scholarly journals Tuberculous meningitis: new tools and new approaches required

2019 ◽  
Vol 4 ◽  
pp. 181 ◽  
Author(s):  
James A Seddon ◽  
Guy E Thwaites ◽  

Tuberculous meningitis is the most severe form of tuberculosis and causes widespread mortality and morbidity. Understanding of the epidemiology and pathogenesis is incomplete, and the optimal diagnosis and treatment are poorly defined. To generate research collaboration and coordination, as well as to promote sharing of ideas and advocacy efforts, the International Tuberculous Meningitis Research Consortium was formed in 2009. During the most recent meeting of this group in Lucknow, India, in March 2019, the Consortium decided to bring together key articles on tuberculous meningitis in one supplement. The supplement covers recent scientific updates, expert perspectives on specific clinical challenges, consensus statements on how to conduct research, and a set of priorities for future investigation.

2019 ◽  
Vol 4 ◽  
pp. 188
Author(s):  
James A Seddon ◽  
Robert Wilkinson ◽  
Reinout van Crevel ◽  
Anthony Figaji ◽  
Guy E Thwaites ◽  
...  

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), accounting for around 1-5% of the global TB caseload, with mortality of approximately 20% in children and up to 60% in persons co-infected with human immunodeficiency virus even in those treated. Relatively few centres of excellence in TBM research exist and the field would therefore benefit from greater co-ordination, advocacy, collaboration and early data sharing. To this end, in 2009, 2015 and 2019 we convened the TBM International Research Consortium, bringing together approximately 50 researchers from five continents. The most recent meeting took place on 1st and 2nd March 2019 in Lucknow, India. During the meeting, researchers and clinicians presented updates in their areas of expertise, and additionally presented on the knowledge gaps and research priorities in that field. Discussion during the meeting was followed by the development, by a core writing group, of a synthesis of knowledge gaps and research priorities within seven domains, namely epidemiology, pathogenesis, diagnosis, antimicrobial therapy, host-directed therapy, critical care and implementation science. These were circulated to the whole consortium for written input and feedback. Further cycles of discussion between the writing group took place to arrive at a consensus series of priorities. This article summarises the consensus reached by the consortium concerning the unmet needs and priorities for future research for this neglected and often fatal disease.


2018 ◽  
Vol 13 (02) ◽  
pp. 141-152
Author(s):  
Amina Ahmed

AbstractCentral nervous system tuberculosis (CNS-TB) manifests as tuberculous meningitis, intracranial tuberculoma, or spinal tuberculous arachnoiditis. Children are disproportionately affected, with high rates of mortality and morbidity reported even in the era of treatment. Most guidelines for the treatment of drug-susceptible CNS-TB recommend 9 to 12 months of a standard regimen of isoniazid, rifampin, pyrazinamide, and ethambutol, with the adjunctive use of corticosteroids early in therapy. Recent trials have demonstrated improved outcomes with intensified regimens using nonstandard regimens or higher dosages of standard drugs. Accumulating evidence also supports shorter duration of treatment. Further investigation is warranted to identify the optimal regimen and duration of treatment for CNS-TB. Complications such as hydrocephalus may be managed medically or surgically. Although outcomes have improved with effective chemotherapy and immunomodulation of disease, prompt diagnosis and treatment in the early stages of disease remain paramount to improve prognosis.


PEDIATRICS ◽  
1967 ◽  
Vol 40 (5) ◽  
pp. 923-923
Author(s):  
JEROLD F. LUCEY ◽  
AUDREY K. BROWN ◽  
ALICE GAMBLE BEARD ◽  
MARVIN CORNBLATH ◽  
MOSES GROSSMAN ◽  
...  

