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1.  Multicenter epidemiological and clinical study on imported Chagas diseases in Alicante, Spain 
Pathogens and Global Health  2012;106(6):340-345.
Recently, there has been an increase in the number of patients with Chagas disease outside of areas that are generally considered endemic. The aim of this investigation is to describe the clinical profile of a series of patients with Chagas disease in Alicante, Spain, which is a province located on the coast of the Mediterranean Sea. This study was performed at four general hospitals in Alicante between January 2002 and May 2011. A total of 128 patients from seven countries were diagnosed with Trypanosoma cruzi. The main country of origin of these patients was Bolivia (n = 101; 78.9%), and the median of age of these patients was 35 years (range: 0–72 years). Four (3.3%) patients were children under 14 years of age, and 81 (63.3%) were female. Polymerase chain reaction (PCR) was used to analyze 106 patients, 66.0% of whom demonstrated positive PCR results. Visceral involvement was diagnosed in 26.8%: 24.1% demonstrated cardiac involvement, 0.9% demonstrated gastrointestinal involvement, 0.9% demonstrated cardiac and gastrointestinal involvement, and 0.9% demonstrated involvement of the central nervous system. Syncope was found to be associated with cardiomyopathy (28.0% versus 5.2%) (odds ratio: 6.5; 95% confidence interval: 1.5–27.1). Seventy-six patients received treatment with benznidazole, of whom 57 (75.0%) completed the treatment course without significant adverse events and 17.1% discontinued benznidazole due to adverse events. In total, 50% of patients experienced documented adverse reactions. Among patients with positive PCR results before treatment, all demonstrated negative PCR results following treatment. In conclusion, majority of our patients were female Bolivians immigrants, one of four of our patients demonstrated cardiac involvement, and treatment tolerance was poor. It is important to improve the clinical and epidemiological knowledge of Chagas disease in nonendemic with additional multicenter studies in order to determine the magnitude of this problem and provide improved public health and health resource planning.
PMCID: PMC4005132  PMID: 23182138
Chagas disease; American trypanosomiasis; Trypanosoma cruzi infection; Spain; Immigrant; Bolivia
2.  Hospital admissions in Alicante (Spain): a comparative analysis of foreign citizens from high-income countries, immigrants from low-income countries, and Spanish citizens 
Over the last decade, the number of foreign citizens (FCs) in Spain has increased. There is no doubt that their health has become a relevant subject from the point of view of public healthcare. Our study aimed to describe hospital admission rates, diagnoses at hospital discharge, and mortality during hospital admissions in FCs from high-income countries (FCHICs), FCs from low-income countries (FCLICs), and autochthonous citizens (ACs).
A cross-sectional study was performed at two public hospitals in the city of Alicante (Spain) and its surrounding area. Utilization rates were estimated. Multivariate analysis adjusting for age and sex was performed on hospital admission rates, diagnoses at hospital discharge, service of admission, and mortality during hospital admission in FCHICs and FCLICs compared with ACs (adjusted odds ratio [AOR] with 95% confidence intervals [CI]).
42,839 patients ≥15 years were discharged from the hospitals. The utilization rate was lower in FCs than ACs, whose crude rate ratio was 0.676 (95% CI: 0.656-0.696). FCHICs had more risk of being diagnosed at discharge in the categories of the circulatory system (AOR: 1.55; 95% CI: 1.35-1.77), neoplasms (AOR: 1.21; 95% CI: 1.03-1.42), and injury and poisoning (AOR: 1.33; 95% CI: 1.11-1.58). FCLICs had more risk of being diagnosed in the categories of pregnancy, childbirth & puerperium (AOR: 1.33; 95% CI: 1.29-1.59), and injury and poisoning (AOR: 1.19; 95% CI: 1.03-1.36), and less risk in the mental disorder category (AOR: 0.32; 95% CI: 0.22-0.45). The length of hospitalization (in days) was lower in FCLICs (median: 3; IQR: 2–6) than both ACs (median: 4; IQR: 2–8) and FCHICs (median: 4; IQR: 2–8) (p < 0.001). The mortality rates on admission of ACs, FCHICs, and FCLICs were 4.2%, 3.3%, and 1.3%, respectively, but after adjusting for age and sex, the mortality rate risks were similar in FCHICs and FCLICs.
