Skip to main content

Advertisement

SpringerLink
Log in

Is GRA6 Gene a Suitable Marker for Molecular Typing of Toxoplasma Gondii? A Scoping Systematic Review

  • Review
  • Published:
Acta Parasitologica Aims and scope Submit manuscript

Abstract

Toxoplasmosis is a zoonotic disease with a worldwide prevalence that is caused by Toxoplasma gondii. This study aimed to summarize available data on genotyping T. gondii strains based on the GRA6 gene marker in different hosts around the world. We conducted a comprehensive literature search using five international databases (PubMed, Scopus, Science Direct, Web of Science, and Google Scholar) from inception until December 2021. We identified 32 papers eligible for inclusion in this systematic review. The majority of studies (50%) were carried out in Iran (n = 16) to identify T. gondii genotypes based on the GRA6 gene. Other countries with reported studies include China, Japan, Sweden, and Italy (n = 2 each). Out of 3,434 samples collected from various hosts, most studies (n = 11) focused on human samples (34.4%), followed by ovine (n = 7), pig (n = 4), goat (n = 3) and soil and cattle (n = 2).

Using various molecular methods such as conventional PCR, nested-PCR, real-time PCR, microsatellite analysis, and Restriction Fragment Length Polymorphism (RFLP), we found DNA positive results in 805 out of 3,434 samples. Of these, 285 (35.40%), 207 (25.71%), 182 (22.60%), 65 (8.07%), and 18 (2.23%) were infected with types I, II, III, mix I, II, III, and mix II, III, respectively. Our data demonstrate that the GRA6 gene marker has sufficient polymorphism to detect three types of T. gondii genotypes in various hosts. Identifying the specific genotype could be valuable in developing new strategies for treatment, vaccination, diagnosis, control, and prevention of T. gondii infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data of this study are provided in the paper.

References

  1. Dubey J, Zhu X, Sundar N, Zhang H, Kwok O, Su C (2007) Genetic and biologic characterization of Toxoplasma Gondii isolates of cats from China. Vet Parasitol 145(3–4):352–356. https://doi.org/10.1016/j.vetpar.2006.12.016

    Article  CAS  PubMed  Google Scholar 

  2. Dardé M, Ajzenberg D, Smith J (2007) Population structure and epidemiology of Toxoplasma gondii. Toxoplasma gondii, Elsevier: 49–80. https://doi.org/10.1016/B978-012369542-0/50005-2

  3. Arefkhah N, Pourabbas B, Asgari Q, Moshfe A, Mikaeili F, Nikbakht G et al (2019) Molecular genotyping and serological evaluation of Toxoplasma Gondii in mothers and their spontaneous aborted fetuses in southwest of Iran. Comp Immunol Microbiol Infect Dis 66:101342. https://doi.org/10.1016/j.cimid.2019.101342

    Article  PubMed  Google Scholar 

  4. Khademi SZ, Ghaffarifar F, Dalimi A, Dayer MS, Abdoli A (2021) Toxoplasma gondii in slaughtered sheep in high-and low-humidity regions in the south of iran: Molecular prevalence and genotype identification. Vet Med Int 2021. https://doi.org/10.1155/2021/5576771

  5. Norouzi M, Tabaei SJS, Niyyati M, Saber V, Behniafar H (2016) Genotyping of Toxoplasma gondii strains isolated from patients with ocular toxoplasmosis in Iran. Iran J Parasitol 11(3):316 PMID: 28127336

    PubMed  PubMed Central  Google Scholar 

  6. Dubey J, Velmurugan G, Chockalingam A, De Pena HFdJ LN, Leifer C et al (2008) Genetic diversity of Toxoplasma Gondii isolates from chickens from Brazil. Vet Parasitol 157(3–4):299–305. https://doi.org/10.1016/j.vetpar.2008.07.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Golkar M, Shokrgozar M-A, Rafati S, Musset K, Assmar M, Sadaie R et al (2007) Evaluation of protective effect of recombinant dense granule antigens gra2 and gra6 formulated in monophosphoryl lipid a (mpl) adjuvant against Toxoplasma chronic infection in mice. Vaccine 25(21):4301–4311. https://doi.org/10.1016/j.vaccine.2007.02.057

