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5. Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Central Nervous System Infections: Advances and Challenges

Author

Su, LingHui David, Chiu, Charles Y, Gaston, David, Hogan, Catherine A, Miller, Steve, Simon, Dennis W, Thakur, Kiran T, Yang, Shangxin, and Piantadosi, Anne

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Infectious Diseases, Biotechnology, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Infection, Good Health and Well Being, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Central nervous system (CNS) infections carry a substantial burden of morbidity and mortality worldwide, and accurate and timely diagnosis is required to optimize management. Metagenomic next-generation sequencing (mNGS) has proven to be a valuable tool in detecting pathogens in patients with suspected CNS infection. By sequencing microbial nucleic acids present in a patient's cerebrospinal fluid, brain tissue, or samples collected outside of the CNS, such as plasma, mNGS can detect a wide range of pathogens, including rare, unexpected, and/or fastidious organisms. Furthermore, its target-agnostic approach allows for the identification of both known and novel pathogens. This is particularly useful in cases where conventional diagnostic methods fail to provide an answer. In addition, mNGS can detect multiple microorganisms simultaneously, which is crucial in cases of mixed infections without a clear predominant pathogen. Overall, clinical mNGS testing can help expedite the diagnostic process for CNS infections, guide appropriate management decisions, and ultimately improve clinical outcomes. However, there are key challenges surrounding its use that need to be considered to fully leverage its clinical impact. For example, only a few specialized laboratories offer clinical mNGS due to the complexity of both the laboratory methods and analysis pipelines. Clinicians interpreting mNGS results must be aware of both false negatives-as mNGS is a direct detection modality and requires a sufficient amount of microbial nucleic acid to be present in the sample tested-and false positives-as mNGS detects environmental microbes and their nucleic acids, despite best practices to minimize contamination. Additionally, current costs and turnaround times limit broader implementation of clinical mNGS. Finally, there is uncertainty regarding the best practices for clinical utilization of mNGS, and further work is needed to define the optimal patient population(s), syndrome(s), and time of testing to implement clinical mNGS.

Published
2024

8. Neuroinfectious Diseases

Author

Diaz, Monica M., Boruah, Abhilasha P., Beauchamp, Morgan, Saylor, Deanna, Thakur, Kiran T., Ovbiagele, Bruce, editor, Lewis, Sharon, editor, Correa, Daniel José, editor, Thomas, Reena, editor, and CharlestonIV, Larry, editor

Published
2024
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9. Smart Biosensors for Precision Agriculture

Author

Rana, Anchal, Thakur, Kiran, Thakur, Meenakshi, Al-Khayri, Jameel M., Series Editor, Jain, S. Mohan, Series Editor, Alnaddaf, Lina M., editor, Jain, Shri Mohan, editor, and Penna, Suprasanna, editor

Published
2024
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11. Peach

Author

Thakur, Disha, Rimpika, Thakur, Kiran, Thakur, Manish, Ajender, Thakur, Kishore, Singh, Anurudh Kumar, Series Editor, Rajasekharan, P. E., editor, and Rao, V. Ramanatha, editor

Published
2024
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16. Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Author

Paradkar, Mandar S, D, Bella Devaleenal, Mvalo, Tisungane, Arenivas, Ana, Thakur, Kiran T, Wolf, Lisa, Nimkar, Smita, Inamdar, Sadaf, Giridharan, Prathiksha, Selladurai, Elilarasi, Kinikar, Aarti, Valvi, Chhaya, Khwaja, Saltanat, Gadama, Daphne, Balaji, Sarath, Kattagoni, Krishna Yadav, Venkatesan, Mythily, Savic, Radojka, Swaminathan, Soumya, Gupta, Amita, Gupte, Nikhil, Mave, Vidya, Dooley, Kelly E, Agiwal, Shivali, Ahire, Rupali, Balasubramanian, Usha, Bendre, Manjushree, Chandane, Jyoti, Chopade, Kavita, Dalimbkar, Shamala, Deshpande, Prasad, Dhage, Rajendra, Ithape, Mahesh, Jadhav, Varsha, Kante, Sonali, Kapre, Pallavi, Khan, Nawshaba, Kulkarni, Vandana, Madewar, Renu, Meshram, Shashibhushan, Muttha, Kunal, Nadgeri, Vaishali, Nagargoje, Arti, Nagraj, Amita, Nijampurkar, Aparna, Onawale, Prerana, Pawar, Namrata, Pawar, Prashant, Pradhan, Neeta, Shaikh, Varsha, Shaikh, Zaheda, Shere, Dhananjay, Wani, Gouri, Kulkarni, Rajesh, Rajput, Uday, Ganesan, Mangalambal, Arasan, Gunasundari, Shankar, Shakila, Mary, S Stella, Karuppaiah, Sureshwari, Pauline, Leema, Pramila, Snegha Karunakaran, Arul, Priyadharshini, Ganesh, Sankar, Hanna, Luke Elizabeth, Ramesh, K, Kannan, M, Vijayakumar, Ruthra, Sivakumar, Surekha S, Devika, K, Radhakrishnan, A, Preethi, AR, Rajkumar, S, Saravanan, N, Ramachandran, Geetha, Kumar, AK Hemanth, Dharman, M, Sudha, V, Hissar, Syed, Nagarajan, Valarmathi, Jennifer, Linda, Supriya, R, Manimegalai, R, Kandan, Santhanam, Maniselvi, Archana, Puspha, Oli, Vaishnavi, S, Selvi, R, Neelakandan, Logeswari, Chiunda, Mary, Chunga, Moreen, Kamanga, Madalo, Kamthunzi, Portia, Kanthiti, Elizabeth, Mbewe, Abineli, Msiska, Emmie, Mumba, Noel, Phiri, Ian Zifa, Palichina, Victor, and Sichali, Dorothy

