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Contacts:
Federico Giannoni (federico.giannoni@iss.it)
Supranational TB Reference Laboratory in Rome, Italy
Address:
Istituto Superiore di Sanità,
Department of Infectious, Parasitic and Immune-mediated Diseases,
Via Regina Elena 299, 00161 Rome, Italy
Description
The TB group (responsible Lanfranco Fattorini) of the Dept of Infectious Diseases of the Istituto Superiore di Sanità (ISS) performs institutional and research activities on TB.
Institutional: we perform drug-susceptibility proficiency testing (DS-PT) in 4 TB laboratories: NRL of Sofia, Bulgaria; NRL of Ankara, Turkey; NRL of Doha, Qatar; Central Public Health Laboratory of Muscat, Oman. In 2018 these labs participated to the 8th DS-PT organized by the ISS. Formal Collaboration Agreements between the SRL of Rome and the NRLs of Ankara (Turkey) and Sofia (Bulgaria) were signed.
In Italy, we coordinate the national surveillance of drug-resistant TB (data collection and DS-PT in 43 labs), and annually send aggregated data to Ministry of Health and ECDC/WHO. Furthermore, starting from 2016 we collect data on nontuberculous mycobacteria (NTM).
Research: 1) Diagnosis: novel methods to decrease false M. tuberculosis resistance to pyrazinamide by MGIT 960; 2) Fundamental research: drug activity of known drugs and novel molecules (alone and in combination) against replicating and non-replicating (dormant) M. tuberculosis. Gene expression of dormants and persisters.
Structure and organization
Structure: a biosafety level 3 (BSL3) room including 2 class II biosafety cabinets (BS), a MGIT 960 apparatus, 5 incubators, a Mini-Bead Beater, a water-bath, 2 centrifuges, a water-bath sonicator, 3 freezers, 2 microscopes. A BSL2 room with a class II BS and a real-time PCR is also available.
Staff: 3 permanent positions, 1 researcher for two year
Organization: the TB laboratory is included in the Department of Infectious Diseases of the ISS (Director, Giovanni Rezza), Unit of Antibiotic-resistance and special pathogens (Director, Annalisa Pantosti).
Services provided by the SRL
Institutional services abroad: overall, in 2003-2018 we performed 8 DS-PT to the NRL of Albania, Turkey, Bulgaria, Macedonia, Kosovo, Oman, Qatar, Bahrain.
Institutional services in Italy: surveillance of drug-resistant TB, including DS-PT (7 rounds in 1998-2016; in 2019, the 8th round is planned) and collection of antibiograms from 43 laboratories of 19/20 Italian regions (SMIRA: Studio Multicentrico Italiano Resistenze Antitubercolari). Lanfranco Fattorini is the ECDC country operational contact point (OCP) for TB. In 2017, the ISS received 2,654 individual antibiograms from SMIRA labs, corresponding to about 67% nationwide notified TB cases. The SMIRA labs also send us MDR-and XDR M. tuberculosis strains, for maintenance of the national collection at ISS. Diagnosis: drug-susceptibility to first-line and second-line anti-TB drugs.
Methods available in the laboratory
1) Drug-susceptibility to first- and second-line anti-TB drugs by MGIT-960 (Becton Dickinson)
2) MICs of MDR and XDR M. tuberculosis strains and of NTM strains by Sensititre (Thermo)
3) Mycobacterial species identification and M. tuberculosis susceptibility to first- and second-line drugs (LPA by Hain Genotypes)
4) Sequencing of drug-resistant genes.
Current links and partnerships outside of SRLN
1) Collaboration with the coordinator of the WHO SRL lab of Antwerp (Armand van Deun), with the NRLs of Turkey, Bulgaria, Oman, Qatar and with the 43 Italian labs of the SMIRA network.
2) Participation as country OCP in the ECDC project European Reference Laboratory network for TB (ERLTB-net) coordinated by Vladyslav Nikolayevskyy (PHE, London)
3) Collaboration with the SRL of Milan (Daniela Cirillo), WHO (Andrei Dadu), ECDC (Vahur Hollo).
4) Collaboration with investigators involved in novel methods of diagnosis of drug-resistant TB, and with researchers synthesizing novel drugs against M. tuberculosis.
