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Toxoplasmosis, a severe complication in allogeneic hematopoietic stem cell transplantation: successful treatment strategies during a 5-year single-center experience.

Toxoplasmosis is a rare but often fatal complication that occurs after patients undergo allogeneic hematopoietic stem cell transplant. At our institution, toxoplasmosis was diagnosed in 8 of 301 patients who received stem cell transplants. Disseminated toxoplasmosis with a rapid fatal course was observed in 2 patients. Six patients had cerebral toxoplasmosis diagnosed on the basis of neurological signs and observation of the patients' mental confusion, seizures, and typical lesions (which were assessed by computed tomography, magnetic resonance imaging, or both). Seroconversion of antitoxoplasma immunoglobulin and a discovery of toxoplasma deoxyribonucleic acid in the cerebrospinal fluid (confirmed by use of polymerase chain reaction) were documented in all patients. Treatment consisted of clindamycin therapy (for 2 patients) and of pyrimethamine-clindamycin therapy, sulfadiazine therapy, or both (for 5 patients). Patients showed improvement after therapy, as assessed by clinical and radiological means. Three of 8 patients survive-1 without any residual neurological symptoms and 2 with minimal neurological symptoms.

Adult↗

Pulmonary toxoplasmosis in bone marrow transplant recipients: report of two cases and review.

Toxoplasma gondii may cause disseminated disease in bone marrow transplant (BMT) recipients. Pulmonary toxoplasmosis in BMT patients is rarely described. Mortality rates of >90% have been previously reported. Since pulmonary toxoplasmosis is extremely difficult to diagnose, it is very often detected only at autopsy. Two cases of pulmonary toxoplasmosis in BMT recipients that were diagnosed by visualization of T. gondii tachyzoites in bronchoalveolar lavage fluid and by a new semi-nested PCR method amplifying 18S rRNA from bronchoalveolar lavage fluid are presented, and the literature on pulmonary toxoplasmosis in BMT patients is reviewed.

Adult↗

Pulmonary toxoplasmosis in patients infected with human immunodeficiency virus: a French National Survey.

We reviewed all cases of pulmonary toxoplasmosis (PT) that were documented by detection of Toxoplasma gondii in bronchoalveolar lavage fluid specimens during a French nationwide review of extracerebral toxoplasmosis in patients infected with human immunodeficiency virus (HIV). Only 64 cases of proven PT were recorded during the 33-month survey. The patients were similar to other patients with AIDS in terms of age, sex, and risk factors for HIV infection. PT occurred mainly in patients with advanced immunodeficiency (mean [+/- SD] CD4+ lymphocyte count, 40 +/- 75/mm3). Clinical features of PT usually include fever, cough and dyspnea; the associated radiological findings were mainly diffuse interstitial infiltrates. Serological data were uninformative. The treatment for PT was the same as that for cerebral toxoplasmosis. A clinical response was observed for 47% of patients, 23% of whom relapsed. Twenty-four patients (37%) died of toxoplasmosis, and 17 (27%) died of other causes. The median survival time was 150 days. We conclude that PT is an infrequent but severe infection in HIV-patients in France.

AIDS-Related Opportunistic Infections↗

Prevention of congenital toxoplasmosis in Szeged, Hungary.

BACKGROUND: Toxoplasma gondii infection of the fetus can only be discovered or prevented by the appropriate serological screening and subsequent treatment of the mother and her offspring. In Hungary, there is no obligatory toxoplasma screening for pregnant women and both the reporting and follow-up of congenital toxoplasmosis cases is limited. In 1987 we started a systematic study in the Szeged region of Hungary, in which all pregnant women were screened and appropriate treatment given to all mothers and their offspring where congenital toxoplasmosis was suspected. METHODS: All pregnant women were routinely screened within the first 16 weeks of gestation for toxoplasma antibodies by complement fixation test (CFT). Seronegative cases were retested for possible seroconversion every second month. Patients with CFT titres > or = 1:256 were retested for anti-P30 immunoglobulin A (IgA), IgM and IgG antibodies by ELISA and/or SDS-PAGE-Western immunoblot in order to distinguish the acute and chronic phases of the infection. RESULTS: Up to the end of 1994, the sera of 17,735 gravidae were screened. Ten women were found to have seroconverted during pregnancy and 78 had high initial antibody levels accompanied by anti-P30 IgA antibodies at the very first screening. These two groups together were considered as definitely (10) or possibly (78) infected with Toxoplasma during pregnancy and were treated with Spiramycin. All of their offspring were also treated for one month and followed-up by systematic serological and clinical screening for 2 years. No congenital toxoplasmosis was found in any of the offspring. CONCLUSIONS: Antenatal, early diagnosis and treatment of toxoplasmosis in mothers, together with treatment and follow-up of their offspring, may considerably reduce the incidence of the disease in the offspring.

