Seroprevalence and Risk of Toxoplasma gondii Reactivation in Pediatric Patients with Hematological Malignancies Undergoing Chemotherapy: A Case-Control Study
Abstract
Background: Toxoplasmosis, caused by Toxoplasma gondii, affects around 40% of the Iranian population and can be severe in vulnerable patients, such as those receiving chemotherapy. In this study, the titers of IgG and IgM antibodies in 92 children treated for chemotherapy have been compared with 92 matched controls. We also looked into demographic and lifestyle factors in association with the antibody levels as a contribution to the development of improved preventive and management techniques.
Methods: In this case-control study conducted at Shahid Madani Hospital, Khorramabad, Iran, blood samples of both groups were tested for IgG and IgM anti-Toxoplasma gondii antibodies by ELISA. Participants were selected randomly, and demographic, clinical, and lifestyle data were obtained from structured interviews and from the hospital records. Statistical analyses were performed using SPSS software, considering p-values less than 0.05 as significant. Approval for ethics was obtained, and informed consent was provided by the guardians.
Results: The results revealed that the prevalence of IgG antibodies was significantly higher in chemotherapy patients (35.9%) compared to the controls (14.1%), indicating a strong association between immunosuppression and elevated IgG levels (p = 0.001, OR = 2.026). No significant difference in IgM antibodies was found, suggesting that chemotherapy increases the risk of reactivation rather than new infections. Subgroup analysis showed that IgG positivity was more common in younger immunocompromised patients (under 10 years old). However, factors such as gender, residence, and dietary habits did not significantly affect IgG or IgM positivity. In the control group, urban residents had a higher IgG positivity rate than rural ones.
Conclusion: In conclusion, pediatric patients who have undergone chemotherapy are more prone to chronic infection with Toxoplasma gondii. Serological tests and prevention measures must be carried out regularly to reduce the risk of reactivation in such patients.
References
Liu Q, Wang Z-D, Huang S-Y, Zhu X-Q. Diagnosis of toxoplasmosis and typing of Toxoplasma gondii. Parasites & vectors. 2015;8:1-14.
Nayeri T, Sarvi S, Daryani A. Toxoplasma gondii in mollusks and cold-blooded animals: a systematic review. Parasitology. 2021;148(8):895-903.
Shapiro K, Bahia-Oliveira L, Dixon B, Dumètre A, de Wit LA, VanWormer E, et al. Environmental transmission of Toxoplasma gondii: Oocysts in water, soil and food. Food Waterborne Parasitol. 2019;15:e00049.
Daryani A, Sarvi S, Aarabi M, Mizani A, Ahmadpour E, Shokri A, et al. Seroprevalence of Toxoplasma gondii in the Iranian general population: a systematic review and meta-analysis. Acta tropica. 2014;137:185-94.
Bando H, Murata Y, Han Y, Sugi T, Fukuda Y, Bzik DJ, et al. Toxoplasma gondii chitinase-like protein TgCLP1 regulates the parasite cyst burden. Frontiers in Cellular and Infection Microbiology. 2024;14.
Pinto-Ferreira F, Caldart ET, Pasquali AKS, Mitsuka-Breganó R, Freire RL, Navarro IT. Patterns of Transmission and Sources of Infection in Outbreaks of Human Toxoplasmosis. Emerg Infect Dis. 2019;25(12):2177-82.
Marín-García P-J, Planas N, Llobat L. Toxoplasma gondii in Foods: Prevalence, Control, and Safety. Foods. 2022;11(16):2542.
Pintos GB, Pires F, Zini N, da Silva R, Silva Junior FIM, da Silva RF, et al. Serological Profile of Anti-Toxoplasma gondii Antibodies in Liver Transplant Recipients. Trop Med Infect Dis. 2025;10(1).
Butani L, Tancredi D. Outcomes of Kidney Transplants From Toxoplasma-Positive Donors: An Organ Procurement and Transplant Network Database Analysis. Transplant International. 2024;37.
Wesołowski R, Pawłowska M, Mila-Kierzenkowska C. The Medical Relevance of Toxoplasma Infections in Terms of the Safety of Blood Recipients under Immunosuppression-A Meta-Analysis. Microorganisms. 2023;11(8).
Ybañez RHD, Ybañez AP, Nishikawa Y. Review on the Current Trends of Toxoplasmosis Serodiagnosis in Humans. Frontiers in Cellular and Infection Microbiology. 2020;10.
Carranza-Rodríguez C, Bolaños-Rivero M, Pérez-Arellano JL. Toxoplasma gondii Infection in Humans: A Comprehensive Approach Involving the General Population, HIV-Infected Patients and Intermediate-Duration Fever in the Canary Islands, Spain. Diagnostics (Basel). 2024;14(8).
