Mycobacterium tuberculosis-specific CD8 T cells are functionally and phenotypically different between latent infection and active disease

Purpose/Objective: Tuberculosis (TB) is the second worldwide leading cause of death from an infectious disease after HIV infection. Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 T-cells is controversial. We performed comprehensive functional and phenotypic characterizations of Mtb-specific CD8 T-cell responses in 273 subjects with either latent Mtb infection (LTBI) or active TB disease (TB) to assess their profile and relevance in TB. Materials and methods: Using multi-parametric flow cytometry, we assessed Mtb-specific CD8 T-cell functional (production of IFNgamma, IL-2 and TNF-alpha; proliferation capacity and cytotoxicity) and phenotypic (T-cell differentiation and exhaustion) profiles in cells isolated from peripheral blood and correlated these profiles with distinct clinical presentations. Results: Mtb-specific CD8 T-cells were detected in most TB patients and few LTBI subjects (65% and 15%, respectively; P < 0.00001) and were of similar magnitude with a comparable cytokines profile (IFNg+TNFa+IL2-) in both groups. Mtb-specific CD8 T-cells were mostly TEMRA (CD45RA+ CCR7-) co-expressing 2B4 and CD160 in LTBI subjects and mostly TEM (CD45RA-CCR7-) lacking PD-1/ CD160/2B4 in TB patients. Furthermore, Mtb-specific CD8 T-cells mostly expressed very little perforin and granulysin but contained granzymes A and B or lacked all these cytotoxic markers in TB and LTBI subjects, respectively. However, in vitro expanded Mtb-specific CD8 T-cells acquired perforin, granulysin and granzymes. Finally, Mtb-specific CD8 T-cell responses were more robust and prone to proliferate in patients with extrapulmonary compared to pulmonary TB. Conclusions: The clinical status and TB presentation are associated to specific profiles of Mtb-specific CD8 T-cell responses, thus indicating distinct dynamics between the mycobacteria, the CD8 T-cell response and the clinical outcome. Our data shed light on the controversial reached by studies performed in human and animal models, thus advancing the current knowledge on the complex dynamic of TB immunity.

Trust in medical organizations predicts pandemic (H1N1) 2009 vaccination behavior and perceived efficacy of protection measures in the Swiss public

Following the recent avian influenza and pandemic (H1N1) 2009 outbreaks, public trust in medical and political authorities is emerging as a new predictor of compliance with officially recommended protection measures. In a two-wave longitudinal survey of adults in French-speaking Switzerland, trust in medical organizations longitudinally predicted actual vaccination status 6 months later, during the pandemic (H1N1) 2009 vaccination campaign. No other variables explained significant amounts of variance. Trust in medical organizations also predicted perceived efficacy of officially recommended protection measures (getting vaccinated, washing hands, wearing a mask, sneezing into the elbow), as did beliefs about health issues (perceived vulnerability to disease, threat perceptions). These findings show that in the case of emerging infectious diseases, actual behavior and perceived efficacy of protection measures may have different antecedents. Moreover, they suggest that public trust is a crucial determinant of vaccination behavior and underscore the practical importance of managing trust in disease prevention campaigns.

Prévalence des maladies infectieuses au Centre hospitalier universitaire vaudois [Prevalence of infectious diseases at the Vaud University Hospital Center].

The prevalence of infectious diseases at our hospital (Centre hospitalier universitaire vaudois, Lausanne [CHUV], 900 beds) was studied retrospectively over a two years period (1980-1981). The medical diagnosis of 30203 patients recorded in the computerized medical archives, representing 93% of the patients admitted during the period of observation, was reviewed. To assess the reliability of the computerized data, quality control was carried out through detailed analysis of all the histologically proven appendicitis recorded during 1981. 88% of the histologically proven appendicitis were registered in the computer and the diagnosis was specific in 87% of cases. An infectious disease was the primary reason for admission in 12.8% of the patients (3873) during the study period. Altogether, 20.2% of patients presented with an infection during their hospital stay. Because of the retrospective nature of the study it was not possible to determine whether these additional infections were nosocomially acquired. The organ systems most frequently infected were the respiratory tract (28.5% of all infections), the digestive tract (20.5%), the skin and osteoarticular system (16%) and the urogenital tract (11.6%). An infection was the primary reason for admission of 40.2% of the patients hospitalized in the dermatology service, of 19.7% of patients admitted in internal medicine, of 15-17% of the patients admitted in pediatrics, ENT and general surgery, and of 1-2% of the patients admitted in neurosurgery and radiotherapy. These observations highlight the continuing importance of infectious diseases in a modern hospital, in spite of high socio-economic levels, stringent hygiene and epidemiologic measures, and modern antibiotic availability.

