Risk factors for positive tuberculin skin tests among migrant and resident children in Lausanne, Switzerland

Résumé en français Cadre : Policlinique pédiatrique à Lausanne en Suisse, pays rencontrant une proportion importante de tuberculose au sein de la population de migrants. But : Déterminer les facteurs de risque associés à un test tuberculinique positif (ou test de Mantoux), notamment l'influence du BCG (Bacille Calmette Guérin) et d'un contact avec un personne ayant une tuberculose active. Les patients concernés étaient des enfants examinés dans le cadre d'un contrôle de santé ou dans le cadre d'une étude d'entourage d'un cas déclaré de tuberculose. Méthode : Etude descriptive comprenant des enfants ayant eu un test tuberculinique (2 unités RT23) entre novembre 2002 et avril 2004. L'âge, le sexe, l'anamnèse de contact avec une personne ayant une tuberculose active, la vaccination par le BCG, le pays d'origine et le lieu de naissance (en Suisse ou hors de la Suisse) étaient répertoriés. Résultats : Parmi les 234 enfants de l'étude, 176 (75%) avaient une réaction tuberculinique égal à zéro et 31 (13%) avaient une réaction positive (> 10mm). Dans le modèle de régression linéaire, la taille de la réaction tuberculinique variait significativement selon l'anamnèse de contact avec une personne ayant une tuberculose active, l'âge, l'incidence de la tuberculose dans le pays d'origine et la vaccination par le BCG. Le sexe ou le lieu de naissance n'influençait pas la taille de la réaction. Dans le modèle de régression logistique incluant toutes les valeurs répertoriées, les paramètres significativement associés avec un Mantoux positif étaient l'âge (Odds Ratio = 1.21, 95% CI 1.08 ; 1.35), l'anamnèse de contact avec une personne ayant une tuberculose active (OR = 7.31, 95% CI 2.23 ; 24) et l'incidence de la tuberculose dans le pays d'origine (OR = 1.01, 95% CI 1.00 ; 1.02). Le sexe (OR = 1.18, 95% CI 0.50 ; 2.78) et la vaçcination par le BCG (OR = 2.97, 95% CI 0.91 ; 9.72) n'étaient pas associés avec une réaction tuberculinique positive. Conclusions : L'incidence de la tuberculose dans le pays d'origine, la vaccination par le BCG et l'âge influencent le test de Mantoux (taille ou proportion de réaction > 10mm). Toutefois, le facteur de risque le plus important d'avoir une réaction tuberculinique positive est l'anamnèse de contact avec. une personne ayant une tuberculose active.

Inducible gene and shRNA expression in resident hematopoietic stem cells in vivo.

Hematopoietic stem cells (HSC) are probably the best understood somatic stem cells and often serve as a paradigm for other stem cells. Nevertheless, most current techniques to genetically manipulate them in vivo are either constitutive and/or induced in settings of hematopoietic stress such as after irradiation. Here, we present a conditional expression system that allows for externally controllable transgenesis and knockdown in resident HSCs, based on a lentiviral vector containing a tet-O sequence and a transgenic mouse line expressing a doxycyclin-regulated tTR-KRAB repressor protein. HSCs harvested from tTR-KRAB mice are transduced with the lentiviral vector containing a cDNA (i.e., Green Fluorescent Protein (GFP)) and/or shRNA (i.e., p53) of interest and then transplanted into lethally irradiated recipients. While the vector is effectively repressed by tTR-KRAB during homing and engraftment, robust GFP/shp53 expression is induced on doxycyclin treatment in HSCs and their progeny. Doxycylin-controllable transcription is maintained on serial transplantation, indicating that repopulating HSCs are stably modified by this approach. In summary, this easy to implement conditional system provides inducible and reversible overexpression or knock down of genes in resident HSCs in vivo using a drug devoid of toxic or activating effects.

Urban health: l'irrémédiable urbanisation de la vie et de la médecine [Urban health: the irremediable urbanization of life and medicine].

Since 2007, the number of people living in cities exceeds that of rural areas. Thus, cities and their organizations have a major influence on all spheres of human life, especially health. This influence may generate inequality, suffering and disease, but also represent an opportunity for health and well-being. This paper introduces the concept of urban health, particularly in terms of primary care medicine and presents solutions that encompass a wide field (politics, urban planning, social inequality, education). Improving urban health requires collaboration of medical with non-medical actors, in order to become of development (re-) urban structure and promotes the health of all.

Characterization of cardiac-resident progenitor cells expressing high aldehyde dehydrogenase activity.

High aldehyde dehydrogenase (ALDH) activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDH(br)) cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDH(br) cells in the heart has not been evaluated so far. We have characterized ALDH(br) cells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDH(br). ALDH(very-br) cells were more frequent in neonatal hearts than adult. ALDH(br) cells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDH(very-br) cells, intermediate in ALDH(br) cells, and lowest in ALDH(dim) cells. ALDH1A2 expression was highest in ALDH(very-br) cells, intermediate in ALDH(dim) cells, and lowest in ALDH(br) cells. ALDH1A3 and ALDH2 expression was detectable in ALDH(very-br) and ALDH(br) cells, unlike ALDH(dim) cells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDH(br) cells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDH(br) cells, unlike ALDH(dim) cells, could be grown in culture for more than 40 passages. They expressed sarcomeric α -actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDH(br) cells declined with cell passage. In conclusion, the cardiac-derived ALDH(br) population is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDH(br) cells remains to be evaluated.

