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2. Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study

Author

Maharani, Kartika, Dian, Sofiati, Ganiem, Ahmad Rizal, Imran, Darma, Estiasari, Riwanti, Ardiansyah, Edwin, Andini, Putri Widya, Kristina, Fransisca, Pangeran, David, Chaidir, Lidya, Alisjahbana, Bachti, Rukmana, Andriansjah, Kusumaningrum, Ardiana, Adawiyah, Robiatul, Subekti, Decy, Yunihastuti, Evy, Yunus, Reyhan Eddy, Waslia, Lia, van Ingen, Jakko, van Laarhoven, Arjan, Hamers, Raph L., and van Crevel, Reinout

Published
2024
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6. Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis

Author

Arts, Rob J.W., Bijker, Else M., Bruno, Mariolina, Hobo, Willemijn, Hoppenreijs, Esther, de Jonge, Marien I., van Laarhoven, Arjan, van der Molen, Renate, Oud, Manon, Schatorje, Ellen J.H., Smeets, Ruben, Sprenkeler, Evelien G.G., Stol, Kim, Verhagen, Lilly M., Zonneveld-Huijssoon, Evelien, Vorsteveld, Emil E., Van der Made, Caspar I., Smeekens, Sanne P., Schuurs-Hoeijmakers, Janneke H., Astuti, Galuh, Diepstra, Heleen, Gilissen, Christian, Hoenselaar, Evelien, Janssen, Alice, van Roozendaal, Kees, Engelen, Jettie Sikkema-van, Steyaert, Wouter, Weiss, Marjan M., Yntema, Helger G., Mantere, Tuomo, AlZahrani, Mofareh S., van Aerde, Koen, Derfalvi, Beata, Faqeih, Eissa Ali, Henriet, Stefanie S.V., van Hoof, Elise, Idressi, Eman, Issekutz, Thomas B., Jongmans, Marjolijn C.J., Keski-Filppula, Riikka, Krapels, Ingrid, te Loo, Maroeska, Mulders-Manders, Catharina M., ten Oever, Jaap, Potjewijd, Judith, Sarhan, Nora Tarig, Slot, Marjan C., Terhal, Paulien A., Thijs, Herman, Vandersteen, Anthony, Vanhoutte, Els K., van de Veerdonk, Frank, van Well, Gijs, Netea, Mihai G., Simons, Annet, and Hoischen, Alexander

Published
2024
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7. Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward

Author

Donovan, Joseph, Cresswell, Fiona V, Thuong, Nguyen Thuy Thuong, Boulware, David R, Thwaites, Guy E, Bahr, Nathan C, Aarnoutse, Rob E, Anderson, Suzanne TB, Bang, Nguyen D, Boyles, Tom, te Brake, Lindsey HM, Chandra, Satish, Chow, Felicia C, van Crevel, Reinout, Davis, Angharad G, Dian, Sofiati, Dooley, Kelly E, Figaji, Anthony, Ganiem, A Rizal, Garg, Ravindra Kumar, Gibb, Diana M, Hamers, Raph L, Hiep, Nguyen TT, Imran, Darma, Imron, Akhmad, Jain, Sanjay K, Jain, Sunil K, Kalita, Jayantee, Kumar, Rashmi, Kumar, Vinod, van Laarhoven, Arjan, Lai, Rachel P-J, Manesh, Abi, Marais, Suzaan, Mave, Vidya, Meintjes, Graeme, Meya, David B, Misra, Usha K, Modi, Manish, Ordonez, Alvaro A, Phu, Nguyen H, Pradhan, Sunil, Prasad, Kameshwar, Proust, Alize M, Ramakrishnan, Lalita, Rohlwink, Ursula, Ruslami, Rovina, Schoeman, Johannes F, Seddon, James A, Sharma, Kusum, Siddiqi, Omar, Solomons, Regan S, Thuong, Nguyen TT, van Toorn, Ronald, Tucker, Elizabeth W, Wasserman, Sean A, and Wilkinson, Robert J

Subjects
Rare Diseases, Tuberculosis, Infectious Diseases, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Diagnostic Tests, Routine, Humans, Molecular Diagnostic Techniques, Mycobacterium tuberculosis, Sensitivity and Specificity, Tuberculosis, Meningeal, Tuberculous Meningitis International Research Consortium, Ultra, Xpert, cerebrospinal fluid, diagnosis, tuberculous meningitis, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to "rule out" TBM.

