Bibliometric analysis of the Spanish scientific production in Infectious Diseases and Microbiology (2014-2021).

INTRODUCTION: The profound impact of the Covid-19 pandemic, together with other factors such as globalisation and climate change, has emphasised the growing relevance of Infectious Diseases and Microbiology. METHODS: The Spanish scientific production in both categories of the Web of Science databases over the period 2014-2021 has been analysed. RESULTS: 8037 documents have been identified in Infectious Diseases and 12008 documents in Microbiology (6th most productive country worldwide in both cases, with growth rates of 41% and 46.2%, respectively). Both areas present a high degree of international collaboration (45-48% of the documents) and between 45-66% of the documents have been published in journals of excellence (first quartile) according to the rankings of the Journal Citation Reports. CONCLUSIONS: Spain is in a prominent position worldwide in both areas, with an outstanding scientific production in journals of high visibility and impact.

Bibliometric and thematic characterization of the research on HIV-AIDS in Spain (2010-2019).

INTRODUCTION: The establishment of the Spanish AIDS Research Network (RIS) was a milestone for the promotion of HIV research in Spain. We analyse Spanish HIV research, assessing the role that RIS has played in it. METHODS: We identified publications on HIV-AIDS with the participation of Spanish institutions in the Web of Science over the period 2010-2019, characterising research activity by means of bibliometrics and identifying the thematic areas of research through a cluster analysis. RESULTS: A total of 3960 documents have been identified (average of 396 documents/year), 42% of which have been signed in international collaboration. RIS researchers have participated in 60% of the documents, presenting a scientific production and citation significantly higher than authors not linked to the RIS. Five thematic clusters articulate the research, focusing on the clinical and therapeutic approach to people living with HIV, co-infection and co-morbidity with other diseases, the genetic characterisation of the virus, the development of vaccines and the study of its transmission in specific groups or associated with sexual behaviour. CONCLUSION: Spanish HIV research, largely driven by RIS groups, has reached a stage of maturity, with a notable increase in scientific production, participation in international cooperative networks and an outstanding impact and visibility.

Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients.

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.

[Bacterial, mycobacterial and fungal opportunistic infections in HIV-infected immigrants: diagnosis and treatment]. / Infecciones bacterianas, micobacterianas y micóticas oportunistas en el inmigrante infectado por el VIH: diagnóstico y tratamiento.

The number of HIV infected immigrants has increased sharply in Spain. These patients are prone to contracting several different types of opportunistic infections, including bacterial, mycobacterial, fungal and parasitic infections. The present article provides an in-depth review of bacterial and fungal infections, with particular emphasis on those not endemic in our country.

Antifungal drug resistance to azoles and polyenes.

There is an increased awareness of the morbidity and mortality associated with fungal infections caused by resistant fungi in various groups of patients. Epidemiological studies have identified risk factors associated with antifungal drug resistance. Selection pressure due to the continuous exposure to azoles seems to have an essential role in developing resistance to fluconazole in Candida species. Haematological malignancies, especially acute leukaemia with severe and prolonged neutropenia, seem to be the main risk factors for acquiring deep-seated mycosis caused by resistant filamentous fungi, such us Fusarium species, Scedosporium prolificans, and Aspergillus terreus. The still unacceptably high mortality rate associated with some resistant mycosis indicates that alternatives to existing therapeutic options are needed. Potential measures to overcome antifungal resistance ranges from the development of new drugs with better antifungal activity to improving current therapeutic strategies with the present antifungal agents. Among the new antifungal drugs, inhibitors of beta glucan synthesis and second-generation azole and triazole derivatives have characteristics that render them potentially suitable agents against some resistant fungi. Other strategies including the use of high doses of lipid formulations of amphotericin B, combination therapy, and adjunctive immune therapy with cytokines are under investigation. In addition, antifungal control programmes to prevent extensive and inappropriate use of antifungals may be needed.

[Community-acquired pneumonia associated with influenza virus]. / Neumonía adquirida en la comunidad asociada a infección por el virus de la gripe.

