Table 3 - uploaded by Soyeon Kim
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Diagnostic components included in NIH definition and corresponding criteria applied to the P1041 database
Source publication
Setting:
Standardized clinical case definitions represent the best option for pediatric tuberculosis (TB) disease diagnosis and classification.
Objective:
To apply published guidelines for intrathoracic TB classification for use in reporting diagnostic studies with passive case finding to presumed TB patients from International Maternal Pediatri...
Contexts in source publication
Context 1
... 2 shows the P1041 and NIH definitions used. 4,5 Of note, because this was a retrospective study, requirements for NIH criteria could not be evaluated precisely and divergences in application to the P1041 data set are outlined in Table 3. The following diagnostic components included in the NIH definitions were assessed for each presumed TB case: microbial confirmation, clinical signs/ symptoms suggestive of TB (persistent cough, weight loss/failure to thrive, persistent unexplained fever, persistent unexplained lethargy or reduced playful- ness), interpretation of CXR, TB exposure, immuno- logical evidence of Mycobacterium tuberculosis infection, and response to anti-tuberculosis treat- ment. ...
Context 2
... This study includes a number of limitations. While P1041 clinical criteria were prospectively captured, retrospective application of NIH classifications to the P1041 database required some adaptation (Table 3). Because of the retrospective nature of this study we were only able define signs/symptoms criteria based on what was captured in the database (fever .1 week, cough .2 ...
Citations
... The diagnosis of pulmonary tuberculosis disease was established according to the first 3 diagnostic categories of NIH criteria. 12 The first category included confirmed tuberculosis cases with positive smear of sputum or early morning gastric aspirate and/or positive culture for Mycobacterium tuberculosis. The second category included highly probable cases having clinical symptoms and radiological signs of tuberculosis disease with an active or recently treated family member with tuberculosis disease. ...
Objective: Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) are useful biomarkers of inflammation used to evaluate bacteremia, disease activity, recurrence rate, surveillance and prognosis in many diseases. In this study, we evaluated NLR and MLR of 92 children with tuberculosis versus 45 healthy children to show whether they can be used as inflammation markers. Aim of this study was to evaluate the diagnostic valure of NLR and MLR in childhood tuberculosis.Materials and Methods: In this retrospective study, hospital records of 92 children with tuberculosis were reviewed. The NLR and MLR values of the patients were compared with the control group of 45 healthy children.Results: A significant difference was found between NLO and MLO values between tuberculosis and control groups (p <0.001). A cut off value of NLR>1.41was optimal for discriminating patients with tuberculosis from controls (sensitivity 75%, specifity 82.2%, positive predictive value 89.6%, negative predictive value 61.7%). A cut off value of MLR>0.22 was optimal for discriminating patients with tuberculosis from controls (sensitivity 50%, specifity 91.1%, positive predictive value 93.3%, negative predictive value 53.2%).Conclusions: NLR and MLR can both be used as inflammation biomarkers in the diagnosis of childhood tuberculosis. Prospective and more comprehensive studies are needed to make a clearer decision.
... The diagnosis of tuberculosis disease was established according to the first 3 diagnostic categories of NIH criteria. [13] The first category included confirmed tuberculosis cases with positive smear of sputum or early morning gastric aspirate and/ or positive culture for M.tuberculosis. The second category included highly probable cases having clinical symptoms and radiological signs of tuberculosis disease with an active or recently treated family member with tuberculosis disease. ...
Background: The neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio(MLR) are useful biomarkers of inflammation used in many diseases to evaluate bacteremia, disease activity, recurrence rate, surveillance and prognosis.
Objective: Aim of this study was to evaluate NLR and MLR in the differential diagnosis of children with pulmonary tuberculosis disease from CAP.
Materials and Methods: I reviewed hospital-records of 50 children with pulmonary tuberculosis disease in the Pediatric Infectious Disease Ward between June 2016 and December 2018, and compared; NLR and MLR with 50 CAP and 50 healthy children. Also; erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) were compared between the tuberculosis and CAP group.
Results: When 3 groups were compared there was significant difference among NLR and MLR values between 3 groups. In pairwise-comparisons, there was significant difference among NLR and MLR values between tuberculosis versus healthy controls, and CAP versus healthy controls. However, there was no significant difference among NLR, MLR values between tuberculosis versus CAP groups.
Conclusion: This study is unique that evluates NLR and MLR in tuberculosis differentiation. Although NLR and MLR values are useful biomarkers of inflammation in both pulmonary tuberculosis and CAP seperately, they’re not as useful as expected in differentiating tuberculosis from CAP in children.
... When appropriate, investigators may wish to improve specificity by combining them with data from a clinical evaluation or prescription of treatment. One potential contributor to the observed discrepancies between NIH case definitions and clinical decision making is that the NIH case definitions were not designed for the setting of active case finding 13,14 and some of children presented to health facilities following contact tracing activities. Another consideration is that NIH case definitions apply equal weight to each criterion, while clinicians may implicitly or explicitly weight factors differently or consider factors beyond those noted in case definitions (e.g., access to care). ...
We followed 35 children meeting a research definition for unconfirmed tuberculosis but in whom a pediatric pulmonologist did not diagnose or treat tuberculosis. After a median follow-up of 16.4 months, most children were not diagnosed with tuberculosis following a comprehensive evaluation. However, two were diagnosed with tuberculosis, demonstrating high TB risk (6%; exact 95% confidence interval: 1%-19%). In some contexts, researchers may wish to supplement these research definitions with clinical decision data and longitudinal follow-up in order to improve specificity.