Published
2020

8. Neurocognitive and functional impairment in adult and paediatric tuberculous meningitis

Author

Davis, Angharad G, Nightingale, Sam, Springer, Priscilla E, Solomons, Regan, Arenivas, Ana, Wilkinson, Robert J, Anderson, Suzanne T, Chow, Felicia C, Aarnoutse, Rob E, Anderson, Suzanne TB, Bahr, Nathan C, Bang, Nguyen D, Boulware, David R, Boyles, Tom, Brake, Lindsey HM te, Chandra, Satish, Cresswell, Fiona V, van Crevel, Reinout, Dian, Sofiati, Donovan, Joseph, Dooley, Kelly E, Figaji, Anthony, Ganiem, A Rizal, Garg, Ravindra Kumar, Gibb, Diana M, Hamers, Raph L, Hiep, Nguyen TT, Imran, Darma, Imron, Akhmad, Jain, Sanjay K, Jain, Sunil K, Jeejeebhoy, Byramee, Kalita, Jayantee, Kumar, Rashmi, Kumar, Vinod, van Laarhoven, Arjan, Lai, Rachel P-J, Manesh, Abi, Marais, Suzaan, Mave, Vidya, Meintjes, Graeme, Meya, David B, Misra, Usha K, Modi, Manish, Ordonez, Alvaro A, Phu, Nguyen H, Pradhan, Sunil, Prasad, Kameshwar, Proust, Alize M, Ramakrishnan, Lalita, Rohlwink, Ursula, Ruslami, Rovina, Schoeman, Johannes F, Seddon, James A, Sharma, Kusum, Siddiqi, Omar, Solomons, Regan S, Thuong, Nguyen TT, Thwaites, Guy E, van Toorn, Ronald, Tucker, Elizabeth W, and Wasserman, Sean A

Subjects
Biomedical and Clinical Sciences, Health Sciences, Neurosciences, Brain Disorders, Behavioral and Social Science, Mental health, Good Health and Well Being, Tuberculous Meningitis International Research Consortium, Functional, Neurobehavioural, Neurocognitive, Neurodevelopmental, Psychiatric, Tuberculous Meningitis, Biomedical and clinical sciences, Health sciences
Abstract

In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research.

Published
2019

9. Standardized approaches for clinical sampling and endpoint ascertainment in tuberculous meningitis studies

Author

Rohlwink, Ursula K, Chow, Felicia C, Wasserman, Sean, Dian, Sofiati, Lai, Rachel PJ, Chaidir, Lidya, Hamers, Raph L, Wilkinson, Robert J, Boulware, David R, Cresswell, Fiona V, and van Laarhoven, Arjan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Good Health and Well Being, Tuberculous Meningitis International Research Consortium, endpoints, imaging, immunology, metabolomics, microbiology, outcome, proteomics, sampling, tuberculous meningitis, Biomedical and clinical sciences, Health sciences
Abstract

Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, has poorly understood immunopathology and high mortality and morbidity despite antituberculous therapy. This calls for accelerated clinical and basic science research in this field. As TBM disproportionally affects poorer communities, studies are often performed in resource-limited environments, creating challenges for data collection and harmonisation. Comparison of TBM studies has been hampered by variation in sampling strategies, study design and choice of study endpoints.  Based on literature review and expert consensus, this paper provides firstly, practical recommendations to enable thorough diagnostic, pathophysiological and pharmacokinetic studies using clinical samples, and facilitates better data aggregation and comparisons across populations and settings. Secondly, we discuss clinically relevant study endpoints, including neuroimaging, functional outcome, and cause of death, with suggestions of how these could be applied in different designs for future TBM studies.

Published
2019

10. Establishing the cascade of care for patients with tuberculous meningitis

Author

Imran, Darma, Hill, Philip C, McKnight, Jacob, van Crevel, Reinout, Aarnoutse, Rob E, Anderson, Suzanne TB, Bahr, Nathan C, Bang, Nguyen D, Boulware, David R, Boyles, Tom, Brake, Lindsey HM te, Chandra, Satish, Chow, Felicia C, Cresswell, Fiona V, Davis, Angharad G, Dian, Sofiati, Donovan, Joseph, Dooley, Kelly E, Figaji, Anthony, Ganiem, A Rizal, Garg, Ravindra Kumar, Gibb, Diana M, Hamers, Raph L, Hiep, Nguyen TT, Imron, Akhmad, Jain, Sanjay K, Jain, Sunil K, Jeejeebhoy, Byramee, Kalita, Jayantee, Kumar, Rashmi, Kumar, Vinod, van Laarhoven, Arjan, Lai, Rachel P-J, Manesh, Abi, Marais, Suzaan, Mave, Vidya, Meintjes, Graeme, Meya, David B, Misra, Usha K, Modi, Manish, Ordonez, Alvaro A, Phu, Nguyen H, Pradhan, Sunil, Prasad, Kameshwar, Proust, Alize M, Ramakrishnan, Lalita, Rohlwink, Ursula, Ruslami, Rovina, Schoeman, Johannes F, Seddon, James A, Sharma, Kusum, Siddiqi, Omar, Solomons, Regan S, Thuong, Nguyen TT, Thwaites, Guy E, van Toorn, Ronald, Tucker, Elizabeth W, Wasserman, Sean A, and Wilkinson, Robert J

