Oral microbiome is the second largest microbial community in humans after gut. Human immunodeficiency virus (HIV) infection triggers an impairment of the immune system which could favour the growth and the colonization of pathogens in the oral cavity, and this dysbiosis has been associated with oral manifestations that worsen the quality of life of these patients. Antiretroviral therapy (ART) could also drive changes in specific oral bacterial taxa associated with such periodontal diseases. Integrase strand transfer inhibitors (INSTIs), therapy of choice in the treatment of naive HIV-patients, are able to reverse the impact of HIV infection on systemic inflammation, gut permeability, and gut bacterial diversity/richness. The objective of this study was to analyse the effects of HIV infection per se and INSTIs on salivary bacteriome composition, taking into consideration other factors such as smoking, that could also have a significant impact on oral microbiome. To accomplish this objective, 26 non-HIV-infected volunteers and 30 HIV-infected patients (15 naive and 15 under INSTIs-regimen) were recruited. Salivary samples were collected to measure lysozyme levels. Oral bacteriome composition was analysed using 16S rRNA gene sequencing. Naive HIV-infected patients showed statistically higher levels of lysozyme compared to controls (p < 0.001) and INSTIs-treated patients (p < 0.05). Our study was unable to detect differences in α nor β-diversity among the three groups analysed, although significant differences in the abundance of some bacterial taxonomical orders were detected (higher abundance in the phylum Pseudomonadota, in the order Acholeplasmatales, and in the genera Ezakiella and Acholeplasma in the naive group compared to controls; and higher abundance in the phylum Mycoplasmatota, in the order Acholeplasmatales, and in the genera Acholeplasma and uncultured Eubacteriaceae bacterium in the INTIs-treated HIV-infected patients compared to controls). These differences seem to be partially independent of smoking habit. HIV infection and INSTIs effects on oral microbiota seem not to be very potent, probably due to the modulation of other factors such as smoking and the greatest outward exposure of the oral cavity.

Viruses are the most abundant components of the human gut microbiome with a significant impact on health and disease. The effects of human immunodeficiency virus (HIV) infection on gut virome has been scarcely analysed. Several studies suggested that integrase strand transfers inhibitors (INSTIs) are associated with a healthier gut. Thus, the objective of this work was to evaluate the effects of HIV infection and INSTIs on gut virome composition. 26 non-HIV-infected volunteers, 15 naive HIV-infected patients and 15 INSTIs-treated HIV-infected patients were recruited and their gut virome composition was analysed using shotgun sequencing. Bacteriophages were the most abundant and diverse viruses present in gut. HIV infection was accompanied by a decrease in phage richness which was reverted after INSTIs-based treatment. β-diversity of phages revealed that samples from HIV-infected patients clustered separately from those belonging to the control group. Differential abundant analysis showed an increase in phages belonging to Caudoviricetes class in the naive group and a decrease of Malgrandaviricetes class phages in the INSTIs-treated group compared to the control group. Besides, it was observed that INSTIs-based treatment was not able to reverse the increase of lysogenic phages associated with HIV infection or to modify the decrease observed on the relative abundance of Proteobacteria-infecting phages. Our study describes for the first time the impact of HIV and INSTIs on gut virome and demonstrates that INSTIs-based treatments are able to partially restore gut dysbiosis at the viral level, which opens several opportunities for new studies focused on microbiota-based therapies.

During recent decades, a tick-borne rickettsial syndrome, characterized by eschar and painful lymphadenopathy after Dermacentor marginatus-bite, has been described as an emerging rickettsiosis in Europe. Our group named it DEBONEL (Dermacentor-borne-necrosis-erythema-lymphadenopathy), regarding the vector and the main infection signs. Other groups called it TIBOLA (tick-borne-lymphadenophathy) and, later, SENLAT (scalp-eschar-and-neck-lymphadenopathy-after-tick-bite), expanding, in the latter, the etiological spectrum to other pathogens. Objective: To investigate the etiology of DEBONEL agents in our area, and to compare their epidemiological/clinical/microbiological characteristics. During 2001–2020, 216 patients clinically diagnosed of DEBONEL (the largest series from one center) in La Rioja (northern Spain) were examined. Rickettsia spp. were amplified in 14/104 (13.46%) blood samples, 69/142 (48.59%) eschar swabs, 7/7 (100%) biopsies, and 71/71 (100%) D. marginatus from patients. For samples in which Rickettsia was undetected, no other microorganisms were found. ‘Candidatus Rickettsia rioja’, Rickettsia slovaca, Rickettsia raoultii, and Rickettsia DmS1 genotype were detected in 91, 66, 4, and 3 patients, respectively. DEBONEL should be considered in patients with clinical manifestations herein described in areas associated to Dermacentor. The most frequently involved agent in our environment is ‘Ca. R. rioja’. The finding of Rickettsia sp. DmS1 in ticks attached to DEBONEL patients suggests the implication of other rickettsia genotypes.

