology. All the cases were treated with ivermectin, six (33%) also received albendazole and one case received thiabendazole followed by ivermectin. All needed inpatient management, involving a mean hospitalization stay of 25 days (range 1-164). Two cases received intensive care and eventually died. CONCLUSIONS: Only eighteen cases of disseminated S.stercoralis infection/hyperinfection syndrome were identified from the 15-year period, most of which were considered to have been imported cases. Among those, immunosuppression was frequent, and mortality due to S.stercoralis was lower than previously described.

Surveillance of strongyloidiasis in Spanish in-patients (1998-2014).

BACKGROUND: Strongyloides stercoralis is a parasite that causes strongyloidiasis, a neglected tropical disease. S. stercoralis is a soil-transmitted helminth that is widely distributed in tropical and subtropical regions of the world. Strongyloidiasis can occur without any symptoms or as a chronic infection characterized by mild, unspecific symptoms such as pruritus, abdominal pain or discomfort; respiratory impairment also may manifest as a potentially fatal hyperinfection or disseminated infection. Most studies on strongyloidiasis in Spain have been related to chronic forms in immigrants or travellers from endemic zones and have mainly analysed out-patient populations. Studies of the impact of strongyloidiasis cases admitted to hospitals in Spain are lacking. Therefore, the aim of this study was to analyse the impact of strongyloidiasis in hospital care in Spain. METHODOLOGY: We designed a retrospective descriptive study using the Minimum Basic Data Set (MBDS, CMBD in Spanish) for inpatients with ICD-9: 127.2 (strongyloidiasis) diagnoses admitted to hospitals in the Spanish National Health System between 1998 and 2014. PRINCIPAL FINDINGS: A total of 507 hospitalizations with diagnosis of strongyloidiasis were recorded, 324 cases (63.9%) were males. The mean (±SD) age was 42.1±20.1 years. The impact of strongyloidiasis on the total population of Spain was 0.06 cases per 105 person-years, and the infection burden increased progressively over time (from 0.01 cases per 105 person-years in 1999 to 0.10 cases per 105 person-years in 2014). 40 cases (7.9%) died. The total cost was approximately €8,681,062.3, and the mean cost per patient was €17,122.4±97,968.8. CONCLUSIONS: Our data suggest that strongyloidiasis is frequent in Spain and is increasing in incidence. Therefore, it would be desirable to improve the oversight and surveillance of this condition. Due to the fact that strongyloidiasis can be fatal, we believe that there is a need to establish risk categories for inclusion in national guidelines/protocols for screening individuals at risk of developing strongyloidiasis.

Prevalence of Trypanosoma cruzi's Discrete Typing Units in a cohort of Latin American migrants in Spain.

Chagas disease is caused by the protozoan Trypanosoma cruzi. This is an endemic disease in the Americas, but increased migration to Europe has made it emerge in countries where it was previously unknown, being Spain the second non endemic country in number of patients. T. cruzi is a parasite with a wide genetic diversity, which has been grouped by consensus into 6 Discrete Typing Units (DTUs) affecting humans. Some authors have linked these DTUs either to a specific epidemiological context or to the different clinical presentations. Our main objective was to describe the T. cruzi DTUs identified from a population of chronically infected Latin American migrants attending a reference clinic in Madrid. 149 patients meeting this condition were selected for the study. Molecular characterization was performed by an algorithm that combines PCR of the intergenic region of the mini exon-gene, the 24Sα and 18S regions of rDNA and the variable region of the satellite DNA. A descriptive analysis was performed and associations between geographical/clinical data and the different DTUs were tested. DTUs could be determined in 105 out of 149 patients, 93.3% were from Bolivia, 67.7% were women and median age was 35 years (IQR 29-44). The most common DTU found was TcV (58; 55.2%), followed by TcIV (17; 16.2%), TcII (10; 9.5%) and TcI (4; 3.8%). TcIII and TcVI were not identified from any patient, and 15.2% patients presented mixed infections. In addition, we determined DTUs after treatment in a subset of patients. In 57% patients had different DTUs before and after treatment. DTUs distribution from this study indicates active transmission of T. cruzi is occurring in Bolivia, in both domestic and sylvatic cycles. TcIV was confirmed as a cause of chronic human disease. The current results indicate no correlation between DTU and any specific clinical presentation associated with Chagas disease, nor with geographical origin. Treatment with benznidazole does not always clear T. cruzi's genetic material from blood, and DTUs detected in the same patient may vary over time indicating that polyparasitism is frequent.

