Risk of cardiovascular disease in patients with HIV infection undergoing antiretroviral therapy. / Riesgo de enfermedad cardiovascular en pacientes con infección VIH en tratamiento antirretroviral.

BACKGROUND: The increased survival of patients with HIV infection thanks to antiretroviral therapy (ART) is accompanied by a higher rate of cardiovascular disease (CVD). We analysed the prevalence of the cardiovascular risk factors (CRFs) and estimated the risk of CVD in a cohort of patients with HIV in Spain. METHODS: We conducted a cross-sectional, observational study of CRFs in the Spanish VACH cohort of patients with HIV who undergo ART. RESULTS: The study assessed 15,559 patients with HIV (76% men; mean age, 46 years). Some 3.7% had experienced at least 1 CVD event. The prevalence of CRFs was high (hyperlipidaemia, 64%; tobacco use, 47%; arterial hypertension, 22%; and diabetes, 16%). According to the Framingham scale, 10.9% of the patients presented a high CVD risk, and 28.8% presented a moderate risk. Of the patients with a high CVD risk, 49% took protease inhibitors and 43% took abacavir. Fifty-three percent of the patients diagnosed with arterial hypertension took antihypertensive drugs, and 2.6% of the patients with diabetes took antidiabetic agents. CONCLUSIONS: Classical CRFs are common in patients with HIV undergoing ART in Spain, and a large proportion of them have a moderate-high risk of CVD. Therefore, controlling the modifiable CRFs in patients with HIV should be improved, and the use of drugs with a better cardiovascular risk profile should be assessed.

Retinol-binding protein 4 (RBP4), a potential biomarker of frailty in HIV-infected people on stable antiretroviral therapy.

OBJECTIVES: A 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. METHODS: A 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. RESULTS: A 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). CONCLUSIONS: Differential biomarker expression was present according to Fried status. Longitudinal studies will clarify the utility of these biomarkers as targets for diagnostic or therapeutic intervention.

[The microbiota-gut-brain axis and its great projections]. / El eje microbiota-intestino-cerebro y sus grandes proyecciones.

INTRODUCTION: The microbiota is the set of millions of microorganisms that coexist in a symbiotic way in our body. It is mainly located in the digestive tract, being distributed in function of the chemical properties and the functions of the different organs. The factors that influence its composition are multiple (diet, individual habits, diseases or drugs). It also participates in several functions of the organism such as metabolism, immunity or even the function of the central nervous system. DEVELOPMENT: This last interrelationship is called: gut-brain axis. For years the relationship between the microbiota and the central nervous system has been known and how they influence one over the other. It is postulated that communication occurs through three systems: the vagus nerve, the systemic pathway (with the release of hormones, metabolites and neurotransmitters) and the immune system (by the action of cytokines). CONCLUSIONS: There are still many unknowns to be clarified in this field, but this microbiota-intestine-brain relationship is postulated as a possible pathogenic basis for neurological diseases of great health impact such as Alzheimer, Parkinson or multiple sclerosis. There are currently studies with probiotics with hopeful results in patients with Alzheimer's disease.

TITLE: El eje microbiota-intestino-cerebro y sus grandes proyecciones.Introduccion. Se denomina microbiota al conjunto de millones de microorganismos que conviven de manera simbiotica en nuestro organismo. Este conjunto bacteriano, que se localiza principalmente en el tracto digestivo, se distribuye a lo largo de los diferentes organos en funcion de las propiedades quimicas. Los factores que influyen en su composicion son multiples (dieta, habitos individuales, farmacos). La microbiota colabora en varias funciones, como pueden ser el metabolismo o la inmunidad. Desarrollo. En los ultimos años se ha puesto de relieve el papel bidireccional de la microbiota del tracto digestivo y del sistema nervioso central, es el denominado eje intestino-cerebro. En lo que a este eje se refiere, se cree que la 'comunicacion' se produce a traves de tres vias: el nervio vago, la via sistemica (mediante la liberacion de hormonas, metabolitos y neurotransmisores) y el sistema inmune (por la accion de las citocinas). Conclusiones. Aunque aun quedan muchas incognitas por esclarecer, este eje se postula como una posible base patogena para numerosos trastornos neurologicos de gran impacto sanitario, como la enfermedad de Alzheimer, la enfermedad de Parkinson o la esclerosis multiple. En el momento actual se estan llevando a cabo estudios que intentan evaluar el impacto de los probioticos sobre algunas de estas enfermedades neurologicas.

The beneficial effect of probiotics as a supplementary treatment in drug-resistant epilepsy: a pilot study.