Animals↗

Congenital toxoplasmosis in Uberlândia, MG, Brazil.

Almost all babies suffering from congenital toxoplasmosis, if undiagnosed and untreated, will develop visual or neurological impairments by adulthood. The aim of this study was to investigate the occurrence of congenital toxoplasmosis in two hospitals from Uberlândia, Brazil. A total of 805 serum samples of cord blood were collected, 500 from public hospital and 305 from private hospital, and all patients answered a questionnaire about pregnancy and newborns. ELISA was accomplished to detect IgG antibodies to Toxoplasma gondii and positive sera were re-tested to verify specific IgM and IgA antibodies in a capture ELISA. Seroprevalence of IgG antibodies against T. gondii was 51.6 per cent in the hospitals, while the frequency of congenital toxoplasmosis was 0.5 per cent, with specific IgM and/or IgA antibodies. The main clinical alteration was chorioretinitis (an inflammatory process of the retina and uveal tract). The high seroprevalence in this population and expressive rate of congenital disease show the requirement of screening programmes for toxoplasmosis during pregnancy.

Antibodies, Protozoan↗

Ga-67 citrate myocardial uptake in a patient with AIDS, toxoplasmosis, and myocarditis.

A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis.

Acquired Immunodeficiency Syndrome↗

Contrast-enhanced fast MRI in differentiating brain toxoplasmosis and lymphoma in AIDS patients.

OBJECTIVE: Dynamic contrast-enhanced MRI was used to investigate space-occupying lesions of the brain in 22 AIDS patients without prior neurologic disease. Final diagnoses were toxoplasmosis in 13 patients (19 lesions), primary lymphoma in 7 patients (9 lesions), and both diseases in two (2 lesions, respectively). MATERIALS AND METHODS: Dynamic contrast-enhanced MRI was done by using a heavily T1-weighted GE sequence (TR/TE 100/5, 80 degrees flip angle) performed before and repeatedly for a period of 15 min after intravenous bolus injection of Gd-DOTA (0.1 mmol/kg). Signal enhancement of the lesions and normal brain was measured as the difference of signal intensity before and after intravenous administration of contrast medium. RESULTS: Lymphomas displayed significantly greater enhancement (mean 67%; SD 18%) than toxoplasmosis did (mean 34%; SD 16%; p < 0.001) on FLASH images. The enhancement ratios of the two lesions were significantly (p < 0.01) different between 30 and 600 s after injection. The difference between toxoplasmosis (mean 49%; SD 17%) and lymphoma (mean 69%; SD 26%) enhancement ratios on delayed SE images was less significant (p = 0.04). CONCLUSION: Preliminary evidence suggests that dynamic sequences increase the specificity of MR in distinguishing between toxoplasmosis and lymphoma, and this has important clinical implications.

AIDS-Related Opportunistic Infections↗

Staphylococcal protein A in the serologic diagnosis of congenital rubella and toxoplasmosis.

Staphylococcal protein A (SPA) has been used to remove maternal IgG from cord or neonatal sera to make serologic testing for congenital infection more IgM specific. To evaluate the clinical usefulness of this procedure, sera sent for TORCH titers that had rubella hemagglutination inhibition (RHI) reciprocal titers greater than or equal to 8 or toxoplasmosis indirect fluorescent antibody (TFA) titers greater than or equal to 16 were adsorbed with SPA and retested. Nine of 109 sera were TFA positive by routine testing, and all but one from an infant with congenital toxoplasmosis became negative after SPA adsorption. A repeat TFA at 4 to 26 months of age was negative in all six children without evidence of toxoplasmosis who returned for follow-up. Fifty of 55 sera were RHI positive by routine testing, and all but one from an infant with congenital rubella became negative after SPA adsorption. The repeat routine RHI was negative in 32 of 35 children whose sera were initially negative after SPA adsorption. SPA adsorption greatly increased the specificity of routine RHI and TFA tests in the diagnosis of congenital rubella and toxoplasmosis.

Female↗

Diagnostic value of polymerase chain reaction in blood and aqueous humor in immunocompetent patients with ocular toxoplasmosis.