    Article  CAS  PubMed  Google Scholar 

  8. Hosseini S, Amouei A, Sharif M, Sarvi S, Galal L, Javidnia J et al (2019) Human toxoplasmosis: a systematic review for genetic diversity of Toxoplasma Gondii in clinical samples. Epidemiol Infect 147:e36. https://doi.org/10.1017/S0950268818002947

    Article  Google Scholar 

  9. Su C, Khan A, Zhou P, Majumdar D, Ajzenberg D, Dardé M-L et al (2012) Globally diverse Toxoplasma Gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proc Natl Acad Sci 109(15):5844–5849. https://doi.org/10.1073/pnas.1203190109

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sibley LD, Boothroyd JC (1992) Virulent strains of Toxoplasma Gondii comprise a single clonal lineage. Nature 359(6390):82–85. https://doi.org/10.1038/359082a0

    Article  CAS  PubMed  Google Scholar 

  11. Arshadi M, Akhlaghi L, Meamar AR, Alizadeh Ghavidel L, Nasiri K, Mahami-Oskouei M et al (2019) Sero-molecular detection, multi-locus genotyping, and clinical manifestations of ocular toxoplasmosis in patients in northwest Iran. rans R Soc Trop Med Hyg 113(4):195–202. https://doi.org/10.1093/trstmh/try137

    Article  CAS  Google Scholar 

  12. Amouei A, Sarvi S, Sharif M, Aghayan SA, Javidnia J, Mizani A et al (2020) A systematic review of Toxoplasma gondii genotypes and feline: geographical distribution trends. Transbound Emerg Dis 67(1):46–64. https://doi.org/10.1111/tbed.13340

    Article  PubMed  Google Scholar 

  13. Ghaffari AD, Dalimi A (2019) Molecular identification of Toxoplasma Gondii in the native slaughtered cattle of tehran province, Iran. J Food Qual Hazards Control 6(4). https://doi.org/10.18502/jfqhc.6.4.1993

  14. Danehchin L, Razmi G, Naghibi A (2016) Isolation and genotyping of Toxoplasma gondii strains in ovine aborted fetuses in Khorasan Razavi province, Iran. Korean J Parasitol 54(1):15. https://doi.org/10.3347/kjp.2016.54.1.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fazaeli A, Carter P, Darde M, Pennington T (2000) Molecular typing of Toxoplasma gondii strains by gra6 gene sequence analysis. Int J Parasitol Parasites 30(5):637–642. https://doi.org/10.1016/s0020-7519(00)00036-9

    Article  CAS  Google Scholar 

  16. Rahdar M, Arab L, Samarbaf-zadeh AR (2020) Genotyping of Toxoplasma Gondii in sheep and cattle meat using pcr-rflp technique. Vet Sci Res 2(2):37–41. https://doi.org/10.30564/vsr.v2i2.2673

    Article  Google Scholar 

  17. Firouzeh N, Borj HF, Ziaali N, Kareshk AT, Ahmadinejad M, Shafiei R (2023) Genetic diversity of Toxoplasma Gondii by serological and molecular analyzes in different sheep and goat tissues in northeastern Iran. Iran J Parasitol 18(2):217. https://doi.org/10.18502/ijpa.v18i2.13188

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (prisma-p) 2015 statement. Syst Rev 4:1–9. https://doi.org/10.1136/bmj.g7647

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chuanxin Y, Xeren Y, Yinchangj Z (2002) Clone of the gene of the dense granule antigen (gra6) of the Toxoplasma gondii pig strain. Southeast Asian J Trop Med Public Health 33(2):235–240 PMID: 23082548

