Executive Summary of the Spanish Guidelines for the Diagnosis and Management of Imported Febrile Illnesses from the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Imported Pathology Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEPI-SEIMC), the Spanish Society of Family and Community Medicine (SEMFYC), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Emergency Medicine (SEMES).

The Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Society of Family and Community Medicine (SEMFYC) have prepared a consensus statement on the diagnosis and management of patients with imported febrile illnesses. Twenty authors with different backgrounds and representing different healthcare perspectives (ambulatory primary care, travel and tropical medicine specialists, emergency medicine, hospital care, microbiology and parasitology and public health), identified 39 relevant questions, which were organised in 7 thematic blocks. After a systematic review of the literature and a thoughtful discussion, the authors prepared 125 recommendations, as well as several tables and figures to be used as a consulting tool. The present executive summary shows a selection of some of the most relevant questions and recommendations included in the guidelines.

Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Clinical profile and management of a Spanish single-center retrospective cohort of patients with post-chikungunya associated complications.

BACKGROUND: This study aims to describe post-chikungunya complications chronically developed cases in returning travelers from some epidemic/endemic regions, and the variables that are associated with the progression of acute or subacute cases to the chronic phase. METHODS: This single-center retrospective cohort study included chikungunya fever cases treated at La Paz-Carlos III University Hospital in Madrid, Spain, April 2014 to September 2016, when the chikungunya outbreak in Latin America started through the time of its greatest impact. RESULTS: The analysis included 119 cases. Of these, 67.2 % were male, with a median age of 41.0 years [IQR 16.0 to 76.0] years. Only 25.6 % of the patients attended a pre-travel advice consultation. Most patients reported arthralgias, which significantly impacted their daily quality of life (86 %). The mean duration of joint symptoms was 129.4 days, with a median of 90 days [IQR 0 to 715]. Factors found to be associated with chronic arthralgia include female sex, country of infection, age at diagnosis, previous diseases, symptoms during the acute phase, pain in previously injured tendons/joints, acute phase severity, and various laboratory markers such as hemoglobin, hematocrit, total serum bilirubin, and creatinine. Progression to chronic arthralgia significantly increased the need for changes in daily activity. Furthermore, 42.6 % of patients with chronic arthralgia reported recurrence of symptoms once they felt they had disappeared. Targeted treatment regimens led to significant improvements in these patients. CONCLUSIONS: The results of this study underscore the need for: (1) comprehensive pre-travel advice; (2) effective management of patients in specialized units, alongside early diagnosis and treatment, to prevent trivialization of these viral infections; and (3) the development of interdisciplinary recommendations to assist physicians in treating patients and enhancing outcomes.

Imported infectious diseases in migrants from Latin America: A retrospective study from a referral centre for tropical diseases in Spain, 2017-2022.

INTRODUCTION: Detecting imported diseases by migrants and individuals visiting friends and relatives (VFR) is key in the prevention and management of emergent infectious diseases acquired abroad. METHODS: Retrospective descriptive study on migrants and VFR from Central and South America between 2017 and 2022 attended at a National Referral Centre for Tropical Diseases in Madrid, Spain. Demographic characteristics, syndromes and confirmed travel-related diagnoses were obtained from hospital patient medical records. RESULTS: 1654 cases were registered, median age of 42 years, 69.1% were female, and 55.2% were migrants. Most cases came from Bolivia (49.6%), followed by Ecuador (12.9%). Health screening while asymptomatic (31.6%) was the main reason for consultation, followed by Chagas disease follow-up (31%). Of those asymptomatic at screening, 47,2% were finally diagnosed of any disease, mainly Chagas disease (19,7%) and strongyloidiasis (10,2%) CONCLUSION: Our study emphasizes the importance of proactive health screening to detect asymptomatic conditions in migrants and VFR, enabling timely intervention and improved health outcomes. By understanding the unique health profiles of immigrant populations, targeted public health interventions can be devised to safeguard the well-being of these vulnerable groups.

[Rabies: Epidemiological update and pre- and post-exposure management]. / Rabia: actualización epidemiológica y abordaje pre y postexposición.

Rabies is a deadly neurotropic viral infection but is preventable through vaccination. Its impact on human and animal health is often devastating. Despite advances in research and control of this disease, along with an effective vaccine, rabies continues to be a lingering threat in many parts of the world. Its high incidence reinforces the constant need to address it with scientific and public health measures. In this review article, we will explore the most important characteristics of the disease, its distribution, symptoms, prevention methods, and the global efforts that have been made to eradicate this deadly disease. The most recent research and advancements in the field of rabies will also be discussed in an effort to understand and combat this deadly disease more effectively.

