ABSTRACT
Diagnosis of tuberculosis (TB) among young children (<5 years) is challenging due to the paucibacillary nature of clinical disease and clinical similarities to other childhood diseases. We used machine learning to develop accurate prediction models of microbial confirmation with simply defined and easily obtainable clinical, demographic, and radiologic factors. We evaluated eleven supervised machine learning models (using stepwise regression, regularized regression, decision tree, and support vector machine approaches) to predict microbial confirmation in young children (<5 years) using samples from invasive (reference-standard) or noninvasive procedure. Models were trained and tested using data from a large prospective cohort of young children with symptoms suggestive of TB in Kenya. Model performance was evaluated using areas under the receiver operating curve (AUROC) and precision-recall curve (AUPRC), accuracy metrics. (i.e., sensitivity, specificity), F-beta scores, Cohen's Kappa, and Matthew's Correlation Coefficient. Among 262 included children, 29 (11%) were microbially confirmed using any sampling technique. Models were accurate at predicting microbial confirmation in samples obtained from invasive procedures (AUROC range: 0.84-0.90) and from noninvasive procedures (AUROC range: 0.83-0.89). History of household contact with a confirmed case of TB, immunological evidence of TB infection, and a chest x-ray consistent with TB disease were consistently influential across models. Our results suggest machine learning can accurately predict microbial confirmation of M. tuberculosis in young children using simply defined features and increase the bacteriologic yield in diagnostic cohorts. These findings may facilitate clinical decision making and guide clinical research into novel biomarkers of TB disease in young children.
ABSTRACT
Background: Despite Kenya's roll-out of the Strengthening Laboratory Management Towards Accreditation programme in 2010, most laboratories had not made significant or tangible improvements towards accreditation by 2016. In April 2016, the University of Maryland, Baltimore enrolled 27 facilities in the standard Strengthening Laboratory Management Towards Accreditation programme. Objective: This study aimed to describe and evaluate the implementation of an intensified mentorship strategy on laboratory accreditation. Methods: In October 2017, the University of Maryland, Baltimore implemented intensive mentorship in 27 hospital laboratories in Nairobi, Kiambu, Meru, Embu, Muranga, Nyeri, Laikipia, Nyandarua, Tharaka-Nithi, and Kirinyaga counties in Kenya. Laboratories were paired with competent mentors whose skills were matched to facility gaps. Baseline and follow-up assessments were done between April 2016 and March 2019 using the World Health Organization's Stepwise Laboratory Quality Improvement Process Towards Accreditation Checklist and overall scores of the 12 Quality System Essentials and star ratings (from zero to five, based on scores) used to evaluate the effectiveness of the intensified mentorship. Results: In September 2017, 14 laboratories scored zero stars, three scored one star, eight scored two stars, one scored three stars, and one laboratory was accredited. By March 2019, eight laboratories were accredited, five scored four stars, 10 scored three stars, three scored two stars, and only one scored one star. The average score change with the intensified approach was 81.5 versus 53.9 for the standard approach. Conclusion: The intensified mentorship strategy resulted in fast-tracked progress towards laboratory accreditation and can be adopted in similar resource-limited settings.
ABSTRACT
Background: Despite Kenya's roll-out of the Strengthening Laboratory Management Towards Accreditation programme in 2010, most laboratories had not made significant or tangible improvements towards accreditation by 2016. In April 2016, the University of Maryland, Baltimore enrolled 27 facilities in the standard Strengthening Laboratory Management Towards Accreditation programme. Objective: This study aimed to describe and evaluate the implementation of an intensified mentorship strategy on laboratory accreditation. Methods: In October 2017, the University of Maryland, Baltimore implemented intensive mentorship in 27 hospital laboratories in Nairobi, Kiambu, Meru, Embu, Muranga, Nyeri, Laikipia, Nyandarua, Tharaka-Nithi, and Kirinyaga counties in Kenya. Laboratories were paired with competent mentors whose skills were matched to facility gaps. Baseline and follow-up assessments were done between April 2016 and March 2019 using the World Health Organization's Stepwise Laboratory Quality Improvement Process Towards Accreditation Checklist and overall scores of the 12 Quality System Essentials and star ratings (from zero to five, based on scores) used to evaluate the effectiveness of the intensified mentorship.Results: In September 2017, 14 laboratories scored zero stars, three scored one star, eight scored two stars, one scored three stars, and one laboratory was accredited. By March 2019, eight laboratories were accredited, five scored four stars, 10 scored three stars, three scored two stars, and only one scored one star. The average score change with the intensified approach was 81.5 versus 53.9 for the standard approach.Conclusion: The intensified mentorship strategy resulted in fast-tracked progress towards laboratory accreditation and can be adopted in similar resource-limited settings
Subject(s)
Humans , Male , Female , Bibliography of Medicine , Accreditation , Laboratories , Mentors , Early Ambulation , Hospital AccreditationABSTRACT
Importance: Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. Objective: To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. Design, Setting, and Participants: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. Main Outcomes and Measures: Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. Results: Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). Conclusions and Relevance: NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.
