# Host-derived biomarker signatures for the diagnosis of acute rickettsial diseases

> **NIH VA I01** · DURHAM VA MEDICAL CENTER · 2021 · —

## Abstract

Rickettsial diseases such as those caused by Spotted Fever Group rickettsii (SFGR) and Scrub typhus
(ST) are estimated to account for millions of illnesses a year worldwide. SFGR infections affect Veterans and
other members of the public throughout the US, and both SFGR and Scrub typhus are continuous threats to
active duty warfighters stationed throughout the world. Effective therapy exists, but there is currently no clinically
available test capable of yielding reliable diagnostic information within the timeframe required to guide
therapeutic decisions. Through this proposal we intend to explore the pathophysiology of natural human infection
with SFGR and ST as defined by the host response, and to utilize this information to generate a practical test
capable of diagnosing these diseases in the acute setting. Prior published work and our preliminary data suggest
that these rickettsial infections trigger conserved inflammatory pathways in human hosts, and it is these unique
host responses that we will harness in order to identify patterns of gene expression within circulating white blood
cells that identify the presence of these organisms in febrile patients. In order to generate such a ‘signature’ of
infection, this project will utilize a unique combination of two main clinical cohorts. The first cohort is made up of
US Veterans with acute rickettsial illness diagnosed here in the US, both previously enrolled patients with acute
SFGR infection as well as ongoing enrollment of new cases. The second cohort is made up of a large existing
sample set of individuals enrolled from around the world with a variety of acute febrile SFGR infections as well
as Scrub typhus, which we have shown mimics the host responses seen in SFGR infection. This combination
will give us the ability to generate a rickettsial gene signature that both identifies acute disease in Veterans here
in the US as well as having the potential for utility beyond our borders for travelers and active duty military
members stationed internationally. We will utilize RNA Sequencing (RNASeq) to identify complex patterns of
gene expression in peripheral blood samples from subjects and controls with other types of febrile illnesses
(including viral and bacterial infections, both from the US and globally). However, high dimensional RNASeq
analysis is not a modality that can produce diagnostic answers in a clinically relevant timeframe. Therefore, we
will ‘prune’ these complex signature(s) down to smaller genomic classifiers appropriate for RT-PCR platforms,
as using RT-PCR probes lends itself to both existing clinical laboratory infrastructure as well as to a number of
burgeoning point-of-care platforms in development, thus beginning the final steps towards bringing such a test
to the point of actual clinical utility. Thus, through this proposal we intend to explore the pathophysiology of
natural human infection with SFGR and Scrub typhus as defined by the host response, and to utilize this
in...

## Key facts

- **NIH application ID:** 9860904
- **Project number:** 5I01CX001850-02
- **Recipient organization:** DURHAM VA MEDICAL CENTER
- **Principal Investigator:** Micah T. McClain
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9860904

## Citation

> US National Institutes of Health, RePORTER application 9860904, Host-derived biomarker signatures for the diagnosis of acute rickettsial diseases (5I01CX001850-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9860904. Licensed CC0.

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