Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-28T13:10:30.147Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdel-Magied, AA, El-Kholya, EI, Abou El-Khair, SM, Abdelmegeed, ES, Hamoudaa, MM, Mohamed, SA and El-Tantawy, NL (2017) The genetic diversity of metronidazole susceptibility in Trichomonas vaginalis clinical isolates in an Egyptian population. Parasitology Research 116, 3125–3130.CrossRefGoogle Scholar
Ahuja, V, Dhar, A, Bal, C and Sharma, MP (1998) Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country. Alimentary Pharmacology and Therapeutics 12, 551–555.CrossRefGoogle ScholarPubMed
Argaez-Correa, W, Alvarez-Sanchez, ME, Arana-Argaez, VE, Ramirez-Camacho, MA, Novelo-Castilla, JS, Coral-Martinez, TI and Torres-Romero, JC (2019) The role of iron status in the early progression of metronidazole resistance in Trichomonas vaginalis under microaerophilic conditions. Journal of Eukaryotic Microbiology 66, 309–315.Google ScholarPubMed
Bouchemal, K, Bories, C and Loiseau, PM (2017) Strategies for prevention and treatment of Trichomonas vaginalis infections. Clinical Microbiology Reviews 30, 811–825.CrossRefGoogle ScholarPubMed
Bradic, M, Secor, WE, Conrad, M and Carlton, JM (2012) Distribution of drug resistance and its genetic basis in global isolates of Trichomonas vaginalis. American Journal of Tropical Medicine and Hygiene 87, 313.Google Scholar
Bradic, M, Warring, SD, Tooley, GE, Scheid, P, Secor, WE, Land, KM, Huang, PJ, Chen, TW, Lee, CC, Tang, P, Sullivan, SA and Carlton, JM (2017) Genetic indicators of drug resistance in the highly repetitive genome of Trichomonas vaginalis. Genome Biology and Evolution 9, 1658–1672.CrossRefGoogle ScholarPubMed
Brown, DM, Upcroft, JA, Dodd, HN, Chen, N and Upcroft, P (1999) Alternative 2-keto acid oxidoreductase activities in Trichomonas vaginalis. Molecular and Biochemical Parasitology 98, 203–214.CrossRefGoogle ScholarPubMed
Butler, SE, Augostini, P and Secor, WE (2010) Mycoplasma hominis infection of Trichomonas vaginalis is not associated with metronidazole-resistant trichomoniasis in clinical isolates from the United States. Parasitology Research 107, 1023–1027.CrossRefGoogle Scholar
Conrad, MD, Gorman, AW, Schillinger, JA, Fiori, PL, Arroyo, R, Malla, N, Dubey, ML, Gonzalez, J, Blank, S, Secor, WE and Carlton, JM (2012) Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite Trichomonas vaginalis. PLoS Neglected Tropical Diseases 6, e1573.CrossRefGoogle ScholarPubMed
Coombs, GH (1978) A mechanism of resistance to metronidazole in trichomonads. British Society for Parasitology: Proceedings 77, xxiii.Google Scholar
Cornelius, DC, Mena, L, Lushbaugh, WB and Meade, JC (2010) Genetic relatedness of Trichomonas vaginalis reference and clinical isolates. American Journal of Tropical Medicine and Hygiene 83, 1283–1286.CrossRefGoogle ScholarPubMed
Cosar, C and Julou, L (1959) The activity of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (R. P. 8823) against experimental Trichomonas vaginalis infections. Annales de l'Institut Pasteur 96, 238–241.Google Scholar
da Luz Becker, D, dos Santos, O, Frasson, AP, de Vargas Rigo, G, Macedo, AJ and Tasca, T (2015) High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil. Infection, Genetics and Evolution 34, 181–187.CrossRefGoogle ScholarPubMed
Declerck, PJ and De Ranter, CJ (1986) In vitro reductive activation of nitroimidazoles. Biochemical Pharmacology 35, 59–61.CrossRefGoogle ScholarPubMed
Dias Filho, BP, Andrade, AF, de Souza, W, Esteves, MJ and Angluster, J (1992) Cell surface saccharide differences in drug-susceptible and drug-resistant strains of Trichomonas vaginalis. Microbios 71, 55–64.Google ScholarPubMed