BACKGROUND: Pneumonia is one of the most common complications of influenza infection. However, its characteristics are not well-known. Our aim was to assess the frequency of community-acquired pneumonia (CAP) associated with influenza virus and to determine its clinical and epidemiological characteristics. PATIENTS AND METHOD: A total of 240 patients with CAP were evaluated and cases with serological evidence of influenza virus infection were identified. Patients in whom there was no evidence of infection by other microbial agents were selected and defined as influenza virus infection-associated CAP (CAP-i). Clinical and epidemiological features of CAP-i patients were compared with the rest of patients with CAP. RESULTS: A microbial diagnosis was achieved in 143 (59.6%) of 240 patients with CAP. In 12 cases (5%) there was serological evidence of infection by influenza A virus. In 8 patients no other respiratory pathogens were detected (CAP-i). In a multivariate analysis, the presence of arthromyalgias (odds ratio [OR] = 30, 68; 95% confidence interval [CI], 1-946), plasmatic sodium < 133 mEq/l (OR = 16.92; 95% CI, 1.48-193), bilateral infiltrates in chest X-ray (OR = 8.83; 95% CI, 1.35-57.6), diagnosis of CAP in January or February (OR = 5.60; 95% CI, 0.87-35.8) and blood neutrophil cell count >= 14,000/l, (OR = 5.23; 95% CI, 0.85-32) were all independently associated with CAP-i. The simultaneous presence of all these characteristics had a positive and negative predictive value of 95% and 99%, respectively, to differentiate CAP-i from other CAP. CONCLUSIONS: Influenza virus infection-associated CAP is uncommon. Some clinical and radiographic variables could differentiate CAP-i from other CAP. These parameters could also help identify patients who are more likely to benefit from specific antiviral therapy.

[Changes in the spectrum of morbidity and mortality in hospital admissions of HIV infected patients during the HAART era]. / Cambios en el espectro de la morbilidad y la mortalidad de los ingresos hospitalarios de los pacientes con infección por el virus de la inmunodeficiencia humana durante la era del tratamiento antirretroviral de gran actividad.

BACKGROUND AND OBJECTIVE: After the introduction of highly active antiretroviral therapy (HAART), there was a decrease in hospital admissions and mortality associated with human immunodeficiency virus (HIV) infection. The objective of this study was to analyze the changes in mortality and morbidity during the HAART era. PATIENTS AND METHOD: We reviewed 1,343 hospital admissions from 610 HIV-infected patients between January 1995 and December 2000. We analyzed the morbidity and mortality figures at the pre-HAART last biennium (1995-1996) and those at the first and second HAART biennium (1997-1998, HAART-1, and 1999-2000, HAART-2). RESULTS: Hospital admissions due to AIDS-defining illnesses decreased throughout the HAART era, whereas admissions caused by non-AIDS-defining illnesses increased (p < 0.001) with a significant growth in the frequency of respiratory tract infections (p = 0.004), digestive tract diseases (p < 0.001) and liver diseases (p = 0.03). There was a declining trend in hospital mortality throughout the study period. AIDS-defining illnesses decreased from the pre-HAART biennium to the HAART-1 and -2 periods (p = 0.03), whereas liver diseases increased (p = 0.03). CONCLUSIONS: In the HAART era, hospital admissions and mortality due to AIDS-defining illnesses continue to decrease. Nevertheless, there is a steady increase in the number of admissions and deaths of patients with non-AIDS-defining illnesses.

Análisis bibliométrico de la producción científica española en Enfermedades Infecciosas y en Microbiología (2014-2021) / Bibliometric analysis of the Spanish scientific production in Infectious Diseases and Microbiology (2014-2021)