Characteristics of HIV infected individuals traveling abroad. Results from the +REDIVI Collaborative Network.

INTRODUCTION: The improvement in the prognosis of HIV infection, coupled with the increase in international travel and migration, has led to a rising number of HIV infected travelers. The objective of this study was to describe the epidemiological and clinical features of returning travelers, according to their HIV status. METHODS: An observational prospective study was conducted including travelers and immigrants who traveled to visit friends and relatives (VFRs) registered in the +REDIVI collaborative network (January-2009; October-2014). +REDIVI is a national network that registers information regarding infections imported by travelers and immigrants at 21 different centers using a standardized protocol. RESULTS: A total of 3464 travellers were identified: 72 were HIV+ (2.1%) and 3.392 HIV- (98%). HIV+ vs. HIV- travelers were often older (40.5y vs. 34.2y P=.001), VFRs (79.1% vs. 44.4%; P<.001), and consulted less for pre-travel advice (27% vs. 37%; P=.078). The main destinations for both groups were sub-Saharan Africa and Latin America. The most frequent reasons for consultation after travel were fever, request for a health examination, gastrointestinal complaints, and abnormal laboratory tests (mainly eosinophilia and anemia), which differed between groups. The most frequent diagnoses in HIV+ travelers were malaria (38.8%), newly diagnosed HIV infection (25%), and intestinal parasites (19.4%), while for HIV- travelers the main diagnoses were "healthy" (17.9%), malaria (14%), and intestinal parasites (17.3%). CONCLUSIONS: The typical profile of an HIV+ traveler in +REDIVI was that of a VFR traveler who did not seek pre-travel advice and made high-risk trips. This may increase the chance of acquiring travel-related infections which may pose a special risk for HIV-infected travelers. The post-travel visit was a good opportunity for HIV infection screening.

Clinical and microbiological profile of a retrospective cohort of enteric fever in 2 Spanish tertiary hospitals.

Enteric fever in high-income countries is diagnosed mainly in patients returning from endemic countries. We assess the clinical, microbiological, and prognosis aspects of enteric fever in 2 Spanish tertiary hospitals. A retrospective observational study was conducted at Vall d'Hebron University Hospital and Ramón y Cajal University Hospital in Spain. We reviewed medical records of all patients who were diagnosed with enteric fever from January 2000 to January 2014 at these hospitals. We identified 47 patients with enteric fever episodes. According to their travel history, 35 (74.5%) patients had travelled to highly endemic countries. Imported enteric fever was acquired mainly in Asia (70.3%). Imported infections were implicated in travelers (48.6%), visiting friends and relatives (40%) and immigrants (11.4%). We found that 12 patients were diagnosed with enteric fever without a travel history (autochthonous infection). The resistance profile of the isolates showed decreased ciprofloxacin susceptibility in 66.7% of the imported group and 8.3% of the autochthonous group (P = 0.001). Salmonella strains from patients returning from Asia had an increased risk of having decreased ciprofloxacin susceptibility (odds ratio, 52.25; 95% confidence interval: 8.6-317.7). Patients with imported enteric fever are at higher risk for having a Salmonella strain with decreased ciprofloxacin susceptibility, especially in patients returning from Asia. Initial treatment with third-generation cephalosporin or azithromycin is strongly recommended until a drug-susceptibility test is available. Prevention strategies such as pretravel counseling and immunization before travel may be beneficial.

Screening of imported infectious diseases among asymptomatic sub-Saharan African and Latin American immigrants: a public health challenge.

