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BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe adverse event during treatment with raltegravir. The occurrence of DRESS syndrome during treatment with other drugs is strongly associated with particular HLA alleles. METHODS: We performed HLA testing in 3 of the 5 patients previously reported to have developed raltegravir-induced DRESS syndrome and in 1 previously unreported patient. We then used virtual modeling to visualize interactions between raltegravir and the imputed HLA molecule. RESULTS: Five of the 6 patients who developed raltegravir-induced DRESS syndrome were African, and 1 was Hispanic. HLA typing was performed in 4 patients, all of whom carried both the HLA-B*53 allele and the HLA-C*04 allele to which it is commonly haplotypic. No other HLA alleles were shared by all of the tested patients. Given the approximate prevalence of HLA-B*53 carriage in African (20%) and Hispanic (6%) populations, the probability of all 4 patients being HLA-B*53 carriers, and 2 of 3 African patients being homozygous for HLA-B*53:01, is approximately 0.00002. CONCLUSIONS: These data implicate the prevalent African allele HLA-B*53:01 in the immunopathogenesis of raltegravir-induced DRESS syndrome. Although the immunopathogenic mechanisms are currently unknown, virtual modeling suggests that raltegravir may bind within the antigen binding cleft of the HLA-B*53:01 molecule, but not within the closely related HLA-B*35:01 molecule. Further studies are necessary to confirm the strength of the association between carriage of the HLA-B*53:01 allele and raltegravir-induced DRESS syndrome, and the potential utility of HLA screening before raltegravir treatment.

Objectives: Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods: We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results: Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions: Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Abstract Background Annual seasonal influenza vaccination (SIV) is recommended for people with diabetes, but their SIV rates remain far below public health targets. We aimed to identify temporal trajectories of SIV uptake over a 10-year period among French people with diabetes and describe their clinical characteristics. Methods We identified patients with diabetes in 2006 among a permanent, representative sample of beneficiaries of the French National Health Insurance Fund. We followed them up over 10 seasons (2005/06–2015/16), using SIV reimbursement claims and group-based trajectory modelling to identify SIV trajectories and to study sociodemographic, clinical, and healthcare utilization characteristics associated with the trajectories. Results We identified six trajectories. Of the 15,766 patients included in the model, 4344 (28%) belonged to the “continuously vaccinated” trajectory and 4728 (30%) to the “never vaccinated” one. Two other trajectories showed a “progressive decrease” (2832, 18%) or sharp “postpandemic decrease” (1627, 10%) in uptake. The last two trajectories (totalling 2235 patients, 14%) showed an early or delayed “increase” in uptake. Compared to “continuously vaccinated” patients, those in the “progressively decreasing” trajectory were older and those in all other trajectories were younger with fewer comorbidities at inclusion. Worsening diabetes and comorbidities during follow-up were associated with the “increasing” trajectories. Conclusions Most patients with diabetes had been continuously vaccinated or never vaccinated and thus had stable SIV behaviours. Others adopted or abandoned SIV. These behaviour shifts might be due to increasing age, health events, or contextual factors (e.g., controversies about vaccine safety or efficacy). Healthcare professionals and stakeholders should develop tailored strategies that take each group’s specificities into account.

BACKGROUND. Systems vaccinology allows cutting-edge analysis of innate biomarkers of vaccine efficacy. We explored a strategy to shape the adaptive immune response by targeting innate immune cells through novel immunization routes. METHODS. This randomized phase I/II clinical study (n = 60 healthy subjects aged 18-45 years old) used transcriptomic analysis to discover early biomarkers of immune response quality after transcutaneous (t.c.), intradermal (i.d.), and intramuscular (i.m.) administration of a trivalent influenza vaccine (TIV, season 2012-2013, 1:1:1 ratio). Safety and immunogenicity (hemagglutinin inhibition [HI], microneutralization [MN] antibodies, and CD4+ and CD8+ effector T cells) were measured at baseline day 0 (d0) and at d21. Blood transcriptome was analyzed at d0 and d1. RESULTS. TIV-specific CD8+ granzyme B+ (GRZ) T cells appeared in more individuals immunized by the t.c. and i.d. routes, whereas immunization by the i.d. and i.m. routes prompted high levels of HI antibody titers and MN against A/H1N1 and A/H3N2 influenza viral strains. The early innate gene signature anticipated immunological outcome by discriminating 2 clusters of individuals with either distinct humoral or CD8 cytotoxic responses. Several pathways explained this dichotomy and confirmed that 9 genes and the serum level of CXCL10 were correlated with either TIV-specific cytotoxic CD8+GRZ+ T cell or antibody responses. A logistic regression analysis demonstrated that these 9 genes and the serum levels of CXCL10 at d1/d0 best predicted TIV-specific CD8+GRZ+ T cell and antibody responses at d21. CONCLUSION. This study provides new insight into the impact of immunization routes and innate signature in the quality of adaptive immune responses. TRIAL REGISTRATION. This study has been registered at ClinicalTrials.gov (NCT01707602). FUNDING. This work was supported by grants from the French Ministry of Health PHRCN 2012--RCT 12061, INSERM-DGOS, the Fondation pour la Recherche Medicale, and the Societe Frangaise de Dermatologie (to AS). These funding sources had no direct role in any aspect of the research or article., Introduction Because innate immunity plays an important role in adaptive immune response to vaccination, researchers have been exploring novel strategies to shape the adaptive immune response by targeting innate immune [...]