Klinik Araştırma
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Seroprevalence of patients presenting with a pre-diagnosis of Toxoplasma gondii, Türkiye

Yıl 2024, , 53 - 60, 01.01.2024
https://doi.org/10.31362/patd.1314049

Öz

Purpose: Toxoplasma gondii is a unicellular protozoan parasite. With this study, the aim was to evaluate the T. gondii test results that came to the General Directorate of Public Health, National Parasitology Reference Laboratory between January 2019 and December 2020.
Materials and methods: The seroprevalence were studied with the Sabin-Feldman Dye Test which is gold standard, Anti-T. gondii IgG and IgM and T. gondii IgG avidity with ELISA were evaluated in 1160 patient. The distribution of cases according to gender and age groups was also evaluated statistically.
Results: In this study, SFDT was performed on 589 patients from 1160 patients with suspected Toxoplasmosis samples and Anti-T. gondii IgG and IgM tests were studied by ELISA in 478 patients. IgG avidity test by ELISA was performed on 93 cases with positive Anti-T. gondii IgG. In addition to these, cases in which Anti-T. gondii IgM and IgG were studied together and were positive were also evaluated. The number of samples both positive together was 17 (3.6%). According to Anti-T. gondii IgG/IgM results, no significant relationship was found between toxoplasmosis and gender. Moreover, of 93 cases with positive Anti-T. gondii IgG values, 71% had high avidity, 16% had cutoff value and 13% had low avidity.
Conclusion: Further studies and surveillance studies should be performed to determine the epidemiology and current prevalence of toxoplasmosis.

Destekleyen Kurum

SB Halk Sağlığı Genel Müdürlüğü

Teşekkür

This publication was carried out with the presentation of the results of the master's thesis, which was approved with the name ''Investigation of seroprevalancy of Toxoplasma gondii antibodies with Sabin-Feldman Dye test, ElISA IgG and IgM antibody tests and evaluation of T. gondii IgG avidity test results in patients with suspected toxoplasmosis'' and number 715087, dated 2022, in the Department of Parasitology at the Faculty of Veterinary Medicine of Ankara University.