Dolezal, P, Vanacova, S, Tachezy, J and Hrdy, I (2004) Malic enzymes of Trichomonas vaginalis: two enzyme families, two distinct origins. Gene 329, 81–92.CrossRefGoogle ScholarPubMed
Durel, P, Couture, J, Collart, P and Girot, C (1960) Flagyl (metronidazole). British Journal of Venereal Diseases 36, 154–162.Google Scholar
Edwards, DI, Thompson, EJ, Tomusange, J and Shanson, D (1979) Inactivation of metronidazole by aerobic organisms. Journal of Antimicrobial Chemotherapy 5, 315–316.CrossRefGoogle ScholarPubMed
Ellis, JE, Cole, D and Lloyd, D (1992) Influence of oxygen on the fermentative metabolism of metronidazole-sensitive and resistant strains of Trichomonas vaginalis. Molecular and Biochemical Parasitology 56, 79–88.CrossRefGoogle ScholarPubMed
Ellis, JE, Yarlett, N, Cole, D, Humphreys, MJ and Lloyd, D (1994) Antioxidant defences in the microaerophilic protozoan Trichomonas vaginalis: comparison of metronidazole-resistant and sensitive strains. Microbiology (Reading, England) 140, 2489–2494.CrossRefGoogle ScholarPubMed
Elwakil, HS, Tawfik, RA, Alam-Eldin, YH and Nassar, DA (2017) The effect of iron on metronidazole activity against Trichomonas vaginalis in vitro. Experimental Parasitology 182, 34–36.Google ScholarPubMed
Escobedo, AA, Canete, R, Gonzalez, ME, Pareja, A, Cimerman, S and Almirall, P (2003) A randomized trial comparing mebendazole and secnidazole for the treatment of giardiasis. Annals of Tropical Medicine and Parasitology 97, 499–504.CrossRefGoogle ScholarPubMed
Fichorova, R, Fraga, J, Rappelli, P and Fiori, PL (2017) Trichomonas vaginalis infection in symbiosis with Trichomonas virus and Mycoplasma. Research in Microbiology 168, 882–891.CrossRefGoogle ScholarPubMed
Flegr, J, Cerkasov, J, Kulda, J, Tachezy, J and Stokrov, J (1987) The dsRNA of Trichomonas vaginalis is associated with virus like particles and does not correlate with metronidazole resistance. Folia Microbiologica 32, 345–348.Google Scholar
Fraga, J, Rodriguez, N, Fernandez, C, Mondeja, B, Sariego, I, Fernandez-Calienes, A and Rojas, L (2012) Mycoplasma hominis in Cuban Trichomonas vaginalis isolates: association with parasite genetic polymorphism. Experimental Parasitology 131, 393–398.CrossRefGoogle ScholarPubMed
Furnkranz, U, Henrich, B and Walochnik, J (2018) Mycoplasma hominis impacts gene expression in Trichomonas vaginalis. Parasitology Research 117, 841–847.CrossRefGoogle ScholarPubMed
Graves, KJ, Ghosh, AP, Kissinger, PJ and Muzny, CA (2019). Trichomonas vaginalis virus: a review of the literature. International Journal of STD and AIDS 30, 496–504.CrossRefGoogle ScholarPubMed
Hampl, V, Vanacova, S, Kulda, J and Flegr, J (2001) Concordance between genetic relatedness and phenotypic similarities of Trichomonas vaginalis strains. BMC Evolutionary Biology 1, 11.CrossRefGoogle ScholarPubMed
Heidari, S, Bandehpour, M, Seyyed-Tabaei, SJ, Valadkhani, Z, Haghighi, A, Abadi, A and Kazemi, B (2013) Ferredoxin gene mutation in Iranian Trichomonas vaginalis isolates. Iranian Journal of Parasitology 8, 402–407.Google ScholarPubMed
Honigberg, BM and Brugerolle, G (1990). Structure. In Honigberg, BM (ed.), Trichomonads Parasitic in Humans. New York, NY: Springer, pp. 5–35.CrossRefGoogle Scholar
Honigberg, BM and King, VM (1964) Structure of Trichomonas vaginalis Donn'e. Journal of Parasitology 50, 345–364.CrossRefGoogle ScholarPubMed
Horvathova, L, Safarikova, L, Basler, M, Hrdy, I, Campo, NB, Shin, JW, Huang, KY, Huang, PJ, Lin, R, Tang, P and Tachezy, J (2012) Transcriptomic identification of iron-regulated and iron-independent gene copies within the heavily duplicated Trichomonas vaginalis genome. Genome Biology and Evolution 4, 1017–1029.CrossRefGoogle ScholarPubMed
