The diagnosis of toxoplasmosis in the immune compromised patient

Abstract

Human infection with the obligate intracellular protozoan parasite Toxoplasma gondii may be clinically silent in the immune competent person but can cause fatal disease in immune immature, i.e. the foetus, or compromised individuals, such as human immunodeficiency virus infected patients or organ graft recipients. Whilst a number of assays already exist the fact that immune compromised patients present a limited or for the laboratory diagnosis of toxoplasmosis, ablated immune response to primary infection means that many of these are of limited diagnostic value. The aim of the publications presented for this doctorate was to develop, and technically and clinically evaluate assays which would have particular use for the immune compromised patient. The research demonstrates the development of two new serological assays; the immunosorbent agglutination assay for the detection of toxoplasma-specific immunoglobulin-A which was demonstrated to be the investigation of choice for the post-natal diagnosis of congenital toxoplasmosis; the avidity assay which is of value for confirming recently acquired toxoplasma infection in immunoglobulin-M positive pregnant women and for the exclusion of recent onset toxoplasma infection in patients with prolonged irnmunoglobulin-M responses. It is also of use in the diagnosis of congenital infection. One assay based on detection of parasite deoxyribonucleic acid using the polymerase chain reaction was developed and demonstrated to be optimal in the examination of brain biopsies from acquired immune deficiency syndrome patients with suspected toxoplasma encephalitis, amniotic fluid and foetal blood samples from the potentially infected foetus and cardiac biopsies from transplant recipients. The research also gives a technical evaluation of two existing assaysð€“« the direct agglutination test which proved less sensitive but more specific than the latex agglutination test and demonstrated to be the assay of choice for reducing screening test false positive reactions; the immunosorbent agglutination assay for the detection of toxoplasma-specific immunoglobulin-M which demonstrated to be the investigation of choice for screening women requesting testing during pregnancy, for diagnosis of congenital infection in the foetus and neonate, those suffering from ocular disease and for transplant mismatch cases. The research also clinically evaluates the use of all existing assays for immune compromised patients, concluding with a presentation of a multi-assay approach to diagnosis.