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Infectious Diseases, Health Services, Tuberculosis, HIV/AIDS, Clinical Research, Rare Diseases, 8.1 Organisation and delivery of services, Health and social care services research, Infection, Good Health and Well Being, Tuberculous Meningitis International Research Consortium, cascade of care, health systems, meningitis, patient pathway analysis, tuberculosis, Biomedical and clinical sciences, Health sciences
Abstract

Meningitis is a relatively rare form of tuberculosis, but it carries a high mortality rate, reaching 50% in some settings, with higher rates among patients with HIV co-infection and those with drug-resistant disease. Most studies of tuberculosis meningitis (TBM) tend to focus on better diagnosis, drug treatment and supportive care for patients in hospital. However, there is significant variability in mortality between settings, which may be due to specific variation in the availability and quality of health care services, both prior to, during, and after hospitalization. Such variations have not been studied thoroughly, and we therefore present a theoretical framework that may help to identify where efforts should be focused in providing optimal services for TBM patients. As a first step, we propose an adjusted cascade of care for TBM and patient pathway studies that might help identify factors that account for losses and delays across the cascade. Many of the possible gaps in the TBM cascade are related to health systems factors; we have selected nine domains and provide relevant examples of systems factors for TBM for each of these domains that could be the basis for a health needs assessment to address such gaps. Finally, we suggest some immediate action that could be taken to help make improvements in services. Our theoretical framework will hopefully lead to more health system research and improved care for patients suffering from this most dangerous form of tuberculosis.

Published
2019

11. SARS-CoV-2 RNA in exhaled air of hospitalized COVID-19 patients

Author

Kurver, Lisa, van den Kieboom, Corné H., Lanke, Kjerstin, Diavatopoulos, Dimitri A., Overheul, Gijs J., Netea, Mihai G., ten Oever, Jaap, van Crevel, Reinout, Mulders-Manders, Karin, van de Veerdonk, Frank L., Wertheim, Heiman, Schouten, Jeroen, Rahamat-Langendoen, Janette, van Rij, Ronald P., Bousema, Teun, van Laarhoven, Arjan, and de Jonge, Marien I.

Published
2022
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12. Improving host-directed therapy for tuberculous meningitis by linking clinical and multi-omics data

Author

Avila-Pacheco, Julian, Thuong, Nguyen T.T., Ganiem, A. Rizal, Imran, Darma, Hamers, Raph L., Alisjahbana, Bachti, Dian, Sofiati, Estiasari, Riwanti, Tram, Trinh T.B., Vinh, Dao N., Hai, Hoang T., Donovan, Joseph, Ardiansyah, Edwin, Koeken, Valerie, Kumar, Vinod, Netea, Mihai G., van Laarhoven, Arjan, Clish, Clary, Thwaites, Guy, and van Crevel, Reinout

Published
2021
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17. Cerebral tryptophan metabolism and outcome of tuberculous meningitis: an observational cohort study

Author

van Laarhoven, Arjan, Dian, Sofiati, Aguirre-Gamboa, Raúl, Avila-Pacheco, Julian, Ricaño-Ponce, Isis, Ruesen, Carolien, Annisa, Jessi, Koeken, Valerie A C M, Chaidir, Lidya, Li, Yang, Achmad, Tri Hanggono, Joosten, Leo A B, Notebaart, Richard A, Ruslami, Rovina, Netea, Mihai G, Verbeek, Marcel M, Alisjahbana, Bachti, Kumar, Vinod, Clish, Clary B, Ganiem, A Rizal, and van Crevel, Reinout

Published
2018
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20. Tryptophan metabolism determines outcome in tuberculous meningitis: a targeted metabolomic analysis

Author

Ardiansyah, Edwin, primary, Avila-Pacheco, Julian, additional, Nhat, Le Thanh Hoang, additional, Dian, Sofiati, additional, Vinh, Dao Nguyen, additional, Hai, Hoang Thanh, additional, Bullock, Kevin, additional, Alisjahbana, Bachti, additional, Netea, Mihai G, additional, Estiasari, Riwanti, additional, Tram, Trinh Thi Bich, additional, Donovan, Joseph, additional, Heemskerk, Dorothee, additional, Chau, Tran Thi Hong, additional, Bang, Nguyen Duc, additional, Ganiem, Ahmad Rizal, additional, Ruslami, Rovina, additional, Koeken, Valerie ACM, additional, Hamers, Raph L, additional, Imran, Darma, additional, Maharani, Kartika, additional, Kumar, Vinod, additional, Clish, Clary B, additional, van Crevel, Reinout, additional, Thwaites, Guy, additional, van Laarhoven, Arjan, additional, and Thuong, Nguyen Thuy Thuong, additional

Published
2023
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21. Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity

Author

Arts, Rob J.W., Novakovic, Boris, ter Horst, Rob, Carvalho, Agostinho, Bekkering, Siroon, Lachmandas, Ekta, Rodrigues, Fernando, Silvestre, Ricardo, Cheng, Shih-Chin, Wang, Shuang-Yin, Habibi, Ehsan, Gonçalves, Luís G., Mesquita, Inês, Cunha, Cristina, van Laarhoven, Arjan, van de Veerdonk, Frank L., Williams, David L., van der Meer, Jos W.M., Logie, Colin, O'Neill, Luke A., Dinarello, Charles A., Riksen, Niels P., van Crevel, Reinout, Clish, Clary, Notebaart, Richard A., Joosten, Leo A.B., Stunnenberg, Hendrik G., Xavier, Ramnik J., and Netea, Mihai G.