Human immunodeficiency virus (HIV) infection can be considered a chronic disease thanks to the extended use of antiretroviral treatment (ART). In this context, low-grade chronic inflammation related to gut microbiota (GM) dysbiosis and bacterial translocation (BT) among other factors has been observed despite the use of ART. In addition, different ART regimens have demonstrated differential impacts on GM. However, the role of novel integrase strand transfer inhibitors (INSTIs) has not been investigated yet. The aim of this study was to analyse the effects of INSTIs in first-line of treatment on markers of BT, inflammation, cardiovascular risk, gut permeability and GM composition and derived short-chain fatty acids. Twenty-six non-HIV-infected volunteers and 30 HIV-infected patients (15 naïve and 15 under INSTIs regimen) were recruited. Blood samples were extracted to analyse biochemical parameters and markers of BT, inflammation, cardiovascular risk, gut permeability and bacterial metabolism. GM composition was analysed using 16S rRNA gene sequencing. Our results showed that HIV infection increased BT, inflammation, cardiovascular risk and gut permeability, whereas INSTIs counteracted these effects. Regarding GM, the reduction in bacterial richness induced by HIV infection was restored by INSTIs. Beta diversity revealed that HIV-infected people were separated from the control group independently of treatment. Current antiretroviral regimens based on INSTIs are able to reverse the impact of HIV infection on BT, systemic inflammation, gut permeability and bacterial diversity/richness, reaching similar levels to those observed in an uninfected/control population. These results suggest a protective role of INSTIs in disease progression, subsequent immune activation and in the development of future age-related complications such as cardiovascular events.

SARS-CoV-2 is a betacoronavirus that uses the angiotensinconverting-enzyme-related carboxypeptidase (ACE2) receptor to gain entry to cells.This receptor is widely expressed in cardiopulmonary tissues and in monocytes and macrophages [1].SARS-CoV-2 also encodes proteins that antagonize the interferon (IFN) response to viral infection [2].Interestingly, the ACE2 receptor is also expressed in human natural killer (NK) cells [1].NK cells are best known for killing virally infected cells and also mediate antibody-dependent cell cytotoxicity [3].Additionally, IFN-ɣ produced by NK cells induces macrophage activation, T cell Th1 response [3], and may protect the lung from fibrosis by inhibiting fibroblast proliferation and collagen expression [4].However, scarce information about NK cell counts exists in patients infected with SARS-CoV-2.In order to clarify the role of NK cells in COVID-19, we are conducting a study in 50 patients consecutively admitted to hospital with SARS-CoV-2 confirmed infection, defined as radiological diagnosis of pneumonia and

Background Patients with HIV infection suffer from accelerated aging. In this context, frailty could be a relevant problem that aggravates the quality of life (QoL) and morbi-mortality of these patients. Our objective was to determine the prevalence of frailty and pre-frailty in HIV-infected patients in our cohort as well as their risk factors and QoL. Methods This was a prospective cross-sectional study of HIV-infected people aged ≥18 years on a stable antiretroviral regimen (ART) ≥1 year. Frailty was defined by ≥3 of 5 Fried's criteria: weight loss, low physical activity, exhaustion, weak grip strength and slow walking time. Variables related to sociodemographics, HIV infection, comorbidities, polypharmacy, and QoL were evaluated. Independent predictors of frailty were evaluated using collinearity in a multivariate logistic regression analyses (backward stepwise elimination). Results The 248 people studied has a mean age of 49 years, 63.7% were male, and 81% were Caucasian. The prevalence of pre-frailty and fragility was 39.1% and 4.4%, respectively. The main route of HIV acquisition was heterosexual (47.2%). At the inclusion time 26.6% of the patients had AIDS events, 60.9% were anti-HCV negative, and 91.5% had HIV RNA <50 copies/mL (84.3% for ≥1 year); 10.9% had >2 comorbidities, and 13.3% were receiving >5 non-HIV drugs. Frailty patients had a higher age (p 0.006), more sensitive deficits (visual or auditory) (p 0.002), a greater number of falls during the previous year (p 0.0001), a higher Charlson comorbidity index (p 0.001), and a higher VACS index (p 0.001). All comorbidities, excluding bone and liver, were significantly more frequent in fragile patients. The presence of >2 comorbidities and treatment with >5 drugs not related to HIV they were also more frequent in frail patienst (p 0.0001 and p 0.004, respectively). Independent predictors of pre-frailty/frailty in the multivariable analysis differ in men (VACS index, C-reactive protein [CRP], and falls) and women (CRP, AIDS, and menopause). Patients with pre-frailty/frailty had some indicator of a lower QoL. Conclusion Factors associated with pre-frailty/frailty in HIV-infected patients differ by gender, which should be considered when establishing measures for prevention. The role of menopause in the risk of pre-frailty/frailty warrants further investigations.

