High prevalence of asymptomatic carriers of Tropheryma whipplei in different populations from the North of Spain.

INTRODUCTION: Tropheryma whipplei is the causative agent of Whipple disease. T. whipplei has also been detected in asymptomatic carriers with a very different prevalence. To date, in Spain, there are no data regarding the prevalence of T. whipplei in a healthy population or in HIV-positive patients, or in chronic fatigue syndrome (CFS). Therefore, the aim of this work was to assess the prevalence of T. whipplei in stools in those populations. METHODS: Stools from 21 HIV-negative subjects, 65 HIV-infected, and 12 CFS patients were analysed using real time-PCR. HIV-negative and positive subjects were divided into two groups, depending on the presence/absence of metabolic syndrome (MS). Positive samples were sequenced. RESULTS: The prevalence of T. whipplei was 25.51% in 98 stool samples analysed. Prevalence in HIV-positive patients was significantly higher than in HIV-negative (33.8% vs. 9.09%, p=0.008). Prevalence in the control group with no associated diseases was 20%, whereas no positive samples were observed in HIV-negative patients with MS, or in those diagnosed with CFS. The prevalence observed in HIV-positive patients without MS was 30.35%, and with MS it was 55.5%. The number of positive samples varies depending on the primers used, although no statistically significant differences were observed. CONCLUSIONS: There is a high prevalence of asymptomatic carriers of T. whipplei among healthy and in HIV-infected people from Spain. The role of T. whipplei in HIV patients with MS is unclear, but the prevalence is higher than in other populations.

Beyond the effects of HIV infection and integrase inhibitors-based therapies on oral bacteriome.

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 ß-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.

Epidemiological, Clinical, and Microbiological Characteristics in a Large Series of Patients Affected by Dermacentor-Borne-Necrosis-Erythema-Lymphadenopathy from a Unique Centre from Spain.

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.

Integrase Inhibitors Partially Restore Bacterial Translocation, Inflammation and Gut Permeability Induced by HIV Infection: Impact on Gut Microbiota.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of HIV infection and integrase strand transfer inhibitors-based treatment on the gut virome.

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. ß-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.

Gender differences for frailty in HIV-infected patients on stable antiretroviral therapy and with an undetectable viral load.

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.

Detection of Rickettsia africae in Rhipicephalus (Boophilus) decoloratus ticks from the Republic of Botswana, South Africa.

A total of 53 engorged adult ticks belonging to the species Rhipicephalus (Boophilus) decoloratus (N = 9), Rhipicephalus evertsi evertsi (N = 27), Rhipicephalus appendiculatus (N = 9), Amblyomma hebraeum (N = 5), and Hyalomma marginatum turanicum (N = 3), were removed from oryx in Botswana (South Africa). They were tested for the presence of spotted fever group (SFG) Rickettsia and Anaplasma phagocytophilum using polymerase chain reaction (PCR). Seventy-seven percent of R. decoloratus as well as twenty percent of A. hebraeum were positive for ompA, gltA and 16S rRNA SFG Rickettsia PCR assays. All nucleotide sequences were homologous to Rickettsia africae, the agent of African tick-bite fever (ATBF). None of the tested ticks was positive for 16S rRNA A. phagocytophilum PCR assays. These results suggest for the first time that R. decoloratus ticks may be reservoirs of R. africae, and support the ATBF risk in this area.

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

[Rickettsia africae infection. Three cases confirmed by PCR]. / Infección por Rickettsia africae. Tres casos confirmados por reacción en cadena de la polimerasa.

BACKGROUND AND OBJECTIVE: African tick bite fever or Rickettsia africae infection has been recognized as an emerging health problem in the last few years. The aim of this study was to describe 3 cases of Spanish tourists who suffered from R. africae infection after visiting South Africa. PATIENTS AND METHOD: Three patients with a suspected rickettsial disease according to epidemiological and clinical manifestations (fever, eschar and exanthema) were studied. Antibodies against Rickettsia conorii were determined by IFI assays. Semi-nested PCR reactions (rOmpA) and subsequent sequence analysis of the amplified products were also carried out. RESULTS: Epidemiological and clinical aspects of this rickettsiosis are described. For diagnosis of this rickettsial disease, conventional serological assays (IFI) were less useful than semi-nested rOmpA PCR reactions, which showed a sensitivity of 100% in our samples. CONCLUSIONS: Three cases of R. africae infection are reported. PCR and subsequent sequencing of the amplicons are useful for the microbiological confirmation of this type of infection. We must think about African tick-bite fever as a possible diagnosis in patients with a febrile rash after returning from endemic areas.

Calvarial tuberculosis with parenchymal involvement.

Tuberculosis is an infectious disease caused by the acid-fast bacilli Mycobacterium tuberculosis that usually affects the lungs although it may affect any organ. Tuberculous osteitis of the cranial bones is an uncommon manifestation of disseminated tuberculosis known as calvarial tuberculosis. Cases with parenchymal involvement are infrequent in the literature. We report a case of a patient with multiple osteolytic cranial lesions and a tuberculoma.

Multiple frequency bioimpedance is an adequate tool to assess total and regional fat mass in HIV-positive patients but not to diagnose HIV-associated lipoatrophy: a pilot study.

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.