PURPOSE: To evaluate the diagnostic value of polymerase chain reaction (PCR) in blood and aqueous humor samples from immunocompetent patients with reactivated ocular toxoplasmosis. METHODS: Group 1 was composed of seven patients with a clinical diagnosis of reactivated ocular toxoplasmosis. Group 2 consisted of 33 controls. In each subject, blood and aqueous humor samples were obtained for detection of Toxoplasma gondii DNA by means of simple PCR, seminested PCR, and Southern blot hybridization. RESULTS: Group 1: Simple PCR was positive in 3 of 7 blood samples (42%) and in 2 of 7 (28%) aqueous humor samples. Seminested PCR was positive in 4 of 7 (57%) blood samples and in 3 of 7 (42%) aqueous humor samples. Group 2: Simple and seminested PCR were positive in both samples in 2 of 33 (6%) and 4 of 33 (12%), respectively. Sensitivity 57% (18.41-90.10), specificity 87% (71.80-96.60); positive and negative likelihood ratio 4.38 and 0.49, respectively. CONCLUSIONS: Polymerase chain reaction can be useful for confirming the diagnosis of ocular toxoplasmosis, especially in those eyes where fundus examination does not yield conclusive results. The detection of T. gondii DNA in blood suggests that reactivation of ocular toxoplasmosis cannot be considered a local event.

Adult↗

Toxoplasmosis associated with nephrotic syndrome in an adult.

Symptomatic generalized toxoplasmosis is uncommon in an immunocompetent host. Even more unusual is the association of nephrotic syndrome with toxoplasmosis, which has previously been reported only in congenital or pediatric cases. This is the first reported case of generalized toxoplasmosis with nephrotic syndrome in an immunocompetent adult. This case should serve to alert the clinician to the possibility of toxoplasmosis in the diagnosis of FUO and adult nephrotic syndrome, and it demonstrates resolution without antimicrobial agents.

Female↗

Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x 10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group.

The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.

AIDS-Related Opportunistic Infections↗

Atypical presentations of ocular toxoplasmosis.

The diagnosis of ocular toxoplasmosis is based most often on the presence of characteristic clinical findings, which include focal retinochoroiditis, an adjacent or nearby retinochoroidal scar, and moderate to severe vitreous inflammation. However, a variety of less common, "atypical" presentations may be unfamiliar to clinicians, delaying both diagnosis and treatment. Patients who are immunocompromised or elderly may, for example, present with large, multiple and/or bilateral lesions. Other unusual manifestations include punctate outer retinal toxoplasmosis, retinal vasculitis, retinal vascular occlusions, rhegmatogenous and serous retinal detachments, a unilateral pigmentary retinopathy mimicking retinitis pigmentosa, neuroretinitis and other forms of optic neuropathy, and scleritis. Although in the past most cases of ocular toxoplasmosis were considered to result from reactivation of a congenital infection, it is now believed that postnatally acquired infection accounts for many cases of this disease. With appropriate use of antiparasitic therapy, the visual prognosis for patients with both typical and atypical forms of ocular toxoplasmosis may be good.

Choroiditis↗

Successful toxoplasmosis prophylaxis after orthotopic cardiac transplantation with trimethoprim-sulfamethoxazole.

BACKGROUND: The efficacy of trimethoprim-sulfamethoxazole (TMP/SMX) in the prevention of toxoplasmosis after orthotopic cardiac transplantation has been the subject of some controversy, with many transplant groups preferring to use the combination of pyrimethamine and sulfadiazine. Although effective, this latter regimen does not offer equal protection against other pathogens, such as or. To assess the value of TMP/SMX, we reviewed the experience in our heart transplant patients, all of whom received TMP/SMX (160/800 mg) three times weekly for approximately 8 months after transplantation. METHODS: We report on 417 orthotopic cardiac transplants during a 17-year period. We have 100% one-year patient follow-up after transplantation. Data was collected on pretransplantation donor and recipient anti- serology, immunosuppression, allograft rejection, survival, yearly posttransplantation anti- serology, development of acute toxoplasmosis, and the occurrence of other infections. RESULTS: In this cohort, acute toxoplasmosis developed after transplantation in one case (0.2%). Among the highest risk patients (D+R-) who were treated for at least one episode of rejection, the risk of acute toxoplasmosis was 5% (1 of 22 patients). No change in survival was found between the different anti- IgG serogroups (D-R-, D-R+, D+R-, or D+R+). Anti- IgG seroconversion occurred in eight -seronegative recipients after transplantation; all patients, except the case already noted, were asymptomatic and required no specific anti- therapy. No cases of, or infections were identified. Five proven and two suspected cases of pneumonia were found (only 2 of these 7 patients were receiving TMP/SMX at the time of pneumonia diagnosis). CONCLUSIONS: These data demonstrate that TMP/SMX prophylaxis (160/800 mg) three times per week is effective prophylaxis after orthotopic cardiac transplantation and has prophylactic benefits against other posttransplantation opportunistic pathogens.

Anti-Infective Agents↗

Toxoplasmosis in hairy-cell leukaemia.