Published
2016
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22. Author response: Tryptophan metabolism determines outcome in tuberculous meningitis: a targeted metabolomic analysis

Author

Ardiansyah, Edwin, primary, Avila-Pacheco, Julian, additional, Nhat, Le Thanh Hoang, additional, Dian, Sofiati, additional, Vinh, Dao Nguyen, additional, Hai, Hoang Thanh, additional, Bullock, Kevin, additional, Alisjahbana, Bachti, additional, Netea, Mihai G, additional, Estiasari, Riwanti, additional, Tram, Trinh Thi Bich, additional, Donovan, Joseph, additional, Heemskerk, Dorothee, additional, Chau, Tran Thi Hong, additional, Bang, Nguyen Duc, additional, Ganiem, Ahmad Rizal, additional, Ruslami, Rovina, additional, Koeken, Valerie ACM, additional, Hamers, Raph L, additional, Imran, Darma, additional, Maharani, Kartika, additional, Kumar, Vinod, additional, Clish, Clary B, additional, van Crevel, Reinout, additional, Thwaites, Guy, additional, van Laarhoven, Arjan, additional, and Thuong, Nguyen Thuy Thuong, additional

Published
2023
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23. MUC5AC genetic variation is associated with tuberculous meningitis CSF cytokine responses and mortality

Author

Sabo, Michelle C, primary, Thuong, Nguyen T T, additional, Chang, Xuling, additional, Ardiansyah, Edwin, additional, Tram, Trinh T B, additional, Hai, Hoang T, additional, Nghia, Ho D T, additional, Bang, Nguyen D, additional, Dian, Sofiati, additional, Ganiem, A Rizal, additional, Shaporifar, Shima, additional, Kumar, Vinod, additional, Li, Zheng, additional, Hibberd, Martin, additional, Khor, Chiea Chuen, additional, Thwaites, Guy E, additional, Heemskerk, Dorothee, additional, van Laarhoven, Arjan, additional, van Crevel, Reinout, additional, Dunstan, Sarah J, additional, and Shah, Javeed A, additional

Published
2023
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24. MUC5AC Genetic Variation Is Associated With Tuberculous Meningitis Cerebral Spinal Fluid Cytokine Responses and Mortality.

Author

Sabo, Michelle C, Thuong, Nguyen T T, Chang, Xuling, Ardiansyah, Edwin, Tram, Trinh T B, Hai, Hoang T, Nghia, Ho D T, Bang, Nguyen D, Dian, Sofiati, Ganiem, A Rizal, Shaporifar, Shima, Kumar, Vinod, Li, Zheng, Hibberd, Martin, Khor, Chiea Chuen, Thwaites, Guy E, Heemskerk, Dorothee, Laarhoven, Arjan van, Crevel, Reinout van, and Dunstan, Sarah J

Subjects
TUBERCULOUS meningitis, GENETIC variation, CEREBROSPINAL fluid, SINGLE nucleotide polymorphisms, TUMOR necrosis factors
Abstract

Background The purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes. Methods Independent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with tumor necrosis factor (TNF) concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality. Results MUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF (P = 1.8 × 10−8) and IFN-γ (P = 2.3 × 10−6). In an additive genetic model, rs28737416 T/T genotype was associated with higher susceptibility to TBM (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.03–1.49; P =.02), but not pulmonary tuberculosis (OR, 1.11, 95% CI,.98–1.25; P =.10). TBM mortality was higher among participants with the rs28737416 T/T and T/C genotypes (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank P =.005) in a Vietnam discovery cohort (n = 210), an independent Vietnam validation cohort (n = 87; 9/87, 19.1% vs 1/20, 2.5%; log-rank P =.02), and an Indonesia validation cohort (n = 468, 127/287, 44.3% vs 65/181, 35.9%; log-rank P =.06). Conclusions MUC5AC variants may contribute to immune changes that influence TBM outcomes. [ABSTRACT FROM AUTHOR]

Published
2023
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26. The Influence of Fixation and Cryopreservation of Cerebrospinal Fluid on Antigen Expression and Cell Percentages by Flow Cytometric Analysis

