The parasite Toxoplasma gondii is a single-celled, eukaryotic, coccidian protozoan that must live inside cells [1]. It is in the group of phylum Apicomplexa and relies on the actomyosin system, an active process that invades host cells. Several protozoan parasites utilize the actomyosin system, causing serious illnesses in a range of hosts, including humans and other warm-blooded domestic and wild animals [2]. T. gondii is a prevalent zoonoses, affecting one-third-of the global population [3,4]. It causes toxoplasmosis, a potentially fatal disease in immunocompromised patients, and can lead to congenital defects in the fetuses of women infected during pregnancy [5,6]. Unlike other coccidian, it can infect any nucleated cell, including immature red blood cells (RBC) in warm-blooded animals [7].

T. gondii has a complex life cycle, infecting most warm-blooded species. Similar to Plasmodium, it infects cells by invading the host cell membrane or disrupting the cytoskeleton, often resulting in cell rupture [8,9]. This process, known as cell lysis, occurs during the parasite's exit [10]; The exact mechanism of the exit is still unclear, but it is a facultative heterogeneous process, involving sexual and asexual phases in different hosts [11,12].

T. gondii infection can occur in two stages: acute toxoplasmosis, which is often asymptomatic in healthy adults, and chronic persistence of cysts in immune-competent individuals [13]. Chronic infection and cell-mediated immunodeficiency can cause toxoplasmosis symptoms to reoccur and lead to a decrease in the CD4+ cell count [14]. Immunocompromised individuals may experience headaches, confusion, poor coordination, seizures, lung problems, and blurred vision due to retinal inflammation [15]. Latent toxoplasmosis typically presents with mild symptoms but can cause lesions in the heart, skeletal muscle, and central nervous system [16,17]. In humans, the initial T. gondii infection typically does not show any noticeable symptoms. However, some individuals may experience ocular toxoplasmosis or cervical lymphadenopathy [18].

During pregnancy, the parasite can cross the placenta and infect the fetus, posing significant risks to both the fetus and the mother. Vertical transmission from an infected mother can lead to miscarriage, congenital infection, severe fetal damage, retinochoroiditis, and even death or infertility in women [4,12,19].

CD4+ T cells play a crucial role in controlling both acute and chronic Toxoplasma infections. While CD8+ T cells are essential for managing chronic infection, their maintenance depends on CD4+ T cells. CD8+ T cell exhaustion can lead to reactivation of the infection [20,21]. Non-exhausted antigen-specific CD4+ T cells can restore function and prevent infection reactivation [22].

In humans, infection with T. gondii induces both cellular and humoral immune responses in immunocompetent individuals. The immune system significantly reduces the number of parasites, although the encysted form survives. Acquired immunity is long-lasting and protects against reinfection. Cellular immunity is a critical component of the host's immune response to Toxoplasma infection [23].

Global infection rates of T. gondii in pregnant women aged from 18 to ​49 range from 2% to 90% [11]. Risk factors and transmission routes significantly impact the health of pregnant women. Specifically, infection rates correlate with environmental exposure to cat populations and are further influenced by hygiene practices, such as hand washing, sanitation, and the consumption of contaminated food or water [5,12,24]. Accurate detection and the use of sensitive diagnostic methods are crucial for effective control and treatment of infections. This study aims to determine the effect of T. gondii infections on hematological parameters and on the CD4+ cell count among pregnant women attending antenatal care at a public hospital in Northwest Ethiopia. The findings provide baseline information for planning and implementing control and prevention strategies, as well as for advancing the understanding of the epidemiology and management of toxoplasmosis.

This study highlights a significant association between T. gondii infection and hematological alterations in pregnant women. Specifically, women who tested seropositive for T. gondii exhibited significantly lower levels of WBC, lymphocytes, neutrophils, RBC, Hb, Hct, and CD4+ T cell counts compared to their seronegative counterparts. These hematological disturbances may reflect the parasite’s ability to impair hematopoiesis through direct invasion of progenitor cells or immune-mediated mechanisms [25].

