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Ramona Groenheit (ramona.groenheit@folkhalsomyndigheten.se)
Supranational TB Reference Laboratory in Stockholm, Sweden
Address:
Department of Microbiology
The Public Health Agency of Sweden
FOLKHÄLSOMYNDIGHETEN
SE-171 82 Solna, Sweden
Description
SRL Stockholm was established in 1994 and is presently supporting the following eight countries; Estonia, Finland, Iran, Kuwait, Lithuania, Norway, Romania and Sudan with laboratory strengthening activities.
SRL Stockholm with its biosafety level 3 laboratory is situated at the Public Health Agency of Sweden (PHAS) in Solna. PHAS is a governmental agency accountable to the Government (Ministry of Health and Social Affairs) and has a national responsibility for public health issues and works to ensure good public health. The agency also works to make sure that the population is protected against communicable diseases and other health threats. On the national level the SRL Stockholm performs molecular epidemiological typing and extended drug susceptibility testing (DST) on Swedish clinical TB isolates.
Structure and organization
The National TB Reference Laboratory (NRL) at the Public Health Agency of Sweden has for many years worked closely together with the five clinical TB-laboratories where primary diagnostics is performed. Swedish isolates are sent to the NRL where extended drug susceptibility testing, MIC-determinations and molecular epidemiological typing is performed. Swedish TB isolates are since October 2016 routinely whole genome sequenced.
The Director of SRL Stockholm, Dr Groenheit, specializes on surveillance and molecular epidemiological typing, Dr Werngren on drug susceptibility testing, and other staff members include two microbiologists and two technicians.
SRL Stockholm participates in various international research collaborations and networks that for instance are aiming at developing, improving and supporting the introduction of molecular rapid tests, biosafety and DST techniques.
Services provided by the SRL
The SRL supports the countries in our sub-network with:
1. Yearly proficiency panels of M. tuberculosis strains for EQA of phenotypic and genotypic DST
2. Surveillance project to monitor Delamanid and Bedaquiline resistance
3. Various laboratory strengthening consultancies and workshops upon request
4. DRS support in regard to development of lab diagnostics and QC parts of the national technical DRS protocol. Confirmation of DST results of selected strains isolated during a DRS.
5. In some cases, DST of drugs that are not tested in the respective country
6. In some cases, WGS for molecular epidemiology with suspected transmission/outbreaks of M/XDR-TB
Current links and partnerships outside of SRLN
SRL Stockholm is currently involved in a number of national and international networks and working groups.
Additional information
Research activities
• Evaluation of new phenotypic and molecular DST methodologies
• MIC determination and correlation to gene mutations and clinical relevance
• MIC determination of potential new drugs
• Development of new DST algorithms
• Studies to increase knowledge behind drug resistance development and transmission capacity
• Surveillance studies
• Molecular epidemiology
Selected publications from SRL Stockholm:
Systematic review of whole genome sequencing data to predict phenotypic drug resistance and susceptibility in Swedish Mycobacterium tuberculosis isolates 2016-2018.
Enkirch T, Werngren J, Groenheit R, Alm E, Advani R, Lind Karlberg M, Mansjö M.
Antimicrob Agents Chemother. 2020 Mar 2. pii: AAC.02550-19.
Non-commercial phenotypic assays for the detection of Mycobacterium tuberculosis drug resistance: a systematic review.
Kontsevaya I, Werngren J, Holicka Y, Klaos K, Tran A, Nikolayevskyy V.
Eur J Clin Microbiol Infect Dis. 2019 Oct 30.
Molecular and genomic typing for tuberculosis surveillance: A survey study in 26 European countries.
Andrés M, van der Werf MJ, Ködmön C, Albrecht S, Haas W, Fiebig L; Survey study group.
PLoS One. 2019 Mar 13;14(3):e0210080
Minimum Inhibitory Concentrations of Fluoroquinolones and Pyrazinamide Susceptibility Correlate to Clinical Improvement in Multidrug-resistant Tuberculosis Patients: A Nationwide Swedish Cohort Study Over 2 Decades.
Forsman LD, Jonsson J, Wagrell C, Werngren J, Mansjö M, Wijkander M, Groenheit R, Hammar U, Giske CG, Schön T, Bruchfeld J.