Ali MI, Abd El Wahab WM, Hamdy DA, Hassan A. Toxoplasma gondii in cancer patients receiving chemotherapy: seroprevalence and interferon gamma level. J Parasit Dis. 2019;43(3):464-71.
Wesołowski R, Pawłowska M, Smoguła M, Szewczyk-Golec K. Advances and Challenges in Diagnostics of Toxoplasmosis in HIV-Infected Patients. Pathogens. 2023;12(1).
Pan M, Ge C-C, Fan Y-M, Jin Q-W, Shen B, Huang S-Y. The determinants regulating Toxoplasma gondii bradyzoite development. Frontiers in Microbiology. 2022;13.
Cerutti A, Blanchard N, Besteiro S. The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis. Pathogens. 2020;9(3).
Bollani L, Auriti C, Achille C, Garofoli F, De Rose DU, Meroni V, et al. Congenital toxoplasmosis: the state of the art. Frontiers in pediatrics. 2022;10:894573.
McLeod R, Cohen W, Dovgin S, Finkelstein L, Boyer K. Chapter 4-Human Toxoplasma Infection. Toxoplasma gondii. 2020:117-227.
Graham AK, Fong C, Naqvi A, Lu J-Q. Toxoplasmosis of the central nervous system: Manifestations vary with immune responses. Journal of the Neurological Sciences. 2021;420:117223.
Tűzkő N, Bartek V, Simonyi A, Harmath Á, Szabó I, Virok DP, et al. Associations between Fetal Symptoms during Pregnancy and Neonatal Clinical Complications with Toxoplasmosis. Children. 2024;11(9):1111.
Dupont D, Fricker-Hidalgo H, Brenier-Pinchart M-P, Garnaud C, Wallon M, Pelloux H. Serology for Toxoplasma in immunocompromised patients: still useful? Trends in parasitology. 2021;37(3):205-13.
Wang ZD, Liu HH, Ma ZX, Ma HY, Li ZY, Yang ZB, et al. Toxoplasma gondii Infection in Immunocompromised Patients: A Systematic Review and Meta-Analysis. Front Microbiol. 2017;8:389.
Durieux M-F, Lopez J-G, Banjari M, Passebosc-Faure K, Brenier-Pinchart M-P, Paris L, et al. Toxoplasmosis in patients with an autoimmune disease and immunosuppressive agents: A multicenter study and literature review. PLoS neglected tropical diseases. 2022;16(8):e0010691.
Haghbin M, Maani S, Bagherzadeh MA, Bazmjoo A, Shakeri H, Taghipour A, et al. Latent Toxoplasmosis among Breast Cancer Patients in Jahrom, South of Iran. International Journal of Breast Cancer. 2023;2023(1):4792260.
Štajner T, Vujić D, Srbljanović J, Bauman N, Zečević Ž, Simić M, et al. Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis. Clinical Microbiology and Infection. 2022;28(5):733. e1-. e5.
Layton J, Theiopoulou D-C, Rutenberg D, Elshereye A, Zhang Y, Sinnott J, et al. Clinical spectrum, radiological findings, and outcomes of severe toxoplasmosis in immunocompetent hosts: a systematic review. Pathogens. 2023;12(4):543.
Aronson B, Acosta Sanchez I, Ascoli C. When to Reassess: A Case of Toxoplasma-induced Pneumonitis in a Bone Marrow Transplant Patient. C105 INFECTIONS IN THE ICU: THE BEST OF THE BEST CASES: American Thoracic Society; 2023. p. A6074-A.
Tateno T, Onozawa M, Hashiguchi J, Ishio T, Yuzawa S, Matsuoka S, et al. Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images. Transplant Infectious Disease. 2017;19(4):e12720.
Ali MI, Abd El Wahab WM, Hamdy DA, Hassan A. Toxoplasma gondii in cancer patients receiving chemotherapy: seroprevalence and interferon gamma level. Journal of parasitic diseases. 2019;43:464-71.
Khurana S, Dubey M, Malla N. Association of parasitic infections and cancers. Indian Journal of Medical Microbiology. 2005;23(2):74-9.
Kalantari N, Darabi ZA, Siadati S, Nikbakhsh N, Ghasemi M, Ghaffari T, et al. Detection of Toxoplasma gondii DNA in malignant breast tissues in breast cancer patients. International journal of molecular and cellular medicine. 2017;6(3):190.
Abdollahi A, Razavian I, Razavian E, Ghodsian S, Almukhtar M, Marhoommirzabak E, et al. Toxoplasma gondii infection/exposure and the risk of brain tumors: A systematic review and meta-analysis. Cancer epidemiology. 2022;77:102119.
ElBlihy A, Alhusseiny S, Abd Elmabood S, El-Beshbishi S. Toxoplasma gondii seropositivity among Egyptian children with haematological malignancies. Parasitologists United Journal. 2023;16(1):57-63.
