scholarly journals Standardized approaches for clinical sampling and endpoint ascertainment in tuberculous meningitis studies

2020 ◽  
Vol 4 ◽  
pp. 204
Author(s):  
Ursula K Rohlwink ◽  
Felicia C Chow ◽  
Sean Wasserman ◽  
Sofiati Dian ◽  
Rachel PJ Lai ◽  
...  
Keyword(s):  
Tuberculous Meningitis ◽  
Science Research ◽  
Clinical Samples ◽  
Pharmacokinetic Studies ◽  
Sampling Strategies ◽  
Antituberculous Therapy ◽  
Mortality And Morbidity ◽  
Resource Limited ◽  
Severe Manifestation ◽  
Practical Recommendations

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.

scholarly journals Standardized approaches for clinical sampling and endpoint ascertainment in tuberculous meningitis studies

2019 ◽  
Vol 4 ◽  
pp. 204 ◽  
Author(s):  
Ursula K Rohlwink ◽  
Felicia C Chow ◽  
Sean Wasserman ◽  
Sofiati Dian ◽  
Rachel PJ Lai ◽  
...  
Keyword(s):  
Tuberculous Meningitis ◽  
Science Research ◽  
Clinical Samples ◽  
Pharmacokinetic Studies ◽  
Sampling Strategies ◽  
Antituberculous Therapy ◽  
Mortality And Morbidity ◽  
Resource Limited ◽  
Severe Manifestation ◽  
Practical Recommendations

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.

scholarly journals Tuberculous meningitis – clinical and laboratory review of 100 patients

1986 ◽  
Vol 96 (2) ◽  
pp. 231-238 ◽  
Author(s):  
M. E. Kilpatrick ◽  
N. I. Girgis ◽  
M. W. Yassin ◽  
A. A. Abu El Ella
Keyword(s):  
Central Nervous System ◽  
Tuberculous Meningitis ◽  
Clinical Course ◽  
Laboratory Data ◽  
Severity Of Illness ◽  
X Rays ◽  
Antituberculous Therapy ◽  
Mortality And Morbidity ◽  
Neurologic Sequelae ◽  
Physical Findings

SUMMARYIn developing countries tuberculous meningitis is a difficult infection to differentiate from other central nervous system (CNS) infections. This paper presents the history, physical findings, laboratory data, and clinical course of 100 patients who were admitted to a special ward and had CSF cultures positive for Mycobacterium tuberculosis. Fifty-four patients were comatose when admitted and 76 had meningeal signs. Mean admission CSF values were WBC 531, glucose 23 mg/dl, and protein 166 mg/dl. Only two CSF AFB smears were positive. Sixty-one percent of the chest X-rays taken were consistent with pulmonary tuberculous and 39% were normal. Twenty-four patients died within the first week after admission, before the clinical diagnosis was made and anti-tuberculous therapy could be started. Fifty-three of 76 patients given antituberculous therapy died. Neurologic sequelae developed in 48% of the survivors. The high mortality and morbidity rates in this patient-group were due to the severity of illness on admission and the predominance of children (54%).

scholarly journals Pulmonary tuberculosis due to Mycobacterium microti: a study of six recent cases in France

2010 ◽  
Vol 59 (8) ◽  
pp. 984-989 ◽  
Author(s):  
G. Panteix ◽  
M. C. Gutierrez ◽  
M. L. Boschiroli ◽  
M. Rouviere ◽  
A. Plaidy ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Clinical Significance ◽  
Molecular Techniques ◽  
Clinical Samples ◽  
Microbiological Diagnosis ◽  
Review Of The Literature ◽  
Antituberculous Therapy ◽  
Clinical Illness ◽  
Mycobacterium Microti ◽  
Immunocompetent Patients

Human tuberculosis caused by Mycobacterium microti is rare, but its prevalence and clinical significance may have been underestimated. To the best of our knowledge, 21 cases have been reported in the literature in the last decade. We report six recent pulmonary cases caused by M. microti over a period of 5 years detected in French clinical mycobacteriology laboratories of the hospital network. Our data confirm the potential of M. microti to cause clinical illness in immunocompetent patients. M. microti grew slowly from specimens, delaying the final microbiological diagnosis. Therefore, patients with tuberculosis caused by M. microti could benefit from the use of rapid diagnostic molecular techniques directly on clinical samples. From a review of the literature and this study, a classical antituberculous therapy seems effective in treating patients with M. microti disease.

scholarly journals Precincts and Prospects in the Use of Focus Groups in Social and Behavioral Science Research