Clin Infect Dis. 2019 Sep 27;69(8):1394-1402
Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study.
Zignol M, Cabibbe A, Dean A, Glaziou P, Alikhanova N, Ama C, Andres S, Barbova A, Borbe-Reyes A, Chin D, Cirillo D, Colvin C, Dadu A, Dreyer A, Driesen M, Gilpin C, Hasan R, Hasan Z, Hoffner S, Hussain A, Ismail M, Kamal M, Khanzada FM, Kimerling M, Kohl T, Mansjö M, Miotto P, Mukadi YD, Mvusi L, Niemann S, Omar S, Rigouts L, Schito M, Sela I, Seyfaddinova M, Skenders G, Skrahina A, Tahseen S, Wells W, Zhurilo A, Weyer K, Floyd K, Raviglione M.
The Lancet Infectious Diseases, 2018, https://doi.org/10.1016/S1473-3099(18)30073-2
Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China: a study protocol of a prospective observational cohort study.
Davies Forsman L, Niward K, Hu Y, Zheng R, Zheng X, Ke R, Cai W, Hong C, Li Y, Gao Y, Werngren J, Paues J, Kuhlin J, Simonsson USH, Eliasson E, Alffenaar JW, Mansjö M, Hoffner S, Xu B, Schön T, Bruchfeld J.
BMJ Open. 2018 Oct 4;8(9):e023899.
Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting.
Niward K, Davies Forsman L, Bruchfeld J, Chryssanthou E, Carlström O, Alomari T, Carlsson B, Pohanka A, Mansjö M, Jonsson Nordvall M, Johansson AG, Eliasson E, Werngren J, Paues J, Simonsson USH, Schön T.
J Antimicrob Chemother. 2018 Oct 1;73(10):2838-2845.
Cross border outbreak of extensively drug resistant tuberculosis linked to a university in Romania.
Popovici O, Monk P, Chemtob D, Chiotan D, Freidlin PJ, Groenheit R, Haanperä M, Homorodean D, Mansjö M, Robinson E, Rorman E, Smith G, Soini H, van der Werf M.
Epidemiol Infect. 2018 May;146(7):824-831.
Time-and-motion tool for the assessment of working time in tuberculosis laboratories: a multicentre study.
Mathys V, Roycroft E, Raftery P, Groenheit R, Folkvardsen DB, Homorodean D, Vasiliauskiene E, Vasiliauskaite L, Kodmon C, van der Werf MJ, Drobniewski F, Nikolayevskyy V.
Int J Tuberc Lung Dis. 2018 Apr 1;22(4):444-451.
Screening of migrants for tuberculosis identifies patients with multidrug-resistant tuberculosis but is not sufficient.
Helbling P, Kröger S, Haas W, Brusin S, Cirillo DM, Groenheit R, Guthmann JP, Soini H, Hendrickx D, van der Werf MJ.
Clin Microbiol Infect. 2018 Mar 17. pii: S1198-743X(18)30225-8.
A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study.
Walker TM, Merker M, Knoblauch AM, Helbling P, Schoch OD, van der Werf MJ, Kranzer K, Fiebig L, Kröger S, Haas W, Hoffmann H, Indra A, Egli A, Cirillo DM, Robert J, Rogers TR, Groenheit R, Mengshoel AT, Mathys V, Haanperä M, Soolingen DV, Niemann S, Böttger EC, Keller PM; MDR-TB Cluster Consortium.
Lancet Infect Dis. 2018 Jan 8.
Genetic diversity and potential routes of transmission of Mycobacterium bovis in Mozambique.
Machado A, Rito T, Ghebremichael S, Muhate N, Maxhuza G, Macuamule C, Moiane I, Macucule B, Marranangumbe AS, Baptista J, Manguele J, Koivula T, Streicher EM, Warren RM, Kallenius G, van Helden P, Correia-Neves M.
PLoS Negl Trop Dis. 2018 Jan 18;12(1):e0006147.
Detection of Mycobacterium tuberculosis pncA Mutations by the Nipro Genoscholar PZA-TB II Assay Compared to Conventional Sequencing.
Willby MJ, Wijkander M, Havumaki J, Johnson K, Werngren J, Hoffner S, Denkinger CM, Posey JE.
