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.

Consensus definitions in imported human schistosomiasis: a GeoSentinel and TropNet Delphi study.

Terminology in schistosomiasis is not harmonised, generating misunderstanding in data interpretation and clinical descriptions. This study aimed to achieve consensus on definitions of clinical aspects of schistosomiasis in migrants and returning travellers. We applied the Delphi method. Experts from institutions affiliated with GeoSentinel and TropNet, identified through clinical and scientific criteria, were invited to participate. Five external reviewers revised and pilot-tested the statements. Statements focusing on the definitions of acute or chronic; possible, probable, or confirmed; active; and complicated schistosomiasis were managed through REDCap and replies managed in a blinded manner. Round 1 mapped the definitions used by experts; subsequent rounds were done to reach consensus, or quantify disagreement, on the proposed statements. Data were analysed with percentages, medians, and IQRs of a 5-point Likert scale. The study was terminated on the basis of consensus or stability-related and time-related criteria. 28 clinicians and scientists met the criteria for experts. 25 (89%) of 28 experts replied to Round 1, 18 (64%) of 28 to Round 2, 19 (68%) of 28 to Round 3, and 21 (75%) of 28 to at least two rounds. High-level consensus (79-100% agreement and IQRs ≤1) was reached for all definitions. Consensus definitions will foster harmonised scientific and clinical communication and support future research and development of management guidelines for schistosomiasis.

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.

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.

Chagas disease is related to structural changes of the gut microbiota in adults with chronic infection (TRIPOBIOME Study).

BACKGROUND: The implications of the gut microbial communities in the immune response against parasites and gut motility could explain the differences in clinical manifestations and treatment responses found in patients with chronic Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: In this pilot prospective cross-sectional study, we included 80 participants: 29 with indeterminate CD (ICD), 16 with cardiac CD (CCD), 15 with digestive CD (DCD), and 20 controls without CD. Stool was collected at the baseline visit and faecal microbial community structure DNA was analyzed by whole genome sequencing. We also performed a comprehensive dietary analysis. Ninety per cent (72/80) of subjects were of Bolivian origin with a median age of 47 years (IQR 39-54) and 48.3% (29/60) had received benznidazole treatment. There were no substantial differences in dietary habits between patients with CD and controls. We identified that the presence or absence of CD explained 5% of the observed microbiota variability. Subjects with CD exhibited consistent enrichment of Parabacteroides spp, while for Enterococcus hirae, Lactobacillus buchneri and Megamonas spp, the effect was less clear once excluded the outliers values. Sex, type of visceral involvement and previous treatment with benznidazole did not appear to have a confounding effect on gut microbiota structure. We also found that patients with DCD showed consistent Prevotella spp enrichment. CONCLUSIONS: We found a detectable effect of Chagas disease on overall microbiota structure with several potential disease biomarkers, which warrants further research in this field. The analysis of bacterial diversity could prove to be a viable target to improve the prognosis of this prevalent and neglected disease.

Rickettsioses imported by travellers and migrants to Spain attended in the +Redivi network, 2009-2020.

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.

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.

Management of imported complicated urogenital schistosomiasis in Europe: a TropNet retrospective study.

BACKGROUND: Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma. Schistosoma haematobium causes urogenital schistosomiasis (UGS), a chronic disease characterized by pathology of the urogenital tract leading to potentially severe morbidity for which the treatment is poorly standardized. We conducted a survey in TropNet centres on the clinical presentations and management strategies of complicated urogenital schistosomiasis (cUGS). METHODS: We reviewed the clinical records of patients seen at TropNet centres over a 20-year timespan (January 2001-December 2020). Case definition for cUGS included the presence of urogenital cancer, obstructive uropathy, kidney insufficiency of all grades and female or male genital involvement leading to infertility. Collected data included demographic information, patient category (traveller or migrant), imaging data, microbiological data (serology results and presence/absence of eggs in urine), histological features and outcome at last visit recorded. RESULTS: Eight centres contributed with at least one case. Overall, 31 patients matched the inclusion criteria. Sub-Saharan Africa was the most likely place of infection for included patients. Median age was 30.6 years (range 21-46, interquartile ranges, IQR 27-33). Most patients (28/31, 90.3%) were males. Hydronephrosis was the most frequent complication, being present in 18 (58.1%) patients, followed by cancer, present in 5 patients (16.1%); 27 patients (87.1%) required surgical management of some sort. Use of praziquantel varied across centres, with six different regimens employed. DISCUSSION: Very few cases of cUGSs were found in our survey, possibly indicating underdiagnosis of this condition. Hydronephrosis was the most frequently observed urogenital complication, and most patients required invasive procedures. Infection by S. haematobium can result in considerable morbidity, resulting in clinically challenging presentations requiring a multidisciplinary approach. As such, development of common protocols for early diagnosis and treatment is urgently needed.