Hrdy, I, Cammack, R, Stopka, P, Kulda, J and Tachezy, J (2005) Alternative pathway of metronidazole activation in Trichomonas vaginalis hydrogenosomes. Antimicrobial Agents and Chemotherapy 49, 5033–5036.CrossRefGoogle ScholarPubMed
Ingham, HR, Sisson, PR and Selkon, JB (1982) Interactions between micro-organisms and metronidazole. Journal of Antimicrobial Chemotherapy 10, 84–87.CrossRefGoogle ScholarPubMed
Johnson, PJ, Schuck, BL and Delgadillo, MG (1994) Analysis of a single-domain P-glycoprotein-like gene in the early-diverging protist Trichomonas vaginalis. Molecular and Biochemical Parasitology 66, 127–137.CrossRefGoogle ScholarPubMed
Kazemi, F, Hooshyar, H, Zareikar, B, Bandehpour, M, Arbabi, M, Talari, S, Alizadeh, R and Kazemi, B (2010) Study on ITS1 gene of Iranian Trichomonas vaginalis by molecular methods. Iranian Journal of Parasitology 5, 9–14.Google Scholar
Kirkcaldy, RD, Augostini, P, Asbel, LE, Bernstein, KT, Kerani, RP, Mettenbrink, CJ, Pathela, P, Schwebke, JR, Secor, WE, Workowski, KA, Davis, D, Braxton, J and Weinstock, HS (2012) Trichomonas vaginalis antimicrobial drug resistance in 6 US cities, STD surveillance network, 2009–2010. Emerging Infectious Diseases 18, 939–943.CrossRefGoogle Scholar
Kissinger, P and Adamski, A (2013) Trichomoniasis and HIV interactions: a review. Sexually Transmitted Infections 89, 426–433.CrossRefGoogle ScholarPubMed
Krashin, JW, Koumans, EH, Bradshaw-Sydnor, AC, Braxton, JR, Evan Secor, W, Sawyer, MK and Markowitz, LE (2010) Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population. Sexually Transmitted Diseases 37, 440–444.Google Scholar
Kulda, J (1999) Trichomonads, hydrogenosomes and drug resistance. International Journal for Parasitology 29, 199–212.CrossRefGoogle ScholarPubMed
Kulda, J, Tachezy, J and Cerkasovova, A (1993) In vitro induced anaerobic resistance to metronidazole in Trichomonas vaginalis. Journal of Eukaryotic Microbiology 40, 262–269.CrossRefGoogle ScholarPubMed
Land, KM, Clemens, DL and Johnson, PJ (2001) Loss of multiple hydrogenosomal proteins associated with organelle metabolism and high-level drug resistance in trichomonads. Experimental Parasitology 97, 102–110.CrossRefGoogle ScholarPubMed
Land, KM, Delgadillo, MG and Johnson, PJ (2002) In vivo expression of ferredoxin in a drug resistant trichomonad increases metronidazole susceptibility. Molecular and Biochemical Parasitology 121, 153–157.CrossRefGoogle Scholar
Leitsch, D, Kolarich, D, Binder, M, Stadlmann, J, Altmann, F and Duchene, M (2009) Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Molecular Microbiology 72, 518–536.CrossRefGoogle ScholarPubMed
Leitsch, D, Kolarich, D and Duchene, M (2010) The flavin inhibitor diphenyleneiodonium renders Trichomonas vaginalis resistant to metronidazole, inhibits thioredoxin reductase and flavin reductase, and shuts off hydrogenosomal enzymatic pathways. Molecular and Biochemical Parasitology 171, 17–24.CrossRefGoogle ScholarPubMed
Leitsch, D, Drinic, M, Kolarich, D and Duchene, M (2012) Down-regulation of flavin reductase and alcohol dehydrogenase-1 (ADH1) in metronidazole-resistant isolates of Trichomonas vaginalis. Molecular and Biochemical Parasitology 183, 177–183.Google ScholarPubMed
Leitsch, D, Janssen, BD, Kolarich, D, Johnson, PJ and Duchene, M (2014) Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance. Molecular Microbiology 91, 198–208.CrossRefGoogle ScholarPubMed
Lloyd, D and Kristensen, B (1985) Metronidazole inhibition of hydrogen production in vivo in drug-sensitive and resistant strains of Trichomonas vaginalis. Journal of General Microbiology 131, 849–853.Google ScholarPubMed