2015 ◽  
Author(s):  
Dominic Sagoe
Keyword(s):  
Focus Group ◽  
Focus Groups ◽  
Behavioral Science ◽  
Science Research ◽  
Group Method ◽  
Behavioural Science ◽  
Behavioral Science Research ◽  
Social And Behavioral Science ◽  
Focus Group Method ◽  
Practical Recommendations

Over the past few years, the focus group method has assumed a very important role as a method for collecting qualitative data in social and behavioural science research. This article elucidates theoretical and practical problems and prospects associated with the use of focus groups as a qualitative research method in social and behavioural science research. The core uses of focus groups in social and behavioural science research are discussed. In addition, the strengths and limitations of employing focus groups in social and behavioural science research are elucidated. Furthermore, the article discusses practical recommendations for strengthening the focus group method in social and behavioural science research.

scholarly journals Direct Viral RNA Detection of SARS-CoV-2 and DENV in Inactivated Samples by Real-Time RT-qPCR: Implications for Diagnosis in Resource Limited Settings with Flavivirus Co-Circulation

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1558
Author(s):  
Zhan Qiu Mao ◽  
Mizuki Fukuta ◽  
Jean Claude Balingit ◽  
Thi Thanh Ngan Nguyen ◽  
Co Thach Nguyen ◽  
...  
Keyword(s):  
Real Time ◽  
Early Stage ◽  
Rna Extraction ◽  
Viral Rna ◽  
Clinical Samples ◽  
Heat Inactivation ◽  
Resource Limited Settings ◽  
Rna Detection ◽  
Resource Limited ◽  
Starting Point

The RT-qPCR method remains the gold standard and first-line diagnostic method for the detection of SARS-CoV-2 and flaviviruses, especially in the early stage of viral infection. Rapid and accurate viral detection is a starting point in the containment of the COVID-19 pandemic and flavivirus outbreaks. However, the shortage of diagnostic reagents and supplies, especially in resource-limited countries that experience co-circulation of SARS-CoV-2 and flaviviruses, are limitations that may result in lesser availability of RT-qPCR-based diagnostic tests. In this study, the utility of RNA-free extraction methods was assessed for the direct detection of SARS-CoV-2 and DENV-2 in heat-inactivated or chemical-inactivated samples. The findings demonstrate that direct real-time RT-qPCR is a feasible option in comparison to conventional real-time RT-qPCR based on viral genome extraction-based methods. The utility of heat-inactivation and direct real-time RT-qPCR for SARS-CoV-2, DENV-2 viral RNA detection was demonstrated by using clinical samples of SARS-CoV-2 and DENV-2 and spiked cell culture samples of SARS-CoV-2 and DENV-2. This study provides a simple alternative workflow for flavivirus and SARS-CoV-2 detection that includes heat inactivation and viral RNA extraction-free protocols, with aims to reduce the risk of exposure during processing of SARS-CoV-2 biological specimens and to overcome the supply-chain bottleneck, particularly in resource limited settings with flavivirus co-circulation.

scholarly journals Selecting topic areas for developing quality standards in a resource-limited setting

2019 ◽  
Vol 8 (1) ◽  
pp. e000491
Author(s):  
Roongnapa Khampang ◽  
Sarayuth Khuntha ◽  
Phorntida Hadnorntun ◽  
Suthasinee Kumluang ◽  
Thunyarat Anothaisintawee ◽  
...  
Keyword(s):  
Priority Setting ◽  
Quality Standards ◽  
Healthcare Services ◽  
Priority Setting Process ◽  
Deliberative Process ◽  
Mortality And Morbidity ◽  
Stakeholder Consultation ◽  
Healthcare Settings ◽  
Resource Limited ◽  
Setting Process

Variation in practices of and access to health promotion and disease prevention (P&P) across geographical areas have been studied in Thailand as well as other healthcare settings. The implementation of quality standards (QS)—a concise set of evidence-informed quality statements designed to drive and measure priority quality improvements—can be an option to solve the problem. This paper aims to provide an overview of the priority setting process of topic areas for developing QS and describes the criteria used. Topic selection consisted of an iterative process involving several steps and relevant stakeholders. Review of existing documents on the principles and criteria used for prioritising health technology assessment topics were performed. Problems with healthcare services were reviewed, and stakeholder consultation meetings were conducted to discuss current problems and comment on the proposed prioritisation criteria. Topics were then prioritised based on both empirical evidence derived from literature review and stakeholders’ experiences through a deliberative process. Preterm birth, pre-eclampsia and postpartum haemorrhage were selected. The three health problems had significant disease burden; were prevalent among pregnant women in Thailand; led to high mortality and morbidity in mothers and children and caused variation in the practices and service uptake at health facilities. Having agreed-on criteria is one of the important elements of the priority setting process. The criteria should be discussed and refined with various stakeholders. Moreover, key stakeholders, especially the implementers of QS initiative, should be engaged in a constructive way and should be encouraged to actively participate and contribute significantly in the process.