Epilepsy is a neurological disease with high global prevalence. Despite the range of drug-based treatments currently available to control the condition, one in 3 patients experiences epileptic seizures. Therapeutic alternatives for these patients include the ketogenic diet, surgery or the cerebral implantation of neurostimulators; however these are benefits with limits. The target of this study is to find a new complementary treatment for these patients, studying the effectiveness of probiotics for controlling epileptic seizures in patients with drug-resistant epilepsy. A prospective study was designed in which a group of patients with drug-resistant epilepsy was administered a probiotic mixture for 4 months. Patients were assessed before and after taking the probiotics; among other variables, number of seizures and patients' quality of life (QOLIE-10) were monitored. Levels of cD-14, interleukin 6, and γ-aminobutyric acid were also analysed throughout the study. 45 patients were included in the study. In an intention-to-treat analysis, 28.9% of all patients displayed a greater than 50% reduction in the number of seizures (the parameter required in clinical trials). A significant improvement was also observed in patients' quality of life. We found that probiotics may be an option for supplementary therapy. Since the use of probiotics is safe, they may contribute to improving seizure control, and therefore quality of life, in patients with drug-resistant epilepsy. The study has been registered in https://clinicaltrials.gov with number NCT03403907.

Impact of dolutegravir and efavirenz on immune recovery markers: results from a randomized clinical trial.

OBJECTIVES: CD4/CD8 ratio and CD4+ T-cell percentage (CD4%) predicts the risk of AIDS and non-AIDS events. Multiple T-cell marker recovery (MTMR) has been proposed as the most complete level of immune reconstitution. We quantified differences in the CD4/CD8 ratio, CD4% recovery and MTMR after starting HIV-1 treatment with dolutegravir/abacavir/lamivudine vs. efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC). METHODS: Exploratory post hoc analysis of the SINGLE study, a randomized double-blind, clinical trial. Percentage differences and corresponding precision based on 95% confidence intervals, and p values were calculated for CD4/CD8 ratio normalization, CD4% normalization and the achievement of MTMR. Cox models taking into account competing risks were used to estimate sub-hazard ratios when comparing the times to normalization of the CD4/CD8 ratio and the CD4% by treatment arm. RESULTS: Data from 833 participants were analysed (414 in the dolutegravir/abacavir/lamivudine arm). There were no statistically significant differences in the proportion of patients who reached a CD4/CD8 ratio ≥0.5 at weeks 48 and 96. However, at week 96, the proportion of patients with a CD4/CD8 ratio ≥1 was higher in the EFV-TDF-FTC group (difference, 11.70; 95% confidence interval, 4.49-18.91; p 0.002). The decrease from baseline in CD8+ cell count was consistently greater in the EFV-TDF-FTC arm. Analysis of CD4+ percentages showed no significant differences during the study. The proportion of patients attaining a MTMR was higher in the EFV-TDF-FTC group, although the difference was only statistically significant at week 96 (p 0.001). CONCLUSIONS: EFV-TDF-FTC showed significantly greater increases in CD4/CD8 ratio ≥1.0 or MTMR beyond treatment week 96. Additional studies are necessary to better understand the impact of these findings.

Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

OBJECTIVES: Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). METHODS: A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. RESULTS: After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. CONCLUSIONS: When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.

Design of an accurate wireless data logger for vibration analysis with Android interface.

In this work a new accurate wireless data logger using the Android interface was developed to monitor vibrations at low-cost. The new data logger is completely autonomous and extremely reduced in size. This instrument enables data collection wirelessly and the ability to display it on any tablet or smartphone with operating system Android. The prototype allows the monitoring of any industrial system with minimal investment in material and installation costs. The data logger is capable of making 12.8 kSPS enough to sample up to 5 kHz signals. The basic specification of the data logger includes a high resolution 1-axis piezoelectric accelerometer with a working range of ±30 G. In addition to the acceleration measurements, temperature can also be recorded. The data logger was tested during a 6-month period in industrial environments. The details of the specific hardware and software design are described. The proposed technology can be easily transferred to many other areas of industrial monitoring.

Use of cohort data to estimate national prevalence of transmitted drug resistance to antiretroviral drugs in Spain (2007-2012).

Prevalence of transmitted drug resistance (pTDR) to antiretroviral drugs in Spain (2007-2012) was estimated using the CoRIS cohort, adjusting its territorial distribution and transmission route to the reference population from the Spanish Information System on New human immunodeficiency virus diagnoses. A total of 2702 patients from ten autonomous communities and with naive FASTA sequence within 6 months of human immunodeficiency virus diagnosis were selected. Weighted pTDR, estimated using the inverse probability of selection in the sample by autonomous communities and transmission group, was 8.12% (95% CI 6.44-9.80), not significantly different from unweighted pTDR. We illustrate how proportional weighting can maximize representativeness of cohort-based data, and its value to monitor pTDR at country level.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Interpreting the reasons for the choice and changing of two drug regimens in an observational cohort: comparison of a ritonavir-boosted protease inhibitor-based versus a nonnucleoside reverse transcriptase inhibitor-based first-line regimen.