Additional information:
Research activities
1) Surveillance of drug resistant tuberculosis in migrants and Italians
2) Novel diagnostic method for determination of resistance to pyrazinamide by MGIT 960
3) Activity of drugs against non-replicating (dormant) M. tuberculosis. Gene expression of dormants and persisters.
Publications
Surveillance of drug resistance and proficiency testing:
1. Mustazzolu A, Borroni E, Cirillo DM, Giannoni F, Iacobino A; Italian Multicentre Study on Resistance to Anti-TB Drugs (SMIRA), Fattorini L. Trend in rifampicin-, multidrug- and extensively drug-resistant TB in Italy, 2009-2016. Eur Respir J. 2018;52(1). pii: 1800070.
2. Blasi F, Matteelli A, Sotgiu G, Cirillo DM, Palmieri F, Fattorini L, Migliori GB. Moving towards TB elimination: a call for action from Italy and a possible model for other low TB incidence countries. Eur Respir J. 2017;49(2). pii: 1602242.
3. Nikolayevskyy V, Hillemann D, Richter E, Ahmed N, van der Werf MJ, Kodmon C, Drobniewski F, Ruesch-Gerdes S; ERLTB-Net Network. External Quality Assessment for TB Diagnosis and Drug Resistance in the European Union: A Five Year Multicentre Implementation Study. PLoS One. 2016;11(4):e0152926.
4. Del Giudice A, Mustazzolu A, Iacobino A, Perna R, Smeraglia R, Marino R, Fattorini L, Santoro G. Drug-resistant tuberculosis in Naples, 2008-2013. Ann Ist Super Sanita. 2016;52:603-607.
5. Fattorini L, Mustazzolu A, Borroni E, Piccaro G, Giannoni F, Cirillo DM; Italian Multicentre Study on Resistance to Anti-TB Drugs Group. TB in migrants from 106 countries, 2008-2014. Eur Respir J. 2016, 47:1273-6.
6. Ingrosso L, Vescio F, Giuliani M, Migliori GB, Fattorini L, Severoni S, Rezza G. Risk factors for TB in foreign-born people (FBP) in Italy: a systematic review and meta-analysis. PLoS One. 2014;9:e94728.
7. Fattorini L, Mustazzolu A, Piccaro G, Pardini M, Filippini P, Giannoni F, Migliori GB, Sotgiu G, Borroni E, Cirillo DM; Italian Multicentre Study on Resistance to Anti-TB Drugs Group. Drug-resistant TB among foreign-born persons in Italy. Eur Respir J. 2012;40:497-500.
8. Fattorini L, Migliori GB, Cassone A, Mustazzolu A, Piccaro G, Filippini P, Cirillo DM, Borroni E; Italian Multicentre Study on Resistance to Anti-TB Drugs Group. Proficiency testing of first- and second-line anti-TB drugs in Italy. Eur Respir J. 2012;39:1263-6.
Diagnosis of drug resistance:
1. Mustazzolu A, Iacobino A, Giannoni F, Piersimoni C; Italian Multicentre Study on Resistance to Anti-TB Drugs (SMIRA) Group, Fattorini L. Improved Bactec MGIT 960 Pyrazinamide Test Decreases Detection of False M. tuberculosis Pyrazinamide Resistance. J Clin Microbiol. 2017;55:3552-3553.
2. Merker M, Kohl TA, Roetzer A, Truebe L, Richter E, Rüsch-Gerdes S, Fattorini L, Oggioni MR, Cox H, Varaine F, Niemann S. Whole genome sequencing reveals complex evolution patterns of multidrug-resistant M. tuberculosis Beijing strains in patients. PLoS One. 2013;8:e82551.
3. Piersimoni C, Mustazzolu A, Giannoni F, Bornigia S, Gherardi G, Fattorini L. Prevention of False Resistance Results Obtained in Testing the Susceptibility of M. tuberculosis to Pyrazinamide with the Bactec MGIT 960 System Using a Reduced Inoculum. J Clin Microbiol. 2013;51:291-4.
4. Miotto P, Cabibbe AM, Mantegani P, Borroni E, Fattorini L, Tortoli E, Migliori GB, Cirillo DM. 2012. GenoType MTBDRsl performance on clinical samples with diverse genetic background. Eur Respir J. 2012;40:690-8.