Author

Singh, Gabriela, primary, Laarhoven, Arjan, additional, Adams, Rozanne, additional, Reid, Timothy Dawson, additional, Combrinck, Jill, additional, Dorp, Suzanne, additional, Riou, Catherine, additional, Thango, Nqobile, additional, Enslin, Johannes, additional, Kruger, Stefan, additional, Figaji, Anthony Aaron, additional, and Rohlwink, Ursula Karin, additional

Published
2022
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27. Plasma metabolome predicts trained immunity responses after antituberculosis BCG vaccination

Author

Koeken, Valerie A. C. M., primary, Qi, Cancan, additional, Mourits, Vera P., additional, de Bree, L. Charlotte J., additional, Moorlag, Simone J. C. F. M., additional, Sonawane, Vidhisha, additional, Lemmers, Heidi, additional, Dijkstra, Helga, additional, Joosten, Leo A. B., additional, van Laarhoven, Arjan, additional, Xu, Cheng-Jian, additional, van Crevel, Reinout, additional, Netea, Mihai G., additional, and Li, Yang, additional

Published
2022
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28. Interleukin-1 receptor antagonist anakinra as treatment for paradoxical responses in HIV-negative tuberculosis patients: A case series

Author

van Arkel, Cynthia, primary, Boeree, Martin, additional, Magis-Escurra, Cécile, additional, Hoefsloot, Wouter, additional, Carpaij, Neeltje, additional, van Ingen, Jakko, additional, Pegge, Sjoert, additional, Wielders, Pascal, additional, Smeenk, Frank, additional, Aarnoutse, Rob, additional, Netea, Mihai G., additional, van Crevel, Reinout, additional, and van Laarhoven, Arjan, additional

Published
2022
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29. MUC5AC genetic variation is associated with tuberculosis meningitis CSF cytokine responses and mortality

Author

Sabo, Michelle C., primary, Thuong, Nguyen T.T., additional, Chang, Xuling, additional, Ardiansyah, Edwin, additional, Tram, Trinh T.B., additional, Hai, Hoang T., additional, Nghia, Ho D.T., additional, Bang, Nguyen D., additional, Dian, Sofiati, additional, Ganiem, A. Rizal, additional, Kumar, Vinod, additional, Li, Zheng, additional, Hibberd, Martin, additional, Khor, Chiea Chuen, additional, Thwaites, Guy E., additional, Heemskerk, Dorothee, additional, van Laarhoven, Arjan, additional, van Crevel, Reinout, additional, Dunstan, Sarah J., additional, and Shah, Javeed A., additional

Published
2022
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30. Presentation, etiology, and outcome of brain infections in an Indonesian hospital: A cohort study

Author

Imran, Darma, Estiasari, Riwanti, Maharani, Kartika, Sucipto, Lestari, Delly Chipta, Yunus, Reyhan Eddy, Yunihastuti, Evy, Karyadi, Teguh Haryono, Oei, Diana, Timan, Ina S., Wulandari, Dewi, Wahyuningsih, Retno, Adawiyah, Robiatul, Kurniawan, Agnes, Mulyadi, Rahmad, Karuniawati, Anis, Jaya, Ungke Anton, Safari, Dodi, van Laarhoven, Arjan, Alisjahbana, Bachti, Dian, Sofiati, Chaidir, Lidya, Ganiem, Ahmad Rizal, Lastri, Diatri Nari, Aye Myint, Khin Saw, and van Crevel, Reinout

Published
2018
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31. Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients

Author

Timmermans, Kim, Kox, Matthijs, Vaneker, Michiel, van den Berg, Maarten, John, Aaron, van Laarhoven, Arjan, and van der Hoeven, Hans

Subjects
Cytokines -- Research -- Health aspects, Medical research -- Health aspects, Medicine, Experimental -- Health aspects, Gene expression -- Research -- Health aspects, HLA histocompatibility antigens -- Research -- Health aspects, Heat shock proteins -- Health aspects -- Research, Ethylenediaminetetraacetic acid -- Research, Infection -- Risk factors -- Research, Emergency medical services -- Research -- Health aspects, Disease susceptibility -- Research -- Risk factors, Histocompatibility antigens -- Research -- Health aspects, Mitochondrial DNA -- Research -- Health aspects, Health care industry
Abstract