ObjectivesA quantitative biomarker for identification of pre‐frail and frail persons is still lacking. This study aimed to identify biomarker predictors of frailty in HIV‐infected patients.MethodsA cross‐sectional study of HIV‐infected patients who had been on antiretroviral therapy (ART) for at least 1 year and who presented an undetectable viral load (< 50 HIV‐1 RNA copies/mL) at baseline was carried out. For each frail patient, up to four pre‐frail and robust patients were randomly selected. The frailty status assessment was based on the five‐item criteria described by Fried et al. Sociodemographic, anthropometric, biochemical and HIV‐related characteristics were evaluated. Multiple potential biomarkers of frailty and a biological age biomarker were analysed.ResultsA total of 73 HIV‐infected patients on ART for at least 1 year were evaluated. The patients were categorized as robust (n = 33), pre‐frail (n = 32) and frail (n = 8) using the Fried criteria. All patients were on ART, with 100% undetectable viral load (< 50 copies/mL) at baseline. No significant differences in demographic, clinical or analytical characteristics were observed among patients in the different categories based on Fried criteria, with the exception of the veterans aging cohort study index (VACS). Similarly, no differences were observed in HIV‐related characteristics, although nucleoside reverse transcriptase inhibitor (NRTI) use was less common in frail persons. The distribution of biomarker values varied according to frailty status, with frail persons having higher levels of interleukin (IL)‐8, IL‐18, CXC chemokine ligand 10 (CXCL10) and retinol‐binding protein 4 (RBP4). In multivariable analysis, the assocation of frailty with RBP4 showed a tendency to statistical significance (odds ratio 1.0; 95% confidence interval 0.99–1.00; P < 0.05).ConclusionsDifferential biomarker expression was present according to Fried status. Longitudinal studies will clarify the utility of these biomarkers as targets for diagnostic or therapeutic intervention.

BackgroundWe aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen.MethodsWe analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen.ResultsAmong 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4<200 cells/μL and HIV-RNA>100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//μL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location.ConclusionsThe choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location.

Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism IS related to CD4+ recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4+ T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4+ T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4+ T-cells count <200 cells/mm3. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4+ T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy–Weinberg equilibrium (p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4+ T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4+ T-cells increase (AMR = 1.19; p = 0.004), and higher CD4+ T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4+ T-cells at the end of follow-up ≥500 CD4+ cells/mm3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini–Hochberg), only the increase of ≥ 400 CD4+ cells/mm3 lost statistical significance (p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4+ T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4+ T-cells count <200 cells/mm3.