Toxoplasma serology was performed in 28 patients with hairy-cell leukaemia and was positive in eight patients (29%). In two patients (7%) reactivated toxoplasmosis was proven by either isolation of Toxoplasma gondii or by significant antibody titre rise with generation of specific IgM-antibodies. In four patients (14%), a clinical diagnosis of active toxoplasmosis was based on signs and symptoms, serologic tests, and response to specific treatment. The high proportion of patients in which active toxoplasmosis was proven or probable (six; 21%) may be related to the presence of severe monocytopenia. In patients with hairy-cell leukaemia developing fever of unknown origin and myositis, toxoplasma serology should be performed, particularly because treatment of active toxoplasmosis usually is successful.

Adult↗

Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias.

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re-examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85--95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.

Antibodies↗

Toxoplasmosis as a cause of repeated abortion.

The extent to which toxoplasmosis causes habitual abortion is still controversial. The present study was carried out on 100 cases of repeated abortions, and 40 multiparous pregnant women at 20th week gestation as a control. Tests for the presence of toxoplasma IgG and/or IgM antibodies were done for both groups. It was found that 19% of the selected cases, and 7.5% of the control were seropositive for IgM. The difference was statistically insignificant, therefore acute toxoplasmosis, most probably, is not related to habitual abortions, whereas 37% of the selected cases and only 10% of the control group were seropositive at high dilution for IgG antibody, this statistical significant difference indicates that chronic toxoplasmosis, most probably is a significant cause of repeated abortion. Also it has been found that toxoplasmosis has a significant relation to abortion at first trimester.

Abortion, Habitual↗

Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG avidity assay and complement fixation for the diagnosis of acute toxoplasmosis.

A panel of sera from patients with known case histories representative of acute toxoplasmosis (primarily lymphadenopathy, n = 106), latent toxoplasmosis (asymptomatic, n = 368) and negative samples (n = 54) was used to evaluate the capacity of five serological tests to differentiate among patients with acute or latent toxoplasmosis and non-infected individuals. Positive IgA, IgE and IgM ELISA results and low IgG avidity and complement fixation test (CFT) titres of >or=256 were considered to be indicative of acute toxoplasmosis. The most sensitive methods were IgM ELISA (98.1%) and CFT (97.1%), albeit with low specificity (65.0% and 64.5%, respectively) and positive predictive values (43.3% and 42.7%, respectively). IgG avidity assay and IgE ELISA had the highest specificity (97.7% and 91.7%, respectively) and the highest positive predictive values (89.4% and 75.6%, respectively). The best association between serological results and clinical findings was obtained with IgE ELISA (86%, as expressed via Youden's index). In a subset of 259 samples categorised by the period between the onset of clinical symptoms and sampling, >50% of patients had enlarged lymph nodes for <4 months, despite a broad range of differences. However, IgM remained positive for 12-18 months, IgA for 6-9 months and IgE for 4-6 months. IgG avidity remained low for a maximum of 4 months, after which avidity increased despite the persistence of enlarged lymph nodes and a positive IgE assay. Detection of IgE appears to be a highly specific test for confirming the acute nature of Toxoplasma infections that have been detected by other sensitive methods.

Acute Disease↗

Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of amniotic fluid.

OBJECTIVE: To determine the accuracy of polymerase chain reaction (PCR) analysis of amniotic fluid for fetal toxoplasmosis according to clinical predictors of outcome and study centre. DESIGN: Prospective cohort study. SETTING: Nine European centres. POPULATION: Women with suspected toxoplasma infection identified by prenatal screening. METHODS: Logistic regression was used to examine the effects of gestational age at maternal seroconversion, treatment and timing of amniocentesis, on PCR accuracy, and to calculate the post-test probability of congenital toxoplasmosis. MAIN OUTCOME MEASURES: Infants had congenital toxoplasmosis if specific IgG persisted beyond 11.5 months. Uninfected infants had undetectable IgG in the absence of anti-toxoplasma treatment. RESULTS: Of 593 PCR results, 64 were positive (57 confirmed infected), and 529 were negative (23 confirmed infected). The likelihood ratio for a positive PCR result decreased significantly with trimester at seroconversion, but did not change significantly for a negative result. Weak associations were detected between sensitivity and, inversely, with specificity, and gestational age at maternal seroconversion. There was no significant association between sensitivity and centre, type or duration of treatment, or timing of amniocentesis. Specificity differed significantly between centres (P < 0.001). The change in pre- to post-test probability of infection was maximal for a positive PCR after first trimester seroconversion, affecting 1% of women tested, and a negative PCR after third trimester seroconversion, affecting half the women tested. CONCLUSIONS: Prediction of the risk of congenital toxoplasmosis should combine estimates of test accuracy and maternal-fetal transmission, which take account of the gestational age at which the mother seroconverted. Local laboratory standards will affect the generalisability of these results.

Amniotic Fluid↗