Kaynakça

  • 1. Thompson RCA. Parasite zones and wildlife: one health, spillover and human activity. Int J Parasitol 2013;43:1079-1088. https://doi.org/10.1016/j.ijpara.2013.06.007
  • 2. Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia. Emerging Infectious Disease 2003;9:1375-1380. https://doi.org/10.3201/eid0911.030143
  • 3. Hashısm MT, Al Kaseer E, Al-Diwan JK, Aziz NSA, Hassan MA. Changes in personality and mood profile of women with toxoplasmosis. The Iraqı Postgraduate Medical Journal 2011;10:249-252.
  • 4. Beaman MH, Mccabe RE, Wong SY, Remıngton JS. Toxoplasma gondii Mandell Douglass and Bennett’s principles and practice of infectious diseases. Ed.: Mandell GL, Bennet JE, Dolin R. 4th Ed., Churcill, Livingstone, New York. 1995: 2455-2475.
  • 5. Robert Gangneux F, Dardé M. Epidemiology of and diagnostic strategies for toxoplasmosis. CMR 2012;25:264-296. https://doi.org/10.1128/CMR.05013-11
  • 6. Babur C, Kilic S, Taylan Ozkan A, Esen B. Evaluation of Sabin-Feldman Dye Test results conducted between 1995 and 2000 under the Presidency of Refik Saydam Hygiene Center. Turkiye Parazitol Derg 2002;26:124-128.
  • 7. Beder D, Esenkaya Tasbent F. General features and laboratory diagnosis of Toxoplasma gondii Infection. Turkiye Parazitol Derg 2020;44:94-101. https://doi.org/10.4274/tpd.galenos.2020.6634
  • 8. Babur C, Kilic S, Taylan Ozkan A, Esen B. Evaluation of toxo-EIA IgM, IgG and Sabin-Feldman Dye Test results in patients with prediagnosis of toxoplasmosis between 1995 and 2000 National Parasitology Reference. Turkiye Parazitol Derg 2002;26:129-133.
  • 9. Iraz M, Gultepe B, Ceylan A, Doymaz MZ. Seroprevalence of toxoplasma and rubella in childbearing age women. Abant Medical Journal 2015;4:11-14. https://doi.org/10.5505/abantmedj.2015.18189
  • 10. Babur C, Yucesan B, Sezen F, Kilic S. Evalution of seropositivity of Toxolpasmosis suspected patients admitted to the National Paraistologh Reference Laboratoratory between 2009-2019. Turkiye Parazitol Derg 2021;45:181-189. https://doi.org/10.4274/tpd.galenos.2021.02419
  • 11. Bahar IH, Karaman M, Kırdar S, Yilmaz O, Celıloğlu M, Mutlu D. The importance and validity of anti-Toxoplasma gondii IgG, IgM, IgA antibodies and IgG Avidity Tests in the diagnosis of Toxoplasmosis infection during pregnancy. Turkiye Parazitol Derg 2005;29:76-79.
  • 12. Montoya JG, Liesenfeld O, Kinney S, Press C, Remington JS. VIDAS test for avidity of Toxoplasma-specific immünoglobulin G for confirmatory testing of pregnant women. Journal of Clinical Microbiology 2002;40:2504-2508. https://doi.org/10.1128/JCM.40.7.2504-2508.2002
  • 13. Saadatnia G, Golkar M. A review on human toxoplasmosis. Scandinavian Journal of Infectious Diseases 2012;44:805-814. https://doi.org/10.3109/00365548.2012.693197
  • 14. Yucesan B, Guldemir D, Babur C, Kilic S, Cakmak A. Whole-genome sequencing of a Toxoplasma gondii strain from a Turkish isolate using next-generation sequencing technology. Acta Trop 2021;218:105907. https://doi.org/10.1016/j.actatropica.2021.105907
  • 15. Meerburg BG, Kıjlstra A. Changing climate-changing pathogens: Toxoplasma gondii in North-Western Europe. Parasitology Research 2009;105:17-24. https://doi.org/10.1007/s00436-009-1447-4
  • 16. Fernanda PF, Caldart ET, Pasqualı AKS, Mitsuka Breganó R, Freire LR, Navarro IT. Patterns of transmission and source of infection in outbreaks of human toxoplasmosis. Emerging Infectious Diseases 2019;25:2177-2182. https://doi.org/10.3201/eid2512.181565
  • 17. Gras L, Gılbert RE, Wallon M, Peyron F, Cortına Borja M. Duration of the IgM response in women acquiring Toxoplasma gondii during pregnancy: implications for clinical practice and cross-sectional incidence studies. Epidemiology and Infection 2004;132:541-548. https://doi.org/10.1017/s0950268803001948
  • 18. Villard O, Cimon B, L’Ollivier C, et al. Serological diagnosis of Toxoplasma gondii infection. Diagnostic Microbiology and Infectious Disease 2016;84:22-33. https://doi.org/10.1016/j.diagmicrobio.2015.09.009
  • 19. Rahbari AH, Keshavarz H, Shojaee S, Mohebali M, Rezaeian M. IgG avidity ELISA test for diagnosis of acute toxoplasmosis in humans. Korean J Parasitol 2012;50:99-102. https://doi.org/10.3347/kjp.2012.50.2.99
