Catherine Goujon

High Rate of Acquisition but Short Duration of Carriage of Multidrug-Resistant Enterobacteriaceae After Travel to the Tropics

BACKGROUND Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known. METHODS From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier. RESULTS Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return. CONCLUSIONS MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. CLINICAL TRIALS REGISTRATION NCT01526187.

Autoimmune hepatitis in two psoriasis patients treated with inflixmab

REFERENCES 1. Sidoroff A, Dunant A, Viboud C, Halevy S, Bavinck J, Naldi L, et al. Risk factors for acute generalized exanthematous pustulosis-results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007;157:989-96. 2. Girardi M, Duncan K, Tigelaar R, Imaeda S, Watsky K, McNiff J. Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis. Am J Dermatopathol 2005;27:343-6. 3. Britschgi M, Pichler W. Acute generalized exanthematous pustulosis, a clue to neutrophil-mediated inflammatory processes orchestrated by T cells. Curr Opin Allergy Clin Immunol 2002;2:325-31. 4. Britschgi M, Steiner U, Schmid S, Depta J, Senti G, Bircher A, et al. T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest 2001;107:1433-41. 5. Betto P, Germi L, Bonoldi E, Bertazzoni M. Acute localized exanthematous pustulosis (ALEP) caused by amoxicillinclavulanic acid. Int J Dermatol 2008;47:295-6.

Echographic measurement of skin thickness in sites suitable for intradermal vaccine injection in infants and children

Whereas the knowledge of skin thickness is essential to determine microneedle length and ensure proper administration of and better responses to intradermal vaccines, very few figures are available, especially in infants and children. Using ultrasound echography, we investigated skin thickness in 384 children aged 4-7, 12-18, and 54-66 months at potential body sites for intradermal vaccine delivery: deltoid, suprascapular, upper back, and lumbar area. The mean epidermis plus dermis thickness was significantly higher at the suprascapular than at the deltoid site (1.29mm vs. 1.22mm) and remained relatively unchanged whatever the BMI, age, sex, and skin phototype. In the 43 children aged 54-66 months, the mean skin thickness was significantly higher in the upper than in the lumbar area (1.39mm vs. 1.31mm). In this study setting, the heterogeneity in skin thickness cannot be considered sufficient to indicate various microneedle lengths for various ages or injection sites.

UV Radiation Induces the Epidermal Recruitment of Dendritic Cells that Compensate for the Depletion of Langerhans Cells in Human Skin

UVR causes skin injury and inflammation, resulting in impaired immune function and increased skin cancer risk. Langerhans cells (LCs), the immune sentinels of the epidermis, are depleted for several days following a single UVR exposure and can be reconstituted from circulating monocytes. However, the differentiation pathways leading to the recovery of a normal pool of LCs is still unclear. To study the dynamic changes in human skin with UV injury, we exposed a cohort of 29 healthy human volunteers to a clinically relevant dose of UVR and analyzed sequential epidermal biopsies for changes in leukocyte and dendritic cell (DC) subsets. UV-induced depletion of CD1a(high) LC was compensated by sequential appearance of various epidermal leukocytes. CD14(+) monocytes were recruited as early as D1 post exposure, followed by recruitment of two inflammatory DC subsets that may represent precursors of LCs. These CD1a(low) CD207(-) and the heretofore unknown CD1a(low) CD207(+) DCs appeared at day 1 and day 4 post UVR, respectively, and were endowed with T-cell-activating properties similar to those of LCs. We conclude that recruitment of monocytes and inflammatory DCs appear as a physiological response of the epidermis in order to repair UVR-induced LC depletion associated with immune suppression.

Diffuse reflectance spectroscopy: a clinical study of tuberculin skin tests reading

Diffuse reflectance spectroscopy is a technique widely used to determine optical properties of tissues: scattering and absorption coefficients. In this study, we present the development of a low-cost optical instrument usable in a clinical environment based upon the spatially resolved diffuse reflectance spectroscopy approach. This instrument has been used in a clinical study to support the diagnosis of tuberculosis. The idea is to establish a new scanning method for an early detection of inflammation due to a reagent injection, before the onset of visual signs. Results comparing the instrumental and classical clinical readings are presented.

Nine μg intradermal influenza vaccine and 15 μg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults

Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n = 38) or IM 15 μg (n = 42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine.

Blocking T helper 1/T helper 17 pathways has no effect on patch testing

Blocking T helper 1/T helper 17 pathways has no effect on patch testing Audrey Nosbaum1,2, Aurore Rozieres2, Brigitte Balme3, Catherine Goujon1, Jean-Francois Nicolas1,2 and Frederic Berard1,2 1Department of Allergology and Clinical Immunology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495 Pierre Benite Cedex, France, 2 INSERM, U851, 21 Avenue Tony Garnier, Lyon F-69007, France, and 3Department of Pathology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon F-69007, France

IL-1β induces thymic stromal lymphopoietin and an atopic dermatitis-like phenotype in reconstructed healthy human epidermis

Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and marked TH2 polarization. Recent studies suggest that IL‐1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL‐1β signalling on the epidermal homeostasis of both healthy subjects and AD patients [with functional filaggrin (FLG) alleles], with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL‐1β promoted (i) robust secretion of TSLP in an NF‐κB‐dependent manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex. These effects were prevented by treatment of RHE with the anti‐IL‐1β mAb canakinumab and by the IL‐1 receptor antagonist anakinra. Interestingly, RHE generated from AD donors behaved like that of healthy individuals and showed comparable responses to IL‐1β signals. Collectively, our results suggest that IL‐1β may be an early key mediator for the acquisition of an AD phenotype through induction of TSLP and alteration of the epidermal homeostasis. Copyright

Tolerance of methotrexate in a daily practice cohort of adults with atopic dermatitis

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CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles

For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area. SUBJECTS AND METHODS A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-27days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27days between receiving the measles vaccine and yellow fever vaccine. The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample. RESULTS One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1. DISCUSSION The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27days. The absence of protective antibodies against yellow fever was observed only among infants who received both vaccines simultaneously. CONCLUSION These results may support a revision of current vaccination recommendations concerning the administration of these two live attenuated vaccines either on the same day or at least 28days apart. Our findings show no statistically significant difference if the interval between both vaccines is more than 24 h, but the immune response seems to be reduced when the two vaccines are given at the same time.