Lloyd, D and Pedersen, JZ (1985) Metronidazole radical anion generation in vivo in Trichomonas vaginalis: oxygen quenching is enhanced in a drug-resistant strain. Journal of General Microbiology 131, 87–92.Google Scholar
Lloyd, D, Yarlett, N and Yarlett, NC (1986) Inhibition of hydrogen production in drug-resistant and susceptible Trichomonas vaginalis strains by a range of nitroimidazole derivatives. Biochemical Pharmacology 35, 61–64.CrossRefGoogle ScholarPubMed
Lossick, JG, Muller, M and Gorrell, TE (1986) In vitro drug susceptibility and doses of metronidazole required for cure in cases of refractory vaginal trichomoniasis. Journal of Infectious Diseases 153, 948–955.CrossRefGoogle ScholarPubMed
Malla, N, Kaul, P, Sehgal, R and Gupta, I (2011) The presence of dsRNA virus in Trichomonas vaginalis Isolates from symptomatic and asymptomatic Indian women and its correlation with in vitro metronidazole sensitivity. Indian Journal of Medical Microbiology 29, 152–157.CrossRefGoogle ScholarPubMed
Mead, JR, Fernadez, M, Romagnoli, PA and Secor, WE (2006) Use of Trichomonas vaginalis clinical isolates to evaluate correlation of gene expression and metronidazole resistance. Journal of Parasitology 92, 196–199.CrossRefGoogle ScholarPubMed
Meites, E, Gaydos, CA, Hobbs, MM, Kissinger, P, Nyirjesy, P, Schwebke, JR, Secor, WE, Sobel, JD and Workowski, KA (2015) A review of evidence-based care of symptomatic trichomoniasis and asymptomatic Trichomonas vaginalis infections. Clinical Infectious Diseases 61, S837–S848.CrossRefGoogle ScholarPubMed
Muller, M (1986) Reductive activation of nitroimidazoles in anaerobic microorganisms. Biochemical Pharmacology 35, 37–41.CrossRefGoogle ScholarPubMed
Muller, M and Gorrell, TE (1983) Metabolism and metronidazole uptake in Trichomonas vaginalis isolates with different metronidazole susceptibilities. Antimicrobial Agents and Chemotherapy 24, 667–673.CrossRefGoogle ScholarPubMed
Muzny, CA, Van Gerwen, OT and Kissinger, P (2020) Updates in Trichomonas treatment including persistent infection and 5-nitroimidazole hypersensitivity. Current Opinion in Infectious Diseases 33, 73–77.CrossRefGoogle ScholarPubMed
Newman, L, Rowley, J, Vander Hoorn, S, Wijesooriya, NS, Unemo, M, Low, N, Stevens, G, Gottlieb, S, Kiarie, J and Temmerman, M (2015) Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS ONE 10, e0143304.CrossRefGoogle ScholarPubMed
Nyirjesy, P, Gilbert, J and Mulcahy, LJ (2011) Resistant trichomoniasis: successful treatment with combination therapy. Sexually Transmitted Diseases 38, 962–963.Google ScholarPubMed
Pal, D, Banerjee, S, Cui, J, Schwartz, A, Ghosh, SK and Samuelson, J (2009) Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases). Antimicrobial Agents and Chemotherapy 53, 458–464.CrossRefGoogle Scholar
Patel, EU, Gaydos, CA, Packman, ZR, Quinn, TC and Tobian, AAR (2018) Prevalence and correlates of Trichomonas vaginalis infection among men and women in the United States. Clinical Infectious Diseases 67, 211–217.CrossRefGoogle ScholarPubMed
Paulish-Miller, TE, Augostini, P, Schuyler, JA, Smith, WL, Mordechai, E, Adelson, ME, Gygax, SE, Secor, WE and Hilbert, DW (2014) Trichomonas vaginalis metronidazole resistance is associated with single nucleotide polymorphisms in the nitroreductase genes ntr4Tv and ntr6Tv. Antimicrobial Agents and Chemotherapy 58, 2938–2943.CrossRefGoogle ScholarPubMed
Perez, S, Fernandez-Verdugo, A, Perez, F and Vazquez, F (2001) Prevalence of 5-nitroimidazole-resistant Trichomonas vaginalis in Oviedo, Spain. Sexually Transmitted Diseases 28, 115–116.CrossRefGoogle ScholarPubMed
Quon, DV, d'Oliveira, CE and Johnson, PJ (1992) Reduced transcription of the ferredoxin gene in metronidazole-resistant Trichomonas vaginalis. Proceedings of the National Academy of Sciences of the United States of America 89, 4402–4406.CrossRefGoogle ScholarPubMed