    Google Scholar 

  20. Petersen E, Edvinsson B, Lundgren B, Benfield T, Evengård B (2006) Diagnosis of pulmonary infection with Toxoplasma Gondii in immunocompromised hiv-positive patients by real-time pcr. Eur J Clin Microbiol Infect Dis 25:401–404. https://doi.org/10.1007/s10096-006-0156-5

    Article  CAS  PubMed  Google Scholar 

  21. Zakimi S, Kyan H, Oshiro M, Sugimoto C, Xuenan X, Fujisaki K (2006) Genetic characterization of gra6 genes from Toxoplasma Gondii from pigs in okinawa, Japan. J Vet Med Sci 68(10):1105–1107. https://doi.org/10.1292/jvms.68.1105

    Article  CAS  PubMed  Google Scholar 

  22. Edvinsson B, Dardé M-L, Pelloux H, Evengård B (2007) Rapid genotyping of Toxoplasma Gondii by pyrosequencing. Clin Microbiol Infect 13(4):424–429. https://doi.org/10.1111/j.1469-0691.2006.01661.x

    Article  CAS  PubMed  Google Scholar 

  23. Messaritakis I, Detsika M, Koliou M, Sifakis S, Antoniou M (2008) Prevalent genotypes of Toxoplasma Gondii in pregnant women and patient from crete and Cyprus. Am J Trop Med Hyg 79(2):205. https://doi.org/10.4269/ajtmh.2008.79.205

    Article  CAS  PubMed  Google Scholar 

  24. Opsteegh M, Langelaar M, Sprong H, den Hartog L, De Craeye S, Bokken G et al (2010) Direct detection and genotyping of Toxoplasma Gondii in meat samples using magnetic capture and pcr. Int J Food Microbiol 139(3):193–201. https://doi.org/10.1016/j.ijfoodmicro.2010.02.027

    Article  CAS  PubMed  Google Scholar 

  25. Di Guardo G, Di Cesare A, Otranto D, Casalone C, Iulini B, Mignone W et al (2011) Genotyping of Toxoplasma Gondii isolates in meningo-encephalitis affected striped dolphins (stenella coeruleoalba) from italy. Vet Parasitol 183(1–2):31–36. https://doi.org/10.1016/j.vetpar.2011.07.004

    Article  CAS  PubMed  Google Scholar 

  26. Kyan H, Taira M, Yamamoto A, Inaba C, Zakimi S (2012) Isolation and characterization of Toxoplasma gondii genotypes from goats at an abattoir in okinawa. Jpn J Infect Dis 65(2):167–170 PMID: 22446126

    Article  PubMed  Google Scholar 

  27. Khademvatan S, Saki J, Yousefi E, Abdizadeh R (2013) Detection and genotyping of Toxoplasma gondii strains isolated from birds in the southwest of Iran. Br Poult Sci 54(1):76–80. https://doi.org/10.1080/00071668.2013.763899

    Article  CAS  PubMed  Google Scholar 

  28. Saki J, Khademvatan S, Yousefi E, Tavalla M, Abdizadeh R (2017) Detection and genotyping of Toxoplasma Gondii isolated from soil in ahvaz, southwest of Iran. J Parasit Dis 41:202–205. https://doi.org/10.1007/s12639-016-0778-1

    Article  CAS  PubMed  Google Scholar 

  29. Biradar SS, Saravanan BC, Tewari AK, Sreekumar C, Sankar M, Sudhakar NR (2014) Genetic characterization of Toxoplasma Gondii isolates from chickens in India by gra6 gene sequence analysis. Acta Parasitol 59:666–674. https://doi.org/10.2478/s11686-014-0288-1

    Article  PubMed  Google Scholar 

  30. Ling-Juan C, Yu-Xi G, Li L, Mi L, Ju G, Wei L et al (2014) Comparation of Toxoplasma gondii separated from hiv-positive people and rh strain gra6 gene. Chin J Schistosomiasis 26(4): 434. PMID: 25434146

  31. Tolba MM, El-Taweel HA, Khalil SS, Hazzah WA, Heshmat MG (2014) Genotype analysis of t. Gondii strains associated with human infection in Egypt. Parasitol Res 113:1563–1569. https://doi.org/10.1007/s00436-014-3801-4