Activity of drugs against dormant M. tuberculosis, and other issues.
1. Iacobino A, Giannoni F, Fattorini L, Brucoli F. Activity of DNA-targeted C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates against aerobically and hypoxically grown M. tuberculosis under acidic and neutral conditions. J Antibiot (Tokyo). 2018;71:831-834.
2. Mirnejad R, Asadi A, Khoshnood S, Mirzaei H, Heidary M, Fattorini L, Ghodousi A, Darban-Sarokhalil D. Clofazimine: A useful antibiotic for drug-resistant TB Biomed Pharmacother. 2018;105:1353-1359.
3. Lohrasbi V, Talebi M, Bialvaei AZ, Fattorini L, Drancourt M, Heidary M, Darban-Sarokhalil D. Trends in the discovery of new drugs for M. tuberculosis therapy with a glance at resistance. Tuberculosis (Edinb). 2018;109:17-27.
4. Iacobino A, Piccaro G, Giannoni F, Mustazzolu A, Fattorini L. M. tuberculosis Is Selectively Killed by Rifampin and Rifapentine in Hypoxia at Neutral pH. Antimicrob Agents Chemother. 2017;61(3). pii: e02296-16.
5. Iacobino A, Piccaro G, Giannoni F, Mustazzolu A, Fattorini L. Fighting TB by drugs targeting nonreplicating M. tuberculosis bacilli. Int J Mycobacteriol. 2017;6:213-221.
6. Iacobino A, Piccaro G, Giannoni F, Mustazzolu A, Fattorini L. Activity of drugs against dormant M. tuberculosis. Int J Mycobacteriol. 2016;5 Suppl 1:S94-S95.
7. Iona E, Pardini M, Mustazzolu A, Piccaro G, Nisini R, Fattorini L, Giannoni F. M. tuberculosis gene expression at different stages of hypoxia-induced dormancy and upon resuscitation. J Microbiol. 2016;54:565-72.
8. Piccaro G, Poce G, Biava M, Giannoni F, Fattorini L. Activity of lipophilic and hydrophilic drugs against dormant and replicating M. tuberculosis. J Antibiot (Tokyo). 2015;68:711-4.
9. Piccaro G, Pietraforte D, Giannoni F, Mustazzolu A, Fattorini L. Rifampin Induces Hydroxyl Radical Formation in M. tuberculosis. Antimicrob Agents Chemother. 2014;58:7527-33.
10. Piccaro G, Giannoni F, Filippini P, Mustazzolu A, Fattorini L. Activity of drug combinations against M. tuberculosis grown in aerobic and hypoxic acidic conditions. Antimicrob Agents Chemother. 2013;40:1428-33.
11. Iona E, Pardini M, Gagliardi MC, Colone M, Stringaro AR, Teloni R, Brunori L, Nisini R, Fattorini L, Giannoni F. Infection of human THP-1 cells with dormant M. tuberculosis. Microbes Infect. 2012;14:959-67.
Trainings
A) June 2018: A staff personnel from the NRL of Sofia (Bulgaria) visited the SRL of Rome. She attended a practical course on i) manipulation of M. tuberculosis in the BSL3 room and maintenance of BSL3 equipment, ii) first- and second-line DS-PT, iii) standard operating procedures for bedaquiline and delamanid susceptibility testing.
B) October 2017: A researcher from the Public Health Service of Tel Aviv (Israel) visited the SRL and gave the lecture “CRISPR-associated cas-1 gene is deleted or potentially defective in important families of M. tuberculosis”
C) August 2016: Two researchers from the University of Teheran (Iran) visited the SRL of Rome, to know information on: i) organization of the work in the BSL3 room, ii) institutional activities on the surveillance of drug-resistant TB, iii) diagnostic activities (Genotypes strips, MICs), iv) research on dormant M. tuberculosis.
D) September 2013: A microbiologist sent by the NRL of Ankara visited the SRL of Rome, to know information on: i) manipulation of M. tuberculosis in the BSL3 room, ii) institutional activities on drug-resistant TB, iii) research on dormant M. tuberculosis.
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