| 1. |
- Gaudenzi, Giulia, et al.
(författare)
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Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda) : Observational Cohort Study Protocol of the "PI-POC" Trial
- 2020
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 22:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid-based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
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| 2. |
- Kahn, Robin, et al.
(författare)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
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| 3. |
- Rasti, Reza, et al.
(författare)
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Health care workers' perceptions of point-of-care testing in a low-income country-A qualitative study in Southwestern Uganda
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Point-of-care (POC) tests have become increasingly available and more widely used in recent years. They have been of particular importance to low-income settings, enabling them with clinical capacities that had previously been limited. POC testing programs hold a great potential for significant improvement in low-income health systems. However, as most POC tests are developed in high-income countries, disengagement between developers and end-users inhibit their full potential. This study explores perceptions of POC test end-users in a low-income setting, aiming to support the development of novel POC tests for low-income countries. Methods A qualitative study was conducted in Mbarara District, Southwestern Uganda, in October 2014. Fifty health care workers were included in seven focus groups, comprising midwives, laboratory technicians, clinical and medical officers, junior and senior nurses, and medical doctors. Discussions were audio-recorded and transcribed verbatim. Transcripts were coded through a data-driven approach for qualitative content analysis. Results Nineteen different POC tests were identified as currently being in use. While participants displayed being widely accustomed to and appreciative of the use of POC tests, they also assessed the use and characteristics of current tests as imperfect. An ideal POC test was characterized as being adapted to local conditions, thoughtfully implemented in the specific health system, and capable of improving the care of patients. Tests for specific medical conditions were requested. Opinions differed with regard to the ideal distribution of POC tests in the local health system. Conclusion POC tests are commonly used and greatly appreciated in this study setting. However, there are dissatisfactions with current POC tests and their use. To maximize benefit, stakeholders need to include end-user perspectives in the development and implementation of POC tests. Insights from this study will influence our ongoing efforts to develop POC tests that will be particularly usable in low-income settings.
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| 4. |
- Rasti, Reza
(författare)
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Point-of-care diagnostics of childhood central nervous system infections, with a focus on usability in low-resource settings
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The inaccessibility of laboratory services sustains the high burden of paediatric infectious diseases, such as central nervous system (CNS) infections, in low-resource settings. New contextually fit and well-implemented point-of-care tests (POCTs) could relieve such a burden and narrow the diagnostic divide between rich and poor. Yet, current disengagement between product developers, end-users, and implementors of POCTs impedes their clinical use and utility in low-resource settings. Also, the lack of evidence gathered through field evaluations of many diagnostic instruments in low-resource settings raises questions of their clinical utility there. Objectives: The main aim of this thesis was to provide clinical and contextual guidance for developers of new POCTs for CNS infection diagnosis with high utility, especially in low-resource settings; and to implementors of POCT services towards their optimized clinical benefit. This was addressed through a multidisciplinary combination of qualitative, laboratory, and clinical studies. Methods: Qualitative focus group discussions were conducted with health care workers (HCW) in Mbarara, Uganda (Paper I), and in Stockholm, Sweden (Paper III). Discussions were audio recorded and transcribed verbatim. Qualitative content analysis with an inductive approach was pursued in for data analysis. Comparisons between the two settings were discussed. In Paper II, a vertical flow DNA microarray printed on paper was developed for the detection of Neisseria meningitidis – a major aetiology of paediatric bacterial CNS infection worldwide. The analytical performance of the microarray was laboratory evaluated on DNA extracted from the bacteria, through the detection of the ctrA gene sequence specific to N. meningitidis. In Paper IV, a commercially available polymerase chain reaction (PCR) instrument with the capability of multiplex single-sample cerebrospinal fluid (CSF) microbiology was prospectively field-evaluated for the diagnosis of paediatric CNS infection in Mbarara, Uganda. Clinical turnaround time (cTAT) was defined as time spent from lumbar puncture until reporting of microbiology analyses to clinicians. The PCR instrument’s influence on clinical and patient-centered outcomes (yield, cTAT, duration of hospitalization and antibiotic exposure, patient outcome) was compared to that of bacterial culture. Results: Fifty and 24 HCWs of different professions participated in the qualitative studies in Mbarara and Stockholm, respectively, expressing greater similarities than differences in perspectives of POCT use. POCTs were routinely used at both sites and credited for facilitating differential diagnostics and clinical decision-making. While the Ugandan setting with low laboratory accessibility was highly dependent on POCTs for sample analyses, the Swedish setting credited their use for having clinical and social value. Contrary to the described beneficial aspects, current POCTs were deemed contextually unfit in Mbarara, and their use to cause clinical distraction in Stockholm. Deficient implementation of POCT services was exposed in both places. Requests for ideal