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Toxoplasma gondii has worldwide distribution in nearly one-third of the human population. It is a neurotropic protozoan parasite so a potential role of T. gondii infection for some neuropsychiatric disorders was postulated. Patients with psychiatric disorders had high toxoplasmosis se- roprevalence. Limited information about toxoplasmosis seroprevalence in psychiatric patients was known in southern area of Saudi Arabia. The current cross sectional case control study aims at determination of the prevalence of T. gondii IgG & IgM in neuropsychiatric patients in Jazan Province. A total of 162 neuropsychiatric patients from Al-Amal hospital for psychiatric health and 162 subjects without neuropsychiatric manifestations from Jazan General Hospital, Jazan City, KSA. were enrolled in the study. Psychiatric diagnosis was based on the International Classification of Diseases-10 (ICD-10 classification). Serological analysis for latent toxoplasmosis (IgG) and active toxoplasmosis (IgM) was done using Enzyme Linked Immunosorbent Assay (ELISA). Investigations for the association with socio-demographic, clinical and behavioral characteristics in psychiatric patients were also done. The serofrequency of IgG antibodies among neuropsychiatric patients was significantly higher than that of the controls (35.8% vs 14.8%) P = 0.0022. OR 3.2 with 95% CI= (1.4952 to 6.8774). However; serofrequency of toxoplasma IgM antibody between neuro-psychiatric patients and controls was not statistically significant (P > 0.05).,Bivariate and multivariate analysis for socio-demographics and possible associated risk factors showed that contact to cats and/or dogs, eating under cooked meat, and contact to soil were significantly higher in neuropsychiatric patients than controls.