OBJECTIVES: We compared reasons for the choice of regimen, time to and reasons for third drug modification, virological response and change in CD4 T-cell counts in patients started on atazanavir/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line regimens. METHODS: We included patients from the Cohort of the Spanish HIV Research Network (CoRIS), a multicentre cohort of HIV-positive treatment-naïve subjects, in the study. We used logistic regression to assess factors associated with choosing ATV/r vs. EFV, proportional hazards models on the subdistribution hazard to estimate subdistribution hazard ratios (sHRs) for third drug modification, logistic regression to estimate odds ratios (ORs) for virological response and linear regression to assess mean differences in CD4 T-cell count increase from baseline. RESULTS: Of 2167 patients, 10.7% started on ATV/r. ATV/r was more likely than EFV to be prescribed in injecting drug users [adjusted OR 1.85; 95% confidence interval (CI) 1.03-3.33], in 2009-2010 (adjusted OR 1.63; 95% CI 1.08-2.47) and combined with abacavir plus lamivudine (adjusted OR 1.53; 95% CI 0.98-2.43). Multivariate analyses showed no differences, comparing ATV/r vs. EFV, in the risk of third drug modification (sHR 1.04; 95% CI 0.74-1.46) or in virological response (OR 0.81; 95% CI 0.46-1.41); differences in mean CD4 T-cell count increase from baseline were at the limit of statistical significance (mean difference 29.8 cells/µL; 95% CI -4.1 to 63.6 cells/µL). In patients changing from EFV, 48% of changes were attributable to toxicity/adverse events, 16% to treatment failure/resistance, 3% to simplification, and 8 and 12%, respectively, to patients' and physicians' decisions; these percentages were 24, 6, 12, 14 and 24%, respectively, in those changing from ATV/r. CONCLUSIONS: ATV/r- and EFV-based regimens meet the requirements of both efficacy and safety for initial combination antiretroviral regimen, which relate to better durability.

Modified cementless total coxofemoral prosthesis: development, implantation and clinical evaluation / Prótese coxofemoral não cimentada: desenvolvimento, implantação e avaliação clínica

The aim of this study was to modify canine coxofemoral prostheses and the clinical evaluation of the implantation. Fifteen canine hips and femora of cadavers were used in order to study the surface points of modification in prostheses and develop a perforation guide. Femoral stems and acetabular components were perforated and coated with biphasic calcium phosphate layer. Twelve young adult male mongrel dogs were implanted with coxofemoral prostheses. Six were operated upon and implanted with cemented canine modular hip prostheses, establishing the control group. The remaining six were implanted with a novel design of cementless porous tricalcic phosphate-hydroxyapatite coated hip prostheses. Clinical and orthopedic performance, complications, and thigh muscular hypotrophy were assessed up to the 120th post-operatory day. After 120 days, animals with cementless prostheses had similar clinical and orthopedic performance compared to the cemented group despite the increased pain thigh hypotrophy. Animals that underwent cementless hip prosthesis evidenced more pain, compared to animals with cemented hip prosthesis that required longer recuperation time. No luxations, two fractures and two isquiatic neurapraxies were identified in the course of the study. Using both the cemented and the bioactive coated cementless model were suitable to dogs, showing clinical satisfactory results. Osseointegration and biological fixation were observed in the animals with the modified cementless hip prosthesis.

O objetivo deste estudo foi modificar a prótese coxofemoral canina cimentada e avaliar os efeitos clínicos. Foram utilizadas 15 pelves e 15 fêmures de cadáveres de cães para modificações da haste, do componente acetabular e para a confecção de guia de perfuração. As hastes e componentes acetabulares foram perfurados e revestidos com uma camada de fosfato de cálcio bifásico. Doze cães machos, adultos jovens, sem raça definida, foram submetidos à cirurgia para o implante de prótese coxofemoral total. Seis cães receberam prótese modular cimentada, grupo controle, e seis, a prótese modificada não cimentada com revestimento de fosfato de cálcio bifásico. Foram avaliados a técnica de implantação, o desempenho clínico, o grau de hipotrofia muscular da coxa e as complicações durante 120 dias. Os animais com prótese não cimentada mostraram desempenho clínico similar aos animais com a prótese cimentada, porém mostraram maior hipotrofia muscular decorrente de dor e maior tempo de recuperação. Não foram observadas luxações. No entanto, duas fraturas e dois casos de neurapraxia isquiádica foram observados. A utilização de ambas as próteses coxofemorais, cimentada e não cimentada, com recobrimento bioativo são eficientes no cão, com resultados clínicos satisfatórios, mas a osteointegração e fixação biológica ocorreram na prótese com recobrimento de fosfato de cálcio bifásico, objetivo do tratamento que previne afrouxamento futuro.