Length variation in HIV-1 gp120 as the product of DNA misalignment mechanism

Background: To determine whether misalignment structures such as duplications, repeats, and palindromes are associated to insertions/deletions (indels) in gp120, indicating that indels are indeed frameshift mutations generated by DNA misalignment mechanism. Methods: Cloning and sequencing of a fragment of HIV-1 gp120 spanning C2-C4 derived from plasma RNA in 12 patients with early chronic disease and naïve to antiretroviral therapy. Results: Indels in V4 involved always insertion and deletion of duplicated nucleotide segments, and AAT repeats, and were associated to the presence of palindromic sequences. No duplications were detected in V3 and C3. Palindromic sequences occurred with similar frequencies in V3, C3 and V4; the frequency of palindromes in individual genes was found to be significantly higher in structural (gp120, p ≤ 3.00E-7) and significantly lower in regulatory (Tat, p ≤ 9.00E-7) genes, as compared to the average frequency calculated over the full genome. Discussion: Indels in V4 are associated to misalignment structures (i.e. duplications repeat and palindromes) indicating DNA misalignment as the mechanism underlying length variation in V4. The finding that indels in V4 are caused by DNA misalignment has some very important implications: 1) indels in V4 are likely to occur in proviral DNA (and not in RNA), after integration of HIV into the host genome; 2) they are likely to occur as progressive modifications of the early founder virus during chronic infection, as more and more cells get infected; 3) frameshift mutations involving any number of base pairs are likely to occur evenly across gp120; however, only those mutants carrying a functional gp120 (indels as multiples of three base pairs) will be able to perpetuate the virus cycle and to keep spreading through the population.

The reappearance of a forgotten disease in the oral cavity: syphilis

Syphilis is a sexually transmitted disease (STD) produced by Treponema pallidum, which mainly affects humans and is able to invade practically any organ in the body. Its infection facilitates the transmission of other STDs. Since the end of the last decade, successive outbreaks of syphilis have been reported in most western European countries. Like other STDs, syphilis is a notifiable disease in the European Union. In Spain, epidemiological information is obtained nationwide via the country"s system for recording notifiable diseases (Spanish acronym EDO) and the national microbiological information system (Spanish acronym SIM), which compiles information from a network of 46 sentinel laboratories in twelve Spanish regions. The STDs that are epidemiologically controlled are gonococcal infection, syphilis, and congenital syphilis. The incidence of each of these diseases is recorded weekly. The information compiled indicates an increase in the cases of syphilis and gonococcal infection in Spain in recent years. According to the EDO, in 1999, the number of cases of syphilis per 100,000 inhabitants was recorded to be 1.69, which has risen to 4.38 in 2007. In this article, we review the reappearance and the evolution of this infectious disease in eight European countries, and alert dentists to the importance of a) diagnosing sexuallytransmitted diseases and b) notifying the centres that control them

"Cara inchada" of cattle, an infectious, apparently soil antibiotics-dependant periodontitis in Brazil

