Toxoplasmosis in patients with an autoimmune disease and immunosuppressive agents: A multicenter study and literature review.

BACKGROUND: Cases of Toxoplasma reactivation or more severe primary infection have been reported in patients receiving immunosuppressive (IS) treatment for autoimmune diseases (AID). The purpose of this study was to describe features of toxoplasmosis occurring in patients with AID treated by IS therapy, excluded HIV-positive and transplant patients. METHODS: A multicenter descriptive study was conducted using data from the French National Reference Center for Toxoplasmosis (NRCT) that received DNA extracts or strains isolated from patients, associated with clinical data. Other cases were retrieved through a questionnaire sent to all French parasitology and internal medicine departments. Furthermore, a systematic literature review was conducted. RESULTS: 61 cases were collected: 25 retrieved by the NRCT and by a call for observations and 36 from a literature review. Half of the cases were attributed to reactivation (50.9%), and most of cases (49.2%) were cerebral toxoplasmosis. The most common associated AID were rheumatoid arthritis (28%) and most frequent treatments were antimetabolites (44.3%). Corticosteroids were involved in 60.7% of cases. Patients had a favorable outcome (50.8%) but nine did not survive. For 12 cases, a successful Toxoplasma strain characterization suggested the possible role of this parasitic factor in ocular cases. CONCLUSION: Although this remains a rare condition, clinicians should be aware for the management of patients and for the choice of IS treatment.

Late diagnosis of congenital toxoplasmosis based on serological follow-up: A case report.

Toxoplasma gondii is a protozoan parasite infecting up to one third of the world's population. T. gondii infection is usually benign in immunocompetent patients but can be life-threatening when congenitally transmitted. Congenital toxoplasmosis presentation ranges from severe central nervous system and ocular features, to a well appearing newborn with onset of complications late in childhood. The diagnosis of subclinical form remains important since early treatment reduces later complications such as chorioretinitis. We report an atypical case of congenital toxoplasmosis with a delayed diagnosis, based on Toxoplasma-specific serological follow-up. The infant was born to a mother who became infected during pregnancy, thus inducing infant biological and clinical follow-up. Neither biological nor clinical arguments favored a diagnosis of congenital toxoplasmosis until ten months of life. Congenital toxoplasmosis was then suspected because of an unusual increase of specific IgG levels. Diagnosis was confirmed by detection of newly synthesized newborn Ig isotypes using complementary comparative mother-to-child immunological profile techniques and specific treatment therefore administered. This report highlights the importance to follow up newborns at risk of congenital toxoplasmosis with specific and newborn-appropriate techniques until Toxoplasma-IgG titers are completely negative. This allows not only the exclusion of congenital toxoplasmosis when serology becomes negative, but also the diagnosis and treatment of congenital toxoplasmosis when infection is detected later in development.

Microbiological diagnosis of severe diarrhea in kidney transplant recipients by use of multiplex PCR assays.

Diarrhea is a frequent complication after kidney transplantation, ascribed to adverse effects of the immunosuppressive therapy in case of negative microbiological examination of the stools. The aim of this study was to improve the microbiological diagnosis by implementing molecular tests. Fifty-four severe diarrhea events that occurred in 49 adult kidney transplant recipients from September 2010 to November 2011 were investigated. One or several enteric pathogens were detected in 13 (23%) stool samples using classical microbiological methods versus 39 (72%) for the seven commercially available multiplex PCR assays used retrospectively (P = 0.006). Interestingly, molecular diagnosis identified 15 multiple infections compared to none using classical techniques. The primary pathogens detected were enteropathogenic Escherichia coli (EPEC) (n = 15; 38%), Campylobacter spp. (n = 15; 38%), and Norovirus (n = 14; 36%). Specificities for Campylobacter and Norovirus infection diagnosis were 75 and 100%, respectively, by comparison to reference methods. Based on molecular findings, a cyclosporine-mycophenolate mofetil combination was identified as a risk factor for developing Norovirus-induced diarrhea. Norovirus infections were also responsible for higher weight loss than all the other causes of diarrhea. In samples from asymptomatic immunocompromised and immunocompetent patients, EPEC but not Norovirus and Campylobacter infections were detected at a frequency similar to that observed in symptomatic kidney transplant recipients. In conclusion, molecular tools significantly improved the detection of single and multiple enteric infections by comparison to classical techniques and could quickly become the key element in the management of severe acute diarrhea in transplant recipients.

Use of co-immunoelectrodiffusion to detect presumed disease-associated precipitating antibodies, and time-course value of specific isotypes in bird-breeder's disease.

BACKGROUND AND OBJECTIVE: The practical value of immunological diagnosis of bird-breeder's disease (BBD) is controversial, because of difficulties in distinguishing active disease patients from simple contact subjects. The aim of this study was to determine the diagnostic and prognostic value of (a) presumed disease-associated antibodies precipitating pigeon antigens (immunoglobulin A (IgAp) and P2 component), (b) characterization of specific isotypes (IgG, IgM, and IgA), and (c) antibody kinetics after antigen eradication. METHODS: 405 subjects (775 sera) in contact with birds were studied [by means of co-immunoelectrodiffusion (Co-IED) and enzyme-linked immunofiltration (ELIFA)] with soluble extracts of pigeon droppings and squab crop milk. These patients were divided into two groups based on the final clinical evaluation of the patients' physicians, which was taken as the gold standard (positive in 90 and negative in 315 cases). RESULTS: On the basis of this gold standard, the detection of presumed disease-associated precipitating antibodies by Co-IED had a specificity of 95.5%, a sensitivity of 98.7%, an accuracy of 98%, and positive and negative predictive values of 95.5% and 98.7%, respectively. Most of the patients with a final positive diagnosis of BBD had specific IgG, IgM, and IgA antibodies by ELIFA. After antigen eradication, anti IgAp and/or P2 antibodies disappeared more rapidly than other precipitating systems. CONCLUSION: Identification by Co-IED of precipitating immune complexes IgAp and/or P2 significantly reinforces the intrinsic credibility of immunological diagnosis of BBD. Compared to these presumed disease-associated precipitating antibodies, detection and time course of specific IgM, IgA antibodies, provided no additional diagnostic value or prognostic arguments to judge disease activity after antigen eradication.

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in Colombian patients with acute and chronic ocular toxoplasmosis

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35 per cent) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10 per cent). In group 2 (recurrences) in 1/7 (14 per cent) we found IgM and IgA test positives and in 1/7 (14 per cent) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18 per cent). These results show that serum IgM or IgA or IgE can be present during recurrences.