Phan L, Kasza K, Jalbrzikowski J, Noble AG, Latkany P, Kuo A, et al. Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life. Am J Ophthalmol. 2008;146(3):375-84.
Arruda IF, Millar PR, da Silva Barbosa A, de Souza Abboud LC, Dos Reis IC, da Cruz Moreira AS, et al. Toxoplasma gondii in domiciled dogs and cats in urban areas of Brazil: risk factors and spatial distribution. Parasite. 2021;28:56.
Escudero A, Ribas MP, Obón E, Almería S, Aguilar XF, Gholipour H, et al. Exposure of Urban European Hedgehogs (Erinaceus europaeus) to Toxoplasma gondii in Highly Populated Areas of Northeast Spain. Animals. 2024;14(11):1596.
Morais R, Carmo ELD, Costa WS, Marinho RR, Póvoa MM. T. gondii Infection in Urban and Rural Areas in the Amazon: Where Is the Risk for Toxoplasmosis? Int J Environ Res Public Health. 2021;18(16).
Alim M, Ozcelik S, Ozpinar N. Seroprevalence of Toxoplasma gondii in patients receiving cancer treatment. Cumhuriyet Medical Journal. 2018;40(1):19-24.
Hosseini SA, Sharif M, Sarvi S, Janbabai G, Keihanian S, Abediankenari S, et al. Toxoplasmosis among cancer patients undergoing chemotherapy: a population study based on the serological, molecular and epidemiological aspects. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2021;115(6):677-86.
Mostafa NES, Hamed EFA, Rashed HES, Mohamed SY, Abdelgawad MS, Elasbali AM. The relationship between toxoplasmosis and different types of human tumors. The Journal of Infection in Developing Countries. 2018;12(02):137-41.
Aerts R, Mehra V, Groll AH, Martino R, Lagrou K, Robin C, et al. Guidelines for the management of Toxoplasma gondii infection and disease in patients with haematological malignancies and after haematopoietic stem-cell transplantation: guidelines from the 9th European Conference on Infections in Leukaemia, 2022. The Lancet Infectious Diseases. 2024;24(5):e291-e306.
Luo L, Shen N, Chen W, Luo C, Huang X, Jiang Y, et al. Toxoplasma gondii infection in children after allogeneic hematopoietic stem cell transplantation: a case report and literature review. Pediatric Investigation. 2021;5(03):239-43.
Kitahara M, Hiroshima Y, Norose K, Hikosaka K, Kazumoto H, Uematsu N, et al. Clinical characteristics and incidence of toxoplasmosis after autologous hematopoietic stem cell transplantation: a retrospective study and literature review. Transplant Infectious Disease. 2021;23(6):e13726.
Schwenk HT, Khan A, Kohlman K, Bertaina A, Cho S, Montoya JG, et al. Toxoplasmosis in pediatric hematopoietic stem cell transplantation patients. Transplantation and Cellular Therapy. 2021;27(4):292-300.
Rauwolf KK, Floeth M, Kerl K, Schaumburg F, Groll AH. Toxoplasmosis after allogeneic haematopoietic cell transplantation—disease burden and approaches to diagnosis, prevention and management in adults and children. Clinical Microbiology and Infection. 2021;27(3):378-88.
Malek AE, Al-Juhaishi T, Milton DR, Ramdial JL, Daher M, Olson AL, et al. Outcomes of toxoplasmosis after allogeneic hematopoietic stem cell transplantation and the role of antimicrobial prophylaxis. Bone marrow transplantation. 2024;59(5):699-704.
Contopoulos-Ioannidis DG, Cho SM, Bertaina A, Leung AN, Fischbein N, Lanzman B, et al. Toxoplasmosis among 38 751 hematopoietic stem-cell transplant recipients: a systematic review of disease prevalence and a compilation of imaging and autopsy findings. Transplantation. 2021;105(12):e375-e86.
Osthoff M, Chew E, Bajel A, Kelsey G, Panek‐Hudson Y, Mason K, et al. Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient. Transplant Infectious Disease. 2013;15(1):E14-E9.
Villard O, Cimon B, L’ollivier C, Fricker-Hidalgo H, Godineau N, Houze S, et al. Serological diagnosis of Toxoplasma gondii infection: recommendations from the French National Reference Center for Toxoplasmosis. Diagnostic Microbiology and Infectious Disease. 2016;84(1):22-33.
Martino R, Maertens J, Bretagne S, Rovira M, Deconinck E, Ullmann A, et al. Toxoplasmosis after hematopoietic stem cell transplantation. Clinical Infectious Diseases. 2000;31(5):1188-94.
Khalaf AM, Hashim MA, Alsharabati M, Fallon K, Cure JK, Pappas P, et al. Late-Onset Cerebral Toxoplasmosis After Allogeneic Hematopoietic Stem Cell Transplantation. Am J Case Rep. 2017;18:246-50.