The objective of this review on the investigation of "cara inchada" in cattle (CI), pursued over the last 30 years, was to elucidate the pathogenicity of the disease and come to proper conclusions on its etiology. CI has been widely considered to be of nutritional origin, caused primarily by mineral deficiency or imbalance. However, the disease consists of a rapidly progressive periodontitis, affecting the periodontal tissues at the level of the premolars and molars during the period of tooth eruption generally starting in young calves. The disease led to great economic losses for farmers in central-western Brazil, after the occupation of new land for cattle raising in the 1960s and 1970s. The lateral enlargement of the maxillary bones of affected calves gave the disease the popular name of "cara inchada", i.e., swollen or enlarged face. The enlargement was found to be due to a chronic ossifying periostitis resulting from the purulent alveolitis of CI. Black-pigmented non-saccharolytic Bacteroides melaninogenicus, always together with Actinomyces (Corynebacterium) pyogenes, were isolated in large numbers from the periodontal lesions. B. melaninogenicus could be isolated in small numbers also from the marginal gingiva of a few healthy calves maintained on CI-free farms. "In vitro"-assays showed that streptomycin and actinomycin, as well as the supernatants of cultivates of actinomycetes from soils of CI-prone farms, applied in subinhibitory concentrations to the bacteria tested, enhanced significantly (up to 10 times) the adherence of the black-pigmented B.melaninogenicus to epithelial cells of the bovine gingiva. The antibiotics are apparently produced in large quantities by the increased number of soil actinomycetes, including the genus Streptomyces, that develop when soil microflora are modified by cultivating virgin forest or "Cerrado" (tree-savanna) for the first time for cattle grazing. The epidemiology of CI now provides strong evidence that the ingestion with the forage of such antibiotics could possibly be an important determinant factor for the onset and development of this infectious periodontitis. The antibiotic enhanced adherence of B.melaninogenicus to the sulcus-epithelium of the marginal gingiva, is thought to allow it to colonize, form a plaque and become pathogenic. There is experimental evidence that this determinant factor for the development of the periodontitis is present also in the milk of the mothers of CI-diseased calves. It has been shown that the bacteria isolated from the periodontal CI-lesions produce enzymes and endotoxins capable of destroying the periodontal tissues. The epidemiology of CI, with its decline in incidence and its disappearance after several years, could be explained by the fact that the former equilibrium of the microflora of the once undisturbed virgin soil has been reached again and that the number of antibiotic producing actinomycetes has been anew reduced. By this reasoning and all the data available, CI should be considered as a multifactorial infectious disease, caused primarily by the anaerobic black-pigmented non-saccharolytic Bacteroides melaninogenicus, always together with the micro-anaerobic Actinomyces pyogenes. Accordingly, the onset and development of the infectious periodontitis is apparently determined by ingestion with the forage of subinhibitory concentrations of antibiotics produced in recently cultivated virgin soils. This hypothesis is supported by the recent observation of renewed outbreaks of CI-periodontitis in former CI-prone areas, following fresh cultivation after many years. The infectious nature of CI is confirmed by trials in which virginiamycin was used efficiently for the oral treatment of CI-diseased cattle. Previously it has been shown, that spiramycin and virginiamycin, used as additives in mineral supplements, prevented CI-periodontitis.

A research capacity strengthening project for infectious diseases in Honduras: experience and lessons learned

Background: In Honduras, research capacity strengthening (RCS) has not received sufficient attention, but an increase in research competencies would enable local scientists to advance knowledge and contribute to national priorities, including the Millennium Development Goals (MDGs). Objective: This project aimed at strengthening research capacity in infectious diseases in Honduras, focusing on the School of Microbiology of the National Autonomous University of Honduras (UNAH). The primary objective was the creation of a research-based graduate program for the continued training of researchers. Parallel objectives included institutional strengthening and the facilitation of partnerships and networks. Methods: Based on a multi-stakeholder consultation, an RCS workplan was designed and undertaken from 2007 to 2012. Due to unexpected adverse circumstances, the first 2 years were heavily dedicated to implementing the project's flagship, an MSc program in infectious and zoonotic diseases (MEIZ). In addition, infrastructure improvements and demand-driven continuing education opportunities were facilitated; biosafety and research ethics knowledge and practices were enhanced, and networks fostering collaborative work were created or expanded. Results: The project coincided with the peak of UNAH's radical administrative reform and an unprecedented constitutional crisis. Challenges notwithstanding, in September 2009, MEIZ admitted the first cohort of students, all of whom undertook MDG-related projects graduating successfully by 2012. Importantly, MEIZ has been helpful in expanding the School of Microbiology's traditional etiology-based, disciplinary model to infectious disease teaching and research. By fulfilling its objectives, the project contributed to a stronger research culture upholding safety and ethical values at the university. Conclusions: The resources and strategic vision afforded by the project enhanced UNAH's overall research capacity and its potential contribution to the MDGs. Furthermore, increased research activity and the ensuing improvement in performance indicators at the prime Honduran research institution invoke the need for a national research system in Honduras.

