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Welcome to Radboudumc Community for Infectious Diseases Mycobacterial infectious diseases

Our scientific research

The Radboudumc Community for Infectious Diseases research group aims to optimize treatment and outcome of mycobacterial diseases. We therefore combine basic science with pharmacology, microbiology, radiology, infectiology, and lung diseases.

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Our scientific research

Research overview

Member of the RCI mycobacterial infections perform in six Radboudumc research groups:

Research groups	Involved members	Expertise
Translational pharmacology of anti-microbial drugs, specifically anti-tuberculosis drugs	Rob Aarnoutse Lindsey te Brake Elin Svensson (also Uppsala University, Sweden)	Bio-analysis of drugs PK and PD data-analysis PBPK modeling Clinical trials Drug management Therapeutic Drug Monitoring
Clinical tuberculosis and other mycobacterial infections	Martin Boeree Cecile Magis-Escurra Wouter Hoefsloot Jodie Schildkraut Neeltje Carpaij	Patient management Clinical trials and cohort studies
Global Health and Infectious Diseases	Reinout van Crevel (also Oxford University) Arjan van Laarhoven Andrew Dinardo (also Baylor College of Medicine, USA) Vinod Kumar	Patient management Clinical trials and cohort studies Bio-analysis of inflammatory and defense markers Host-directed therapy Health policy and implementation research
Clinical Microbiology	Heiman Wertheim Jakko van Ingen	Susceptibility testing, time-kill kinetics assays, hollow fiber model Clinical trials and cohort studies Clinical microbiology
Pharmacology and Toxicology	Frans Russel Jan Koenderink	Molecular pharmacology Drug induced tolerance PBPK modelling
Global Health Economics	Rob Baltussen	Health policy and implementation research Health economics

Patients treated at Radboudumc for mycobacterial infections are able to participate in the Mycobacterial Cohort Study that gather clinical, microbiological and pharmacological data and is coupled to the Radboud biobank for later (immunological) measurements.

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PhD candidates

The research program “Treatment optimization for mycobacterial diseases: management and outcome of mycobacterial diseases” has facilitated numerous candidates to pursue their PhD at Radboud University.