First, FCs utilized hospitalization less when compared with ACs. Second, the hospitalization profile for FCHICs was similar to ACs, with more problems in the circulatory system, and the hospitalization profile for FCLICs was different compared with ACs, with more admissions for pregnancy, childbirth & puerperium.
PMCID: PMC3893374  PMID: 24321628
Immigrants; Foreigners; Public hospitals; Morbidity; Citizens; Low-income countries; High-income countries; Hospitalization
3.  Epidemiology of Leprosy in Spain: The Role of the International Migration 
PLoS Neglected Tropical Diseases  2016;10(3):e0004321.
Although incidence of leprosy in Spain has declined steadily over the years, the fivefold increase in immigration since the turn of the century—much of it from countries where leprosy is still prevalent—has been linked to an uptick in registered cases.
To describe the epidemiologic trends of incident leprosy cases detected in Spain among Spanish- and foreign-born population groups.
Observational, retrospective study of suspected leprosy cases in Spain, as reported through the System of Compulsory Notification of Diseases from 2003 to 2013, with results disaggregated by country of birth. We collected statistical data on leprosy burden for other countries from WHO to estimate the expected number of imported cases.
Of the 168 leprosy cases registered during the study period, 40 (24.6%) were in Spanish patients, while 128 (76.2%) were detected in legally resident immigrants. We identified a significantly higher number of imported leprosy cases during the 2008–2010 and 2011–2013 trienniums compared to the reference biennium 2003–2004 (OR 5.38, 95% CI 1.83–14.88 and OR 4.80, 95% CI 1.41–16.33, respectively). Most imported cases were diagnosed in Latin American immigrants (71.9%), especially Brazilians, but also Paraguayans, Bolivians and other nationalities from South and Central America. However, registered incidence was lower than expected for each year. For example, in 2003, the expected new cases in immigrants was 47.12, compared to only four cases that were actually detected (a 91% difference). Likewise, we expected to find 49.6 incident cases among immigrants in 2009, but only 15 new cases were reported (60% fewer than expected).
Imported cases of leprosy are responsible for most leprosy incidence in Spain, and we cannot rule out some under-diagnosis. Clinicians should be made more aware of the potential for leprosy incidence among patients from countries where the disease is endemic.
Author Summary
Most of cases of leprosy that are diagnosed in Europe come from other parts of the world. This study describes the epidemiologic trends of incident leprosy cases detected in Spain among Spanish- and foreign-born population groups from 2003 to 2013. We show that new cases of leprosy will continue to appear in the country regardless of the control measures taken at a domestic level, as people from leprosy-endemic areas will continue to migrate. That said, we also found that the actual number of incident cases registered through the national reporting system was far below the expected cases estimated from WHO statistical data on countries of origin. Nevertheless, leprosy should be considered among the differential diagnoses in patients presenting in Spanish health centres with suspected cutaneous and neurological signs and symptoms, especially if they are from Brazil, Paraguay, Bolivia or other areas where leprosy is prevalent. Given the high proportion of Latin American immigrants in Spain, our findings are very relevant, and it is advisable that the Spanish Medical University Programme reinstate the inclusion of leprosy in training for junior doctors.
PMCID: PMC4777425  PMID: 26939132
4.  Evolution of Cooperation Patterns in Psoriasis Research: Co-Authorship Network Analysis of Papers in Medline (1942–2013) 
PLoS ONE  2015;10(12):e0144837.
Although researchers have worked in collaboration since the origins of modern science and the publication of the first scientific journals in the eighteenth century, this phenomenon has acquired exceptional importance in the last several decades. Since the mid-twentieth century, new knowledge has been generated from within an ever-growing network of investigators, working cooperatively in research groups across countries and institutions. Cooperation is a crucial determinant of academic success.
The aim of the present paper is to analyze the evolution of scientific collaboration at the micro level, with regard to the scientific production generated on psoriasis research.
