Novartis Foundation

About: Novartis Foundation is a nonprofit organization based out in Basel, Switzerland. It is known for research contribution in the topics: Health care & Leprosy. The organization has 99 authors who have published 85 publications receiving 3993 citations.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Abstract: Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

Leprosy Diagnostic Test Development As a Prerequisite Towards Elimination: Requirements from the User's Perspective.

Abstract: Leprosy is the complex disease manifestation of Mycobacterium leprae infection. Although prevalence has declined from 5.2 million globally in the 1980s, new annual case detection rates (CDRs) remain high, at more than 200,000 new cases per year [1], indicating that additional leprosy control strategies are required to halt transmission. An Expert Meeting held in June 2013 in Geneva discussed strategies to transition from control to elimination and concluded that any viable programme would need to include: (i) early diagnosis and prompt multidrug therapy (MDT) for all patients, (ii) tracing and postexposure prophylaxis (PEP) for contacts of newly diagnosed patients, and (iii) strict epidemiological surveillance and systems to monitor progress [2]. Improved diagnostic tools would be of great value to achieve these goals. A subsequent international Expert Panel met, with the goal to define the required attributes of a diagnostic test for leprosy that would support and facilitate leprosy elimination efforts in terms of complete interruption of transmission of M. leprae. A tool for identifying leprosy cases (asymptomatic and any symptomatic form of leprosy) was identified as a prerequisite to elimination, thereby addressing the goals of the 2020 London Declaration on Neglected Tropical Diseases [3,4]. However, given the challenges of developing such a diagnostic test, a two-step strategy, starting with a confirmatory test for clinical diagnosis among symptomatic patients, was considered as a pragmatic approach. This article presents the considerations, target population, target profile, and current research activities for leprosy diagnostic tools from a user’s perspective.

A new TLR2 agonist promotes cross-presentation by mouse and human antigen presenting cells

Abstract: Cross-presentation is the process by which professional APCs load peptides from an extracellularly derived protein onto class I MHC molecules to trigger a CD8(+) T cell response. The ability to enhance this process is therefore relevant for the development of antitumor and antiviral vaccines. We investigated a new TLR2-based adjuvant, Small Molecule Immune Potentiator (SMIP) 2.1, for its ability to stimulate cross-presentation. Using OVA as model antigen, we demonstrated that a SMIP2.1-adjuvanted vaccine formulation induced a greater CD8(+) T cell response, in terms of proliferation, cytokine production and cytolytic activity, than a non-adjuvanted vaccine. Moreover, using an OVA-expressing tumor model, we showed that the CTLs induced by the SMIP2.1 formulated vaccine inhibits tumor growth in vivo. Using a BCR transgenic mouse model we found that B cells could cross-present the OVA antigen when stimulated with SMIP2.1. We also used a flow cytometry assay to detect activation of human CD8(+) T cells isolated from human PBMCs of cytomegalovirus-seropositive donors. Stimulation with SMIP2.1 increased the capacity of human APCs, pulsed in vitro with the pp65 CMV protein, to activate CMV-specific CD8(+) T cells. Therefore, vaccination with an exogenous antigen formulated with SMIP2.1 is a successful strategy for the induction of a cytotoxic T cell response along with antibody production.

Genome wide analysis of inbred mouse lines identifies a locus containing Ppar-γ as contributing to enhanced malaria survival.

Abstract: The genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. We have used a mouse model to detect genes involved in the resistance or susceptibility to Plasmodium berghei malaria infection. To this end we first characterized 32 different mouse strains infected with P. berghei and identified survival as the best trait to discriminate between the strains. We found a locus on chromosome 6 by linking the survival phenotypes of the mouse strains to their genetic variations using genome wide analyses such as haplotype associated mapping and the efficient mixed-model for association. This new locus involved in malaria resistance contains only two genes and confirms the importance of Ppar-γ in malaria infection.