Analyse critique de la culture de sécurité face aux risques biologiques et pandémiques pour les infirmières

Une préoccupation grandissante face aux risques biologiques reliés aux maladies infectieuses est palpable tant au niveau international que national ou provincial. Des maladies émergentes telles que le SRAS ou la grippe A/H1N1 ont amené une prise en charge des risques pandémiques et à l’élaboration de mesures d’urgence pour maîtriser ces risques : développer une culture de sécurité est devenu une priorité de recherche de l’OMS. Malgré tout, peu d’écrits existent face à cette volonté de sécuriser la santé et le bien-être par toute une série de dispositifs au sein desquels les discours occupent une place importante en matière de culture de sécurité face aux risques biologiques. Une réflexion sociopolitique était nécessaire pour les infirmières qui sont aux premières loges en dispensant des soins à la population dans une perspective de prévention et de contrôle des infections (PCI) dans laquelle elles se spécialisent. Dès lors, ce projet avait pour buts d’explorer la perception du risque et de la sécurité face aux maladies infectieuses auprès des infirmières cliniciennes et gestionnaires québécoises; d’explorer plus spécifiquement l'existence ou l'absence de culture de sécurité dans un centre de santé et de services sociaux québécois (CSSS); et d’explorer les discours en présence dans le CSSS en matière de sécurité et de risques biologiques face aux maladies infectieuses et comment ces discours de sécurité face aux risques biologiques se traduisent dans le quotidien des infirmières. Les risques biologiques sont perçus comme identifiables, mesurables et évitables dans la mesure où les infirmières appliquent les mesures de préventions et contrôle des infections, ce qui s’inscrit dans une perspective positiviste du risque (Lupton, 1999). La gestion de ces risques se décline au travers de rituels de purification et de protection afin de se protéger de toute maladie infectieuse. Face à ces risques, une culture de sécurité unique est en émergence dans le CSSS dans une perspective de prévention de la maladie. Toutefois, cette culture de sécurité désirée est confrontée à une mosaïque de cultures qui couvrent différentes façons d’appliquer ou non les mesures de PCI selon les participants. La contribution de cette recherche est pertinente dans ce nouveau domaine de spécialité que constituent la prévention et le contrôle des infections pour les infirmières québécoises. Une analyse critique des relations de pouvoir tel qu’entendu par Foucault a permis de soulever les questions de surveillance infirmière, de politique de l’aveu valorisée, de punition de tout écart à l’application rigoureuse des normes de PCI, de contrôle de la part des cadres infirmiers et d’assujettissement des corps relevant des mécanismes disciplinaires. Elle a permis également de documenter la présence de dispositifs de sécurité en lien avec la tenue de statistiques sur les patients qui sont répertoriés en tant que cas infectieux, mais également en termes de circulation des personnes au sein de l’établissement. La présence d’un pouvoir pastoral est perceptible dans la traduction du rôle d’infirmière gestionnaire qui doit s’assurer que ses équipes agissent de la bonne façon et appliquent les normes de PCI privilégiées au sein du CSSS afin de réguler les taux d’infections nosocomiales présents dans l’établissement. En cas de non-respect des mesures de PCI touchant à l’hygiène des mains ou à la vaccination, l’infirmière s’expose à des mesures disciplinaires passant de l’avertissement, la relocalisation, l’exclusion ou la suspension de l’emploi. Une culture du blâme a été décrite par la recherche d’un coupable au sein de l’institution, particulièrement en temps de pandémie. Au CSSS, l’Autre est perçu comme étant à l’origine de la contamination, tandis que le Soi est perçu comme à l’abri de tout risque à partir du moment où l’infirmière respecte les normes d’hygiène de vie en termes de saines habitudes alimentaires et d’activité physique. Par ailleurs, les infirmières se doivent de respecter des normes de PCI qu’elles connaissent peu, puisque les participantes à la recherche ont souligné le manque de formation académique et continue quant aux maladies infectieuses, aux risques biologiques et à la culture de sécurité qu’elles considèrent pourtant comme des sujets priorisés par leur établissement de santé. Le pouvoir produit des effets sur les corps en les modifiant. Cette étude ethnographique critique a permis de soulever les enjeux sociopolitiques reliés aux discours en présence et de mettre en lumière ce que Foucault a appelé le gouvernement des corps et ses effets qui se capillarisent dans le quotidien des infirmières. Des recherches ultérieures sont nécessaires afin d’approfondir ce champ de spécialité de notre discipline infirmière et de mieux arrimer la formation académique et continue aux réalités infectieuses cliniques.