Migrants from developing countries are usually young and healthy but several studies report they may harbor asymptomatic infections for prolonged periods. Prevalence of infections were determined for asymptomatic immigrants from Latin America and sub-Saharan Africa who ettended to a European Tropical Medicine Referral Center from 2000 to 2009. A systematic screening protocol for selected infections was used. Data from 317 sub-Saharan Africans and 383 Latin Americans were analyzed. Patients were mostly young (mean age 29 years); there were significantly more males among sub-Saharan Africans (83% versus 31.6%) and pre-consultation period was longer for Latin Americans (5 versus 42 months). Diagnoses of human immunodeficiency virus (HIV), chronic hepatitis B and C virus infection, and latent tuberculosis were significantly more frequent in sub-Saharan Africans (2.3% versus 0.3%; 14% versus 1.6%; 1.3 versus 0%; 71% versus 32.1%). There were no significant differences in prevalence for syphilis and intestinal parasites. Malaria and schistosomiasis prevalence in sub-Saharan Africans was 4.6% and 5.9%, respectively, and prevalence of Chagas disease in Latin Americans was 48.5%. Identifying and treating asymptomatic imported infectious diseases may have an impact both for the individual concerned and for public health. Based on these results, a systematic screening protocol for asymptomatic immigrants is proposed.

Parasitic infections in travelers and immigrants: part I protozoa.

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.

Parasitic infections in travelers and immigrants: part II helminths and ectoparasites.

Travel and migration contribute to the emergence of certain parasites which may be imported into nonendemic areas. Noncontrolled importation of food products and animals may also contribute to the diagnosis of infections caused by helminths in nonendemic countries. Some helminth infections such as strongyloidiasis may be life-threatening, especially in immunocompromised patients, and outcome depends on correct diagnosis and treatment. Other helminth infections are neglected tropical diseases associated with chronic disease and/or disability. Major challenges concern the development of improved diagnostic techniques, safer and more effective drug therapies and identification of markers of response to treatment. The study of these imported infections in travelers and immigrants may provide opportunities for research which may not be readily available in resource-poor endemic countries. Updated reviews and guidelines are necessary as new data become available. The second part of this review focuses on infections in travelers and immigrants caused by helminths and ectoparasites.

An approach to the management of Trypanosoma cruzi infection (Chagas' disease) in immunocompromised patients.

The epidemiology of Chagas disease has changed in the last decades due to migration movements, population ageing and the emergence of new transmission routes. In endemic countries, health facilities and access to healthcare are improving and T. cruzi infected patients are also benefiting from medical advances. The HIV epidemic has spread to both endemic and non-endemic areas for T. cruzi, organ transplant rates have increased recently, especially in Latin America, and other medical conditions affecting the immune system are increasing their global burden. The natural course of Chagas disease is mainly determined by the host's cellular immune response. These conditions may therefore overlap with T. cruzi infection and alter the disease's natural history which may present with atypical clinical forms and a higher associated morbidity and mortality in immunocompromised patients. The present review aims to contribute to the management of immunosuppressed patients with T. cruzi infection.

Distribution of Trypanosoma cruzi discrete typing units in Bolivian migrants in Spain.

Chagas disease is caused by the protozoan Trypanosoma cruzi. This parasite is transmitted to humans mainly through the faeces of infected triatomine "kissing" bugs, by blood transfusions or organ donation from infected donors, and can be transmitted from mother to child. This disease is endemic in the Americas, where Bolivia has up to 28.8% prevalence in general population. Increased migration to Europe has made it emerge in countries where it was previously unknown, being Spain the second country in number of patients after the United States. T. cruzi is an organism with a rich genetic diversity, what has been grouped into six discrete typing units (DTUs). Some authors have linked these DTUs either to specific geographical distribution or to the different clinical presentations. Nevertheless little is known about its distribution in migrant populations. Our aim was to describe the T. cruzi strains isolated from a population of chronically infected Bolivian patients attending our clinic in Madrid. Thirty-three consecutive patients meeting this condition were selected for the study. Molecular characterization was performed by an algorithm that combines PCR of the intergenic region of the mini exon-gene, the 24Sα and 18S regions of rDNA and the variable region of the satellite DNA. A descriptive analysis was performed and associations between epidemiological/clinical data and the different DTUs were tested. Twenty-seven out of thirty-three patients had their DTU detected. Mean age was 36 years (IQR 31-43.3) and 23 were women (76.7%). The median time since arrival to Spain was 60 months (IQR 43-81). The most common DTU were TcV, TcIV and TcI. Four patients had cardiac involvement: 2 had TcV and 2 could not have their DTU determined. TcIII was not isolated from any patient. DTUs distribution in migrant population seems to be similar to that observed in the patients' countries of origin.