  • 20. Wong SY, Remington JS. Toxoplasmosis in pregnancy. Clinical Infectious Diseases 1994;18:853-862. https://doi.org/10.1093/clinids/18.6.853
  • 21. Malatyalı E, Yıldız I, Tileklioglu E, Ertabaklar H, Ertug S. Retrospective analysis of Toxoplasma gondii serology results from Adnan Menderes University faculty of medicine parasitology laboratory from 2007 to 2017. Turkiye Parazitol Derg 2019;43:1-4. https://doi.org/10.4274/tpd.galenos.2018.6098
  • 22. Hofhuıs A, Van Pelt W, Van Duynhoven YTHP, et al. Decreased prevalence and age-specific risk factors for Toxoplasma gondii IgG antibodies in the Netherlands between 1995/1996 and 2006/2007. Epidemiol Infect 2011;139:530-538. https://doi.org/10.1017/S0950268810001044
  • 23. Aycan OM, Miman O, Atambay M, Karaman U. Celik T, Daldal N. A Last seven-year investigation of the seropositivity of Toxoplasma gondii in our hospital. İnönü University Medical Faculty 2008;15:199-201. Available at: https://www.annalsmedres.org/index.php/aomr/article/view/3264. Accessed: 03.05.2023
  • 24. Jones JL, Kruszon Moran D, Wilson M. Toxoplasma gondii infection in the United States, 1999-2000. Emerg Infect Dis 2003;9:1371-1374. https://doi.org/10.3201/eid0911.030098
  • 25. Yazar S, Kuk S, Cetinkaya U, Kaya M, Sahin I. The distribution of anti-Toxoplasma gondii antibodies in patients presenting to Erciyes University medical faculty parasitology laboratory. Kafkas Univ Vet Fak Derg 2012;18:89-92. https://doi.org/10.9775/kvfd.2011.6060
  • 26. Boluk S, Ozyurt BC, Girginkardesler N, Kilimcioglu AA. Evaluation of serological results of patients with suspected toxoplasmosis admitted to the medical parasitology laboratory of Celal Bayar University hospital between 2006-2010. Turkiye Parazitol Derg 2012;36:137-141. https://doi.org/10.5152/tpd.2012.33
  • 27. Shin D, Cha D, Hua QJ, Cha G, Lee Y. Seroprevalence of Toxoplasma gondii infection and characteristics of seropositive patients in general hospitals in Daejeon, Korea. Korean J Parasitol 2009;47:125-130. https://doi.org/10.3347/kjp.2009.47.2.125
  • 28. Markovich MP, Shohat T, Riklis I, et al. Seroepidemiology of Toxoplasma gondii infection in the Israeli population. Epidemiology and Infection 2014;142:149-155. https://doi.org/10.1017/S0950268813000903
  • 29. Jones JL, Roberts JM. Toxoplasmosis hospitalizations in the United States, 2008, and trends, 1993–2008. CID 2012;54:58-61. https://doi.org/10.1093/cid/cir990
  • 30. Bellalı H, Pelloux H, Vıllena I, et al. Prevalence of toxoplasmosis in France in 1998: is there a difference between men and women? At what age do children become infected. Revue d’E´ pide´miologie et de Sante´ Publique 2013;61:311-317. https://doi.org/10.1016/j.respe.2012.11.005
  • 31. Fromont EG, Rıche B, Rabılloud M. Toxoplasma seroprevalence in a rural population in France: detection of a household effect. BMC Infectious Diseases 2009;9:1-7. https://doi.org/10.1186/1471-2334-9-76
  • 32. Kolbekova P, Kourbatova E, Novotna M, Kodym P, Flegr J. New and old risk-factors for Toxoplasma gondii infection: prospective cross-sectional study among military personnel in the Czech Republic. Clinical Microbiology and Infection 2007;13:1012-1017. https://doi.org/10.1111/j.1469-0691.2007.01771.x
  • 33. Studenıčová C, Benčaıová G, Holkovár R. Seroprevalence of Toxoplasma gondii antibodies in a healthy population from Slovakia. European Journal of Internal Medicine 2005;17:470-473. https://doi.org/10.1016/j.ejim.2006.07.007
  • 34. Joynson DHM, Payne RA, Rawal BK. Potential role of IgG avidity for diagnosing toxoplasmosis. J Clin Pathol 1990;43:1032-1033. https://doi.org/10.1136/jcp.43.12.1032
  • 35. Yazısız H, Ongut G, Ozturk Eryigit F, et al. Retrospective evalution of anti-Toxoplasma gondii IgG, IgM and IgG avidity resuts in Akdeniz University hospital laboratory. Turk Mikrobiyoloji Cem Derg 2019;49:92-97. https://doi.org/10.5222/TMCD.2019.092
  • 36. Yazar S, Yaman O, Sahin I. Evaluation of the results of IgG avidity testing of Toxoplasma gondii in pregnant women. Turkiye Parazitol Derg 2005;29:221-223.