FGF-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes.

Recent evidence suggests that the heart possesses a greater regeneration capacity than previously thought. In the present study, we isolated undifferentiated precursors from the cardiac nonmyocyte cell population of neonatal hearts, expanded them in culture, and induced them to differentiate into functional cardiomyocytes. These cardiac precursors appear to express stem cell antigen-1 and demonstrate characteristics of multipotent precursors of mesodermal origin. Following infusion into normal recipients, these cells home to the heart and participate in physiological and pathophysiological cardiac remodeling. Cardiogenic differentiation in vitro and in vivo depends on FGF-2. Interestingly, this factor does not control the number of precursors but regulates the differentiation process. These findings suggest that, besides its angiogenic actions, FGF-2 could be used in vivo to facilitate the mobilization and differentiation of resident cardiac precursors in the treatment of cardiac diseases.

The pathogenic role of tissue-resident immune cells in psoriasis.

Psoriasis is a common chronic inflammatory skin disease, the study of which might also be of considerable value to the understanding of other inflammatory and autoimmune-type diseases, such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and diabetes mellitus. There is clear evidence that T cells and dendritic cells have a central role in psoriasis. Based on recent data from humans and animal models, we propose that a psoriasis lesion can be triggered and sustained by the local network of skin-resident immune cells. This concept focuses attention on local, rather than systemic, components of the immune system for rationalized therapeutic approaches of psoriasis and possibly also other chronic inflammatory diseases.

Eleven-year physical activity trends in a Swiss urban area.

OBJECTIVE: Regular physical activity is a major health determinant. Little is known about physical activity trends. We evaluated whether adult physical activity levels are changing in a Swiss urban state (Geneva). METHOD: We analyzed 11-year trends of physical activity indicators, including 3+MET-minutes per week and physical activity outside working hours, in population representative adults (n=9320, aged 35-74years, 50% women), relating declared physical activity to socioeconomic status, lifestyle, and clinical and blood markers. RESULTS: Combining yearly cohorts from 1999 to 2009, we found a significant trend for increased physical activity levels. Weekly age and sex adjusted 3+MET-minutes per week increased from 3023 to 3752, between 1999 and 2009 (P=0.02). The increase also concerned physical activity outside working hours (+18kcal/day/year). There was a shift from low levels of physical activity levels towards higher activities. Physical activity indicators were associated with socioeconomic status, comorbidities, and biological and anthropometric measures. The trend for increased physical activity was more prominent over the latter 5years. CONCLUSION: We found that physical activity levels have increased in an urban Swiss state. The increase is significant but small, and further efforts to promote physical activity are therefore warranted.

Effect of irrigation water on the incidence of Salmonella spp. on lettuces produced by urban agriculture and sold on the markets in Dakar, Senegal

The aim of our survey was to assess the effect of irrigation water of the microbiological quality on the production chain of lettuce in the Dakar area. Microbiological analysis showed that 35% of irrigation water was contaminated by Salmonella spp. between the two water-types used for irrigation (groundwater and wastewater), no significant difference (p>0.05) in their degree of contamination was found. The incidence of different types of irrigation water on the contamination rate of lettuces from the farm (Pikine and Patte d'Oie) was not different either (p>0.05). However, the contamination rate of lettuce from markets of Dalifort and Grand-Yoff that were supplied by the area of Patte d'Oie was greater than those of Sham and Zinc supplied by Pikine (p<0.05). Comparison of serotypes of Salmonella isolated from irrigation water and lettuce showed that irrigation water may affect the microbiological quality of lettuce. Manures, frequently used as organic amendment in cultivating lettuce are another potential source of contamination. These results showed that lettuce may constitute effective vectors for the transmission of pathogens to consumers. Extensive treatment of the used wastewater and/or composting of manure could considerably reduce these risks.

A health behaviour cross-sectional study of immigrants and non-immigrants in a Swiss urban general-practice setting.

BACKGROUND: Little is known about smoking, unhealthy use of alcohol, and risk behaviours for sexually transmitted diseases (STDs) in immigrants from developed and developing countries. METHOD: We performed a cross-sectional study of 400 patients who consulted an academic emergency care centre at a Swiss university hospital. The odds ratios for having one or more risk behaviours were adjusted for age, gender, and education level. RESULTS: Immigrants from developing countries were less likely to use alcohol in an unhealthy manner (OR = 0.35, 95% CI 0.22-0.57) or practise risk behaviours for STDs (OR = 0.31, 95% CI 0.13-0.74). They were also less likely to have any of the three studied risk behaviours (OR = 2.5, 95% CI 1.5-4.3). DISCUSSION: In addition to the usual determinants, health behaviours are also associated with origin; distinguishing between immigrants from developing and developed countries is useful in clinical settings. Surprisingly, patients from developing countries tend to possess several protective characteristics.