# Accuracy of the Xpert Ultra for Diagnosis of Pulmonary Tuberculosis

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $556,523

## Abstract

The Xpert MTB/RIF assay, an automated, integrated nucleic acid amplification diagnostic test, has been
a major breakthrough in tuberculosis (TB) diagnostics. Yet, large proportions of TB suspects are placed on TB
treatment based on empirical decision-making even in settings where Xpert MTB/RIF is available. Empirical TB
treatment decisions can be problematic, resulting both in under-treatment and in over-treatment. A major driver
of empirical TB treatment is Xpert MTB/RIF’s modest sensitivity in smear-negative pulmonary TB patients – Xpert
MTB/RIF detects only about one-half to two-thirds of such patients. A TB test with exceedingly high sensitivity
and negative predictive value would substantially increase clinicians’ confidence in a negative test result and
thereby shift therapeutic decision making away from empiricism and towards a microbiological evidence-based
approach. To maximize the individual and population level impact of rapid TB diagnostics, the Xpert MTB/RIF
assay has been re-engineered to substantially increase test sensitivity, as demonstrated by preliminary data.
The proposed research will establish the clinical diagnostic accuracy of the new Ultra test in adults with
signs/symptoms of pulmonary TB, and will provide information about the potential impact of Ultra-based
diagnostic algorithms on individual and public health. Project aims are 1) to determine the clinical diagnostic
accuracy of the Ultra test for detection of M. tuberculosis in sputum; 2) to refine estimates of Ultra specificity for
detection of rifampin resistance; and 3) to characterize short-term participant outcomes including initiation of
treatment and to model the potential health impact and cost-effectiveness of TB diagnosis using Ultra. Two
hypotheses will be tested with regard to TB case detection – first, that Ultra sensitivity is superior to that of Xpert
MTB/RIF in adults with smear-negative/culture-confirmed pulmonary TB; and second, that the sensitivity of a
single Ultra test is non-inferior to that of a single liquid culture in adults with pulmonary TB. To accomplish these
aims, a multi-site clinical diagnostic accuracy study will be conducted in Uganda, Kenya, South Africa, and Brazil.
This study will incorporate a robust gold standard of multiple sputum cultures at the time of a participant’s
enrollment; an observational component comprised of follow-up over two months will allow characterization of
treatment initiation patterns and collection of parameter estimates for mathematical models. This proposal will
extend an ongoing early phase Ultra accuracy study currently being performed by the DMID/TB-Clinical
Diagnostics Research Consortium in the same settings, and thereby accrue sufficient participants to test these
novel hypotheses in a step-wise technology evaluation process that is seamless and efficient. Study results are
expected to form the evidence base for World Health Organization policy guidance; a finding that Ultra sensitivity
is non-infe...

## Key facts

- **NIH application ID:** 9850197
- **Project number:** 5R01AI129411-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** David Alland
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $556,523
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850197

## Citation

> US National Institutes of Health, RePORTER application 9850197, Accuracy of the Xpert Ultra for Diagnosis of Pulmonary Tuberculosis (5R01AI129411-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850197. Licensed CC0.

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