Liver pathologies and infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) are widespread among HIV-infected patients. However, a possible contribution of toxoplasmosis to the development of various forms of liver diseases in HIV-infected individuals has not yet been determined. This research is a retrospective cohort study. Medical cards of 907 HIV-positive patients, including 119 individuals who died, were studied. The patients were divided into two groups: 531 patients were seropositive to T. gondii and 376 seronegative. General liver pathology was more widespread among patients seropositive to T. gondii than in seronegative patients (63.1 ± 2.1% and 51.9 ± 2.6%, respectively, p < 0.001). The association of seropositive to T. gondii with general liver pathology is weak both in the whole cohort (Pearson's contingency coefficient C = 0.112), and among the deceased patients (C = 0.228). and Chronic HBV-HCV coinfection was more common in the seropositive than in seronegative individuals as it was found both in entire cohorts (26.0 ± 1.9% and 18.6 ± 2.0%, respectively, p = 0.010) and in died patients (31.0 ± 5.5% and 14.6 ± 5.1%, respectively, p = 0.041). Toxoplasma gondii had a weak role in distributing of HBV-HCV coinfection between cohorts (C = 0.187). In both cohorts in patients with chronic hepatitis, regardless of its etiology, there was no significant difference in alanine transaminase activity (ALT). Cirrhosis of the liver occurred 4.5 times more often in deceased seropositive patients than in the entire seropositive cohort (23.9 ± 5.1 and 5.3 ± 2.0, respectively, p = 0.0006) whereas it no significantly increased in seronegative cohort (10.4 ± 4.4 against 4.8 ± 1.1, p > 0.05). In them T. gondii is weakly involved in cirrhosis formation (C = 0.168). Thus, in HIV-infected patients, T. gondii is a weak nonspecific adjunct that supports chronic liver inflammation and progression of cirrhosis, regardless of etiology, but does not influence the degree of hepatitis activity. The increased prevalence of HBV-HCV coinfection in patients seropositive for T. gondii may be related to their risk factor behaviour associated with uncontrolled blood contacts.
Numerous recent studies show that vitamin D deficiency potentiates various chronic physical and psychiatric disorders and diseases. It has been shown that a similar range of disorders is also associated with latent infection with Toxoplasma gondii (Nicolle et Manceaux, 1908). For instance, among cancer, diabetes and schizophrenia patients, we find a higher prevalence of both toxoplasmosis and vitamin D deficiency. Theoretically, therefore, vitamin D deficiency could be the missing link between toxoplasmosis and these disorders. We tested this hypothesis by searching for decreased vitamin D levels in the serum of subjects infected with T. gondii (furthermore called Toxoplasma-infected subjects) in two cross-sectional and one case-control study. Results of the first cross-sectional study (N = 72) suggest that Toxoplasma-infected neurasthenic patients have non-significantly lower levels of calcidiol than Toxoplasma-free patients (study A: P = 0.26 in women, P = 0.68 in men). However, two other studies (study B: N = 400; study C: N = 191) showed a non-significantly higher concentration of vitamin D in Toxoplasma-infected subjects than in Toxoplasma-free subjects both in men (study B: P = 0.70, study C: P = 0.55) and in women (study B: P = 0.64, study C: P = 0.12). Taken together, our preliminary results thus do not support the hypothesis that toxoplasmosis could be associated with vitamin D decrease.
Apoptosis plays crucial role in the pathogenesis of toxoplasmosis, as it limits further development of the disease. The current study aimed to investigate the effects of different concentrations of soluble total antigen (STAg) of Toxoplasma gondii (Nicolle et Manceaux, 1908) on the apoptotic and anti-apoptotic pathways. PMA-activated THP-1 cell line was sensed by T. gondii STAg and the expression patterns of caspase-3, -7, -8, -9, Bax, Bcl-2, and Mcl-1 genes were evaluated. The results showed statistically significant concentration-dependent overexpression of both Bcl-2 (P-value < 0.0001) and Mcl-1 (P-value = 0.0147). The cas-7 showed overexpression in all concentrations (P-value < 0.0001). The cas-3 was suppressed in concentrations 100, 80, and 40 µg, but statistically significant downregulated in concentrations 10 and 20 µg. The Bax was suppressed in concentrations 100 to 20 µg, while it slightly downregulated 1.42 fold (P-value = 0.0029) in concentration 10 µg. The expression of cas-8 and -9 was suppressed in all concentrations. Our results indicated that T. gondii STAg downregulated and suppressed apoptotic and upregulated anti-apoptotic pathways. The upregulation of cas-7 in this study may indicate the role of T. gondii STAg in activation of inflammatory responses.