# Targeted next-generation sequencing to enhance detection and genomic characterization of Mycobacterium tuberculosis and high-impact bacterial pathogens among HIV-infected adults with sepsis in Uganda

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $282,467

## Abstract

Project Summary
Over the past two decades, disseminated Mycobacterium tuberculosis (MTB) has been increasingly
recognized as the leading cause of fatal bloodstream infection in HIV-infected patients with sepsis in high-
burden tuberculosis (TB)/HIV settings worldwide. In these settings, estimated prevalence of MTB bacteremia in
HIV-infected adults presenting with sepsis is as high as 40% with mortality approaching 50%. Despite high
prevalence and mortality, timely and accurate diagnosis of MTB bacteremia and concomitant TB drug
resistance remains challenging and is often diagnosed post-mortem. Novel diagnostic strategies are needed to
expedite identification and treatment of critically ill patients with MTB bacteremia and other severe bloodstream
infections in high-burden TB/HIV settings. The overall goal of this study is to enhance rapid molecular detection
of MTB and other high-impact bacterial pathogens among HIV-infected adults with sepsis through use of an
innovative, highly sensitive next-generation sequencing approach. We propose to utilize a novel positive-
selection nucleic acid enrichment and high-throughput sequencing platform (BacCapSeq) to detect MTB
bacteremia and drug-resistant organisms, optimized at the bench and trialed in a nested case control study of
HIV-associated sepsis in Uganda. Specifically, we will evaluate the performance of BacCapSeq and emerging,
near-point-of-care diagnostics (Xpert MTB/RIF Ultra) for the detection and characterization of MTB bacteremia
and MTB drug resistance using biobanked samples from a prospective cohort of HIV-infected adults with
sepsis in Uganda (Aim 1); and identify and characterize high-priority, antibiotic-resistant bacterial pathogens
associated with sepsis in HIV-infected patients without MTB infection in Uganda (Aim 2). At the conclusion of
this work we will have addressed critical diagnostic gaps for severe HIV/TB disease while providing high-
resolution genomic characterization of pathogens and antimicrobial resistance associated with sepsis, a
frequent pathway to death for HIV-infected adolescents and adults worldwide.

## Key facts

- **NIH application ID:** 10116263
- **Project number:** 5R21AI143417-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Max O'Donnell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $282,467
- **Award type:** 5
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116263

## Citation

> US National Institutes of Health, RePORTER application 10116263, Targeted next-generation sequencing to enhance detection and genomic characterization of Mycobacterium tuberculosis and high-impact bacterial pathogens among HIV-infected adults with sepsis in Uganda (5R21AI143417-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116263. Licensed CC0.

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