    Article  PubMed  Google Scholar 

  32. Eida AM (2015) Direct genotyping of Toxoplasma Gondii in blood samples from pregnant women in jazan, Saudi Arabia. J Egypt Soc Parasitol 45(3):603–608. https://doi.org/10.12816/0017921

    Article  Google Scholar 

  33. Kareshk TA, Mahmoudvand H, Keyhani A, Oliaee TR, Mohammadi M, Babaei Z et al (2017) Molecular detection and genetic diversity of Toxoplasma Gondii in different tissues of sheep and goat in eastern Iran. Trop Biomed 34:681–690. http://eprints.lums.ac.ir/id/eprint/1054

    Google Scholar 

  34. Abdoli A, Dalimi A, Soltanghoraee H, Ghaffarifar F (2017) Molecular detection and genotypic characterization of Toxoplasma Gondii in paraffin-embedded fetoplacental tissues of women with recurrent spontaneous abortion. Int J Fertil Steril 10(4):327. https://doi.org/10.22074/ijfs.2016.4569

    Article  CAS  PubMed  Google Scholar 

  35. Kareshk AT, Oliaee RT, Mahmoudvand H, Keyhani A, Mohammadi MA, Bamorovat M et al (2018) The first survey of isolation and molecular typing of Toxoplasma Gondii by bioassay and pcr method in balb/c mice in camels (camelus dromedarius) from eastern Iran. Iran J Parasitol 13(3):382 PMID: 30483329

    Google Scholar 

  36. Verma SK, Knowles S, Cerqueira-Cézar CK, Kwok OC, Jiang T, Su C et al (2018) An update on Toxoplasma gondii infections in northern sea otters (enhydra lutris kenyoni) from washington state, USA. Vet Parasitol 258:133–137. https://doi.org/10.1016/j.vetpar.2018.05.011

    Article  PubMed  Google Scholar 

  37. Suh SH, Yun HS, Lee S-E, Kwak H-S (2019) Novel peptide nucleic acid melting array for the detection and genotyping of Toxoplasma Gondii. Microbiol Biotechnol Lett 47(4):645–650. https://doi.org/10.4014/mbl.1904.04005

    Article  CAS  Google Scholar 

  38. Arefkhah N, Sarkari B, Asgari Q, Moshfe A, Khalafi MH, Mohammadpour I (2020) Molecular genotyping of Toxoplasma Gondii in sheep aborted fetuses reveals predominance of type i infection in southwest of Iran. Iran J Parasitol 15(3):374. https://doi.org/10.18502/ijpa.v15i3.4202

    Article  PubMed  PubMed Central  Google Scholar 

  39. Valenzuela-Moreno LF, Rico-Torres CP, Cedillo-Peláez C, Luna-Pastén H, Méndez-Cruz ST, Lara-Martínez G et al (2019) Mixed Toxoplasma gondii infection and new genotypes in feral cats of quintana roo, méxico. Acta Trop 193:199–205. https://doi.org/10.1016/j.actatropica.2019.03.006

    Article  PubMed  Google Scholar 

  40. Pavone S, Crotti S, Cruciani D, D’Avino N, Zema J, Morelli S et al (2020) Fatal systemic toxoplasmosis in a 3-month-old young Tibetan goat (capra hircus). BMC Vet Res 16:1–4. https://doi.org/10.1186/s12917-020-02641-8

    Article  Google Scholar 

  41. Nosrati MRC, Shemshadi B, Shayan P, Ranjbar S, Bahadori AE (2020) High prevalence of Toxoplasma gondii infection in ovine aborted fetuses in gilan province, Iran: molecular detection and genotype characterization. J Basic Res Med Sci 7:53–62. http://jbrms.medilam.ac.ir/article-1-559-en.html