Introducción: El profundo impacto que ha tenido la pandemia de COVID-19 junto a otros factores como la globalización o el cambio climático, ha enfatizado la relevancia creciente que tienen las Enfermedades Infecciosas y la Microbiología. Métodos: Se ha analizado la producción científica española en ambas categorías de la Web of Science a lo largo del periodo 2014-2021. Resultados: Se han identificado 8.037 documentos en Enfermedades Infecciosas y 12.008 documentos en Microbiología (6° país más productivo a nivel mundial en ambos casos, con tasas de crecimiento de 41% y 46,2%, respectivamente). Ambas áreas presentan una elevada colaboración internacional (45-48% de los documentos) y entre 45-66% de los documentos han sido publicados en revistas de excelencia (primer cuartil) según los ránquines del Journal Citation Reports. Conclusiones: España se sitúa en una destacada posición a nivel mundial en ambas áreas, con una gran producción científica en revistas de elevada visibilidad e impacto.(AU)

Introduction: The profound impact of the COVID-19 pandemic, together with other factors such as globalisation and climate change, has emphasised the growing relevance of Infectious Diseases and Microbiology. Methods: The Spanish scientific production in both categories of the Web of Science databases over the period 2014-2021 has been analysed. Results: 8037 documents have been identified in Infectious Diseases and 12008 documents in Microbiology (6th most productive country worldwide in both cases, with growth rates of 41% and 46.2%, respectively). Both areas present a high degree of international collaboration (45-48% of the documents) and between 45-66% of the documents have been published in journals of excellence (first quartile) according to the rankings of the Journal Citation Reports. Conclusions: Spain is in a prominent position worldwide in both areas, with an outstanding scientific production in journals of high visibility and impact.(AU)

Caracterización bibliométrica y temática de la investigación sobre VIH-sida en España (2010-2019) / Bibliometric and thematic characterization of the research on HIV-aids in Spain (2010-2019)

Introducción: La constitución de la Red de Investigación en Sida (RIS) constituyó un hito para el impulso de la investigación sobre el VIH en España. Se analiza la investigación española en el área, evaluando específicamente el papel que ha desempeñado la RIS en la misma. Métodos: Se identificaron las publicaciones sobre VIH-sida con la participación de instituciones españolas en la Web of Science a lo largo del período 2010-2019, caracterizando bibliométricamente la actividad investigadora e identificando mediante un análisis de clústeres los ámbitos temáticos de investigación. Resultados: Se han identificado 3.960 documentos (promedio de 396 documentos/año), el 42% de los cuales han sido firmados en colaboración internacional. Los investigadores de la RIS han participado en el 60% de los documentos, presentando una producción científica y citación sensiblemente superior a los autores no vinculados a la misma. Cinco clústeres temáticos articulan la investigación, centrados en el abordaje clínico y terapéutico de las personas que viven con el VIH, la coinfección y la comorbilidad con otras enfermedades, la caracterización genética del virus, el desarrollo de vacunas y el estudio de su transmisión en colectivos específicos o asociado a las conductas sexuales. Conclusión: La investigación española sobre el VIH, impulsada en gran medida por los grupos de la RIS ha alcanzado un estadio de madurez, con un notable incremento de la producción científica, la participación en redes cooperativas internacionales y un destacado impacto y visibilidad.(AU)

Introduction: The establishment of the Spanish AIDS Research Network (RIS) was a milestone for the promotion of HIV research in Spain. We analyse Spanish HIV research, assessing the role that RIS has played in it. Methods: We identified publications on HIV-aids with the participation of Spanish institutions in the Web of Science over the period 2010-2019, characterising research activity by means of bibliometrics and identifying the thematic areas of research through a cluster analysis. Results: A total of 3960 documents have been identified (average of 396 documents/year), 42% of which have been signed in international collaboration. RIS researchers have participated in 60% of the documents, presenting a scientific production and citation significantly higher than authors not linked to the RIS. Five thematic clusters articulate the research, focusing on the clinical and therapeutic approach to people living with HIV, co-infection and co-morbidity with other diseases, the genetic characterisation of the virus, the development of vaccines and the study of its transmission in specific groups or associated with sexual behaviour. Conclusion: Spanish HIV research, largely driven by RIS groups, has reached a stage of maturity, with a notable increase in scientific production, participation in international cooperative networks and an outstanding impact and visibility.(AU)

Characterization of LEDGF/p75 genetic variants and association with HIV-1 disease progression.

