Paediatric Infections Point-Of-Care: Point-of-care Approach for Rapid and Easy Meningitis Diagnosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 351
- 试验地点
- 2
- 主要终点
- Diagnostic accuracy of vertical flow microarray printed on paper for pathogen identification in human cerebrospinal fluid samples
研究概览
简要总结
This study aims to identify the aetiology of childhood meningitis in Southwestern Uganda and develop and evaluate new methods for point-of-care diagnosis of childhood meningitis in a low-income setting. A prospective observational study including 600 children aged 0-12 years will be conducted during 1 year in Mbarara, Uganda. We estimate to recruit about 300 children with suspected meningitis (cases), and 300 with non-severe infection age-matched as controls.
详细描述
The current gold standard for laboratory diagnostics of suspected childhood meningitis are microbiology culture of CSF and polymerase chain reaction (PCR). However, these methods are expensive, time-consuming, require dedicated facilities and trained professionals, that are often lacking in low-income health systems. Our team has developed a new vertical flow paper printed microarray method for rapid, inexpensive and multiplexed microbiology analysis of cerebrospinal fluid (CSF), with potential for point-of-care use in low-income settings. This study will evaluate the diagnostic accuracy of this newly developed paper printed microarray method.
The bioMérieux FilmArray® ME Panel is an existing multiplexed PCR based system for rapid microbiology analyses of CSF. Even though previous studies have reported good diagnostic accuracy of the FilmArray® system, the studies have mostly been focused on evaluating the system in high-income settings.
This study will do a field evaluation of the diagnostic performance and clinical usability of the FilmArray® ME Panel in a low-income setting in Mbarara, Uganda.
A study by Page et al, conducted 2009-2012 in Mbarara, Uganda, identified the most frequent pathogen causing childhood bacterial meningitis to be Streptococcus pneumoniae. This is also the case on a global level, with the addition of the bacteria Neisseria meningitidis and Haemophilus influenzae type B. However, the Page study did not find a single case of Neisseria meningitidis, which is in contrast to most other reports from low-, middle- and high-income countries. Furthermore, after the finalisation of the Page study, pneumococcal conjugate vaccines were introduced to the Ugandan childhood immunisation program. This study will identify the current aetiology of childhood meningitis and the impact of the pneumococcal conjugate vaccine, in Mbarara, Uganda, and also study the carriage and characteristics of Neisseria meningitis in children in the area.
Myxovirus resistance protein A (MxA) blood levels have been reported to be elevated in children with respiratory tract infections of viral aetiology, as compared to bacterial aetiology. Previous studies have also shown a higher abundance of MxA in viral encephalitis, however this only through histological analyses of post-mortem brain tissue samples.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 0 months to 12 years of age, who
- •meet the case or control definition criteria, and where
- •informed consent is obtained from the parent or guardian
排除标准
- •all 3 inclusion criteria not met
- •No, insufficient or inappropriate CSF sample collection
结局指标
主要结局
Diagnostic accuracy of vertical flow microarray printed on paper for pathogen identification in human cerebrospinal fluid samples
时间窗: Patient CSF will be analysed with culture, PCR and FilmArray during ongoing patient management in Mbarara, Uganda. Analyses on frozen patient CSF samples with vertical flow paper printed microarray will be done in Stockholm, Sweden within 1 year.
The newly developed assay will be evaluated with regards to diagnostic accuracy. For this, results will be compared with those from bacterial culture, PCR and FilmArray analyses of the same samples.
次要结局
- Protein profile variance between children with severe and non-severe infection(Frozen patient blood samples will be analyzed using Luminex Multiplex Assays in Stockholm, Sweden, within 1 year after sample collection in Mbarara, Uganda.)
- Variance in concentration of MxA in blood of patients with viral vs. non-viral meningitis and non-severe infection.(MxA concentration measurements will be conducted on the Luminex platform on frozen patient blood samples in Stockholm, Sweden, within a year from sample collection.)
- Diagnostic performance of the FilmArray ME Panel for meningitis diagnostics in children in a low-income setting(FilmArray analyses on fresh patient CSF samples will be conducted immediately after or within 1 day of sample collection.)
- Clinical impact of the FilmArray ME Panel on management of childhood meningits in a low-income setting.(FilmArray analyses on fresh patient CSF samples will be conducted immediately after or within 1 day of sample collection.)
- Usability of the FilmArray ME Panel for meningitis diagnostics in children in a low-income setting.(Questionnaires will be handed out and collected from participants continuously during the 1 year duration of patient inclusion.)
- Mapping of Neisseria meningitidis carriage and prevalence in children in Mbarara, Uganda(Nasopharyngeal swabs will be collected upon inclusion to the study. Sequencing and serotyping will be done in Stockholm, Sweden, within 1 year after sample collection.)
- Etiology of childhood meningitis in the Mbarara district, Uganda.(CSF culture, PCR and FilmArray analyses will be conducted during the 1 year duration of the study, in Mbarara, Uganda.)
- The impact of pneumococcal conjugate vaccines on aetiology of childhood meningits in the Mbarara district.(CSF culture, PCR and FilmArray analyses will be conducted during the 1 year duration of the study, in Mbarara, Uganda.)
研究者
Tobias Alfvén
Associate Professor
Karolinska Institutet