Research Research groups Tuberculosis: From basic biology to population control

About this research group

This research group integrates (international) patient studies and laboratory sciences to understand the biology of tuberculosis (TB) transmission, infection and disease, including its severest form: meningitis.

Research group leader

Reinout van Crevel MD PhD

+31 (0)24 361 88 19
contact

Aims

Our group has several aims.

  • In the coming years we will mainly focus on three aspects regarding tuberculosis.

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    Main focus

    In the coming years we will focus on three aspects:
    1. Identification of biological pathways that underly the high mortality of the most severe manifestation of tuberculosis: TB meningitis linking large-scale clinical and 'multi-comics' (metabolomics, genomics etc) data in two large patient cohorts from Vietnam and Indonesia.
    2. Understanding the role of mycobacterial genotype and host defence in TB transmission and resistance to Mycobacterium tuberculosis infection (‘early clearance’) in TB-household contacts and BCG-revaccination studies in Indonesia.
    3. Unravelling the interaction between diabetes, genotypic drug resistance, host immune defence and Mycobacterium tuberculosis virulence.

  • Additional focus

    We also study prevention, clinical management and control of TB and combined TB and diabetes in TB-endemic countries. Among other things in the coming years we will:
    • Study the effect of TB preventive treatment among people with diabetes and latent tuberculosis infection, and improve practice and policy for people with combined disease, in Africa and Asia.
    • Study the effect of high-dose rifampicin (35 mg/kg) on survival of TB meningitis in a phase 3 RCT in Indonesia, Uganda and South Africa, and improve its diagnosis and management.
    • Study public health aspects of TB control and management of MDR-TB in Indonesia.

Discoveries

Several discoveries were made by our research group.

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Discoveries

Several discoveries were made by our research group.
  • Linkage of human and M. tuberculosis genotypes (derived by whole genome sequencing) with functional immunology to explain differences in TB transmission, susceptibility and outcome.
  • A unique cohort and biorepository of highly-exposed TB household contacts, probably the largest and most and carefully characterized globally, for study of innate resistance to Mycobacterium tuberculosis infection (‘early clearance’).
  • Use of high-dose rifampicin, culminating in first randomized clinical trial globally to show that high-dose rifampicin can reduce TB mortality.
  • The interaction between TB and diabetes, leading a EU-consortium on this topic, with basic research and studies in 4 TB-endemic countries, based on which we help shape international policy for clinical management of TB-DM.
  • Diagnosis and management of TB meningitis, having established the 2nd largest cohort of TB meningitis patients worldwide.