THE physical design of and routine practices in neonatal units (especially nurseries for high-risk infants) are presently influenced almost entirely by considerations related to the risk of spreading infection in the nursery by fomites and personnel. The role of nursery design and specific routines in preventing epidemics is considered so important that the details are encoded in many local, state, and federal health laws or regulations. These are enforced by periodic inspections and conformity is made a prerequisite for official approval, allocation of funds, etc. Although there is little reason to doubt that these policies have had the effect of reducing the incidence of nursery epidemics, there is growing concern that official rigidity in these matters may interfere with optimal care of the very ill infant, as well as with research designed to improve care and find solutions to the overall problems of neonatal mortality and morbidity. Infections are an important and frequent cause of disease in the newborn. They are, however, clearly outdistanced by major non-infectious disorders that account for the majority of deaths and brain damage in the neonatal period (respiratory distress, asphyxia, acidosis, hypoglycemia, and hyperbilirubinemia). Some of the precautionary techniques used to reduce the risk of infections have the practical disadvantages of making it difficult (1) to approach the neonatal patient and (2) to apply modern diagnostic maneuvers and therapeutic aids in order to improve the neonatal patient's chances for intact survival. As a result the nursery-based infants in this country are, in general, quite well protected from the risks of nosocomial infections; but, they receive less than ideal management for cardiorespiratory disorders, a major cause of neonatal mortality. It is obvious that new solutions are required to solve the problem of hospital care of the sick neonate. Unfortunately, both the search for new approaches to neonatal care and the application of some newly established knowledge are now being impaired by rigid rules and construction codes which do not permit innovation. Although these rules cannot be completely abandoned until safe alternatives have been demonstrated, the Committee believes that public health administrators and hospital committees must permit cautious, responsible exploration and evaluation of new approaches to the multiple problems involved.


Author(s):  
Eric Taylor

This chapter presents an account of the clinical picture of attention-deficit/hyperactivity disorder (ADHD) and the severe form hyperkinetic disorder. They are disabilities that change with development and are often accompanied by other problems that can mask it or themselves be masked by it. Clinical and standardized ways of making the diagnosis are described. Inattentiveness and impulsive hyperactivity are rewarding challenges for diagnosis and treatment in adulthood, as well as during childhood and adolescence.


2016 ◽  
Vol 31 (9) ◽  
pp. 1546-1554 ◽  
Author(s):  
Hiroyuki Isayama ◽  
Yousuke Nakai ◽  
Rungsun Rerknimitr ◽  
Christopher Khor ◽  
James Lau ◽  
...  

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A3.2-A3
Author(s):  
Masilo Charles Manyelo ◽  
Regan S Solomons ◽  
Gerhard Walzl ◽  
Novel N Chegou

BackgroundTuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB). It mostly affects young children and results in high morbidity and mortality, mainly due to diagnostic delay. There is an urgent need for new tests for the earlier and accurate diagnosis of the disease. We previously identified a 3-marker cerebrospinal fluid (CSF) biosignature (VEGF, IL-13, and LL-37) with potential to diagnose TBM. In the present study, we show that CSF and blood-based biosignatures may be useful in the diagnosis of TBM.MethodsCSF and serum samples were consecutively collected from 47 children that were admitted to the Tygerberg Academic Hospital in Cape Town, South Africa, on suspicion of having TBM. Using a multiplex platform, the concentrations of 69 host markers were evaluated in the CSF and serum samples from all the study participants, followed by statistical analysis to ascertain the usefulness of these biomarkers as diagnostic candidates for TBM disease.ResultsOut of the 47 study participants, 23 (48.9%) were finally diagnosed with TBM and 6 (12.8%) were infected with HIV. Several CSF and serum biomarkers showed potential individually as diagnostic candidates for TBM as ascertained by area under the receiver operator characteristics curve (AUC). However, the main findings of our study were the identification of a four-marker CSF biosignature which diagnosed TBM with an AUC of 0.97 (95% CI, 0.92–1.00), and a 3-marker serum biosignature which diagnosed TBM with an AUC of 0.84 (95% CI, 0.73–0.96). We also validated a previously identified 3-marker CSF biosignature (VEGF, IL13 and LL37) in the study.ConclusionCSF and serum biosignatures may be useful in the diagnosis of TBM in children. Our findings require further validation in larger, multi-site studies after which the biosignatures may be incorporated into point-of-care diagnostic tests for TBM.


1980 ◽  
Vol 5 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Barbara J. McNeil ◽  
Mark Thompson ◽  
S. James Adelstein

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 38
Author(s):  
Julie Huynh ◽  
Yara-Natalie Abo ◽  
Karen du Preez ◽  
Regan Solomons ◽  
Kelly E Dooley ◽  
...  

Tuberculous meningitis disproportionately affects young children. As the most devastating form of tuberculosis, it is associated with unacceptably high rates of mortality and morbidity even if treated. Challenging to diagnose and treat, tuberculous meningitis commonly causes long-term neurodisability in those who do survive. There remains an urgent need for strengthened surveillance, improved rapid diagnostics technology, optimised anti-tuberculosis drug therapy, investigation of new host-directed therapy, and further research on long-term functional and neurodevelopmental outcomes to allow targeted intervention. This review focuses on the neglected field of paediatric tuberculous meningitis and bridges current clinical gaps with research questions to improve outcomes from this crippling disease.


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