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A systematic review of the literature on mechanisms of 5-nitroimidazole resistance in Trichomonas vaginalis

Published online by Cambridge University Press:  30 July 2020

Keonte J. Graves Open the ORCID record for Keonte J. Graves [Opens in a new window] ,
Jan Novak ,
W. Evan Secor ,
Patricia J. Kissinger ,
Jane R. Schwebke  and
Christina A. Muzny
Keonte J. Graves*
Affiliation:
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
Jan Novak
Affiliation:
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
W. Evan Secor
Affiliation:
Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Patricia J. Kissinger
Affiliation:
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
Jane R. Schwebke
Affiliation:
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
Christina A. Muzny
Affiliation:
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
*
Author for correspondence: Keonte J. Graves, E-mail: keontegraves@uabmc.edu
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Abstract

Background

Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance.

Methods

PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded.

Results

The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance varies and is higher with MTZ (2.2–9.6%) than TDZ (0–2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance. Trichomonas vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations.

Discussion

5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.

Keywords

5-Nitroimidazoledrug resistancemetronidazoletinidazoleTrichomonas vaginalis
Type
Review Article
Information
Parasitology , Volume 147 , Issue 13 , November 2020 , pp. 1383 - 1391
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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