Patients with presumed tuberculosis in sub-Saharan Africa that are not diagnosed with tuberculosis: a systematic review and meta-analysis

Jayasooriya, Shamanthi; Dimambro-Denson, F; Beecroft, Claire; Balen, Julie; Awokola, Babatunde; Mitchell, Caroline; Kampmann, Beate; Campbell, Fiona; Dodd, Peter J.; Mortimer, Kevin

doi:10.1101/2021.05.19.21257444

Cited by 1 publication

(1 citation statement)

References 32 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In terms of sensitivity and specificity in HIV-positive people, symptoms (i.e., the WHO four symptom screen) have 83% sensitivity and 38% specificity, with sensitivity lowest in outpatients on ART and pregnant women, and specificity lowest in inpatients [ 36 ]. The key weakness of syndromic screening is specificity: most patients referred for confirmatory diagnoses will be further investigated unnecessarily for TB and their true underlying healthcare needs will remain undiscovered [ 37 ]. Notably, the sensitivity and specificity of the WHO four symptom screen does not meet TPP benchmarks (concerningly, the performance is often further worsened by facilities unable to do high-quality symptom screening [ 31 , 38 , 39 , 40 , 41 ]).…”

Section: Triage Toolsmentioning

confidence: 99%

Diagnosing Tuberculosis: What Do New Technologies Allow Us to (Not) Do?

Abdulgader¹,

Ojo-Okunola²,

Ndlangalavu³

et al. 2022

Respiration

View full text Add to dashboard Cite

New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those – already available tests that remain suboptimally utilized.

show abstract