A bibliographic search in the Medline database containing the MeSH terms “psoriasis” or “psoriatic arthritis” was carried out. The search results were limited to articles, reviews and letters. After identifying the co-authorships of documents on psoriasis indexed in the Medline database (1942–2013), various bibliometric indicators were obtained, including the average number of authors per document and degree of multi-authorship over time. In addition, we performed a network analysis to study the evolution of certain features of the co-authorship network as a whole: average degree, size of the largest component, clustering coefficient, density and average distance. We also analyzed the evolution of the giant component to characterize the changing research patterns in the field, and we calculated social network indicators for the nodes, namely betweenness and closeness.
The main active research clusters in the area were identified, along with their authors of reference. Our analysis of 28,670 documents sheds light on different aspects related to the evolution of scientific collaboration in the field, including the progressive increase in the mean number of co-authors (which stood at 5.17 in the 2004–2013 decade), and the rise in multi-authored papers signed by many different authors (in the same decade, 25.77% of the documents had between 6 and 9 co-authors, and 10.28% had 10 or more). With regard to the network indicators, the average degree gradually increased up to 10.97 in the study period. The percentage of authors pertaining to the largest component also rose to 73.02% of the authors. The clustering coefficient, on the other hand, remained stable throughout the entire 70-year period, with values hovering around 0.9. Finally, the average distance peaked in the decades 1974–1983 (8.29) and 1984–2003 (8.12) then fell over the next two decades, down to 5.25 in 2004–2013. The construction of the co-authorship network (threshold of collaboration ≥ 10 co-authored works) revealed a giant component of 161 researchers, containing 6 highly cohesive sub-components.
Our study reveals the existence of a growing research community in which collaboration is increasingly important. We can highlight an essential feature associated with scientific collaboration: multi-authored papers, with growing numbers of collaborators contributing to them, are becoming more and more common, therefore the formation of research groups of increasing depth (specialization) and breadth (multidisciplinarity) is now a cornerstone of research success.
PMCID: PMC4676628  PMID: 26658481
5.  Human Infection with Rickettsia sibirica mongolitimonae, Spain, 2007–2011 
Emerging Infectious Diseases  2013;19(2):267-269.
Human infection with Rickettsia sibirica mongolitimonae was initially reported in 1996, and reports of a total of 18 cases have been published. We describe 6 additional cases that occurred in the Mediterranean coast region of Spain during 2007–2011. Clinicians should consider this infection in patients who have traveled to this area.
PMCID: PMC3559030  PMID: 23343524
Rickettsia sibirica mongolitimonae; rickettsiosis; LAR; spotted fever; rickettsiae; infection; bacteria; Hyalomma asiaticum; ticks; vector-borne infections; lymphangitis-associated rickettsiosis; Spain
6.  Leprosy ulcers in a rural hospital of Ethiopia: pattern of aerobic bacterial isolates and drug sensitivities 
Plantar ulcers, which commonly occur in leprosy patients, tend to recur increasing physical disability. The aim of this study is to identify both the bacteriological profile of these ulcers and the antibiotic susceptibility of the isolated bacteria.
Materials and methods
68 leprosy patients with chronic ulcers attending the in-patient department of Gambo General Hospital, West Arsi, were included in this study. Proper sample collection, inoculation on culture media, and final identification using biochemical methods were undertaken.
66 patients (97.1%) had a positive culture. A total of 81 microorganisms were isolated. Multiple organisms (two or more) were isolated in 15 (22.7% out of positive culture) patients. The main isolation was Proteus spp (30.9%), followed by Escherichia coli (21.0%), Staphylococcus aureus (18.5%) and Pseudomonas aeruginosa (9.9%). In the total number of the isolated bacteria, the antibiotics with less resistance were gentamicin (18.5%), fosfomycin (22.2%) cefoxitin (24.7%), ceftriaxone (25.9%) ciprofloxacin (25.9%), and amoxicillin-clavulanic acid (28.49%).
The bacteriological study of plantar ulcers of leprosy patients revealed Enterobacteriaceae and S. aureus as the main pathogens involved in such infections. The results of this study may guide empirical therapy in a rural area hospital where culture and susceptibility testing facilities are scarce.
PMCID: PMC4353672  PMID: 25228044
Bacterial isolation; Chronic ulcer; Leprosy; Pathogens; Susceptibility testing
7.  Trypanosoma cruzi infection in Elche (Spain): comparison of the seroprevalence in immigrants from Paraguay and Bolivia 
Pathogens and Global Health  2012;106(2):102-106.