Role of mitochondria in HIV infection and associated metabolic disorders: focus on nonalcoholic fatty liver disease and lipodystrophy syndrome.

Highly active antiretroviral therapy (HAART) has considerably improved the prognosis of HIV-infected patients. However, prolonged use of HAART has been related to long-term adverse events that can compromise patient health such as HIV-associated lipodystrophy syndrome (HALS) and nonalcoholic fatty liver disease (NAFLD). There is consistent evidence for a central role of mitochondrial dysfunction in these pathologies. Nucleotide reverse transcriptase inhibitors (NRTIs) have been described to be mainly responsible for mitochondrial dysfunction in adipose tissue and liver although nonnucleoside transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) have also showed mitochondrial toxicity, which is a major concern for the selection and the long-term adherence to a particular therapy. Several mechanisms explain these deleterious effects of HAART on mitochondria, and evidence points to other mechanisms beyond the "Pol- γ hypothesis." HIV infection has also direct effects on mitochondria. In addition to the negative effects described for HIV itself and/or HAART on mitochondria, HIV-infected patients are more prone to develop a premature aging and, therefore, to present an increased oxidative state that could lead to the development of these metabolic disturbances observed in HIV-infected patients.

Q fever endocarditis associated with a cardiovascular implantable electronic device.

Cardiovascular implantable electronic devices (CIEDs) are frequently related to endocarditis. Most cases of intravascular CIED infections are usually related to skin flora, but a few cases may occur with negative blood culture. Coxiella burnetii is one of the main causes of blood culture-negative endocarditis in native and prosthetic valves, but to date no cases related to CIED have been published. Herein we report two cases of Q fever endocarditis related to these non-valvular cardiovascular devices.

Septic shock in a patient infected with Rickettsia sibirica mongolitimonae, Spain.

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.

[Treatment of human infections caused by Bartonella spp.]. / Tratamiento de las infecciones por Bartonella spp.

Infections by Bartonella spp. include a wide spectrum of emerging and re-emerging infectious diseases. There is not a universal therapy for this infection, therefore treatment should be chosen individually. The aim of this review is to update the therapeutics aspects of this kind of infections.

[The influence of alternative medicine in highly active antiretroviral treatment]. / Influencia de la medicina alternativa en el tratamiento antirretroviral de gran actividad.

OBJECTIVE: Over the last few years, there has been a notable increase in the use of alternative medicine by the general population. The aim of this study is two-fold. Firstly we will analyse the incidence of the use of medicinal plants in patients with HIV undergoing Highly Active Anti-Retroviral Therapy (HAART). Secondly, with the help of existing bibliographic information, we want to study the existence of possible interactions. MATERIAL AND METHODS: We carried out a prospective study with a targeted interview (October to December 2007) on consenting patients with HIV undergoing HAART treatment. RESULTS: Of the 193 patients that agreed to take part in the survey, 16.6 % confirmed they used alternative medicinal therapies. In 46 % of the cases there was a potential interaction with the effectiveness of HAART. 46 % of the potential interactions were in the case of the patients who used grapefruit as an alternative medicine, 21 % in the case of patients using thistle and Echinacea respectively, 4 % for those using omega-3, Chinese herbs and ginseng. CONCLUSION: There is a significant use of natural products by these groups of patients, of which a significant percentage interact with HAART. A better understanding of the possible interactions with HAART and improved information offered to patients with HIV is needed.

Incidence and risk factors for tuberculosis in HIV-positive subjects by HAART status.

OBJECTIVE: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. METHODS: Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. RESULTS: A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16 464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). CONCLUSIONS: HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.

Rickettsiosis in Europe.

In Europe, rickettsioses are long-known infectious diseases. Until recently, it was thought that Mediterranean spotted fever due to Rickettsia conorii was the only tick-borne rickettsiosis in Europe. In the last decade new Rickettsia spp. have been implicated in human pathology (R. slovaca, R. sibirica mongolotimonae, R. helvetica). Furthermore, cases of infection due to flea-borne rickettsioses (R. typhi, R. felis) have been described. Finally, although no outbreak of epidemic typhus has been reported yet in central and southern Europe, we should be aware of the possibility of reemergence of this disease in Europe. Other rickettsioses exist that have not yet been implicated in human pathology. We should consider that climate changes and other factors could contribute to the emergence and reemergence of other new diseases.