BACKGROUND: As Lens epithelium-derived growth factor (LEDGF/p75) is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs). Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 genetic variation, mRNA expression and HIV-1 disease progression in order to guide future clinical use of LEDGINs. METHODS: Samples were derived from a therapy-naïve cohort at Ghent University Hospital and a Spanish long-term-non-progressor cohort. High-resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs) in the coding region, flanking intronic regions and full 3'UTR of LEDGF/p75. In addition, two intronic tagSNPs were screened based on previous indication of influencing HIV disease. LEDGF/p75 mRNA was quantified in patient peripheral blood mononuclear cells (PBMC) using RT-qPCR. RESULTS: 325 samples were investigated from patients of Caucasian (n = 291) and African (n = 34) origin, including Elite (n = 49) and Viremic controllers (n = 62). 21 SNPs were identified, comprising five in the coding region and 16 in the non-coding regions and 3'UTR. The variants in the coding region were infrequent and had no major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828) was significantly under-represented in Caucasian patients (P<0.0001) compared to healthy controls (HapMap). Two SNPs showed a non-significant trend towards association with slower disease progression but not with LEDGF/p75 expression. The observed variation in LEDGF/p75 expression was not correlated with disease progression. CONCLUSIONS: LEDGF/p75 is a highly conserved protein. Two non-coding polymorphisms were identified indicating a correlation with disease outcome, but further research is needed to clarify phenotypic impact. The conserved coding region and the observed variation in LEDGF/p75 expression are important characteristics for clinical use of LEDGINs.

[Toxicogenetics of antiretroviral treatment (II): neurotoxicity, hepatotoxicity, lactic acidosis, kidney damage, and other adverse effects of antiretroviral drugs]. / Toxicogenética del tratamiento antirretroviral (y II): neurotoxicidad, hepatotoxicidad, acidosis láctica, daño renal y otros efectos adversos del tratamiento antirretroviral.

Several pharmacogenetics studies have analyzed the influence of specific genetic polymorphisms on the toxicity of antiretroviral treatment. The present review describes some of the adverse effects of antiretroviral drugs in which a genetic predisposition may be involved: efavirenz-induced neurological toxicity, generally associated with the 516G>T polymorphism of liver enzyme cytochrome P450 2B6 (CYP2B6); hypersensitivity reactions to nevirapine, associated with specific alleles of major histocompatibility complex, mainly the HLA-DRB1*0101 allele, which, in combination with a high CD4 lymphocyte count, has been associated with systemic reactions and hepatitis in Caucasians, and the HLA-Cw8 allele, which is associated with hypersensitivity reactions in persons from the Italian island of Sardinia and from Japan; nevirapine-induced hepatotoxicity associated with the C>T polymorphism in position 3435T of the ABCB1 (MDR-1) gene codifying for glycoprotein P (lower risk); hyperbilirubinemia in patients exposed to atazanavir or indinavir carrying the UGT1A1*28 polymorphism; peripheral neuropathy with nucleoside analogues associated with haplogroup T of the mitochondrial genome (higher risk) and with the HFE C282Y genotype of the hemochromatosis gene (lower risk); the mutation in codon 964 (R964C) of the POLG gene that codifies the mitochondrial polymerase DNA gamma described in a Thai patient with lactic acidosis; the ABCC2 gene haplotypes associated with tenofovir-induced proximal tubulopathy, and the risk of pancreatitis in persons with mutations in the CFTR and SPINK-1 genes.

[History of the infectious disease specialty in Spain]. / Relato histórico de la infectología española.

This paper includes a brief summary of the clinical history of the diagnosis and treatment of infectious diseases in Spain. Firstly, the origins of a specialty arising from the need for specialists to attend to, in a practical and modern form, the different health problems of patients affected by infectious diseases, are described. Secondly, the appearance of AIDS, at the beginning of the 1980's, prompted the creation of specific units dedicated to the care of problems associated with human immunodeficiency virus (HIV) infection and the concomitant opportunistic infections arising from the immunodeficiency arising from the HIV infection. Thirdly, in the last decades and even today, nosocomial infections have appeared as an alarming problem, needing the presence of specialist physicians in this field. Finally, emigration and international travel require specialists in infectious diseases with specific expertise in international health, once more highlighting the importance of the specialty of Infectious Diseases.