Rabiee, S, Bazmani, A, Matini, M and Fallah, M (2012) Comparison of resistant and susceptible strains of Trichomonas vaginalis to metronidazole using PCR method. Iranian Journal of Parasitology 7, 24–30.Google ScholarPubMed
Rasoloson, D, Tomkova, E, Cammack, R, Kulda, J and Tachezy, J (2001) Metronidazole-resistant strains of Trichomonas vaginalis display increased susceptibility to oxygen. Parasitology 123, 45–56.CrossRefGoogle Scholar
Rasoloson, D, Vanacova, S, Tomkova, E, Razga, J, Hrdy, I, Tachezy, J and Kulda, J (2002) Mechanisms of in vitro development of resistance to metronidazole in Trichomonas vaginalis. Microbiology 148, 2467–2477.CrossRefGoogle ScholarPubMed
Robinson, SC (1962) Trichomonal vaginitis resistant to metranidazole. Canadian Medical Association Journal 86, 665.Google ScholarPubMed
Rossignol, JF, Maisonneuve, H and Cho, YW (1984) Nitroimidazoles in the treatment of trichomoniasis, giardiasis, and amebiasis. International Journal of Clinical Pharmacology, Therapy, and Toxicology 22, 63–72.Google ScholarPubMed
Rowley, J, Toskin, I and Ndowa, F (2012) Global incidence and prevalence of selected curable sexually transmitted infections – 2008. World Health Organization, Geneva.Google Scholar
Schmid, G, Narcisi, E, Mosure, D, Secor, WE, Higgins, J and Moreno, H (2001) Prevalence of metronidazole-resistant Trichomonas vaginalis in a gynecology clinic. Journal of Reproductive Medicine 46, 545–549.Google Scholar
Schwebke, JR and Barrientes, FJ (2006) Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and tinidazole. Antimicrobial Agents and Chemotherapy 50, 4209–4210.CrossRefGoogle ScholarPubMed
Schwebke, JR, Rompalo, A, Taylor, S, Sena, AC, Martin, DH, Lopez, LM, Lensing, S and Lee, JY (2011) Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens – a randomized clinical trial. Clinical Infectious Diseases 52, 163–170.CrossRefGoogle ScholarPubMed
Schwebke, JR, Morgan, FG Jr, Koltun, W and Nyirjesy, P (2017) A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis. American Journal of Obstetrics and Gynecology 217, 678.e1–678.e9.CrossRefGoogle ScholarPubMed
Sena, AC, Miller, WC, Hobbs, MM, Schwebke, JR, Leone, PA, Swygard, H, Atashili, J and Cohen, MS (2007) Trichomonas vaginalis infection in male sexual partners: implications for diagnosis, treatment, and prevention. Clinical Infectious Diseases 44, 13–22.CrossRefGoogle Scholar
Silver, BJ, Guy, RJ, Kaldor, JM, Jamil, MS and Rumbold, AR (2014) Trichomonas vaginalis as a cause of perinatal morbidity: a systematic review and meta-analysis. Sexually Transmitted Diseases 41, 369–376.CrossRefGoogle ScholarPubMed
Snipes, LJ, Gamard, PM, Narcisi, EM, Beard, CB, Lehmann, T and Secor, WE (2000) Molecular epidemiology of metronidazole resistance in a population of Trichomonas vaginalis clinical isolates. Journal of Clinical Microbiology 38, 3004–3009.Google Scholar
Sobel, JD, Nyirjesy, P and Brown, W (2001) Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis. Clinical Infectious Diseases 33, 1341–1346.CrossRefGoogle ScholarPubMed
Stiles, JK, Shah, PH, Xue, L, Meade, JC, Lushbaugh, WB, Cleary, JD and Finley, RW (2000) Molecular typing of Trichomonas vaginalis isolates by HSP70 restriction fragment length polymorphism. American Journal of Tropical Medicine and Hygiene 62, 441–445.CrossRefGoogle ScholarPubMed
Sutton, M, Sternberg, M, Koumans, EH, McQuillan, G, Berman, S and Markowitz, L (2007) The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001–2004. Clinical Infectious Diseases 45, 1319–1326.Google ScholarPubMed