Toxoplasma gondii ön tanısı ile başvuran hastalarda seroprevalans, Türkiye

Yıl 2024, , 53 - 60, 01.01.2024
https://doi.org/10.31362/patd.1314049

Öz

Amaç: Toxoplasma gondii, tek hücreli bir protozoon parazittir. Bu çalışma ile Halk Sağlığı Genel Müdürlüğü Ulusal Parazitoloji Referans Laboratuvarına Ocak 2019-Aralık 2020 tarihleri arasında gelen T. gondii test sonuçlarının değerlendirilmesi amaçlanmıştır.
Gereç ve yöntem: Altın standart olan Sabin-Feldman Boya Testi ile seroprevalans çalışıldı, Anti-T. gondii IgG ve IgM ve T. gondii IgG aviditesi ELISA ile 1160 hastada değerlendirildi. Vakaların cinsiyet ve yaş gruplarına göre dağılımı da istatistiksel olarak değerlendirildi.
Bulgular: Bu çalışmada Toksoplazmoz şüphesi olan 1160 hastadan 589'una SFDT yapıldı ve 478 hastada ELISA ile Anti-T. gondii IgG ve IgM testleri çalışıldı. Anti-T. gondii IgG'si pozitif olan 93 olguya ELISA ile IgG avidite testi uygulandı. Bunlara ek olarak Anti-T. gondii IgM ve IgG birlikte çalışıldı ve pozitif olanlar da değerlendirildi. İkisi
birlikte pozitif olan örnek sayısı 17 (%3,6) idi. Anti-T. gondii IgG/IgM sonuçlarına göre toksoplazmoz ile cinsiyet arasında anlamlı bir ilişki bulunmadı. Ayrıca Anti-T. gondii IgG değerleri pozitif olan 93 olgunun %71'inde yüksek avidite, %16'sında cutoff değeri ve %13'ünde düşük avidite vardı.
Sonuç: Toksoplazmozun epidemiyolojisini ve güncel prevalansını belirlemek için ileri çalışmalar ve sürveyans çalışmaları yapılmalıdır.