Purpose Danger-associated molecular patterns (DAMPs) released of trauma could contribute to an immune suppressed state that renders patients vulnerable towards nosocomial infections. We investigated DAMP release in trauma patients, starting in the prehospital phase, and assessed its relationship with immune suppression and nosocomial infections. Methods Blood was obtained from 166 adult trauma patients at the trauma scene, emergency room (ER), and serially afterwards. Circulating levels of DAMPs and cytokines were determined. Immune suppression was investigated by determination of HLA-DRA gene expression and ex vivo lipopolysaccharide-stimulated cytokine production. Results Compared with healthy controls, plasma levels of nuclear DNA (nDNA) and heat shock protein-70 (HSP70) but not mitochondrial DNA were profoundly increased immediately following trauma and remained elevated for 10 days. Plasma cytokines were increased at the ER, and levels of anti-inflammatory IL-10 but not of pro-inflammatory cytokines peaked at this early time-point. HLA-DRA expression was attenuated directly after trauma and did not recover during the follow-up period. Plasma nDNA (r = -0.24, p = 0.006) and HSP70 (r = -0.38, p < 0.0001) levels correlated negatively with HLA-DRA expression. Ex vivo cytokine production revealed an anti-inflammatory phenotype already at the trauma scene which persisted in the following days, characterized by attenuated TNF-[alpha] and IL-6, and increased IL-10 production. Finally, higher concentrations of nDNA and a further decrease of HLA-DRA expression were associated with infections. Conclusions Plasma levels of DAMPs are associated with immune suppression, which is apparent within minutes/hours following trauma. Furthermore, aggravated immune suppression during the initial phase following trauma is associated with increased susceptibility towards infections., Author(s): Kim Timmermans [sup.1] [sup.2], Matthijs Kox [sup.1] [sup.2], Michiel Vaneker [sup.2] [sup.3], Maarten van den Berg [sup.1], Aaron John [sup.1] [sup.2], Arjan van Laarhoven [sup.4], Hans van der Hoeven [...]

Published
2016
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32. Prediction of Moxifloxacin Concentrations in Tuberculosis Patient Populations by Physiologically Based Pharmacokinetic Modeling

Author

Litjens, Carlijn H. C., Verscheijden, Laurens F. M., Bolwerk, Celine, Greupink, Rick, Koenderink, Jan B., van den Broek, Petra H. H., van den Heuvel, Jeroen J. M. W., Svensson, Elin, Boeree, Martin J., Magis-Escurra, Cecile, Hoefsloot, Wouter, van Crevel, Reinout, van Laarhoven, Arjan, van Ingen, Jakko, Kuipers, Saskia, Ruslami, Rovina, Burger, David M., Russel, Frans G. M., Aarnoutse, Rob E., Te Brake, Lindsey H. M., Litjens, Carlijn H. C., Verscheijden, Laurens F. M., Bolwerk, Celine, Greupink, Rick, Koenderink, Jan B., van den Broek, Petra H. H., van den Heuvel, Jeroen J. M. W., Svensson, Elin, Boeree, Martin J., Magis-Escurra, Cecile, Hoefsloot, Wouter, van Crevel, Reinout, van Laarhoven, Arjan, van Ingen, Jakko, Kuipers, Saskia, Ruslami, Rovina, Burger, David M., Russel, Frans G. M., Aarnoutse, Rob E., and Te Brake, Lindsey H. M.

Abstract

Moxifloxacin has an important role in the treatment of tuberculosis (TB). Unfortunately, coadministration with the cornerstone TB drug rifampicin results in suboptimal plasma exposure. We aimed to gain insight into the moxifloxacin pharmacokinetics and the interaction with rifampicin. Moreover, we provided a mechanistic framework to understand moxifloxacin pharmacokinetics. We developed a physiologically based pharmacokinetic model in Simcyp version 19, with available and newly generated in vitro and in vivo data, to estimate pharmacokinetic parameters of moxifloxacin alone and when administered with rifampicin. By combining these strategies, we illustrate that the role of P-glycoprotein in moxifloxacin transport is limited and implicate MRP2 as transporter of moxifloxacin-glucuronide followed by rapid hydrolysis in the gut. Simulations of multiple dose area under the plasma concentration-time curve (AUC) of moxifloxacin (400 mg once daily) with and without rifampicin (600 mg once daily) were in accordance with clinically observed data (predicted/observed [P/O] ratio of 0.87 and 0.80, respectively). Importantly, increasing the moxifloxacin dose to 600 mg restored the plasma exposure both in actual patients with TB as well as in our simulations. Furthermore, we extrapolated the single dose model to pediatric populations (P/O AUC ratios, 1.04-1.52) and the multiple dose model to children with TB (P/O AUC ratio, 1.51). In conclusion, our combined approach resulted in new insights into moxifloxacin pharmacokinetics and accurate simulations of moxifloxacin exposure with and without rifampicin. Finally, various knowledge gaps were identified, which may be considered as avenues for further physiologically based pharmacokinetic refinement.

