DR.

AII - Infectious Diseases Affiliatie VU Pediatric Infectious Diseases / Rheumatology / Immunology Medical Specialist, Pediatrics

PI
Specialization

 

⇒PATIENT CARE: PEDIATRIC INFECTIOUS DISEASES AND IMMUNOLOGY

  1. Central nervous system infectious/inflammatory disease
    • symptomatic congenital CMV infection
    • bacterial meningitis
    • tuberculous meningitis
    • other types of viral meningitis/encephalitis
    • auto-immune encephalitis
  2. Lymph node diseases
    • infectious lymphadenopathy, in particular non tuberculous mycobacterial lymphadenitis
    • immune mediated lymphadenopathy
  3. Primary immunodeficiencies
    • antibody deficiencies
    • combined immunodeficiencies
    • phagocyte disorders
    • complement deficiencies
    • immune dysregulation disorders
    • autoinflammatory disorders
    • defects in innate immunity

⇒TEACHING: Trainer 'Communication in complex situations for residents' - editor/co-writer book 'De Alles-Arts';  various infectious diseases and immunology topics for students, resident, nurses, pediatricians, other medical specialists; organiser yearly 'Texel kinderartsen nascholing Emma'

 

⇒RESEARCH:

(A) CENTRAL NERVOUS SYSTEM INFECTION AND INFLAMMATION

  1. Bacterial meningitis in the Netherlands
    • Postmeningitis study: a cross-sectional
      follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes (PhD project 8)
  2. Tuberculous meningitis in South Africa
    • post mortem brain immunohistochemistry (PhD project 3 & 12)
    • urine and CSF metabolomics (PhD projects 4 & 7)
    • brain tissue proteomics (PhD project 6)
    • multicompartmental metabolomics (PhD project 13)

(B) NEW DIAGNOSTIC TECHNIQUES FOR EARLY DIAGNOSIS OF INFECTIOUS DISEASES

  1. DIAMONDS - Diagnosis and Management of Febrile Illness using RNA Personalised Molecular Signature Diagnosis, co researcher at Emma Children's Hospital
    • PEARL: Profiling Exhaled Air for Recognizing Lung-infections (PhD project 9)
  2. Molecular culture of sepsis and meningitis, co researcher at Emma Children's Hospital (PhD project 10)

(C) Status of refugee children living in temporary settlements in Europe (co promotor PhD project 5)

Focus of research

details see specialisation section

(A) CENTRAL NERVOUS SYSTEM INFECTION AND INFLAMMATION

(B) NEW DIAGNOSTIC TECHNIQUES FOR EARLY DIAGNOSIS OF INFECTIOUS DISEASES

(C) STATUS OF REFUGEE CHILDREN LIVING IN TEMPORARY SETTLEMENTS IN EUROPE


In my research, I focus on the two major life-threatening bacterial infectious syndromes: sepsis and meningitis. I study the central nervous system pathophysiology of tuberculous meningitis and work on biomarker discovery and early diagnostics for both meningitis and sepsis.

In the Netherlands, bacteria such as meningococci, pneumococci, and Escherichia coli can cause meningitis, potentially resulting in neurological sequelae ranging from very mild to severe. We are currently studying the long-term cognitive, functional, and anatomical consequences of childhood bacterial meningitis in a large cohort of adults who survived bacterial meningitis during childhood. Cognitive outcomes are assessed using questionnaires and neuropsychological measures, while structural and functional effects are studied using MRI.

Over the past years, we have also used in silico models and zebrafish models (PhD project 1) to study the pathogenesis of tuberculous meningitis. This work focused particularly on granuloma formation, the role of tumor necrosis factor alpha (TNF-α), and mechanisms involved in blood-brain barrier disruption and bacterial translocation.

Currently, in collaboration with research groups in South Africa, we study immune, proteomic, and metabolic responses in children with tuberculous meningitis. Using brain tissue, cerebrospinal fluid, blood, and urine, we aim to unravel the pathogenesis of tuberculous meningitis and identify biomarkers that may improve early diagnosis and prediction of outcome. In addition to retrospective studies using existing biological material, we conduct prospective observational studies in hospitalized children with tuberculous meningitis.

A further research focus in the Netherlands is the evaluation of a novel molecular diagnostic approach for sepsis and meningitis. The method -molecular culture -, detects microbial DNA directly from blood and cerebrospinal fluid. Following current studies in early- and late-onset neonatal sepsis, we are starting to evaluate this technique in broader paediatric and adult populations with suspected bloodstream infection and sepsis, aiming to improve rapid pathogen detection and targeted antimicrobial treatment.

PhD students in past and present in role as co-promotor in the Netherlands (NL) and South Africa (SA):

1. Lisanne van Leeuwen (NL): Tuberculous meningitis at the host-pathogen interface (finished in 2018).

2. Sabine van Elsland (SA): Home-based treatment of children with HIV infection or tuberculous meningitis in South Africa (finished in 2019).

3. Dan Zaharie (SA): New insights in the pathogenesis of granuloma formation in neurotuberculosis (finished in 2024).

4. Simon Isaiah (SA): Urinary metabolomic profiling for characterization, diagnosis and treatment response in paediatric tuberculous meningitis (finished in 2025).

5. Hanaâ Benjedi (NL): The Health of Displaced Children: Studies on the nutritional status and quality of life in Mavrovouni Refugee Camp, 
Lesbos (thesis scheduled for September 2026).

6. Abisola Isaiah (SA): Proteomic profiling of granuloma formation in tuberculous meningitis (thesis scheduled for December 2026).

7. Ontefetse Plaatjie (SA): LC-MS CSF metabolomics in tuberculous meningitis (thesis scheduled for December 2026).

8. Dook Koch (NL): MATURE: Meningitis sequelae in Adulthood: Towards an Understanding of Residual Effects after childhood bacterial infection  (thesis scheduled for 2027).

9. Carlijn van der Zee (NL): PEARL: Profiling Exhaled Air for Recognizing Lung-infections (thesis scheduled for 2027).

10. Jip Groen (NL): CHAMPIONS: Children’s Health Assessment and Molecular Pathogen Identification for Optimized Novel Sepsis therapy (thesis scheduled for 2027).

11. Gina Buijsers (NL): Beneath the surface; understanding non-tuberculous mycobacterial cervicofacial lymphadenitis in children (thesis scheduled for 2028).

12. Ursula Paulsen (SA): Blood Vessel Pathology in Tuberculous meningitis and its complications (thesis scheduled for 2028).

13. Magriet van Niekerk (SA): The Utility of Metabolomics in the Diagnosis of Paediatric TBM in Cape Town, South Africa (thesis scheduled for 2028).