Our aims were to investigate the adherence to national guidelines of initial antiretroviral therapy (ART) in the Spanish multicenter CoRIS cohort during the years 2010–2015, to identify the reasons for the prescription of nonrecommended treatments, and to explore the role of institutional constraints to guideline compliance. ART regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Physicians were asked the reasons for prescribing nonrecommended regimens. Factors associated with the prescription of non recommended regimens were assessed using multivariable logistic regression. During the study period, 586 (10.7%) of 5479 patients who started ART were given a regimen not recommended in the guidelines. The most frequent reasons for prescribing nonrecommended regimens were: enrolment in clinical trials (43.3%), comorbidities and/or interactions (10.2%), pregnancy (8.7%), and cost (7.7%). Among 37 participating centers, 16 (43%), treating 3561 patients, reported limitations related with the cost of ART, and 20 (54%), treating 1365 patients, reported restrictions for prescribing at least one recommended antiretroviral. In multivariable analysis, a higher risk of receiving nonrecommended regimens was associated with male gender, HIV acquisition by heterosexual transmission, low viral loads, initiation of treatment during the years 2011 to 2015, and initiation of treatment in a center with restricted access to at least one antiretroviral drug. Compliance to clinical guidelines was high. A high proportion of centres reported cost limitations for ART or restricted access to at least one recommended antiretroviral drug, with a significant impact on the choice of initial regimens. Nuestros objetivos fueron investigar la adecuación del tratamiento antirretroviral (TAR) inicial a las guías nacionales en la cohorte multicéntrica española CoRIS durante los años 2010-2015, identificar las razones para la prescripción de pautas no recomendadas y estudiar la influencia de limitaciones institucionales en el cumplimiento de las guías. Se clasificaron las pautas de TAR en recomendadas, alternativas o no recomendadas según las guías de GeSIDA/Plan Nacional sobre el sida. Se preguntaron las razones para haber prescrito pautas no recomendadas a los médicos prescriptores. Se evaluaron los factores asociados a la prescripción de pautas no recomendadas mediante regresión logística multivariable. Durante el periodo de estudio 586 (10,7%) de 5.479 pacientes que iniciaron TAR recibieron una pauta no recomendada. Las razones más frecuentes para prescribir pautas no recomendadas fueron: participación en ensayo clínico (43,3%), comorbilidades y/o interacciones (10,2%), embarazo (8,7%) y coste (7,7%). Entre los 37 centros participantes 16 (43%), que incluían 3.561 pacientes, referían limitaciones en el coste del TAR y 20 (54%), que incluían 1.365 pacientes, referían restricciones para la prescripción de al menos un fármaco recomendado. En el análisis multivariable el riesgo de recibir una pauta no recomendada se asoció a ser varón, adquisición del VIH por vía heterosexual, carga viral baja, inicio del tratamiento durante los años 2011 a 2015 e inicio del tratamiento en un centro con acceso restringido al menos a un antirretroviral. El cumplimiento de las guías de TAR fue elevado. Una alta proporción de centros refirieron limitaciones de coste para el TAR o acceso restringido al menos a uno de los fármacos antirretrovirales recomendados; esto último influyó en la elección de pautas no recomendadas.

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41-6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain. Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000-2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively. Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2-79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999-2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin. Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics.

INTRODUCTION:We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality.METHODS:All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected.RESULTS:Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality.CONCLUSIONS:Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

OBJECTIVE:To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients.METHODS:The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy.RESULTS:Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0).CONCLUSION:The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

We assessed the effect of co-infection by hepatitis C virus (HCV) on immunological and virological response at 48 weeks from initiation of antiretroviral therapy (ART). We included patients from the Cohort of Spanish HIV Research Network (CoRIS) starting ART between January 2004 and November 2014, had at least 1 CD4 T-cell count and viral load measurements both in the previous 6 months and at 48 (+/- 12) weeks from ART initiation, and HCV serology before ART initiation. We used linear regression for mean differences in CD4 T-cell count increase from ART initiation and logistic regression to estimate odds ratios for virological response. Of 12,239 patients by November 30, 2015, 5070 met inclusion criteria: 4382 (86.4%) HIV mono-infected and 688 (13.6%) HIV/HCV co-infected. Co-infected patients were more likely to have acquired HIV through injecting drugs use (57.4% vs. 1.1%), to be women, older, and Spanish, have a lower educational level, and having started ART with lower CD4 counts and acquired immunodeficiency syndrome. CD4 T-cell count increase at 48 weeks was 229.7 cell/mL in HIV-monoinfected and 161.9 cell/mL in HIV/HCV-coinfected patients. The percentages of patients achieving a virological response at 48 weeks were 87.0% and 78.3% in mono and coinfected patients, respectively. Multivariable analyses showed that at 48 weeks, coinfected patients increased 44.5 (95% confidence interval [CI]: 24.8-64.3) cells/mL less than monoinfected and had lower probability of virological response (odds ratio: 0.62; 95% CI: 0.44-0.88). HIV/HCV-coinfected patients have lower immunological and virological responses at 48 weeks from ART initiation than monoinfected patients.

The aim was to evaluate the etiologies of Fever of Intermediate Duration(FID) in a prospective study performed at an Infectious Diseases Department in Spain( January 2005-August 2008 and January-July 2010).An infectious cause (62.50% bacteria and 37.50% viruses) was attributed in 77.67% cases, 4.85% were non-infectious cases, and for 17.48% the etiology was unknown. Using immunofluorescence assays (IFA, IgG) and/or PCR targeting 16S rRNA gene and ompA and omp Brickettsial genes followed by sequence analysis, 33 patients (32.04%) showed evidence of spotted fever group Rickettsia infection (Mediterranean spotted fever). IgG antibodies against Coxiella burnetii were detected in 15/103 patients (14.56%) by IFA, and one serum sample showed IgG antibodies against Rickettsia typhi (0.97%). Francisella tularensisspecific antibodies were detected in 1/103 patients (0.97%) using microagglutination test. Based ELISA or chemiluminiscence assays, Cytomegalovirus (CMV) and EpsteinBarr virus (EBV)infections were the most frequent viral infections (12.62 and 9.71%, respectively), followed by Erythrovirus B-19 infection in 4/103 patients (3.88%) and Human Immunodeficiency Virus (HIV) acute infection in 3/103 patients (2.91%), respectively. In conclusion, Rickettsia spp. and C.burnetii were the most important etiological agents of FID. The empirical use of doxycycline could be appropriate since it is effective for most patients.