scholarly journals Aetiology, Clinical Presentation, and Outcome of Meningitis in Patients Coinfected with Human Immunodeficiency Virus and Tuberculosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Smita Bhagwan ◽  
Kogieleum Naidoo
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Tuberculous Meningitis ◽  
Clinical Presentation ◽  
Case Series ◽  
Antituberculous Therapy ◽  
Endemic Region ◽  
Neck Stiffness ◽  
Immunodeficiency Virus ◽  
Poor Outcomes

We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART.

scholarly journals Tuberculous Meningitis in Children: Reducing the Burden of Death and Disability

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 38
Author(s):  
Julie Huynh ◽  
Yara-Natalie Abo ◽  
Karen du Preez ◽  
Regan Solomons ◽  
Kelly E Dooley ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Tuberculous Meningitis ◽  
Rapid Diagnostics ◽  
Targeted Intervention ◽  
Neurodevelopmental Outcomes ◽  
New Host ◽  
Mortality And Morbidity ◽  
Research Questions ◽  
Meningitis In Children

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.

scholarly journals Social Science Methods to Study Human–Cheetah Interactions

2018 ◽  
Author(s):  
Niki Rust ◽  
Courtney Hughes
Keyword(s):  
Social Science ◽  
Social Science Research ◽  
Science Research ◽  
Human Dimensions ◽  
Science Methods ◽  
Sampling Strategies ◽  
Advantages And Disadvantages ◽  
Social Science Methods

We are living in a new geological era – the Anthropocene - so called because of humanity’s far-reaching effects on the environment. As our population grows, threats towards biodiversity, including those associated with human-cheetah conflict, also increase. Social science research enables conservationists to understand and address the human dimensions of these challenges. This chapter describes common social science paradigms, theories, methodologies, methods and sampling strategies useful for studying human-cheetah interactions, as these types of studies are lacking. We explain the advantages and disadvantages of these methods, ethical and practical considerations, and use existing or comparable examples to highlight their use in cheetah research and conservation. Social science methods can be challenging to conduct, so we advise the importance for cheetah ecologists and practitioners to collaborate with social science experts.

scholarly journals High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)

2020 ◽  
Vol 4 ◽  
pp. 190
Author(s):  
Suzaan Marais ◽  
Fiona V Cresswell ◽  
Raph L. Hamers ◽  
Lindsey H.M. te Brake ◽  
Ahmad R. Ganiem ◽  
...  
Keyword(s):  
Tuberculous Meningitis ◽  
Survival Benefit ◽  
Standard Dose ◽  
Standard Of Care ◽  
Phase Iii ◽  
World Health ◽  
Hiv Positive ◽  
High Dose ◽  
Pharmacokinetic Studies ◽  
Dose Oral

Background: Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), results in death or neurological disability in >50%, despite World Health Organisation recommended therapy. Current TBM regimen dosages are based on data from pulmonary TB alone. Evidence from recent phase II pharmacokinetic studies suggests that high dose rifampicin (R) administered intravenously or orally enhances central nervous system penetration and may reduce TBM associated mortality. We hypothesize that, among persons with TBM, high dose oral rifampicin (35 mg/kg) for 8 weeks will improve survival compared to standard of care (10 mg/kg), without excess adverse events. Protocol: We will perform a parallel group, randomised, placebo-controlled, double blind, phase III multicentre clinical trial comparing high dose oral rifampicin to standard of care. The trial will be conducted across five clinical sites in Uganda, South Africa and Indonesia. Participants are HIV-positive or negative adults with clinically suspected TBM, who will be randomised (1:1) to one of two arms: 35 mg/kg oral rifampicin daily for 8 weeks (in combination with standard dose isoniazid [H], pyrazinamide [Z] and ethambutol [E]) or standard of care (oral HRZE, containing 10 mg/kg/day rifampicin). The primary end-point is 6-month survival. Secondary end points are: i) 12-month survival ii) functional and neurocognitive outcomes and iii) safety and tolerability. Tertiary outcomes are: i) pharmacokinetic outcomes and ii) cost-effectiveness of the intervention. We will enrol 500 participants over 2.5 years, with follow-up continuing until 12 months post-enrolment. Discussion: Our best TBM treatment still results in unacceptably high mortality and morbidity. Strong evidence supports the increased cerebrospinal fluid penetration of high dose rifampicin, however conclusive evidence regarding survival benefit is lacking. This study will answer the important question of whether high dose oral rifampicin conveys a survival benefit in TBM in HIV-positive and -negative individuals from Africa and Asia. Trial registration: ISRCTN15668391 (17/06/2019)

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