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.

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

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. 

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. 


Contact Radboudumc Community for Infectious Diseases

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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

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. 

 

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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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. 

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International consortia and collaborators

International consortia

RCI members also contribute to international consortia.

Clinical trials and pharmacokinetics of tuberculosis drugs

  • UNITE4TB consortium (prof. Martin Boeree, prof. Rob Aarnoutse, dr. Lindsey te Brake, prof Reinout van Crevel, dr. Cecil Magis, dr. Jakko van Ingen, dr. Elin Svensson): watch the video of UNITE4TB
  • PanACEA consortium (prof. Martin Boeree, prof. Rob Aarnoutse, dr. Lindsey te Brake, dr. Elin Svensson)

Tuberculosis diagnostics 

Prevention of diabetes-associated tuberculosis 

Tuberculous meningitis

  • Phase 3 RCT on high-dose rifampicin (HARVEST consortium on TB meningitis (prof. Rob Aarnoutse, prof. Reinout van Crevel, dr. Lindsey te Brake) 
  • Multi-omics analysis on pathogenesis and survival in adults (ULTIMATE; NIH/R01-AI145781-01) and children (INTERCEPT; R01AI165721) prof. Reinout van Crevel, dr. Arjan van Laarhoven, dr Vinod Kumar.

International collaborators

  • Universitas Padjadjaran (Bandung, Indonesia) 
  • University of Indonesia (Jakarta, Indonesia) 
  • KCMC/KCRI (Moshi, Tanzania) 
  • NIMR-MMRC (Mbeya, Tanzania) 
  • Makarere University (Kampala, Uganda)
  • TASK (Cape Town, South Africa)  
  • Nat. Instit. of Resp. Diseases and the Environment (Asunción, Paraguay) 
  • University College London (London, UK) 
  • University of Zaragoza (Zaragoza, Spain) 
  • Forschungszentrum Borstel (Borstel, Germany) 
  • Centre for Tropical Medicine and Global Health, University of Oxford, UK
  • Otago University (Dunedin , New Zealand)

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’)

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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

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.
 

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