Chagas disease is a global public health problem due to the recent emigration of people from Latin America to other regions, including Europe. The aim of this study is to determine the prevalence of Trypanosoma cruzi infection among Paraguayans and Bolivians living in Elche (Spain), a city located in the Mediterranean Coast of Spain. A cross-sectional study was conducted. Capillary blood samples were obtained through a finger prick, and collected on filter paper. An enzyme-linked immunosorbent assay and indirect immunofluorescence tests were performed to search for anti-T. cruzi IgG antibodies in the filter papers. Thirteen out of 201 participants were infected with T. cruzi in this study, seven out of 73 Bolivians and six out of 128 Paraguayans, corresponding to seroprevalences of 9.59% (95%CI, 4.72–18.5%) and 4.69% (95%CI, 2.17–9.85%), respectively. Palpitation, chest pain, and migration from rural endemic areas were the most common clinical and epidemiological risk factors associated with T. cruzi infection detected in the Paraguayan group. This study highlights that Chagas disease is no longer limited to the Bolivian population living in Spain. It is important to note this wider prevalence and, therefore, not discount Paraguayans in the screening for Chagas disease in Spain. Indeed, this should be considered for all immigrants from Latin America.
PMCID: PMC4001495  PMID: 22943545
Chagas disease; Trypanosoma cruzi infection; Paraguay; Bolivia; Immigrants
8.  Bibliometric analysis of leishmaniasis research in Medline (1945-2010) 
Parasites & Vectors  2013;6:55.
Publications are often used as a measure of success of research work. Leishmaniasis is considered endemic in 98 countries, most of which are developing. This article describes a bibliometric review of the literature on leishmaniasis research indexed in PubMed during a 66-year period.
Medline was used via the PubMed online service of the US National Library of Medicine. The search strategy was Leishmania [MeSH] or leishmaniasis [MeSH] from 1 January 1945 until 31 December 2010. Neither language nor document type restrictions were employed.
A total of 20,780 references were retrieved. The number of publications increased steadily over time, with 3,380 publications from 1945-1980 to 8,267 from 2001-2010. Leishmaniasis documents were published in 1,846 scientific journals, and Transactions of the Royal Society of Tropical Medicine and Hygiene (4.9%) was the top one. The USA was the predominant country by considering the first author’s institutional address (16.8%), followed by Brazil (14.9%), and then India (9.0%), however Brazil leads the scientific output in 2001-2010 period (18.5%), followed by the USA (13.5%) and India (10%). The production ranking changed when the number of publications was normalised by population (Israel and Switzerland), by gross domestic product (Nepal and Tunisia), and by gross national income per capita (India and Ethiopia). For geographical area, Europe led (31.7%), followed by Latin America (24.5%).
We have found an increase in the number of publications in the field of leishmaniasis. The USA and Brazil led scientific production on leishmaniasis research.
PMCID: PMC3602049  PMID: 23497410
Leishmaniasis; Leishmania; Bibliometry; Scientific production; Mapping; Leishmaniasis visceral; Leishmaniasis cutaneous; Leishmaniasis mucocutaneous; Diffuse cutaneous Leishmaniasis
9.  Gender differential on characteristics and outcome of leprosy patients admitted to a long-term care rural hospital in South-Eastern Ethiopia 
In previous studies, women are less aware of causation and symptoms of leprosy and have less access to health care coverage than men, thus contributing to their delay in seeking for treatment. We assess the gender differences in leprosy cases admitted to a rural referral hospital in Ethiopia for 7 and a half years.
Retrospective data of the leprosy patients admitted to referral hospital were collected using leprosy admission registry books from September 2002 to January 2010. Variables were entered in an Excel 97 database.
During the period of study, 839 patients with leprosy were admitted; 541 (64.5%) were male, and 298 (35.6%) female. Fifteen per cent of female patients, and 7.3% of male patients were paucibacillary leprosy cases while 84.8% of female patients and 92.7% of males were multibacillary leprosy cases (p<0.001). Female leprosy patients were younger than male ones (median: 36 versus 44 years) (p<0.001). In the multivariate analysis, age (odds ratio [OR]: 0.97; 95% confidence interval [CI]: 0.96-0.98; p<0.001), admission for cardiovascular diseases (OR: 7.6, 95% CI: 1.9-29.3; p=0.004), admission for gastroenteritis (OR: 14.0; 95% CI: 1.7-117; p=0.02), admission from out patients clinic (OR: 2.04; 95% CI: 1.1-4.01; p=0.02), and mortality as final outcome (OR: 3.1, 95% CI: 1.2-8.0; p=0.02) were independently associated with female gender.