    Google Scholar 

  42. Haghparast-Kenari B, Sarvi S, Sharif M, Ahmadpour E, Hosseini SA, Daryani A (2020) Isolation and genotypic characterization of Toxoplasma Gondii based on gra6 gene from environmental soil samples in mazandaran province, north of Iran. Iran J Parasitol 15(2):158. https://doi.org/10.18502/ijpa.v15i2.3297

    Article  PubMed  PubMed Central  Google Scholar 

  43. Armand B, Solhjoo K, Kordshooli MS, Davami MH, Pourahmad M, Orfaee V (2017) Toxoplasma gondii type I, predominant genotype isolated from sheep in South of Iran. Vet World 10(4):386. https://doi.org/10.14202/vetworld.2017.386-392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Basavaraju A (2016) Toxoplasmosis in hiv infection: an overview. Trop Parasitol 6(2):129. https://doi.org/10.4103/2229-5070.190817

    Article  PubMed  PubMed Central  Google Scholar 

  45. Li X-L, Wei H-X, Zhang H, Peng H-J, Lindsay DS (2014) A meta analysis on risks of adverse pregnancy outcomes in Toxoplasma Gondii infection. PLoS ONE 9(5):e97775. https://doi.org/10.1371/journal.pone.0097775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wujcicka W, Wilczyński J, Nowakowska D (2014) Do the placental barrier, parasite genotype and toll-like receptor polymorphisms contribute to the course of primary infection with various Toxoplasma gondii genotypes in pregnant women? Eur J Clin Microbiol Infect Dis 33:703–709. https://doi.org/10.1007/s10096-013-2017-3

    Article  CAS  PubMed  Google Scholar 

  47. Abdoli A, Arbabi M, Pirestani M, Mirzaghavami M, Ghaffarifar F, Dalimi A et al (2018) Molecular assessment of neospora caninum and Toxoplasma Gondii in hooded crows (corvus cornix) in tehran, Iran. Comp Immunol Microbiol Infect Dis 57:69–73. https://doi.org/10.1016/j.cimid.2018.06.008

    Article  PubMed  Google Scholar 

  48. Escotte-Binet S, Da Silva AM, Cancès B, Aubert D, Dubey J, La Carbona S et al (2019) A rapid and sensitive method to detect Toxoplasma Gondii oocysts in soil samples. Vet Parasitol 274:108904. https://doi.org/10.1016/j.vetpar.2019.07.012

    Article  CAS  PubMed  Google Scholar 

  49. Mazzariol S, Marcer F, Mignone W, Serracca L, Goria M, Marsili L et al (2012) Dolphin morbillivirus and Toxoplasma Gondii coinfection in a mediterranean fin whale (balaenoptera physalus). BMC Vet Res 8:1–5. https://doi.org/10.1186/1746-6148-8-20

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Iranian National Registry Center for Lophomoniasis and Toxoplasmosis, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran

    Rohallah Abedian, Bahman Rahimi Esboei, Mahdi Fakhar, Mostafa Solaymani & Hajar Ziaei Hezarjaribi

  2. Department of Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Rohallah Abedian & Hajar Ziaei Hezarjaribi

  3. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

    Rohallah Abedian

  4. Department of Obstetrics and Gynecology, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran

    Zahra Rahmani

  5. Toxoplasmosis Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Mahbobeh Montazeri

  6. Department of Parasitology, Sari Medical School, Mazandaran University of Medical Sciences, 48168-95475, Sari, PC, Iran

    Hajar Ziaei Hezarjaribi

Authors
  1. Rohallah Abedian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bahman Rahimi Esboei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahdi Fakhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zahra Rahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahbobeh Montazeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mostafa Solaymani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hajar Ziaei Hezarjaribi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zahra Rahmani, Mahbobeh Montazeri or Hajar Ziaei Hezarjaribi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abedian, R., Esboei, B.R., Fakhar, M. et al. Is GRA6 Gene a Suitable Marker for Molecular Typing of Toxoplasma Gondii? A Scoping Systematic Review. Acta Parasit. 69, 175–182 (2024). https://doi.org/10.1007/s11686-023-00790-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11686-023-00790-y

Keywords

Search

Navigation