overview PhD candidates

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PhD candidates

PhD candidate	Title	Year	Promotores	Co-promotores
Alma Tostmann	Challenges in tuberculosis treatment and control: studies from the Netherlands and Tanzania	2009	Richard Dekhuijzen	Martin Boeree, Rob Aarnoutse
Hanneke Nijland	Optimizing drug treatment in the fight against tuberculosis. Focus on clinical pharmacokinetics	2009	Chiel Hekster	Rob Aarnoutse, Reinout van Crevel
Ida Parwati	Factors Underlying the Success of the Mycobacterium tuberculosis Beijing genotype in Indonesia	2009	Jos van der Meer	Reinout van Crevel, Adri van der Zanden
Jakko van Ingen	Nontuberculous mycobacteria: From gene sequences to clinical relevance	2009	Richard Dekhuijzen, Dick van Soolingen	Martin Boeree
Rovina Ruslami	Clinical Pharmacology of anti-tuberculosis treatment in Indonesia	2009	Jos van der Meer	Rob Aarnoutse, Reinout van Crevel
Jossy van den Boogaard	Non-adherence to tuberculosis treatment: An untegral approach to measure and prevent it	2011	Richard Dekhuijzen	Rob Aarnoutse, Martin Boeree, Gibson Kibiki
Ahmad Rizal Ganiem	Etiology and clinical management of adult meningitis in Indonesia	2013	André van der Ven	Reinout van Crevel, Rovina Ruslami
Cecile Magis-Escurra	Clinical and epidemiological studies from a tuberculosis referral centre in the Netherlands	2013	Richard Dekhuijzen	Martin Boeree, Rob Aarnoutse
Wouter Hoefsloot	Nontuberculous mycobacteria: new insights in epidemiology and clinical relevance	2013	Richard Dekhuijzen, Dick van Soolingen	Martin Boeree, Jakko van Ingen
Merrin Rutherford	Management of children living with tuberculosis patients; studies from Indonesia	2013	André van der Ven, Philip Hill	Reinout van Crevel, Rovina Ruslami
Charles Mtabho	Improving the management of tuberculosis in Tanzania: clinical and epidemiological studies	2014	André van der Ven, Gibson Kibiki	Rob Aarnoutse, Martin Boeree
Hadija Semvua	Clinical pharmacological studies in tuberculosis patients: research from the Kilimanjaro Region,Tanzania	2014	David Burger, Gibson Kibiki	Rob Aarnoutse, Martin Boeree
Johanneke Klein-nijenhuis	Host response to mycobacteria: innate recognition and memory	2015	Mihai Netea	Reinout van Crevel
Sami Simons	Drug susceptibility testing for optimising tuberculosis treatment	2015	Richard Dekhuijzen, Dick van Soolingen	Martin Boeree, Jakko van Ingen
Lindsey te Brake	Translational research in tuberculosis: crossing barriers between molecular and clinical pharmacology	2016	David Burger, Frans Russel	Rob Aarnoutse, Jan Koenderink
Beatriz Ferro	Strategies to improve treatment of nontuberculous mycobacterial disease	2017	Johan Mouton, Dick van Soolingen	Jakko van Ingen
Ekta Lachmandas	Host response to tuberculosis: impact of diabetes and cellular metabolism of immune cells	2017	Mihai Netea, Reinout van Crevel
Lidya Chaidir	Tuberculosis Diagnosis and Genotyping in Indonesia	2017	Reinout van Crevel	Bachti Alisjahbana
Arjan van Laarhoven	Host response in relation to tuberculosis susceptibility, transmission and outcome	2018	Reinout van Crevel, Mihai Netea
Mohammed Khogali	Bridging the knowledge gap: Operational research to improve access to health care in Ethiopia	2018	Richard Dekhuijzen, Anthony Harries	Martin Boeree, Rony Zachariah
Jessica de Beer	Molecular typing of Mycobacterium tuberculosis complex: the answers you can and cannot get	2018	Dick van Soolingen	Jakko van Ingen
Sofiati Dian	High-dose rifampicin and other factors associated with outcome of tuberculous meningitis	2018	Reinout van Crevel, Rovina Ruslami	Rob Aarnoutse, Ahmad Rizal Ganiem
Serge Ade	Operational research to document and improve case finding and treatment outcomes in patients with tuberculosis in Benin, West Africa	2019	Richard Dekhuijzen, Anthony Harries	Martin Boeree, Rony Zachariah
Carolien Ruesen	Understanding tuberculosis drug resistance, disease phenotype and transmission by mycobacterial genome analysis	2019	Reinout van Crevel, Martijn Huijnen	Lidya Chaidir, Jakko van Ingen
Madhugiri Venkatachalaiah	Operational Research for improving the care of HIV-infected TB patients in India	2019	Richard Dekhuijzen, Anthony Harries	Martin Boeree, Rony Zachariah
Kudakwashe Takarinda	The burden of tuberculosis in Zimbabwe: operational research to document and improve tuberculosis control activities in a high HIV-prevalence setting	2019	Richard Dekhuijzen, Anthony Harries	Martin Boeree, Rony Zachariah
Carlijn Litjens	Building bridges between preclinical and clinical pharmacology in tuberculosis treatment	2021	Rob Aarnoutse, Frans Russel	Lindsey te Brake, Jan Koenderink
Massoud Dara	Tuberculosis in the WHO European Region, Research for Evidence-based Policies	2021	Martin Boeree	Rony Zachariah
Hemant Shewade	Effectiveness of community-based active case finding for tuberculosis in India	2021	Martin Boeree, Anthony Harries	Ajay Kumar
Mike Ruth	A lung in a bottle; an in vitro pipeline to optimize treatment regimens for NTM disease	2021	Heiman Wertheim	Jakko van Ingen
Valerie A. C. M. Koeken	Host response in tuberculosis and BCG vaccination	2021	Reinout van Crevel, Mihai Netea	Arjan van Laarhoven