[Lipid alterations and cardiovascular risk associated with antiretroviral therapy]. / Alteraciones lipídicas y riesgo cardiovascular asociado a la terapia antirretroviral.

Dyslipidemia is common in HIV-infected patients receiving antiretroviral therapy (ART) and it is often associated with the use of specific antiretroviral drugs. The phenotypic profile can include elevated triglycerides or cholesterol alone, or mixed patterns with varying changes in LDL and HDL lipoproteins, which imply different levels of cardiovascular risk. Growing evidence indicates that ART-associated hyperlipidemia accelerates the development of atherosclerosis and coronary heart disease in HIV-infected patients. In recent years, a number of retrospective database reviews and prospective cohort studies have reported a higher incidence of coronary events in patients receiving ART, which seems to be closely related with the presence of dyslipidemia and the duration of exposure to ART. Although the clinical benefit of treating ART-related dyslipidemia remains unproven, most experts recommend a policy of cardiovascular disease prevention and management similar to that used in non-HIV-infected individuals. In addition, the use of antiretrovirals associated with a more favorable lipid profile is considered. Clinical experience with lipid-lowering therapy in HIV-infected patients is still limited, but there is increasing data confirming its efficacy and safety in this setting. Drug interactions should be taken into account when statins are used in patients receiving protease inhibitors.

[Health in the immigrant population: prevalence of latent tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus and syphilis infection]. / Examen de salud en la población inmigrante: prevalencia de infección tuberculosa latente, hepatitis B, hepatitis C, infección por el VIH y sífilis.

INTRODUCTION: To describe the prevalence of infectious diseases in immigrants. METHODS: The Mantoux tuberculin skin test and serology testing for hepatitis B, hepatitis C, HIV and syphilis were performed in 488 immigrants. RESULTS: A positive reaction to the Mantoux (> or = 10 mm) was found in 19.1% of individuals from Africa, 9.6% from Eastern Europe and 5.8% from South America (p < 0.001). With regard to hepatitis B, 2.5% of the Africans, 2.1% of the Eastern Europeans and none of the South Americans were carriers of the virus (p 5 0.02). CONCLUSIONS: The prevalence of infectious diseases in immigrants varies according to their country of origin.

[In vitro activity of caspofungin against fluconazole-resistant Candida isolates from patients with HIV infection]. / Actividad in vitro de caspofungina frente a aislados clínicos de Candida resistentes a fluconazol en pacientes con infección por el VIH.

INTRODUCTION: Antifungal therapy for mucosal candidiasis caused by fluconazole-resistant Candida species is problematic. The aim of this study was to investigate the in vitro activity of caspofungin against Candida strains with reduced susceptibility to fluconazole isolated from HIV-infected patients. METHODS: The in vitro activity of caspofungin was assessed in 28 fluconazole-resistant Candida isolates obtained from the oral cavity of a cohort of 174 consecutive HIV-infected patients. Minimum inhibitory concentrations (MICs) were determined by a standardized broth microdilution method, as recommended by the NCCLS. RESULTS: Overall, caspofungin MICs ranged from < or = 0.06 microg/ml to 1 microg/ml. MICs at which 50% (MIC50) and 90% (MIC90) of isolates were inhibited were 0.25 microg/ml and 0.5 microg/ml, respectively. MICs ranged from < or = 0.06 microg/ml to 0.5 microg/ml for Candida albicans (n = 11), and < 0.06 microg/ml to 1 microg/ml or Candida glabrata (n = 11). MICs for the two strains of Candida krusei were 0.125 microg/ml and 1 microg/ml. The range of MICs for Candida tropicalis and Candida inconspicua strains was 0.25 microg/ml to 0.5 microg/ml. CONCLUSION: Caspofungin was very active in vitro against a variety of fluconazole-resistant Candida strains recovered from a clinical cohort of HIV-infected patients. The MIC50 values and MIC ranges were slightly higher for Candida glabrata than for Candida albicans.