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

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.

Imported fascioliasis in Spain: Report of 12 cases from the +REDIVI collaborative network (2009-2019).

BACKGROUND: There are few reports of imported fascioliasis in Spain. This study aimed to describe the characteristics of cases registered in +REDIVI network. METHODS: 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. RESULTS: 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. CONCLUSIONS: Fascioliasis is a rare imported parasitosis in Spain. Eosinophilia, along with geographical origin, is the main clue for diagnosis.

Effectiveness and Safety of a Single-Dose Ivermectin Treatment for Uncomplicated Strongyloidiasis in Immunosuppressed Patients (ImmunoStrong Study): The Study Protocol.

Strongyloidiasis affects an estimated 600 million people worldwide, especially in tropical and subtropical areas. Single-dose ivermectin treatment has shown to be effective among immunocompetent patients with uncomplicated strongyloidiasis. Here, we present the protocol of the ImmunoStrong study, a prospective observational study aiming to evaluate the effectiveness and safety of a single-dose ivermectin for treatment of uncomplicated strongyloidiasis in immunosuppressed patients. The secondary objectives are to assess accuracy of molecular techniques for the follow-up of these patients and to determine the population pharmacokinetics of ivermectin. The information retrieved by this study will cover relevant information gaps in the strongyloidiasis management among immunosuppressed patients.

Imported Mansonella perstans infection in Spain.

BACKGROUND: Mansonella perstans infection can be considered one of the most neglected tropical infectious diseases. Very few studies have reported on the clinical picture caused by infection with this nematode. Therefore, our study was aimed to describe the clinical patterns and treatment of imported M. perstans infection by migrants from Africa. METHODS: The present study evaluated a large cohort of migrants who have been diagnosed, examined and treated for imported M. perstans infection at a Spanish reference center (Hospital Carlos III Tropical Medicine Unit, Madrid, Spain) over a 19-year period. Most patients voluntarily attend the emergency unit or are referred from primary care or general hospitals in Madrid. Chi-square test was used to compare the association between categorical variables. The continuous variables were compared by Student's t-test or the Mann-Whitney test. The corresponding regression models were used for multivariate analysis. RESULTS: Five hundred three cases of migrants from tropical and subtropical areas with M. perstans infection were identified. Two hundred sixty-four patients were female (52.5%). The mean age (± SD) was 44.6 ± 18.2 years (range: 16-93 years). The mean time (± SD) between the arrival in Spain and the first consultation was 8.6 ± 18.0 months. The major origin of the patients was Equatorial Guinea (97.6%). Regarding the clinical picture, 257 patients were asymptomatic (54.7%) and 228 were symptomatic (45.3%); 190 patients had pruritus (37.8%), 50 (9.9%) had arthralgia, 18 patients had Calabar-like swelling (3.6%), and 15 (3%) had abdominal pain. Four hundred forty-two (87.9%) migrants had hyper-IgE, and 340 (67.6%) had eosinophilia. One hundred ninety-five patients had coinfections with other filarial nematodes (38.8%), and 308 migrants had only M. perstans infection (61.2%). Four hundred thirty-seven cases (86.9%) had been treated with anti-filarial drugs; 292 cases were treated with one anti-filarial drug, and 145 cases were treated with combined anti-filarial therapy. Additionally, 20 (4%) cases received steroids and 38 (7.6%) cases received antihistamines. CONCLUSIONS: A long series of M. perstans infections is presented in sub-Saharan immigrants whose data indicate that it should be included in the differential diagnosis in patients with pruritus or analytical alterations such as eosinophilia or hyper-IgE presentation, and they also have a high number of coinfections with other microorganisms whose treatment needs to be protocolized.