POCTs were aligned with those stipulated by the ‘ASSURED’ criteria of the World Health Organization. Specific POCTs for infectious diseases, including CNS infections, were requested. The laboratory study demonstrated an analytical sensitivity of 38 copies of ctrA per assay, with high specificity. The clinical study enrolled 212 children aged 0-12 years who were suspected of having CNS infection, with 193 of them being evaluated using the commercially available PCR instrument. A vast majority of children had been pre-administered antibiotics prior to lumbar puncture. Bacterial yield for the instrument was 12 % vs. 1.5 % for culture, with the addition of the instrument’s detection of viruses in 23 samples. Median cTAT for the instrument was 4.2 hours vs. 2 days for culture. Use of the instrument was associated with a statistically significant shorter antibiotic exposure of bacteria-negative vs. positive patients of five days, measured as from the time of reporting of laboratory results to the responsible clinicians. Similarly, its use was associated with a significantly shorter hospitalization for all-negative patients (five days) compared to those with any microorganism detected by it. No statistically significant differences in patient outcome were found due to its use, nor by its detection of any microorganisms. Conclusion: Point-of-care tests provide laboratory means to settings without laboratory capacity and to situations in need of timely results, and we could show how rapid molecular methods for CSF analysis could benefit paediatric children with suspected CNS infection. Yet, without any observed benefits in patient outcome, and at a cost not financially bearable in most lowresource settings. Contextually fit POCTs for paediatric CNS infections are needed in lowresource settings. Yet, there are design flaws in current POCTs and in implementations for their use, limiting their clinical benefits. Collaborative engagement of product developers, clinicians, laboratory professionals, and health policymakers would better serve low-resource settings with contextually fit POCTs and allow for their optimized implementation. The ‘POCTEST' framework for such an engagement is proposed in this thesis. Finally, as we provided proof of concept for a newly developed paper-printed molecular method, we will pursue its development towards contextual clinical utility in low-resource settings. Should we succeed, we hope to contribute to a decrease in preventable childhood mortality in such settings.
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| 5. |
- Rasti, Reza, et al.
(författare)
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Point-of-care testing in a high-income country paediatric emergency department : a qualitative study in Sweden
- 2021
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In many resource-limited health systems, point-of-care tests (POCTs) are the only means for clinical patient sample analyses. However, the speed and simplicity of POCTs also makes their use appealing to clinicians in high-income countries (HICs), despite greater laboratory accessibility. Although also part of the clinical routine in HICs, clinician perceptions of the utility of POCTs are relatively unknown in such settings as compared with others. In a Swedish paediatric emergency department (PED) where POCT use is routine, we aimed to characterise healthcare providers' perspectives on the clinical utility of POCTs and explore their implementation in the local setting; to discuss and compare such perspectives, to those reported in other settings; and finally, to gather requests for ideal novel POCTs. Design Qualitative focus group discussions study. A data-driven content analysis approach was used for analysis. Setting The PED of a secondary paediatric hospital in Stockholm, Sweden. Participants Twenty-four healthcare providers clinically active at the PED were enrolled in six focus groups. Results A range of POCTs was routinely used. The emerging theme Utility of our POCT use is double-edged illustrated the perceived utility of POCTs. While POCT services were considered to have clinical and social value, the local routine for their use was named to distract clinicians from the care for patients. Requests were made for ideal POCTs and their implementation. Conclusion Despite their clinical integration, deficient implementation routines limit the benefits of POCT services to this well-resourced paediatric clinic. As such deficiencies are shared with other settings, it is suggested that some characteristics of POCTs and of their utility are less related to resource level and more to policy deficiency. To address this, we propose the appointment of skilled laboratory personnel as ambassadors to hospital clinics offering POCT services, to ensure higher utility of such services.
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| 6. |
- Rivas, Lourdes, et al.
(författare)
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A vertical flow paper-microarray assay with isothermal DNA amplification for detection of Neisseria meningitidis
- 2018
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Ingår i: Talanta. - : Elsevier. - 0039-9140 .- 1873-3573. ; 183, s. 192-200
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Tidskriftsartikel (refereegranskat)abstract
- Paper-based biosensors offer a promising technology to be used at the point of care, enabled by good performance, convenience and low-cost. In this article, we describe a colorimetric vertical-flow DNA microarray (DNA-VFM) that takes advantage of the screening capability of DNA microarrays in a paper format together with isothermal amplification by means of Recombinase Polymerase Amplification (RPA). Different assay parameters such as hybridization buffer, flow rate, printing buffer and capture probe concentration were optimized. A limit of detection (LOD) of 4.4 nM was achieved as determined by tabletop scanning. The DNA-VFM was applied as a proof of concept for detection of Neisseria meningitidis, a primary cause of bacterial meningitis. The LOD was determined to be between 38 and 2.1Å~106 copies/VFM assay, depending on the choice of DNA capture probes. The presented approach provides multiplex capabilities of DNA microarrays in a paper-based format for future point-of-care applications.
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