Antimicrob Agents Chemother. 2017 Dec 21;62(1).
Trends and differences in tuberculosis incidences and clustering among natives in Denmark, Sweden and Finland: comparison of native incidences and molecular epidemiology among three low-incidence countries.
Pedersen MK, Lillebaek T, Andersen AB, Soini H, Haanperä M, Groenheit R, Jonsson J, Svensson E.
Clin Microbiol Infect. 2017 Oct 12.
Characterization of pyrazinamide resistance in consecutive multidrug-resistant mycobacterium tuberculosis isolates in Sweden between 2003 and 2015.
Mansjo M, Werngren J, Hoffner S.
Int J Mycobacteriol. 2017 Apr-Jun;6(2):156-161
Non-pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?
Werngren J, Alm E, Mansjö M.
J Clin Microbiol. 2017 Jun;55(6):1920-1927.
Protecting Pyrazinamide, a Priority for Improving Outcomes in Multidrug-Resistant Tuberculosis Treatment.
Anthony RM, Cynamon M, Hoffner S, Werngren J, den Hertog AL, van Soolingen D.
Antimicrob Agents Chemother. 2017 May 24;61(6).
New insights into the mechanism of action of pyrazinamide, implications for susceptibility testing, and future regimens.
Anthony RM, den Hertog A, Mansjö M, Werngren J.
Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S71-S72.
Multi-Country Study to Determine Bedaquiline Minimal Inhibitory Concentration Quality Control Ranges for Phenotypic Drug-Susceptibility Testing.
Kaniga K, Cirillo DM, Hoffner S, Ismail NA, Kaur D, Lounis N, Metchock B, Pfyffer GE, Venter A. A Multi-Laboratory, J Clin Microbiol. 2016 Dec;54(12):2956-2962
Whole genome sequencing of Mycobacterium tuberculosis provides insight into the evolution and genetic composition of drug-resistant tuberculosis in Belarus.
Wollenberg KR, Desjardins CA, Zalutskaya A, Slodovnikova V, Oler AJ, Quiñones M, Abeel T, Chapman SB, Tartakovsky M, Gabrielian A, Hoffner S, Skrahina A, Birren BW, Rosenthal A, Skrahina A, Earl AM. J Clin Microbiol. 2016 Nov 30. pii: JCM.02116-16.
Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project.
Zignol M, Dean AS, Alikhanova N, Andres S, Cabibbe AM, Cirillo DM, Dadu A, Dreyer A, Driesen M, Gilpin C, Hasan R, Hasan Z, Hoffner S, Husain A, Hussain A, Ismail N, Kamal M, Mansjö M, Mvusi L, Niemann S, Omar SV, Qadeer E, Rigouts L, Ruesch-Gerdes S, Schito M, Seyfaddinova M, Skrahina A, Tahseen S, Wells WA, Mukadi YD, Kimerling M, Floyd K, Weyer K, Raviglione MC. Lancet Infect Dis. 2016 Jul 7. pii: S1473-3099(16)30190-6.
Cost-effectiveness analysis of microscopic observation drug susceptibility test versus Xpert MTB/Rif test for diagnosis of pulmonary tuberculosis in HIV patients in Uganda.
Walusimbi S, Kwesiga B, Rodrigues R, Haile M, de Costa A, Bogg L, Katamba A.
BMC Health Serv Res. 2016 Oct 10;16(1):563.
Multicenter Study of the Emergence and Genetic Characteristics of Pyrazinamide-Resistant Tuberculosis in China.
Li D, Hu Y, Werngren J, Mansjö M, Zheng X, Drobniewski F, Hoffner S, Xu B.
Antimicrob Agents Chemother. 2016 Aug 22;60(9):5159-66.
Determination of MIC Breakpoints for Second-Line Drugs Associated with Clinical Outcomes in Multidrug-Resistant Tuberculosis Treatment in China.
Zheng X, Zheng R, Hu Y, Werngren J, Forsman LD, Mansjö M, Xu B, Hoffner S.
Antimicrob Agents Chemother. 2016 Jul 22;60(8):4786-92.
