⇒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

⇒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
   • The Dutch 20|30 Postmeningitis study: a cross-sectional
     follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes (co promotor PhD project 9)
2. Tuberculous meningitis in South Africa
   • post mortem brain immunohistochemistry (co promotor PhD project 3)
   • urine and CSF metabolomics (co promotor 2 PhD projects 5 & 8)
   • brain tissue proteomics (co promotor PhD project 6)
   • clinical study on immune and nutritional status (co promotor PhD project 4)

(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
   • Profiling Exhaled Air for Recognizing Lung-infections (PEARL)
2. Molecular culture in neonatal sepsis, co researcher at Emma Children's Hospital

(C) Status of refugee children living in temporary settlements in Europe (co promotor PhD project 7)

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 mainly focus on bacterial meningitis:

In the Netherlands, bacteria such as meningococs, pneumococs and Escherichia coli can cause meningitis resulting in very mild to severe neurological sequelae later in life. Currently, we start to study long term cognitive (questionaires) and functional/anatomical effects (MRI) in a large cohort of adults that suffered from meningitis in childhood.

In the recent past, we have used an in silico model and a zebrafish model to study the pathogenenesis of tuberculous meningitis. The main focus of this work were aspects of granuloma formation and the role of tumor necrosis factor alpha and blood brain barrier transferral.

Currently, in South Africa, we study the cellular (immune), proteomic and metabolic responses in patients that suffered from tuberculous meningitis. We use brain tissue and urine to unravel the pathogenesis of tuberculous meningitis (retropective work). Also, we do a prospective observational clinical study on immune and nutrional status of hopitalized children with tuberculous meningitis.

Co promotor of PhD projects:

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

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

3. Dan Zaharie: Granuloma formation in tuberculous meningitis; a human post mortem pathology study (finished in 2024)

4. Yajna Kooblal: Nutritional and immune status during admission for childhood tuberculous meningitis; an obervational clinical follow up study (thesis scheduled for December 2024)

5. Simon Isaiah: Urinary metabolic profiling: developing a non-invasive method for early diagnostics and treatment response (thesis scheduled for December 2024)

6. Abisola Sholeye: Proteomic profiling of granuloma formation in tuberculous meningitis (thesis scheduled for December 2024)

7. Hanaa Benjedi: Status of refugee children living in temporary settlements in Europe (thesis scheduled for December 2025)

8. Ontefetse Neo: LC-MS CSF metabolomics in tuberculous meningitis (thesis scheduled for December 2026)

9. Dook Koch: The Dutch 20|30 Postmeningitis study: a cross-sectional follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes (starting September 2023)