Andrew DiNardo	Molecular endotypes and epigenetics underlying tuberculosis risk, severity, and outcomes	2022	Reinout van Crevel, Mihai Netea
Stijn van Beek	Model-informed pharmacological interventions against tuberculosis and malaria	2022	Rob Aarnoutse	Rob ter Heine, Elin Svensson
Alit Koesoemadinata	Tuberculosis and diabetes; towards better screening and outcomes	2023	Reinout van Crevel, Philip Hill	Bachti Alisjahbana
Bony Lestari	Public Health Tools to Improve Tuberculosis Control in Indonesia	2023	Reinout van Crevel, Philip Hill	Bachti Alisjahbana
Jodie Schildkraut	Nontuberculous mycobacteria; from prevalence to prognosis	2023	Heiman Wertheim	Jakko van Ingen, Lindsey te Brake
Rosarita Coronel Teixeira	The electronic nose as a possible point of care diagnostic in Tuberculosis	2023	Martin Boeree	Cécile Magis-Escurra
Engy Ali	Operational research studies conducted to improve effectives and management of severe acute malnutrition for children under 5	ongoing	Koos van der Velden, Martin Boeree	Rony Zachariah
Anca Riza	Genetics and tuberculosis susceptibility and treatment	ongoing	Reinout van Crevel, Mihai Netea	Vinod Kumar
Arnold Ndaro	Clinical pharmacokinetics of anti-tuberculosis drugs in Tanzanian adults and children	ongoing	Rob Aarnoutse	Lindsey te Brake, Hadija Semvua
Arthur Lemson	Optimizing conservative and antibiotic treatment in nontuberculous mycobacterial pulmonary disease	ongoing	Martin Boeree, Rob Aarnoutse	Wouter Hoefsloot, Jakko van Ingen
Caryn Upton	Exploration and optimisation of anti-tuberculous therapy in cerebrospinal fluid penetration	ongoing	Martin Boeree, Rob Aarnoutse, Andreas Diacon
Cynthia van Arkel	Clinical aspects of the tuberculosis patiënt admitted in Dutch referral centres	ongoing	Martin Boeree	Cécile Magis-Escurra, Arjan van Laarhoven
Karapet Davtyan	Operational research for improving tuberculosis care and control in Armenia	ongoing	Martin Boeree	Rony Zachariah
Gerine Nijman	Evaluating the disconnect in the cascade of care of tuberculosis in Indonesia	ongoing	Reinout van Crevel, Philip Hill	Bony Wiem Lestari
Iraseni Swai	Developing contents and testing the effectiveness of Digital Adherence Tools (DAT) in improving adherence among children and adolescents living with HIV in Kilimanjaro, Tanzania	ongoing	Tobias Rinke de Wit (UVA), Rob Aarnoutse	Marion Sumari-de Boer
Isabella van der Feltz	Pharmacometrics and bioanalysis to aid the development of novel treatment regimens against tuberculosis	ongoing	Rob Aarnoutse	Elin Svensson, Lindsey te Brake
Jelmer Raaijmakers	Hollow fiber model simulations to improve treatment regimens in NTM-PD	ongoing	Heiman Wertheim, Rob Aarnoutse	Jakko van Ingen, Wouter Hoefsloot
Julia Brake	Impact of diabetes on immunometabolism of host and Mycobacterium tuberculosis.	ongoing	Reinout van Crevel	Jakko van Ingen, Rinke Stienstra
Kirsten van Abeelen	Multi-Omics Integration to Understand the Pathophysiology of Tuberculosis Meningitis	ongoing	Reinout van Crevel	Arjan van Laarhoven, Vinod Kumar
Lisa Kurver	Immune Dysregulation in Mycobacterial Infections	ongoing	Reinout van Crevel	Arjan van Laarhoven
Ombeni Chimbe	Pharmacological aspects of the implementation of tuberculosis preventive therapy (TPT) with once weekly rifapentine and isoniazid for three months (3HP) in people living with diabetes mellitus	ongoing	Rob Aarnoutse	Lindsey te Brake, Nyanda Elias Ntinginya
Ralf Stemkens	Clinical pharmacology of antimycobacterial drugs	ongoing	Rob Aarnoutse	Lindsey te Brake
Simon Koele	Pharmacometrics for tuberculosis biomarkers and novel therapeutics	ongoing	Rob Aarnoutse	Elin Svensson
Sweetness Laizer	Quality of diabetes and diabetes-tuberculosis care in Tanzania and Uganda	ongoing	Reinout van Crevel, Philip Hill	Kajiru Kilonzo, Nyasatu Chamba
Takindwa Msosa	The effectiveness of a customized digital adherence tool on HIV treatment outcomes in adolescents and young adults living with HIV in Blantyre, Malawi	ongoing	Tobias Rinke de Wit (UVA), Rob Aarnoutse	Marion Sumari-de Boer
Todia Pediatama Setiabu-diawan	Innate protection against Mycobacterium tuberculosis infection in highly exposed individuals	ongoing	Reinout van Crevel	Valerie A. C. M. Koeken
Willyhelmina Olomi	Design and analysis of tuberculosis preventive trials	ongoing	Reinout van Crevel, Katrina Sharples, Philip Hill	Nyanda Ntinginya
Sanne Zweij-pfenning	Non tuberculous mycobacteria: Turning the antibiotic nightmare around	2024	Martin Boeree, Michel van den Heuvel	Wouter Hoefsloot, Jakko van Ingen
Wouter Peeters	Non-Tuberculous Mycobacterial Skin and Soft Tissue Infections	ongoing	Reinout van Crevel	Arjan van Laarhoven, Juul van den Reek, Mumin Ozturk
Victor Dahl	Nontuberculous mycobacterial disease in Denmark and beyond	ongoing	Troels Lillebaek (SSI/Aarhus)	Jakko van Ingen
Ingrid van Weerden-burg	Using data science to improve diagnosis and treatment of infectious diseases	ongoing	Heiman Wertheim	Jakko van Ingen
Hanna Fricke	Mycobacterium-host crosstalk in immunomodulation	ongoing	Heiman Wertheim	Jakko van Ingen