High prevalence of asymptomatic carriers of Tropheryma whipplei in different populations from the North of Spain / Alta prevalencia de portadores asintomáticos de Tropheryma whipplei en distintas poblaciones del norte de España

INTRODUCTION: Tropheryma whipplei is the causative agent of Whipple disease. T. whipplei has also been detected in asymptomatic carriers with a very different prevalence. To date, in Spain, there are no data regarding the prevalence of T. whipplei in a healthy population or in HIV-positive patients, or in chronic fatigue syndrome (CFS). Therefore, the aim of this work was to assess the prevalence of T. whipplei in stools in those populations. METHODS: Stools from 21 HIV-negative subjects, 65 HIV-infected, and 12 CFS patients were analysed using real time-PCR. HIV-negative and positive subjects were divided into two groups, depending on the presence/absence of metabolic syndrome (MS). Positive samples were sequenced. RESULTS: The prevalence of T. whipplei was 25.51% in 98 stool samples analysed. Prevalence in HIV-positive patients was significantly higher than in HIV-negative (33.8% vs. 9.09%, p = 0.008). Prevalence in the control group with no associated diseases was 20%, whereas no positive samples were observed in HIV-negative patients with MS, or in those diagnosed with CFS. The prevalence observed in HIV-positive patients without MS was 30.35%, and with MS it was 55.5%. The number of positive samples varies depending on the primers used, although no statistically significant differences were observed. CONCLUSIONS: There is a high prevalence of asymptomatic carriers of T. whipplei among healthy and in HIV-infected people from Spain. The role of T. whipplei in HIV patients with MS is unclear, but the prevalence is higher than in other populations

INTRODUCCIÓN: Tropheryma whipplei es el agente etiológico de la enfermedad de Whipple. También se ha detectado, con diferentes prevalencias, en portadores asintomáticos. Hasta la fecha, en España, no hay datos sobre su prevalencia en población sana, en pacientes VIH o con síndrome de fatiga crónica (SFC). Por ello, el objetivo de este trabajo fue evaluar la prevalencia de T. whipplei en heces en dichas poblaciones. MÉTODOS: Se analizaron heces de 21 sujetos VIH-negativos, de 65 pacientes VIH-positivos y de 12 con SFC mediante PCR a tiempo real. Los sujetos VIH-negativos y VIH-positivos se dividieron en 2 grupos dependiendo de la presencia/ausencia de síndrome metabólico (SM). Las muestras positivas se secuenciaron. RESULTADOS: De 98 muestras analizadas, la prevalencia de T. whipplei fue del 25,51%. La prevalencia en pacientes VIH-positivos fue significativamente mayor que en los negativos (33,8% vs. 9,09%, p = 0,008). Dentro del grupo control (no VIH) la prevalencia fue del 20% en el grupo sin patologías asociadas, mientras que no se observó ningún positivo en los que presentaban SM ni en los pacientes con SFC. La prevalencia en pacientes VIH-positivos sin SM fue del 30,35%, y del 55,5% en pacientes con SM. El número de muestras positivas varió dependiendo de las dianas utilizadas, aunque no se observaron diferencias significativas. CONCLUSIONES: Existe una alta prevalencia de portadores asintomáticos de T. whipplei en individuos sanos y también en pacientes VIH. El papel de T. whipplei en pacientes VIH con SM no está claro, pero la prevalencia es más alta que en otras poblaciones

Rickettsia monacensis and human disease, Spain.

We identified Rickettsia monacensis as a cause of acute tickborne rickettsiosis in 2 humans. Its pathogenic role was assessed by culture and detection of the organism in patients' blood samples. This finding increases the number of recognized human rickettsial pathogens and expands the known geographic distribution of Mediterranean spotted fever-like cases.

[Endocarditis due to Bartonella spp. Three new clinical cases and Spanish literature review]. / Endocarditis por Bartonella spp. Aportación de tres nuevos casos y revisión de la literatura nacional.

INTRODUCTION: Infections by Bartonella spp. include a wide spectrum of emerging and re-emerging infectious diseases, such as culture-negative endocarditis. METHODS: Description of 3 cases of endocarditis due to Bartonella spp. and review of those previously reported in Spain. RESULTS: Including these 3 new cases of endocarditis due to Bartonella spp., a total of 6 cases have been reported in Spain. The median age of the patients was 51.6 years and 83.3% were men. There was history of contact with cats in 66.7%, and 50% were alcoholic. Only one patient had prior valvular disease. There were no clinical manifestations typical to any of the Bartonella species. The aortic valve was the one most commonly affected. In all cases, B. henselae was the agent implicated. The diagnosis was made by serology in 5 cases (83.3%). The outcome was favorable in all patients, although 4 of them (66.7%) required valve replacement. CONCLUSION: Endocarditis due to Bartonella spp. is present in Spain and is likely to be underestimated. We should suspect this pathogen in patients with negative blood cultures and a history of chronic alcoholism, homeless patients, and those who have had contact with cats or who have been bitten by fleas or lice, as well as patients with endocarditis and positive serology against Chlamydia spp.

Cluster of cases of human Rickettsia felis infection from Southern Europe (Spain) diagnosed by PCR.

The first cluster of cases of human Rickettsia felis infection in Spain diagnosed by PCR is reported.