Leprosy laboratory Oswaldo Cruz Institute FIOCRUZ Antimicrobial resistance: where to go? Milton Ozório Moraes RIIP meeting 2019 São Paulo milton.moraes@fiocruz.br
Leprosy Laboratory : A National Reference Center and a Unit of translational medicine
Patient at the resistance confirmation in 2015 and after 3 months of treatment (2017) 2015 2017
Resistance and relapse timeline in a case from leprosy : irregular treatment and neglected care Patient – man 61 y/o, from Rio de Janeiro, confirmed in 2015 resistance Clinically presented nodules and infliltrated plaques in whole body; swallown hand, com paresthesis from de membros superiores e inferiores consistente com forma LL. Monotherapy- Diagnostics and irregular treatment for 2 mo - dapsona (dds) Diagnosis of esophagous Cancer and cessation of Irregular treatment of RIF MDT completa anti-leprosy treatment 3 MDT doses IBi 3+ IBf 4.5+ until completion chemotherapy and dds for 3 mo BI 3+ 2017 1998 2002 1975-77 1978 1985-90 2013-14 2015 2016 1971 2nd MDT completo 8 MDT doses Tratamento irregular Initiation of alternative MDT complete Treatment IB de 4.7 IBf 2.5+ e confirmação BI dds monoterapia até 1977 RIF and dds de resistência PCR (negative BI) Histopathology PGL-I Probable resistance emergency
Antim imicrobial l Resis istance: Launch of world ld and Brazili lian Action pla lans
Antimicrobial Resistance: The Brazilian National Plan -BNP (i) the promotion of knowledge through communication, education and training campaigns (ii) the development of information systems to monitor resistance in different microorganisms, as well as the volume of antimicrobials used in humans and in agriculture (both in terrestrial and aquatic animals); (iii) strengthening regulation and monitoring of antimicrobial use; (iv) Improve and broaden the knowledge fostering research projects on antimicrobial resistance mechanisms; (vi) To encourage research and innovative approaches using alternatives to antimicrobial agents, as well as new technologies for rapid diagnostics and vaccines in human and animal health; (vii) control and prevent the spread of antimicrobial resistance; (viii) articulate cooperation and funding opportunities within and outside the country for the implementation of the BNP;
Fio iocru ruz ari rised as s a resp sponse to a publi lic healt lth emergency • problem driven • vertical innovation chain • wide scope of synergistic activities The fight against small pox, bubonic plague, and Revolta da Vacina - 1904 yellow fever epidemics
Work force and productivity (nowadays) -12.000 professionals (MD, PhDs, nurses, technicians, pharmacists social workers; historians; psychologists); 1.200 dedicated PhDs for Science and development -Two hospitals; -Three production plants (vaccines/immunobiologicals and pharmaceuticals, Molecular Biology reagentes for DNA-based tests); -Reference centers for infectious diseases surveillance; -2.500 papers in indexed Journals/year;
The FIOCRUZ-AMR initiative: Clinical Public health Basic/applied research: Development and Surveillance: research: BIO, FAR, ICC, IFF, INCQS, innovation: INCQS, INI, INI, IOC, CDTS, BIO, ICC FAR IFF, INI, IOC IOC Education, communication and information 1. Biocides: research and quality evaluation 2. Resistance in Aquatic Environments 3. Residues of Veterinary Drugs in food and environmental samples 4. Molecular study of antimicrobial resistance mechanisms in different bacterial species involved in hospital infection. 5. Study of the genetic diversity of bacteria involved in hospital infection based on the analyzes performed by PFGE, MLST methods. 6. Study of mobilization of resistance genes through research and characterization of mobile genetic elements, 7. Reference and collections 8. Adjuvants (BIO) 9. Diagnostic Kits 10. Vaccines 11. Clinical trials (INI gonorrhea, infant sepsis IFF) 12. Prospecting (FAR and IOC biological collections)
Innovation Program at Fiocruz – calls 30 35 736 254 Research Millions in Proposals Approved areas funding submitted 34% 492 Approval Reviewers
AMR portfolio in the Innovation program • Analysis of the CRISPR / cas system: Impact on the evolution of resistance of pathogenic bacteria • Applicability of high resolution analysis of DNA dissociation curves in the prediction of resistance to isoniazid in clinical isolates of Mycobacterium tuberculosis • Genomic characterization of antimicrobial multiresistance and tolerance to disinfectants in Corynebacterium striatum isolated from healthcare-related infections • Investigation of resistance mechanisms in Klebsiella pneumonia using multi-omics methodology • Analysis of the main determinants of biofilm formation through the computational modeling of the multidrug-resistant Pseudomonas aeruginosa producing SPM-1 (ST277)
Evaluation FIO-AMR initiatives and networks induced under demand Axis 1 - Hospital monitoring and surveillance (IAM, ENSP and IOC); solid wastes and water (INCQS). Axis 2 - Prospecting the biological collections of fungi and Bacillus: bioassay platform (INI) and HCS FAR Axis 3 – Vaccines, adjuvants and alternative methods Axis 4- development of new diagnostic kits for resistance/susceptibility detection (ICC and IOC), strain type, differentiate viral from bacterial infection – novel tools for (meta) genomics Cross-cutting axis- Monitoring, information integration and mathematical modeling of big data (IGM and ICICT) Cross cuting axis - education (UNASUS courses), communication (ICICT, CCS and IOC)
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