Female patients with leprosy admitted to hospital were younger, had a different profile of admission and a higher mortality rate than male ones.
PMCID: PMC3519584  PMID: 23035879
Leprosy; Gender; Sex; Female; Hospital; Ethiopia
10.  Contribution of Interferon gamma release assays testing to the diagnosis of latent tuberculosis infection in HIV-infected patients: A comparison of QuantiFERON-TB Gold In Tube, T-SPOT.TB and tuberculin skin test 
BMC Infectious Diseases  2012;12:169.
Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERON-tuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients.
A prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAs and TST were performed simultaneously. TST induration ≥ 5 mm was considered positive.
QFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/μl with a median nadir of 150/μl. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p < 0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%–16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/μl and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.8; 95% CI, 1.4 – 9.9; and aOR: 3.3; 95% CI, 1.3 – 8.3, respectively).
IGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIV-infected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this population.
PMCID: PMC3482589  PMID: 22849726
11.  Cardiac Troponin T and Illness Severity in the Very-Low-Birth-Weight Infant 
Introduction. Respiratory distress are very common in Very-low-birth-weight (VLBW) infants and Myocardial injury may play a role in the disease outcome. Cardiac troponin T (cTnT) is the most useful marker of injury in adult population, but has not been extensively studied in this population. Aim. To study the role of cTnT in VLBW infants and its association with clinical outcomes. Methods. All VLBW infants admitted to our NICU were included in the study. Echocardiography and blood samples for cTnT determination were collected at 24 and 48 hours of life, and values >0.1 ng/mL were considered CTnT-positive values. Results. A total of 116 neonates had their blood samples collected. The median cTnT concentration within 24 hours was 0.191 (0.1–0.79) ng/mL and within 48 hours was 0.293 (0.1–1.0) ng/mL. A logistic regression analysis showed that PDA, low GA, and use of dopamine were independently associated with positive cTnT and abnormal Dopplerfluxometry and diuretics use had protective effects and was independently associated with troponin values. Conclusion. We observed a high prevalence of positivecTnT values in VLBW infants associated with illness severity. Our findings suggest that cTnT may be a useful and early marker of myocardial injury in VLBW infants.
PMCID: PMC3299249  PMID: 22518175
12.  Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study 
BMC Infectious Diseases  2011;11:265.
Relationship of hepatitis C virus (HCV) infection with an increased risk of cardiovascular disease (CVD) in HIV-infected patients remains controversial. We evaluated endothelial function and subclinical atherosclerosis in HIV-infected patients with and without HCV.
Flow-mediated dilatation (FMD) of the brachial artery and circulating levels of cell adhesion molecules (CAM) were measured in HCV/HIV-coinfected and HIV-monoinfected patients. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT).
63 (31%) HCV/HIV-coinfected and 138 (69%) HIV-monoinfected patients were included. Median soluble vascular CAM-1 (sVCAM-1) and intercellular CAM-1 (sICAM-1) levels were significantly higher in HIV/HCV-coinfected patients (P < 0.001 for both cases). Median (interquartile range) FMD was 6.21% (2.86-9.62) in HCV/HIV-coinfected and 5.54% (2.13-9.13) in HIV-monoinfected patients (P = 0.37). Adjustment for variables associated with HCV and FMD disclosed similar results. FMD correlated inversely with cIMT and age. Carotid IMT did not differ between HCV/HIV-coinfected and HIV-monoinfected patients in unadjusted (0.61 [0.55-0.65] mm vs 0.60 [0.53-0.72] mm; P = 0.39) or adjusted analyses.
HCV infection was associated with higher levels of sICAM-1 and sVCAM-1, but no evidence of increased subclinical atherosclerosis was found when endothelial function was evaluated through FMD, or when assessing the cIMT.
PMCID: PMC3198698  PMID: 21967471

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