Kaynakça

  • 1. Thompson RCA. Parasite zones and wildlife: one health, spillover and human activity. Int J Parasitol 2013;43:1079-1088. https://doi.org/10.1016/j.ijpara.2013.06.007
  • 2. Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia. Emerging Infectious Disease 2003;9:1375-1380. https://doi.org/10.3201/eid0911.030143
  • 3. Hashısm MT, Al Kaseer E, Al-Diwan JK, Aziz NSA, Hassan MA. Changes in personality and mood profile of women with toxoplasmosis. The Iraqı Postgraduate Medical Journal 2011;10:249-252.
  • 4. Beaman MH, Mccabe RE, Wong SY, Remıngton JS. Toxoplasma gondii Mandell Douglass and Bennett’s principles and practice of infectious diseases. Ed.: Mandell GL, Bennet JE, Dolin R. 4th Ed., Churcill, Livingstone, New York. 1995: 2455-2475.
  • 5. Robert Gangneux F, Dardé M. Epidemiology of and diagnostic strategies for toxoplasmosis. CMR 2012;25:264-296. https://doi.org/10.1128/CMR.05013-11
  • 6. Babur C, Kilic S, Taylan Ozkan A, Esen B. Evaluation of Sabin-Feldman Dye Test results conducted between 1995 and 2000 under the Presidency of Refik Saydam Hygiene Center. Turkiye Parazitol Derg 2002;26:124-128.
  • 7. Beder D, Esenkaya Tasbent F. General features and laboratory diagnosis of Toxoplasma gondii Infection. Turkiye Parazitol Derg 2020;44:94-101. https://doi.org/10.4274/tpd.galenos.2020.6634
  • 8. Babur C, Kilic S, Taylan Ozkan A, Esen B. Evaluation of toxo-EIA IgM, IgG and Sabin-Feldman Dye Test results in patients with prediagnosis of toxoplasmosis between 1995 and 2000 National Parasitology Reference. Turkiye Parazitol Derg 2002;26:129-133.
  • 9. Iraz M, Gultepe B, Ceylan A, Doymaz MZ. Seroprevalence of toxoplasma and rubella in childbearing age women. Abant Medical Journal 2015;4:11-14. https://doi.org/10.5505/abantmedj.2015.18189
  • 10. Babur C, Yucesan B, Sezen F, Kilic S. Evalution of seropositivity of Toxolpasmosis suspected patients admitted to the National Paraistologh Reference Laboratoratory between 2009-2019. Turkiye Parazitol Derg 2021;45:181-189. https://doi.org/10.4274/tpd.galenos.2021.02419
  • 11. Bahar IH, Karaman M, Kırdar S, Yilmaz O, Celıloğlu M, Mutlu D. The importance and validity of anti-Toxoplasma gondii IgG, IgM, IgA antibodies and IgG Avidity Tests in the diagnosis of Toxoplasmosis infection during pregnancy. Turkiye Parazitol Derg 2005;29:76-79.
  • 12. Montoya JG, Liesenfeld O, Kinney S, Press C, Remington JS. VIDAS test for avidity of Toxoplasma-specific immünoglobulin G for confirmatory testing of pregnant women. Journal of Clinical Microbiology 2002;40:2504-2508. https://doi.org/10.1128/JCM.40.7.2504-2508.2002
  • 13. Saadatnia G, Golkar M. A review on human toxoplasmosis. Scandinavian Journal of Infectious Diseases 2012;44:805-814. https://doi.org/10.3109/00365548.2012.693197
  • 14. Yucesan B, Guldemir D, Babur C, Kilic S, Cakmak A. Whole-genome sequencing of a Toxoplasma gondii strain from a Turkish isolate using next-generation sequencing technology. Acta Trop 2021;218:105907. https://doi.org/10.1016/j.actatropica.2021.105907
  • 15. Meerburg BG, Kıjlstra A. Changing climate-changing pathogens: Toxoplasma gondii in North-Western Europe. Parasitology Research 2009;105:17-24. https://doi.org/10.1007/s00436-009-1447-4
  • 16. Fernanda PF, Caldart ET, Pasqualı AKS, Mitsuka Breganó R, Freire LR, Navarro IT. Patterns of transmission and source of infection in outbreaks of human toxoplasmosis. Emerging Infectious Diseases 2019;25:2177-2182. https://doi.org/10.3201/eid2512.181565
  • 17. Gras L, Gılbert RE, Wallon M, Peyron F, Cortına Borja M. Duration of the IgM response in women acquiring Toxoplasma gondii during pregnancy: implications for clinical practice and cross-sectional incidence studies. Epidemiology and Infection 2004;132:541-548. https://doi.org/10.1017/s0950268803001948
  • 18. Villard O, Cimon B, L’Ollivier C, et al. Serological diagnosis of Toxoplasma gondii infection. Diagnostic Microbiology and Infectious Disease 2016;84:22-33. https://doi.org/10.1016/j.diagmicrobio.2015.09.009
  • 19. Rahbari AH, Keshavarz H, Shojaee S, Mohebali M, Rezaeian M. IgG avidity ELISA test for diagnosis of acute toxoplasmosis in humans. Korean J Parasitol 2012;50:99-102. https://doi.org/10.3347/kjp.2012.50.2.99
  • 20. Wong SY, Remington JS. Toxoplasmosis in pregnancy. Clinical Infectious Diseases 1994;18:853-862. https://doi.org/10.1093/clinids/18.6.853