Introduction: HIV-associated lipodystrophy syndrome causes systemic metabolic alterations and psychological distress that worsen the quality of life of these patients. An early detection should be considered to efficiently treat it. Objective criteria or reference indices are needed for an early diagnosis. Bioelectrical Impedance Analysis (BIA) is an operator-independent, repeatable and non-invasive method of body composition evaluation that is less expensive than dual-energy X-ray absorptiometry (DXA) and/or CT scans. The aims of this pilot study were to validate the data obtained by BIA to measure fat mass in HIV-positive patients with/without lipoatrophy and to determine if BIA correctly diagnoses lipoatrophy in HIV-positive patients.Methods: Thirty-nine participants were included in this preliminary study. Fourteen were HIV-negative (eight men) whereas 25 were HIV-positive patients (17 men). Eleven of the HIV-positive patients were classified as lipoatrophic according to subjective evaluation by the physicians. Total and regional body composition was measured in basal conditions by DXA and by BIA. To obtain abdominal CT scan fat values, transverse slices with 6-mm thickness were acquired at the L4-L5 intervertebral space.Results: BIA measurements of total and regional body fat were significantly correlated with those obtained by DXA (p<0.05 to <0.01) in HIV-positive patients. However, agreement between methods was poor as not very high ICC (intraclass correlation coefficient) values were observed. BIA and DXA showed higher ICC values in lipoatrophic patients. The visceral index obtained by BIA was correlated with total and visceral fat in L4 measured by CT scan (r = 0.607 and r = 0.617, respectively, p<0.01) in HIV-positive patients. The Fat Mass Ratio (FMR) calculated by BIA did not correlate or agree with DXA values.Conclusions: Multi-frequency BIA could be an effective method to evaluate the evolution of total and regional fat composition in HIV-positive patients with/without lipoatrophy. The correlations between BIA and DXA improved in lipoatrophic patients and in men, suggesting that its efficacy depends on fat mass, gender and probably other factors. The visceral index obtained by BIA seems to be a reliable indicator of abdominal obesity. However, BIA did not fulfil the need for easy quantitative diagnostic tools for lipoatrophy, and it did not provide sufficient diagnostic cut-off values for this syndrome.

In 1996, the first human case of infection by Rickettsia sibirica subsp. mongolitimonae was described in France. Subsequently, other human cases were reported in the same country. The acronym LAR (lymphangitis-associated rickettsiosis) has been proposed to designate this disease because lymphangitis is one of the main clinical manifestations. Later, a few more cases were described in Portugal, South Africa, Egypt, Greece and Spain. We report a case of R. sibirica mongolitimonae infection as a cause of septic shock in a Spanish patient living in La Rioja (northern Spain). In addition, the broad clinical spectrum of this tick-borne disease is discussed.

This study describes the epidemiological, clinical, and microbiological characteristics of a new tick-borne disease in Spain-Dermacentor-borne necrosis erythema lymphadenopathy (DEBONEL). The clinical presentations include an eschar at the site of the tick bite, surrounded by an erythema and painful regional lymphadenopathy. The disease appears during the colder months and its vector is Dermacentor marginatus (D. marginatus). From January 1990 to December 2004, 54 patients presented at Hospital of La Rioja with these clinical and epidemiological data. The ratio of females to males was 32/22. The average age was 37 years. In all cases tick bites were located on the upper body (90% on the scalp). The median incubation period was 4.7 days. Signs and symptoms were mild in all cases. Only a small number of patients presented mild and nonspecific abnormalities in a complete blood cell count and mild elevation of erythrocyte sedimentation rates and C-protein reactive and liver enzyme levels. Serological evidence of acute rickettsiosis was observed in 19 patients (61 %). In 29% sera tested by polymerase chain reactions (PCRs) were positive. The sequence obtained from a PCR product revealed 98% identity with Rickettsia sp. strains RpA4, DnS14, and DnS28. All ticks removed from patients were PCR-positive. Sequencing showed 8 of them identified as R. slovaca and 2 as Rickettsia sp. strains RpA4, DnS14, and DnS28.