Urethritis is a common complaint among men seeking primary care, but its etiology and long-term consequences are incompletely understood. Urethritis of any etiology can augment HIV shedding; urethritis is often associated with either single or multiple known sexually transmitted infections (STI) that can be transmitted to women, who in turn are at risk for reproductive complications. Common etiologies of urethritis include sexually transmitted bacteria, with Neisseria gonorrhoeae (NG) causing gonococcal urethritis (GU), and Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and probably Ureaplasma urealyticum (UU) causing nongonococcal urethritis (NGU). Other bacteria, viruses (adenoviruses, HSV) and the protozoan Trichomonas vaginalis (TV) occasionally cause NGU. However, no pathogen is detected in 25-50% of men with the NGU subset of urethritis; this group is defined as having idiopathic urethritis (IU). The appropriate management and treatment of IU is unknown. The goal of this project is to seek microbial etiologies for IU using modern metagenomic techniques, bioinformatics and statistical approaches applied to a large, carefully defined and described population of men with IU, men with no urethritis, and men with IU and NGU who have clinical treatment failure. We examine our overarching hypothesis, that the composition of the urethral microbiome is crucial to development of IU, in 3 Specific Aims. We hypothesize that some cases of IU are: 1) associated with previously unidentified pathogens (Aim 1); 2) associated with high loads of organisms not otherwise thought to be urethral pathogens (Aim 2); and 3) not associated with specific organisms, but rather with broad microbial community shifts known as dysbiosis. The project constitutes a definitive evaluation of potential microbial associations of IU.

Public Health Relevance

Idiopathic urethritis is an extremely common male genitourinary tract syndrome whose cause is not understood. We will identify novel microorganisms which may cause idiopathic urethritis. Results of this study will lead to improved clinical diagnostics and treatments for urethritis in men, and possibly sexually transmitted infections in both men and women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI116706-03
Application #
9388959
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Turpin, Delmyra B
Project Start
2015-12-01
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E et al. (2017) Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015-2016. Emerg Infect Dis 23:336-339
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Batteiger, Byron E (2017) Azithromycin Efficacy in Asymptomatic Rectal Chlamydial Infection in Men Who Have Sex With Men: A More Definitive Answer Soon? Sex Transm Dis 44:403-405