Clinical studies

Observational studies

Overview of the observational studies patënts can participate in at Radboudumc.

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Observational studies

Mycobacterial Cohort Study (MyCoS) enables all patients with a mycobacterial infection in Radboudumc to participate in a prospective data registry and biobank study to increase our immunological, genetic and pharmacokinetic understanding.

Procedure: MyCoS is embedded in standard care and no study-specific visits are required and blood samples are collected during routine care.
Ethics: CMO NL2021-13231 (niet-WMO plichtig).
Principal investigators: Arjan van Laarhoven & Wouter Hoefsloot.
PhD candidates: Lisa Kurver, Arthur Lemson, Cynthia van Arkel and Wouter Peeters.

Tuberculin Skin Test (TST) substudy of MyCoS enrolls all patients with tuberculosis or non-tuberculous mycobacterial lung disease at the start of antituberculosis treatment to determine the relationship between tissue immune responses to a mycobacterial challenge and the clinical course of infection.

Procedure: patients will receive the standard intradermal tuberculin skin test (normally used to diagnose latent tuberculosis) and a saline injection on the contralateral arm (visit 1). After 48 hours two 3 mm skin biopsies will be taken from the tuberculin and saline skin injection (visit 2) and patients will be followed-up by phone call at day 7.
Ethics: CMO NL2022-13725, Toetsingonline.
Principal investigator: Arjan van Laarhoven.
PhD candidate: Lisa Kurver.

Skin and Soft Tissue (SSTI) substudy of MyCoS enrolls all patients with non-tuberculous (NTM) skin- and soft tissue infections (SSTI) at the start of their antimycobacterial treatment to identify clinical and immunological parameters that predict the course of disease of NTM SSTI. In addition, local and systemic pharmacokinetics are assessed to provide a systemic correlate for local pharmacokinetics.

Procedure: Skin biopsies are collected at baseline, 2 months later, and in case of lesional worsening in a subset of patients. Blood for systemic pharmacokinetic measurements is collected after 2 months.
Ethics: CMO NL2023-16732, ToetsingOnline.
Principal investigator: Arjan van Laarhoven.
PhD candidate: Wouter Peeters.

International MAC-PD cohort enrolls MAC-LD patients starting antimycobacterial treatment into a prospective, international data-registry to assess the culture conversion rate after 6 months of antimycobacterial treatment, adverse drug reactions and treatment modifications.

Procedure: Participant requires follow-up at the Radboudumc during the first 6 months of treatment.
Ethics: CMO 2022-13742, ClinicalTrials.gov: NCT05906316.
Principal investigator: Wouter Hoefsloot.
PhD candidate: Arthur Lemson.

Clinical trials

Overview of the clinical trials patënts can participate in at Radboudumc.

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Clinical trials

SALINE enrolls patients with nodular-bronchiectatic M. avium complex lung disease for a randomized, controlled trial to investigate the effect of hypertonic saline inhalation on quality-of-life compared to standard supportive care. Hypertonic saline, shown to be well tolerated and in some patients sufficient to clear their NTM infection, is inhaled twice daily via a nebulizer device.

Procedure: the trial is largely aligned with our standard-of-care and participation requires two visits to the Radboudumc with a 3-month time interval.
Ethics: CMO NL79735.091.22, ClinicalTrials.gov: NCT05192057
Principal investigator: Wouter Hoefsloot.