  • 21. Malatyalı E, Yıldız I, Tileklioglu E, Ertabaklar H, Ertug S. Retrospective analysis of Toxoplasma gondii serology results from Adnan Menderes University faculty of medicine parasitology laboratory from 2007 to 2017. Turkiye Parazitol Derg 2019;43:1-4. https://doi.org/10.4274/tpd.galenos.2018.6098
  • 22. Hofhuıs A, Van Pelt W, Van Duynhoven YTHP, et al. Decreased prevalence and age-specific risk factors for Toxoplasma gondii IgG antibodies in the Netherlands between 1995/1996 and 2006/2007. Epidemiol Infect 2011;139:530-538. https://doi.org/10.1017/S0950268810001044
  • 23. Aycan OM, Miman O, Atambay M, Karaman U. Celik T, Daldal N. A Last seven-year investigation of the seropositivity of Toxoplasma gondii in our hospital. İnönü University Medical Faculty 2008;15:199-201. Available at: https://www.annalsmedres.org/index.php/aomr/article/view/3264. Accessed: 03.05.2023
  • 24. Jones JL, Kruszon Moran D, Wilson M. Toxoplasma gondii infection in the United States, 1999-2000. Emerg Infect Dis 2003;9:1371-1374. https://doi.org/10.3201/eid0911.030098
  • 25. Yazar S, Kuk S, Cetinkaya U, Kaya M, Sahin I. The distribution of anti-Toxoplasma gondii antibodies in patients presenting to Erciyes University medical faculty parasitology laboratory. Kafkas Univ Vet Fak Derg 2012;18:89-92. https://doi.org/10.9775/kvfd.2011.6060
  • 26. Boluk S, Ozyurt BC, Girginkardesler N, Kilimcioglu AA. Evaluation of serological results of patients with suspected toxoplasmosis admitted to the medical parasitology laboratory of Celal Bayar University hospital between 2006-2010. Turkiye Parazitol Derg 2012;36:137-141. https://doi.org/10.5152/tpd.2012.33
  • 27. Shin D, Cha D, Hua QJ, Cha G, Lee Y. Seroprevalence of Toxoplasma gondii infection and characteristics of seropositive patients in general hospitals in Daejeon, Korea. Korean J Parasitol 2009;47:125-130. https://doi.org/10.3347/kjp.2009.47.2.125
  • 28. Markovich MP, Shohat T, Riklis I, et al. Seroepidemiology of Toxoplasma gondii infection in the Israeli population. Epidemiology and Infection 2014;142:149-155. https://doi.org/10.1017/S0950268813000903
  • 29. Jones JL, Roberts JM. Toxoplasmosis hospitalizations in the United States, 2008, and trends, 1993–2008. CID 2012;54:58-61. https://doi.org/10.1093/cid/cir990
  • 30. Bellalı H, Pelloux H, Vıllena I, et al. Prevalence of toxoplasmosis in France in 1998: is there a difference between men and women? At what age do children become infected. Revue d’E´ pide´miologie et de Sante´ Publique 2013;61:311-317. https://doi.org/10.1016/j.respe.2012.11.005
  • 31. Fromont EG, Rıche B, Rabılloud M. Toxoplasma seroprevalence in a rural population in France: detection of a household effect. BMC Infectious Diseases 2009;9:1-7. https://doi.org/10.1186/1471-2334-9-76
  • 32. Kolbekova P, Kourbatova E, Novotna M, Kodym P, Flegr J. New and old risk-factors for Toxoplasma gondii infection: prospective cross-sectional study among military personnel in the Czech Republic. Clinical Microbiology and Infection 2007;13:1012-1017. https://doi.org/10.1111/j.1469-0691.2007.01771.x
  • 33. Studenıčová C, Benčaıová G, Holkovár R. Seroprevalence of Toxoplasma gondii antibodies in a healthy population from Slovakia. European Journal of Internal Medicine 2005;17:470-473. https://doi.org/10.1016/j.ejim.2006.07.007
  • 34. Joynson DHM, Payne RA, Rawal BK. Potential role of IgG avidity for diagnosing toxoplasmosis. J Clin Pathol 1990;43:1032-1033. https://doi.org/10.1136/jcp.43.12.1032
  • 35. Yazısız H, Ongut G, Ozturk Eryigit F, et al. Retrospective evalution of anti-Toxoplasma gondii IgG, IgM and IgG avidity resuts in Akdeniz University hospital laboratory. Turk Mikrobiyoloji Cem Derg 2019;49:92-97. https://doi.org/10.5222/TMCD.2019.092
  • 36. Yazar S, Yaman O, Sahin I. Evaluation of the results of IgG avidity testing of Toxoplasma gondii in pregnant women. Turkiye Parazitol Derg 2005;29:221-223.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Bulaşıcı Hastalıklar, Sağlık Hizmetleri ve Sistemleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Burcu Aslaner 0000-0001-8112-5806

Serpil Nalbantoğlu 0000-0002-9670-7566

Banuçiçek Yücesan 0000-0001-7051-3045

Erken Görünüm Tarihi 20 Ekim 2023
Yayımlanma Tarihi 1 Ocak 2024
Gönderilme Tarihi 10 Temmuz 2023
Kabul Tarihi 18 Ekim 2023
Yayımlandığı Sayı Yıl 2024

Kaynak Göster

AMA Aslaner B, Nalbantoğlu S, Yücesan B. Seroprevalence of patients presenting with a pre-diagnosis of Toxoplasma gondii, Türkiye. Pam Tıp Derg. Ocak 2024;17(1):53-60. doi:10.31362/patd.1314049
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