Niveles de hemoglobina en los que se indica transfundir en el Hospital Universitario Fundación Santa Fe de Bogotá

Introducción: En los pacientes críticamente enfermos la terapia transfusional es una práctica común. Dentro de los estudios realizados no se han incluido a las ciudades a mayor altura. Este estudio pretende determinar los niveles de hemoglobina sobre los cuales se está transfundiendo a los pacientes en la unidad de cuidados intensivos del Hospital Universitario Fundación Santa Fe de Bogotá a 2600 metros sobre el nivel del mar, para determinar si los niveles de hemoglobina a los que se transfunde a nuestra altura son los óptimos. Métodos: Se realizó un estudio descriptivo retrospectivo, de los pacientes que fueron hospitalizados en la Unidad de Cuidado Intensivo del Hospital Universitario Fundación Santa Fe de Bogotá a partir del 01 de Junio de 2011 y hasta el 31 de Mayo de 2012. Resultados: Del total de los registros analizados el 13,8% de los pacientes presentaron una hemoglobina ≤ 7 y todos fueron transfundidos con glóbulos rojos; y en el rango de 7,1-9 se presentó el mayor porcentaje de transfusión. Se observó que los pacientes con hemoglobina ≤ 7 tienen 18,8 veces mayor riego de fallecimiento, lo que fue estadísticamente significativo (p:0,000). Conclusiones: Encontramos que la terapia transfusional en la unidad de cuidado intensivo, se realiza de acuerdo a recomendaciones dadas por las guías de manejo universalmente aceptadas. Dentro de los resultados de nuestro estudio podemos resaltar una tasa de mortalidad más alta en los pacientes en los cuales se instaura terapia transfusional con un nivel de hemoglobina por debajo de 7g/dl.

Factores asociados a la infección para Clostridium difficile en un hospital universitario de Bogotá

Introducción La infección por Clostridium difficile, es una de las causas más frecuentes de diarrea nosocomial con una alta morbimortalidad, con un aumento exponencial en su incidencia, en Estados Unidos se duplicó, de 261 casos x 100.000 en 1993 pasó a 546 x 100.000 en 2003 2, y en Canadá se encontraron datos similares con un aumento de 4.5 veces, en 1991 de 35.6 casos x 100.000 a 156.3 casos por 100.000 en 2004 3 . Se han descrito varios factores asociados Materiales y Métodos Se trata de un estudio descriptivo de tipo serie de casos en el que se evaluaron pacientes con diagnóstico de infección por C. Difficile y los factores asociados en un Hospital Universitario entre febrero de 2010 hasta septiembre de 2011 Resultados Se recolectaron 31 pacientes la edad promedio fue de 58 años con un rango entre 18 y 93 años, de los cuales 19 (61%) fueron mujeres y 12 (39%) hombres. El factor asociado a la infección por C. Difficile más frecuentemente encontrado fue el uso de inhibidores de bomba de protones con 54.84% (n=17) .No se encontraron pacientes VIH positivos o con diagnóstico de enfermedad inflamatoria intestinal. Ningún paciente presentó complicaciones asociadas a la infección ni mortalidad alguna. Conclusión El factor asociado que más se presentó fue el uso de antimicrobianos en los quince dias previos al inicio del cuadro en el 74% de los pacientes lo que coincide con lo presentado en la literatura mundial.