Mino-PK investigates the pharmacokinetics of minocycline in patients with M. avium complex lung disease with and without concurrent use of rifampicin.

Procedure: two 5-day courses of minocycline (with and without concurrent use of rifampicin) are prescribed within a 6-week time interval, followed by pharmacokinetic analysis. Participation requires 3 visits to the Radboudumc, but will often partially overlap with a hospital admission to initiate NTM treatment as a whole.
Ethics: ClinicalTrials.gov: NCT05861258.
Principal investigator: Wouter Hoefsloot.
PhD student: Arthur Lemson.

PORT enrolls patients with tuberculosis without major comorbidities for optimized dose of rifampicin, to investigate the safety and tolerability of this optimized dose.

Procedure: in this phase 3 trial, patients in the first four weeks of antibiotic treatment are randomised between standard dose and optimized dose of 1800 mg rifampin for six months.
Ethics: CMO NL2022-13538 ClinicalTrials.gov: NCT06057519
Principal investigator(s): Martin Boeree and Cécile Magis-Escurra.
Study team: Jodie Schildkraut and Iris Spelier.

RIAlta enrolls both young (18-65 years) and elderly (>65 years) patients with severe pulmonary (BMI< 18) and/or extrapulmonary (meningitis) tuberculosis and comorbidities (HIV infection, renal and liver disease, DM, and/or substance abuse) to investigate the safety, tolerability and pharmakinetics and pharmacodynamics of an optimized dose of rifampin combined with a standard first line regimen.

Procedure: in this open-label phase 2b/c international multi center trial, patients are treated with 35 mg/kg rifampin for two months +HZE (intensive phase of treatment).
Ethics: CMO NL75346.091.20. ClinicalTrials.gov: NCT04768231.
Principal investigator: Dr. Adrian Sanchez Montalva, Vall d'Hebron
Research Institute, Barcelona, Spain.
Juan Espinosa trial coordinator, VHIR.
Local PI: Cécile Magis-Escurra.
Local study team: Juul Altinga, Timo Hoeijmakers, Marlies de Vos and Giovanni Fumagalli.

Research internships

We offer internships for motivated students in a variety of topics, such as: diagnostics, treatment including pharmacology, and mechanisms of disease including immunology. Please contact us and include your recent curriculum vitae.

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International consortia and collaborators

RCI members also contribute to international consortia and collaborate with various international universities and research centers.

Our education

Where can you learn more about mycobacterial infections at Radboudumc?

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Our education

Where can you learn more about mycobacterial infections at Radboudumc?

Latent tuberculosis pathophysiology (full day lecture, assignments and presentation by prof. Reinout van Crevel & dr. Arjan van Laarhoven in MED-MIN06, Minor Global Health & Infectious Diseases)
Tuberculosis treatment and drug resistance & risk factors for non-tuberculous mycobacterial infections (a lecture by dr. Wouter Hoefsloot & dr. Jakko van Ingen in MED-MIN29, ‘Control of Infectious Diseases’)
Global HIV and tuberculosis co-infection, TB diagnostiscs and treatment latent TB treatment (1,5 day lectures, assignment and interactive clinical puzzle by Prof. Reinout van Crevel & dr. Jakko van Ingen & dr. Mischa Huson & dr. Arjan van Laarhoven in MED-MINK16, ‘Minor in Global Health’)
Introduction to Tuberculosis (lecture by dr. Arjan van Laarhoven in MED-VK30-07, keuzemodule ‘Introduction to Global health')
Central nervous system infections including tuberculous meningitis (lecture by prof. dr. van Crevel in MINK-09, ‘The Fascinating Brain’)

Clinical fellowships

We regularly host doctors in training for medical specialties in pulmonology or internal medicine/infectious diseases (“assistenten in opleiding tot specialist”, AIOS) and pharmacists in training.

Radboudumc center of clinical expertise for tuberculosis and non-tuberculous mycobacterial infectious diseases

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Radboudumc center of clinical expertise for tuberculosis and non-tuberculous mycobacterial infectious diseases

Radboudumc is an acknowledged center of clinical expertise for tuberculosis and non-tuberculous mycobacterial infectious diseases (NTM). Healthcare professionals, such as pulmonologists, internists and other medical specialists, municipal health physicians in tuberculosis prevention, and general practitioners are able to obtain information and advice here. The center of expertise has a TBC-unit which is technically advanced in hygiene. Here, we treats patients from across the Netherlands and sometimes from well beyond its borders.