Published
2022
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34. Prediction of Moxifloxacin Concentrations in Tuberculosis Patient Populations by Physiologically Based Pharmacokinetic Modeling

Author

Litjens, Carlijn H. C., primary, Verscheijden, Laurens F. M., additional, Bolwerk, Celine, additional, Greupink, Rick, additional, Koenderink, Jan B., additional, van den Broek, Petra H. H., additional, van den Heuvel, Jeroen J. M. W., additional, Svensson, Elin M., additional, Boeree, Martin J., additional, Magis‐Escurra, Cecile, additional, Hoefsloot, Wouter, additional, van Crevel, Reinout, additional, van Laarhoven, Arjan, additional, van Ingen, Jakko, additional, Kuipers, Saskia, additional, Ruslami, Rovina, additional, Burger, David M., additional, Russel, Frans G. M., additional, Aarnoutse, Rob E., additional, and te Brake, Lindsey H. M., additional

Published
2021
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35. Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: A case series

Author

van Laarhoven, Arjan, primary, Kurver, Lisa, additional, Overheul, Gijs J., additional, Kooistra, Emma J., additional, Abdo, Wilson F., additional, van Crevel, Reinout, additional, Duivenvoorden, Raphaël, additional, Kox, Matthijs, additional, ten Oever, Jaap, additional, Schouten, Jeroen, additional, van de Veerdonk, Frank L., additional, van der Hoeven, Hans, additional, Rahamat-Langendoen, Janette, additional, van Rij, Ronald P., additional, Pickkers, Peter, additional, and Netea, Mihai G., additional

Published
2021
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38. Improving host-directed therapy for tuberculous meningitis by linking clinical and multi-omics data

Author

van Crevel, Reinout, primary, Avila-Pacheco, Julian, additional, Thuong, Nguyen T.T., additional, Ganiem, A. Rizal, additional, Imran, Darma, additional, Hamers, Raph L., additional, Alisjahbana, Bachti, additional, Dian, Sofiati, additional, Estiasari, Riwanti, additional, Tram, Trinh T.B., additional, Vinh, Dao N., additional, Hai, Hoang T., additional, Donovan, Joseph, additional, Ardiansyah, Edwin, additional, Koeken, Valerie, additional, Kumar, Vinod, additional, Netea, Mihai G., additional, van Laarhoven, Arjan, additional, Clish, Clary, additional, and Thwaites, Guy, additional

Published
2021
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41. Perspective for Precision Medicine for Tuberculosis

Author

Lange, Christoph, Aarnoutse, Rob, Chesov, Dumitru, van Crevel, Reinout, Gillespie, Stephen H., Grobbel, Hans-Peter, Kalsdorf, Barbara, Kontsevaya, Irina, van Laarhoven, Arjan, Nishiguchi, Tomoki, Mandalakas, Anna, Merker, Matthias, Niemann, Stefan, Köhler, Niklas, Heyckendorf, Jan, Reimann, Maja, Ruhwald, Morten, Sanchez-Carballo, Patricia, Schwudke, Dominik, Waldow, Franziska, and DiNardo, Andrew R.

Subjects
mycobacterial genotypes, Mini Review, precision medicine, Immunology, Antitubercular Agents, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Mycobacterium tuberculosis, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], tailor-made regimen, endotypes, tuberculosis, Animals, Humans, Immunology and Allergy
Abstract

Contains fulltext : 229189.pdf (Publisher’s version ) (Open Access) Tuberculosis is a bacterial infectious disease that is mainly transmitted from human to human via infectious aerosols. Currently, tuberculosis is the leading cause of death by an infectious disease world-wide. In the past decade, the number of patients affected by tuberculosis has increased by ~20 percent and the emergence of drug-resistant strains of Mycobacterium tuberculosis challenges the goal of elimination of tuberculosis in the near future. For the last 50 years, management of patients with tuberculosis has followed a standardized management approach. This standardization neglects the variation in human susceptibility to infection, immune response, the pharmacokinetics of drugs, and the individual duration of treatment needed to achieve relapse-free cure. Here we propose a package of precision medicine-guided therapies that has the prospect to drive clinical management decisions, based on both host immunity and M. tuberculosis strains genetics. Recently, important scientific discoveries and technological advances have been achieved that provide a perspective for individualized rather than standardized management of patients with tuberculosis. For the individual selection of best medicines and host-directed therapies, personalized drug dosing, and treatment durations, physicians treating patients with tuberculosis will be able to rely on these advances in systems biology and to apply them at the bedside.

Published
2020

42. Model-based meta-analysis of rifampicin exposure and mortality in Indonesian tuberculous meningitis trials

Author

Svensson, Elin M., Dian, Sofiati, te Brake, Lindsey, Ganiem, Ahmad Rizal, Yunivita, Vycke, van Laarhoven, Arjan, van Crevel, Reinout, Ruslami, Rovina, Aarnoutse, Rob E., Svensson, Elin M., Dian, Sofiati, te Brake, Lindsey, Ganiem, Ahmad Rizal, Yunivita, Vycke, van Laarhoven, Arjan, van Crevel, Reinout, Ruslami, Rovina, and Aarnoutse, Rob E.

Abstract

Background Intensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis. Methods An individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750–1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models. Results Pharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%–6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3–2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival. Conclusions Higher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.