Intestinal protozoa in returning travellers: a GeoSentinel analysis from 2007 to 2019.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Tratamiento y prevención de la viruela del mono / Treatment and prevention of monkeypox

La viruela del mono es una zoonosis que se contagia principalmente a través del contacto directo con los fluidos y las lesiones cutáneas de personas contagiadas con vesículas aun activas. Aunque el virus fue aislado por primera vez en 1958, y el primer caso humano se identificó en un niño en 1970, en la República Democrática del Congo, la enfermedad ha aumentado progresivamente su incidencia en África, alcanzando en mayo de 2022 transmisión sostenida fuera de este continente. Al ser un virus de nueva introducción en nuestro entorno sanitario, es necesario aprender el patrón epidemiológico en un medio diferente al de las zonas tradicionalmente endémicas y conocer los tratamientos antivirales a nuestro alcance, así como las medidas profilácticas que podrían plantearse, sabiendo que como virus emergente en nuestras regiones las evidencias científicas aun son limitadas. Existen antivirales que han demostrado en modelos animales combatir eficazmente la enfermedad con muy buena tolerancia clínica. Esta enfermedad también ha obligado a revisar las características de las vacunas frente a la viruela, ya que han demostrado un efecto protector frente a la viruela del mono. Por ello, es importante disponer de un documento que recopile toda la información científica publicada a este respecto.(AU)

Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.(AU)

Coronavirus-19 disease risk and protective factors associated with HLA/KIR polymorphisms in Ecuadorian patients residing in Madrid.

BACKGROUND: Immigrants represented 21.8% of cases in a Spanish cohort of hospitalised patients with COVID-19, a proportion exceeding the percentage of immigrants in that area's total population. Among the ethnic-related genetic risk factors for COVID-19, human leukocyte antigen (HLA) genotypes in diverse populations might bias the response to SARS-CoV-2 infection and/or progression. Similarly, genetic differences in natural killer-activating and inhibitory receptors could play a role in the immune system's response to the viral infection. METHODS: We characterised HLA alleles and KIR genes in 52 Ecuadorian patients hospitalised for moderate and severe COVID-19 and 87 Ecuadorian controls from the general population living in the same area. RESULTS: There was a significantly increased frequency of the HLA-B*39 antigen and the activating KIR2DS4 receptor in the presence of its HLA-C*04 ligand in the COVID-19 group when compared with the control group. In contrast, there was a significant reduction in the frequency of carriers of KIR2DL1 and of the KIR3DL1/Bw4 receptor/ligand combination among COVID-19 group. On the other hand, HLA-A*24:02 and HLA-DRB1*09:01 alleles showed significantly lower frequencies specifically in the severe COVID-19 group. CONCLUSION: HLA-B*39 alleles might be genetic risk factors for developing COVID-19 in Ecuadorian individuals. In the presence of its ligand C*04, the natural killer-activating receptor KIR2DS4 might also increase the risk of developing COVID-19, while, in the presence of HLA-Bw4 alleles, the inhibitory receptor KIR3DL1 might play a protective role. Patients with COVID-19 who carry HLA-A*24:02 and HLA-DRB1*09:01 alleles might be protected against more severe forms of COVID-19.

Li + HF and Li + HCl Reactions Revisited I: QCT Calculations and Simulation of Experimental Results.

The Li + HF and Li + HCl reactions share some common features. They have the same kinematics, relatively small barrier heights, bent transition states, and are both exothermic when the zero point energy is considered. Nevertheless, the pioneering crossed beam experiments by Lee and co-workers in the 80s (Becker et al., J. Chem. Phys. 1980, 73, 2833) revealed that the dynamics of the two reactions differ significantly, especially at low collision energies. In this work, we present theoretical simulations of their results in the laboratory frame (LAB), based on quasiclassical trajectories and obtained using accurate potential energy surfaces. The calculated LAB angular distributions and time-of-flight spectra agree well with the raw experimental data, although our simulations do not reproduce the experimentally derived center-of-mass (CM) differential cross section and velocity distributions. The latter were derived by forward convolution fitting under the questionable assumption that the CM recoil velocity and scattering angle distribution were uncoupled, while our results show that the coupling between them is relevant. Some important insights into the reaction mechanism discussed in the article by Becker et al. had not been contrasted with those that can be extracted from the theoretical results. Among them, the correlation between the angular momenta involved in the reactions has also been examined. Given the kinematics of both systems, the reagent orbital angular momentum, l, is almost completely transformed into the rotation of the product diatom, j'. However, contrary to the coplanar mechanism proposed in the original paper, we find that the initial and final relative orbital angular momenta are not necessarily parallel. Both reactions are found to be essentially direct, although about 15% of the LiFH complexes live longer than 200 fs.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

BACKGROUND: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. METHODS: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. RESULTS: A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. CONCLUSION: Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.

Healthcare seeking during travel: an analysis by the GeoSentinel surveillance network of travel medicine providers.