... When appropriate, investigators may wish to improve specificity by combining them with data from a clinical evaluation or prescription of treatment. One potential contributor to the observed discrepancies between NIH case definitions and clinical decision making is that the NIH case definitions were not designed for the setting of active case finding 13,14 and some of children presented to health facilities following contact tracing activities. Another consideration is that NIH case definitions apply equal weight to each criterion, while clinicians may implicitly or explicitly weight factors differently or consider factors beyond those noted in case definitions (e.g., access to care). ...
We followed 35 children meeting a research definition for unconfirmed tuberculosis but in whom a pediatric pulmonologist did not diagnose or treat tuberculosis. After a median follow-up of 16.4 months, most children were not diagnosed with tuberculosis following a comprehensive evaluation. However, two were diagnosed with tuberculosis, demonstrating high TB risk (6%; exact 95% confidence interval: 1% - 19%). In some contexts, researchers may wish to supplement these research definitions with clinical decision data and longitudinal follow-up in order to improve specificity.
... As it has been demonstrated in MR, using many ostensible Mendelian factors where some are invalid may have the potential to improve the robustness of MFD analysis (Kang et al., 2016). Finally, the application of MFD to the study of vaccines against other childhood diseases that have unspecific symptoms and no gold-standard case definition, such as pediatric tuberculosis (Beneri et al., 2016), could prove fruitful if plausible mendelian factors can be identified. ...
Accurate estimates of malaria vaccine efficacy require a reliable definition of a malaria case. However, the symptoms of clinical malaria are unspecific, overlapping with other childhood illnesses. Additionally, children in endemic areas tolerate varying levels of parasitemia without symptoms. Together, this makes finding a gold-standard case definition challenging. We present a method to identify and estimate malaria vaccine efficacy that does not require an observable gold-standard case definition. Instead, we leverage genetic traits that are protective against malaria but not against other illnesses, e.g., the sickle cell trait, to identify vaccine efficacy in a randomized trial. Inspired by Mendelian randomization, we introduce Mendelian factorial design, a method that augments a randomized trial with genetic variation to produce a natural factorial experiment, which identifies vaccine efficacy under realistic assumptions. A robust, covariance adjusted estimation procedure is developed for estimating vaccine efficacy on the risk ratio and incidence ratio scales. Simulations suggest that our estimator has good performance whereas standard methods are systematically biased. We demonstrate that a combined estimator using both our proposed estimator and the standard approach yields significant improvements when the Mendelian factor is only weakly protective.
... Definitions will need to be developed for different scenarios such as involving active case finding, for example, during household contact studies, but this is outside the present scope of work. Evaluation of data from active case-finding studies, one as a cohort study with active follow-up [23] and the other as a community-based tuberculosis contact investigation study [24], have reported that 12% and 65%, respectively, of children with confirmed tuberculosis did not have clinical features consistent with the standardized "clinical signs/symptoms suggestive of tuberculosis" used to categorize clinical, unconfirmed cases. Active case finding is likely to identify cases at an earlier stage of disease and a much shorter duration of symptoms compared with children investigated for tuberculosis at the referral level. ...
Consensus case definitions for childhood tuberculosis have been proposed by an international expert panel, aiming to standardize
the reporting of cases in research focusing on the diagnosis of intrathoracic tuberculosis in children. These definitions
are intended for tuberculosis diagnostic evaluation studies of symptomatic children with clinical suspicion of intrathoracic
tuberculosis, and were not intended to predefine inclusion criteria into such studies. Feedback from researchers suggested
that further clarification was required and that these case definitions could be further improved. Particular concerns were
the perceived complexity and overlap of some case definitions, as well as the potential exclusion of children with acute onset
of symptoms or less severe disease. The updated case definitions proposed here incorporate a number of key changes that aim
to reduce complexity and improve research performance, while maintaining the original focus on symptomatic children suspected
of having intrathoracic tuberculosis. The changes proposed should enhance harmonized classification for intrathoracic tuberculosis
disease in children across studies, resulting in greater comparability and the much-needed ability to pool study results.
Accurate estimates of malaria vaccine efficacy require a reliable definition of a malaria case. However, the symptoms of clinical malaria are unspecific, overlapping with other childhood illnesses. Additionally, children in endemic areas tolerate varying levels of parasitemia without symptoms. Together, this makes finding a gold-standard case definition challenging. We present a method to identify and estimate malaria vaccine efficacy that does not require an observable gold-standard case definition. Instead, we leverage genetic traits that are protective against malaria but not against other illnesses, e.g., the sickle cell trait, to identify vaccine efficacy in a randomized trial. Inspired by Mendelian randomization, we introduce Mendelian factorial design, a method that augments a randomized trial with genetic variation to produce a natural factorial experiment, which identifies vaccine efficacy under realistic assumptions. A robust, covariance adjusted estimation procedure is developed for estimating vaccine efficacy on the risk ratio and incidence rate ratio scales. Simulations suggest that our estimator has good performance whereas standard methods are systematically biased. We demonstrate that a combined estimator using both our proposed estimator and the standard approach yields significant improvements when the Mendelian factor is only weakly protective. Our method can be applied in vaccine and prevention trials of other childhood diseases that have no gold-standard case definition and known genetic risk factors.