Published
2020
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43. The effect of BCG vaccination on alveolar macrophages obtained from induced sputum from healthy volunteers

Author

Koeken, Valerie A. C. M., van der Pasch, Eva S., Leijte, Guus P., Mourits, Vera P., de Bree, L. Charlotte J., Moorlag, Simone J. C. F. M., Budnick, Isadore, Idh, Nina, Lerm, Maria, Kox, Matthijs, van Laarhoven, Arjan, Netea, Mihai G., van Crevel, Reinout, Koeken, Valerie A. C. M., van der Pasch, Eva S., Leijte, Guus P., Mourits, Vera P., de Bree, L. Charlotte J., Moorlag, Simone J. C. F. M., Budnick, Isadore, Idh, Nina, Lerm, Maria, Kox, Matthijs, van Laarhoven, Arjan, Netea, Mihai G., and van Crevel, Reinout

Abstract

The anti-tuberculosis vaccine Bacillus Calmette-Guerin (BCG) is able to boost innate immune responses through a process called trained immunity. It is hypothesized that BCG-induced trained immunity contributes to protection against Mycobacterium tuberculosis infection. Since alveolar macrophages are the first cell type to encounter M. tuberculosis upon infection, we aimed to investigate the immunomodulatory effects of BCG vaccination on alveolar macrophages. Searching for a less-invasive method than bronchoalveolar lavage, we optimized the isolation of alveolar macrophages from induced sputum of healthy volunteers. Viable alveolar macrophages could be successfully isolated from induced sputum and showed signs of activation already upon retrieval. Further flow cytometric analyses revealed that at baseline, higher expression levels of activation markers were observed on the alveolar macrophages of smokers compared to non-smokers. In addition, BCG vaccination resulted in decreased expression of the activation markers CD11b and HLA-DR on alveolar macrophages. Future studies should evaluate the functional consequences of this reduced activation of alveolar macrophages after BCG vaccination., Funding Agencies|Netherlands Organization for Scientific ResearchNetherlands Organization for Scientific Research (NWO); National Institute Of Allergy And Infectious Diseases of the National Institutes of Health, ULTIMATE project [1R01AI145781-01]

Published
2020
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44. A Bayesian analysis of the association between Leukotriene A4 Hydrolase genotype and survival in tuberculous meningitis

Author

Whitworth, Laura, primary, Coxon, Jacob, additional, van Laarhoven, Arjan, additional, Thuong, Nguyen Thuy Thuong, additional, Dian, Sofiati, additional, Alisjahbana, Bachti, additional, Ganiem, Ahmad Rizal, additional, van Crevel, Reinout, additional, Thwaites, Guy E, additional, Troll, Mark, additional, Edelstein, Paul H, additional, Sewell, Roger, additional, and Ramakrishnan, Lalita, additional

Published
2021
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45. Berberine and obatoclax inhibit SARS-CoV-2 replication in primary human nasal epithelial cells in vitro

Author

Varghese, Finny S., primary, van Woudenbergh, Esther, additional, Overheul, Gijs J., additional, Eleveld, Marc J., additional, Kurver, Lisa, additional, van Heerbeek, Niels, additional, van Laarhoven, Arjan, additional, Miesen, Pascal, additional, den Hartog, Gerco, additional, de Jonge, Marien I., additional, and van Rij, Ronald P., additional

Published
2020
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47. Author response: A Bayesian analysis of the association between Leukotriene A4 Hydrolase genotype and survival in tuberculous meningitis

Author

Whitworth, Laura, primary, Coxon, Jacob, additional, van Laarhoven, Arjan, additional, Thuong, Nguyen Thuy Thuong, additional, Dian, Sofiati, additional, Alisjahbana, Bachti, additional, Ganiem, Ahmad Rizal, additional, van Crevel, Reinout, additional, Thwaites, Guy E, additional, Troll, Mark, additional, Edelstein, Paul H, additional, Sewell, Roger, additional, and Ramakrishnan, Lalita, additional

Published
2020
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49. Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) – a multicentre, prospective, observational study

Author

Lieveld, Arthur W.E., primary, Kok, Bram, additional, Schuit, Frederik H., additional, Azijli, Kaoutar, additional, Heijmans, Jarom, additional, van Laarhoven, Arjan, additional, Assman, Natascha L., additional, Kootte, Ruud S., additional, Olgers, Tycho J., additional, Nanayakkara, Prabath W.B., additional, and Bosch, Frank H., additional

Published
2020
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50. The effect of BCG vaccination on alveolar macrophages obtained from induced sputum from healthy volunteers

Author

Koeken, Valerie A.C.M., primary, van der Pasch, Eva S., additional, Leijte, Guus P., additional, Mourits, Vera P., additional, de Bree, L. Charlotte J., additional, Moorlag, Simone J.C.F.M., additional, Budnick, Isadore, additional, Idh, Nina, additional, Lerm, Maria, additional, Kox, Matthijs, additional, van Laarhoven, Arjan, additional, Netea, Mihai G., additional, and van Crevel, Reinout, additional

Published
2020
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