The findings of this study align with earlier reports from Tikrit city [25], Saudi Arabia [26], and Iraq [27] that also documented hematological suppression among infected pregnant women. WBCs play an essential role in controlling toxoplasmosis [28], and the parasite’s ability to invade nucleated cells including immature RBC suggests a plausible pathophysiologic mechanism. The clinical implications are concerning, as such alterations could compromise maternal health and fetal outcomes [28]. Neutrophilia was notably higher in seropositive women, indicating an acute inflammatory response potentially induced by the rapid multiplication of tachyzoites [10,26,29]. Neutrophils, guided by chemokine gradients toward the sites of tachyzoite invasion, are among the first responders during infection [26,29].

Interestingly, while some studies from Thailand [30] and Libya [26] report contrasting findings regarding WBC levels, the present results revealed significant leukopenia in infected cases. This suggests regional variability or potential influence from other confounding factors such as nutrition or co-infections. Toxoplasma infection can lead to a significant decline in WBC counts in pregnant women. Because these cells are essential for orchestrating both innate and adaptive immune responses, their depletion may compromise the host's ability to control the parasite [25]. Crucially, T. gondii infection was also associated with a marked reduction in CD4+ T cell counts. CD4+ T lymphocytes are pivotal in orchestrating adaptive immunity and ensuring long-term immunological memory [31]. The findings of the current study support existing evidence that lower CD4+ counts in seropositive pregnant women may result from suppressed interleukin (IL)-12 and interferon gamma (IFN-γ) production and impaired cytotoxic T cell activity. This immune suppression renders these women more susceptible to opportunistic infections and may contribute to reactivation of latent toxoplasmosis or other latent pathogens. Although most participants were in the age range of 18–49 years, significant immune alterations were consistent across the spectrum. The observed decline in CD4+ T cell levels corroborates previous work [32] and underscores the pathogen’s capacity for immune modulation. Notably, some discrepancies were observed when compared to published studies [33–35]. These inconsistencies may be attributed to differences in study design, population demographics, or diagnostic methodologies.

Despite its strengths, this study is constrained by its cross-sectional nature, limiting causal inferences. Moreover, potential confounders like nutritional deficiencies or unrecognized infections were not exhaustively assessed. Nonetheless, the consistent pattern of hematological and immunological disruptions in T. gondii-positive pregnant women suggests a need for routine screening and timely intervention, particularly in endemic settings. By characterizing the hematological impact and immunologic suppression associated with toxoplasmosis, this research reinforces the importance of early diagnosis and immune monitoring in pregnant women. Proactive management can not only mitigate maternal complications but also reduce the risk of vertical transmission to the fetus.

The study demonstrates that T. gondii infections during pregnancy are associated with significant alterations in immune and hematological profiles. We recommend routine screening during antenatal care visits and conducting further research into the implications in humans. Additionally, it is advisable to provide education on prevention and risk factors.

This research did not receive any grants from any funding agencies.

For the sake of maintaining patient confidentiality, the raw data will not be shared. Data supporting this research article are available from the corresponding author or first author on reasonable request.

Ethical clearance was obtained from the Research and Ethical Review Committee of the University of Gondar with a reference number of VP/RTT/05/280/2022. Written consent was secured from all participants. All methods were carried out in accordance with relevant guidelines and regulations.

Conceptualization: Eden Woldegerima, Mastewal Birhan, Mequant Melese,Tadelo Wondmagegn, Nega Berhane; Data analysis: Eden Woldegerima, Destaw Fetene Tesshome, Mequanente Dagnaw; Investigation: Eden Woldegerima,Tadelo Wondmagegn, Nega Berhane; Methodology: Eden Woldegerima, Destaw Fetene Tesshome, Mequanente Dagnaw; Project administration: Eden Woldegerima, Nega Berhane; Supervision: Eden Woldegerima, Nega Berhane; Writing - original draft: Eden Woldegerima, Mastewal Birhan, Mequant Melese,Tadelo Wondmagegn, Nega Berhane; Writing - review & editing: Eden Woldegerima, Destaw Fetene Tesshome, Mequanente Dagnaw, Nega Berhane.