Outcomes of a clinical diagnostic algorithm for management of ambulatory smear and Xpert MTB/Rif negative HIV infected patients with presumptive pulmonary TB in Uganda: a prospective study.
Walusimbi S, Semitala F, Bwanga F, Haile M, De Costa A, Davis L, Joloba M, Hoffner S, Kamya M.
Pan Afr Med J. 2016 Mar 31;23:154
Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment.
Hu Y, Zhao Q, Werngren J, Hoffner S, Diwan VK, Xu B.
BMC Infect Dis. 2016 Jan 7;16:4.
Diagnostic Performance of the New Version (v2.0) of GenoType MTBDRsl Assay for Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs: a Multicenter Study.
Tagliani E, Cabibbe AM, Miotto P, Borroni E, Toro JC, Mansjö M, Hoffner S, Hillemann D, Zalutskaya A, Skrahina A, Cirillo DM.
J Clin Microbiol. 2015 Sep;53(9):2961-9.
Rifampicin heteroresistance in Mycobacterium tuberculosis cultures detected by phenotypic and genotypic drug susceptibility test methods.
Folkvardsen DB, Thomsen VO, Rigouts L, Rasmussen EM, Bang D, Bernaerts G, Werngren J, Toro JC, Hoffner S, Hillemann D, Svensson E. J Clin Microbiol. 2013 Sep 25.
Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.
Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, Blum MG, Rüsch-Gerdes S, Mokrousov I, Aleksic E, Allix-Béguec C, Antierens A, Augustynowicz-Kopeć E, Ballif M, Barletta F, Beck HP, Barry CE 3rd, Bonnet M, Borroni E, Campos-Herrero I, Cirillo D, Cox H, Crowe S, Crudu V, Diel R, Drobniewski F, Fauville-Dufaux M, Gagneux S, Ghebremichael S, Hanekom M, Hoffner S, Jiao WW, Kalon S, Kohl TA, Kontsevaya I, Lillebæk T, Maeda S, Nikolayevskyy V, Rasmussen M, Rastogi N, Samper S, Sanchez-Padilla E, Savic B, Shamputa IC, Shen A, Sng LH, Stakenas P, Toit K, Varaine F, Vukovic D, Wahl C, Warren R, Supply P, Niemann S, Wirth T.
Nat Genet. 2015 Mar;47(3):242-9.
Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European multicentre study.
Cambau E, Viveiros, Machado MD, Raskine L, Ritter C, Tortoli E, Matthys V, Hoffner S, Richter E, Perez Del Molino ML, Cirillo DM, van Soolingen D, Böttger EC.
J Antimicrob Chemother. 2015 Mar;70(3):686-96
Little difference between minimum inhibitory concentrations of Mycobacterium tuberculosis wild-type organisms determined with BACTEC MGIT 960 and Middlebrook 7H10.
Sturegård E, Ängeby KA, Werngren J, Juréen P, Kronvall G, Giske CG, Kahlmeter G, Schön T.
Clin Microbiol Infect. 2015 Feb;21(2):148.e5-7.
Mycobacterium tuberculosis pyrazinamide resistance determinants: a multicenter study.
Miotto P, Cabibbe AM, Feuerriegel S, Casali N, Drobniewski F, Rodionova Y, Bakonyte D, Stakenas P, Pimkina E, Augustynowicz-Kopeć E, Degano M, Ambrosi A, Hoffner S, Mansjö M, Werngren J, Rüsch-Gerdes S, Niemann S, Cirillo DM.
MBio. 2014 Oct 21;5(5):e01819-14.
A 24-well plate assay for simultaneous testing of first and second line drugs against Mycobacterium tuberculosis in a high endemic setting.
Wedajo W, Schön T, Bedru A, Kiros T, Hailu E, Mebrahtu T, Yamuah L, Ängeby K, Werngren J, Onyebujoh P, Dagne K, Aseffa A.
BMC Res Notes. 2014 Aug 10;7:512
Evaluation of a microcolony growth monitoring method for the rapid determination of ethambutol resistance in Mycobacterium tuberculosis.
den Hertog AL, Menting S, Smienk ET, Werngren J, Hoffner S, Anthony RM.
BMC Infect Dis. 2014 Jul 10;14:380.
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Trainings provided in Stockholm or internationally upon request.
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