Subjects
Pediatric, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Adult, Child, Humans, Rifampin, Tuberculosis, Meningeal, Levofloxacin, Ethambutol, Antitubercular Agents, Standard of Care, pediatric tuberculous meningitis, neuropsychological, clinical trial, levofloxacin, high-dose rifampicin, TuBerculous Meningitis in Kids (TBM-KIDS) Study Team, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

BackgroundPediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM.MethodsTBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL).ResultsOf 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P

Published
2022

22. Aqueous extract of pulp of maqui-berry (Aristotelia chilensis) induces apoptosis in human endometrial carcinoma ishikawa cells via mitochondrial and endoplasmic reticulum stress pathways

Author

Zhang, Wang-Wei, Liang, Yan-Cui, Thakur, Kiran, Zhang, Jian-Guo, Vidal-San Martin, Carla, Bastias-Montes, Jose M., Neira-Hinojosa, Jose Y., Mah, Siau Hui, Zengin, Gokhan, Saleem, Hammad, El-Haffidi, Mohammed, Avila-Acevedo, Jose G., Alarcon-Enos, Julio, and Cespedes-Acuña, Carlos L.

Published
2024
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32. Risk Factors for New Neurologic Diagnoses in Hospitalized Patients With COVID-19: A Case-Control Study in New York City.

Author

Thakur, Kiran, Chu, Victoria, Hughes, Christine, Kim, Carla, Fleck-Derderian, Shannon, Barrett, Catherine, Matthews, Elizabeth, Balbi, Alanna, Bilski, Amanda, Chomba, Mashina, Lieberman, Ori, Jacobson, Samuel, Agarwal, Sachin, Roh, David, Park, Soojin, Ssonko, Vivian, Silver, Wendy, Vargas, Wendy, Geneslaw, Andrew, Bell, Michelle, Waters, Brandon, Rao, Agam, Claassen, Jan, Boehme, Amelia, Willey, Joshua, Elkind, Mitchell, Sobieszczyk, Magdalena, Zucker, Jason, McCollum, Andrea, and Sejvar, James

Abstract

BACKGROUND AND OBJECTIVES: There have been numerous reports of neurologic manifestations identified in hospitalized patients infected with SARS-CoV-2, the virus that causes COVID-19. Here, we identify the spectrum of associated neurologic symptoms and diagnoses, define the time course of their development, and examine readmission rates and mortality risk posthospitalization in a multiethnic urban cohort. METHODS: We identify the occurrence of new neurologic diagnoses among patients with laboratory-confirmed SARS-CoV-2 infection in New York City. A retrospective cohort study was performed on 532 cases (hospitalized patients with new neurologic diagnoses within 6 weeks of positive SARS-CoV-2 laboratory results between March 1, 2020, and August 31, 2020). We compare demographic and clinical features of the 532 cases with 532 controls (hospitalized COVID-19 patients without neurologic diagnoses) in a case-control study with one-to-one matching and examine hospital-related data and outcomes of death and readmission up to 6 months after acute hospitalization in a secondary case-only analysis. RESULTS: Among the 532 cases, the most common new neurologic diagnoses included encephalopathy (478, 89.8%), stroke (66, 12.4%), and seizures (38, 7.1%). In the case-control study, cases were more likely than controls to be male (58.6% vs 52.8%, p = 0.05), had baseline neurologic comorbidities (36.3% vs 13.0%, p < 0.0001), and were to be treated in an intensive care unit (62.0% vs 9.6%, p < 0.0001). Of the 394 (74.1%) cases who survived acute hospitalization, more than half (220 of 394, 55.8%) were readmitted within 6 months, with a mortality rate of 23.2% during readmission. DISCUSSION: Hospitalized patients with SARS-CoV-2 and new neurologic diagnoses have significant morbidity and mortality postdischarge. Further research is needed to define the effect of neurologic diagnoses during acute hospitalization on longitudinal post-COVID-19-related symptoms including neurocognitive impairment.

Published
2022

34. Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy

Author

Deffner, Marie, Schneider-Hohendorf, Tilman, Schulte-Mecklenbeck, Andreas, Falk, Simon, Lu, I-Na, Ostkamp, Patrick, Müller-Miny, Louisa, Schumann, Eva Maria, Goelz, Susan, Cahir-McFarland, Ellen, Thakur, Kiran T., De Jager, Philip L., Klotz, Luisa, Meyer zu Hörste, Gerd, Gross, Catharina C., Wiendl, Heinz, Grauer, Oliver M., and Schwab, Nicholas

Published
2024
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48. Pre-existing neurological conditions and COVID-19 co-infection: Data from systematic reviews, meta-analyses, and scoping reviews

Author

Boruah, Abhilasha P., Thakur, Kiran T., Gadani, Sachin P., Kothari, Kavita U., Chomba, Mashina, Guekht, Alla, Heydari, Kimia, Hoo, Fan Kee, Hwang, Soonmyung, Michael, Benedict D., Pandit, Maya V., Pardo, Carlos A., Prasad, Kameshwar, Sardar, Zomer, Seeher, Katrin, Solomon, Tom, Winkler, Andrea S., Wood, Greta K., and Schiess, Nicoline

Published
2023
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