BACKGROUND: International travellers may seek care abroad to address health problems that arise during their trip or plan healthcare outside their country of residence as medical tourists. METHODS: Data were collected on travellers evaluated at GeoSentinel Network sites who reported healthcare during travel. Both unplanned and planned healthcare were analysed, including the reason and nature of healthcare sought, characteristics of the treatment provided and outcomes. Travellers that presented for rabies post-exposure prophylaxis were described elsewhere and were excluded from detailed analysis. RESULTS: From May 2017 through June 2020, after excluding travellers obtaining rabies post-exposure prophylaxis (n= 415), 1093 travellers reported care for a medical or dental issue that was an unanticipated part of the travellers' planned itinerary (unplanned healthcare). Travellers who sought unplanned healthcare abroad had frequent diagnoses of acute diarrhoea, dengue, falciparum malaria and unspecified viral syndrome, and obtained care in 131 countries. Thirty-four (3%) reported subsequent deterioration and 230 (21%) reported no change in condition; a third (n = 405; 37%) had a pre-travel health encounter. Forty-one travellers had sufficient data on planned healthcare abroad for analysis. The most common destinations were the US, France, Dominican Republic, Belgium and Mexico. The top reasons for their planned healthcare abroad were unavailability of procedure at home (n = 9; 19%), expertise abroad (n = 9; 19%), lower cost (n = 8; 17%) and convenience (n = 7; 15%); a third (n = 13; 32%) reported cosmetic or surgical procedures. Early and late complications occurred in 14 (33%) and 4 (10%) travellers, respectively. Four travellers (10%) had a pre-travel health encounter. CONCLUSIONS: International travellers encounter health problems during travel that often could be prevented by pre-travel consultation. Travellers obtaining planned healthcare abroad can experience negative health consequences associated with treatments abroad, for which pre-travel consultations could provide advice and potentially help to prevent complications.

Treatment and prevention of monkeypox.

Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.

Effectiveness of the BNT162b2 mRNA Covid-19 vaccine in Spanish healthcare workers.

INTRODUCTION: Frontline health care workers (HCW) have higher risk than the general population to become infected by SARS.CoV.2, so they were a priority group for Covid-19 vaccine administration. We compared the incidence and prevalence of HCW infected pre-and post-vaccination with the BNT162b2 mRNA COVID-19 vaccine. MATERIAL AND METHODS: Prospective observational study carried out between 01/12/20 and 07/03/21 in La Paz University Hospital, Madrid (Spain). SARS.CoV.2 positive cases in HCW after vaccination were collected and compared to those hospitalized COVID-19 patients at the same hospital. RESULTS: Two weeks after finishing the first round of vaccinations daily new cases of HCW infections (symptomatic and asymptomatic) decreased substantially and cumulative cases of infected HCW and hospitalized COVID-19 patients started to diverge. No new positive cases of HCW infection were registered seven days after the second dose of BNT162b2 mRNA COVID-19 vaccine. CONCLUSIONS: BNT162b2 mRNA COVID-19 vaccine is highly effective in Spanish HCW.

Effectiveness of the BNT162b2 mRNA Covid-19 vaccine in Spanish healthcare workers / Impacto de la vacuna BNT162b2 de mRNA frente a COVID-19 en personal sanitario español

Introduction: Frontline health care workers (HCW) have higher risk than the general population to become infected by SARS.CoV.2, so they were a priority group for Covid-19 vaccine administration. We compared the incidence and prevalence of HCW infected pre-and post-vaccination with the BNT162b2 mRNA COVID-19 vaccine. Material and methods: Prospective observational study carried out between 01/12/20 and 07/03/21 in La Paz University Hospital, Madrid (Spain). SARS.CoV.2 positive cases in HCW after vaccination were collected and compared to those hospitalized COVID-19 patients at the same hospital. Results: Two weeks after finishing the first round of vaccinations daily new cases of HCW infections (symptomatic and asymptomatic) decreased substantially and cumulative cases of infected HCW and hospitalized COVID-19 patients started to diverge. No new positive cases of HCW infection were registered seven days after the second dose of BNT162b2 mRNA COVID-19 vaccine. Conclusions: BNT162b2 mRNA COVID-19 vaccine is highly effective in Spanish HCW.(AU)

Introducción: Los trabajadores sanitarios (TS) de primera línea tienen mayor riesgo de infectarse de SARS-CoV-2 que la población general, por lo que han sido un grupo prioritario para la vacunación frente a COVID-19. Comparamos la incidencia y prevalencia de TS infectados antes y después de la vacunación con BNT162b2 mRNA frente a COVID-19. Material y métodos: Estudio prospectivo observacional realizado entre 01 de diciembre de 2021 en el Hospital Universitario La Paz, Madrid, España. Se registraron los casos positivos para SARS-CoV-2 en TS y se compararon con los hospitalizados por COVID-19. Resultados: Dos semanas tras la primera ronda de vacunación las nuevas infecciones en TS (sintomáticas y asintomáticos) disminuyeron sustancialmente y los casos acumulados de TS infectados y pacientes hospitalizados por COVID-19 empezaron a divergir. No hubo nuevas infecciones en TS vacunados a los siete días de la segunda dosis de la vacuna. Conclusión: La vacuna BNT162b2 mRNA frente a SARS-CoV-2 es altamente eficaz en TS españoles.(AU)