Swygard, H, Sena, AC, Hobbs, MM and Cohen, MS (2004) Trichomoniasis: clinical manifestations, diagnosis and management. Sexually Transmitted Infections 80, 91–95.CrossRefGoogle ScholarPubMed
Tachezy, J, Kulda, J and Tomkova, E (1993) Aerobic resistance of Trichomonas vaginalis to metronidazole induced in vitro. Parasitology 106, 31–37.Google ScholarPubMed
Tasca, T, Borges, FP, Bonan, CD, De Carli, GA, Battastini, AM and Sarkis, JJ (2003) Effects of metronidazole and tinidazole on NTPDase1 and ecto-5′-nucleotidase from intact cells of Trichomonas vaginalis. FEMS Microbiology Letters 226, 379–384.CrossRefGoogle ScholarPubMed
Vanacova, S, Tachezy, J, Kulda, J and Flegr, J (1997) Characterization of trichomonad species and strains by PCR fingerprinting. Journal of Eukaryotic Microbiology 44, 545–552.Google ScholarPubMed
van Belkum, A, van der Schee, C, van der Meijden, WI, Verbrugh, HA and Sluiters, HJ (2001) A clinical study on the association of Trichomonas vaginalis and Mycoplasma hominis infections in women attending a sexually transmitted disease (STD) outpatient clinic. FEMS Immunology and Medical Microbiology 32, 27–32.CrossRefGoogle ScholarPubMed
Van Gerwen, OT and Muzny, CA (2019) Recent advances in the epidemiology, diagnosis, and management of Trichomonas vaginalis infection. F1000Research 8, 1–9.CrossRefGoogle ScholarPubMed
Wang, A (1984) A linear double-stranded RNA in Trichomonas vaginalis and its relationship with resistance to metronidazole. Federation Proceedings 43, 1284.Google Scholar
Wang, AL and Wang, CC (1985) A linear double-stranded RNA in Trichomonas vaginalis. Journal of Biological Chemistry 260, 3697–3702.Google ScholarPubMed
WHO (2017) Essential medicines and health products information portal. 2019, Available at http://apps.who.int/medicinedocs/en/d/Jh2942e/4.9.html#Jh2942e.4.9.Google Scholar
Wiwanitkit, V (2008) Identification of weak points prone for mutation in ferredoxin of Trichomonas vaginalis. Indian Journal of Medical Microbiology 26, 158–159.CrossRefGoogle ScholarPubMed
Wolner-Hanssen, P, Krieger, JN, Stevens, CE, Kiviat, NB, Koutsky, L, Critchlow, C, DeRouen, T, Hillier, S and Holmes, KK (1989) Clinical manifestations of vaginal trichomoniasis. JAMA 261, 571–576.CrossRefGoogle ScholarPubMed
Workowski, KA, Bolan, GA and Centers for Disease and Prevention, C (2015) Sexually transmitted diseases treatment guidelines, 2015. MMWR: Recommendations and Reports 64, 1–137.Google ScholarPubMed
Wright, JM, Webb, RI, O'Donoghue, P, Upcroft, P and Upcroft, JA (2010) Hydrogenosomes of laboratory-induced metronidazole-resistant Trichomonas vaginalis lines are downsized while those from clinically metronidazole-resistant isolates are not. Journal of Eukaryotic Microbiology 57, 171–176.CrossRefGoogle ScholarPubMed
Xiao, JC, Xie, LF, Fang, SL, Gao, MY, Zhu, Y, Song, LY, Zhong, HM and Lun, ZR (2006) Symbiosis of Mycoplasma hominis in Trichomonas vaginalis may link metronidazole resistance in vitro. Parasitology Research 100, 123–130.CrossRefGoogle ScholarPubMed
Yarlett, N, Gorrell, TE, Marczak, R and Muller, M (1985) Reduction of nitroimidazole derivatives by hydrogenosomal extracts of Trichomonas vaginalis. Molecular and Biochemical Parasitology 14, 29–40.CrossRefGoogle ScholarPubMed
Yarlett, N, Yarlett, NC and Lloyd, D (1986 a) Ferredoxin-dependent reduction of nitroimidazole derivatives in drug-resistant and susceptible strains of Trichomonas vaginalis. Biochemical Pharmacology 35, 1703–1708.CrossRefGoogle ScholarPubMed
Yarlett, N, Yarlett, NC and Lloyd, D (1986 b) Metronidazole-resistant clinical isolates of Trichomonas vaginalis have lowered oxygen affinities. Molecular and Biochemical Parasitology 19, 111–116.CrossRefGoogle ScholarPubMed