Loiasis in sub-Saharan migrants living in Spain with emphasis of cases from Equatorial Guinea.

BACKGROUND: Loiasis is an uncommon and poorly understood parasitic disease outside endemic areas of Africa. The aim of this study was to describe the clinical and biological patterns and treatment of imported loiasis by sub-Saharan migrants diagnosed in Madrid, Spain. METHODS: A retrospective study was conducted with sub-Saharan immigrants seen at the Tropical Medicine Unit of the Carlos III Hospital in Madrid, Spain, a reference center, over 19 years. Categorical variables were expressed as frequency counts and percentages. Continuous variables were expressed as the mean and standard deviation (SD) or median and interquartile range (IQR: Q3-Q1). Chi-square tests were used to assess the association between categorical variables. The measured outcomes were expressed as the odds ratio (OR) with a 95% confidential interval. Continuous variables were compared by Student's t-tests or Mann-Whitney U tests. Binary logistic regression models were used. P <  0.05 was considered a statistically significant difference. RESULTS: One hundred thirty-one migrants from tropical and subtropical areas with loiasis were identified. Forty-nine patients were male (37.4%). The migrants' mean age (±SD) was 42.3 ± 17.3 years, and 124 (94.7%) were from Equatorial Guinea. The median time (IQR) between arrival in Spain and the first consultation was 2 (1-7) months. One hundred fifteen migrants had eosinophilia, and one hundred thirteen had hyper-IgE syndrome. Fifty-seven patients had pruritus (43.5%), and thirty patients had Calabar swelling (22.9%). Seventy-three patients had coinfections with other filarial nematodes (54.2%), and 58 migrants had only Loa loa infections (45.8%). One hundred two patients (77.9%) were treated; 45.1% (46/102) patients were treated with one drug, and 54.9% (56/102) patients were treated with combined therapy. Adverse reactions were described in 14 (10.7%) migrants. CONCLUSIONS: Our patients presented early clinical manifestations and few atypical features. Thus, physicians should systematically consider loiasis in migrants with a typical presentation. However, considering that 72.5% of the patients had only positive microfilaremia without any symptoms, we suggest searching for microfilaremia in every migrant from endemic countries for loiasis presenting with eosinophilia.

Rabies postexposure prophylaxis in international travellers: Results from a Spanish travellers referral unit / Profilaxis postexposición de la rabia en viajeros internacionales: resultados de un estudio en una Unidad de Referencia Nacional para Salud Internacional

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

ANTECEDENTES: La rabia representa un importante problema de salud pública para los viajeros, porque la profilaxis pre-exposición (PrEP, por sus siglas en inglés) -vacuna contra la rabia- no está indicada de manera rutinaria. Para aquellos que no están vacunados, una adecuada profilaxis postexposición (PEP), que incluya, si fuera necesario, la inmunoglobulina antirrábica (RIG), es el único método eficaz para prevenir esta enfermedad mortal. MÉTODOS: Estudio descriptivo retrospectivo en una Unidad de Referencia Nacional para Medicina Tropical y Salud Internacional en Madrid, España, con los viajeros atendidos para tratamiento de rabia con PEP (enero de 2012 a diciembre de 2017). Se revisaron los datos demográficos, clínicos y de gestión. RESULTADOS: Ciento sesenta y ocho pacientes fueron tratados por una posible exposición a la rabia (53% mujeres; edad media: 35 años; RIC: 31-42). La región del sudeste asiático representó más de la mitad de los casos (n=86, 57,3%; IC 95%: 49-65%). Los perros fueron los animales más involucrados en la exposición (n=67, 44,9%; IC 95%: 37-53%). Después de que el paciente fue mordido, la PEP contra la rabia se inició en el extranjero en la mitad de los casos (n=88, 52,4%; IC 95%: 44-60%) y la vacuna más la RIG en aproximadamente el 10% (n=22, 13,1%; IC 95%: 8-19%). La mayoría de los pacientes clasificados en la categoría III no recibieron RIG en absoluto (n=88, 69,3%; IC 95%: 60-77%). CONCLUSIONES: Aunque es indicado, la mayoría de los viajeros no recibieron ni la RIG en el extranjero, ni las primeras dosis apropiadas de PEP. Los profesionales de salud deben ser conscientes de la importancia de una PrEP apropiada en individuos seleccionados