Perfil de resistencia microbiológico en ciudados intensivos adultos en la fundación Santa Fe de Bogotá año 2014

Se realizó un estudio descriptivo, retrospectivo; se usó la base de datos de los aislamientos microbiológicos documentados en las UCI de la Fundación Santa fe de Bogotá para el año 2014. La prevalencia de bacterias resistentes en los aislamientos de la FSFB no es baja, por lo que se requiere una terapia empírica acertada acorde con la flora local. Se requieren estudios analíticos para evaluar factores asociados al desarrollo de gérmenes multi resistentes y mortalidad por sepsis

La cooperación en América del Norte : de las seguridades económica y militar a la bioseguridad (2001-2009)

El nuevo orden internacional derivado de la Guerra Fría se caracterizó por la multiplicación de nuevas amenazas a la seguridad y la construcción de bloques regionales con el propósito de enfrentarlas. Esta investigación plantea que bajo tales circunstancias, en América del Norte, fue adoptada una agenda ampliada y profundizada en materia de seguridad que permitió articular las seguridades económica, militar y la bioseguridad. En este sentido, la configuración de dicha agenda fue posible gracias a la adopción de una retórica neoliberal de seguridad económica desde la puesta en marcha del Tratado de Libre Comercio en 1994, la cual luego del 11 de septiembre de 2001 fue articulada con la agenda de seguridad militar propuesta por el gobierno estadounidense en materia de lucha antiterrorista, que a su turno permitió la adopción de una retórica y unas medidas extraordinarias en materia de bioseguridad, motivada por los ataques bioterroristas con ántrax en EE.UU., el brote de SARS en Canadá y la pandemia de AH1N1 en México.

Seroprevalência de border disease em Pequenos ruminantes na região do Baixo Alentejo

A “Border Disease” é uma doença infecciosa causada por um pestivírus que afecta maioritariamente pequenos ruminantes, causando problemas reprodutivos, alterações congénitas e animais persistentemente infectados. Não existem registos da seroprevalência desta patologia em Portugal. O objectivo deste trabalho foi estudar a seroprevalência de “Border Disease” em explorações de pequenos ruminantes na região do Baixo Alentejo e relacioná-la com a raça dos animais, dimensão do efectivo, coabitação com bovinos e localização da exploração. Em 197 animais, observaram-se 10 seropositivos que correspondem a uma seroprevalência de 5%. Em 29 explorações observaram-se 6 positivas nas quais, havia pelo menos um animal seropositivo, que corresponde a 20,6 % das explorações. Não foi observada relação significativa da prevalência nas explorações com as raças dos animais, a dimensão do efectivo e a sua localização geográfica. Existe maior probabilidade de casos seropositivos de “Border Disease” em pequenos ruminantes que coabitem com bovinos. A seroprevalência de “Border Disease” é baixa na região do Baixo Alentejo. Mais estudos devem ser efectuados de forma a identificar a estirpe do vírus “Border Disease” (BDV) presente nesta região, a verificar se a seroconversão poderá ter origem no contacto com o vírus da diarreia viral bovina (BVDV) e estudar o impacto desta doença na produção de pequenos ruminantes no Baixo Alentejo.

Impact of apoE genotype on oxidative stress, inflammation and disease risk

Although in developing countries an apolipoprotein E4 (apoE4) genotype may offer an evolutionary advantage, as it has been shown to offer protection against certain infectious disease, in Westernised societies it is associated with increased morbidity and mortality, and represents a significant risk factor for cardiovascular disease, late-onset Alzheimer's disease and other chronic disorders. ApoE is an important modulator of many stages of lipoprotein metabolism and traditionally the increased risk was attributed to higher lipid levels in E4 carriers. However, more recent evidence demonstrates the multifunctional nature of the apoE protein and the fact that the impact of genotype on disease risk may be in large part due to an impact on oxidative status or the immunomodulatory/anti-inflammatory properties of apoE. An increasing number of studies in cell lines, targeted replacement rodents and human volunteers indicate higher oxidative stress and a more pro-inflammatory state associated with the F,4 allele. The impact of genotype on the antioxidant and immunomodulatory/anti-inflammatory properties of apoE is the focus of the current review. Furthermore, current information on the impact of environment (diet, exercise, smoking status, alcohol) on apoE genotype-phenotype associations are discussed with a view to identifying particular lifestyle strategies that could be adapted to counteract the 'at-risk' E4 genotype.