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PubMed1995

Congenital toxoplasmosis: a significant cause of neurological morbidity in Israel?

The incidence of congenital toxoplasmosis in Israel is largely unknown, as is the impact of this condition on the neurological diseases of childhood. We examined the association between toxoplasmosis and three neurological disorders: epilepsy, cerebral palsy, and nerve deafness. Ninety-five children 1-15 years of age who had one of these three diagnoses but who had not had perinatal meningitis or anoxia and had no genetic predisposition for the documented neurological disorder were eligible for the study; 109 children hospitalized for elective surgery served as age-matched controls. Demographic and serological data were analyzed by logistic regression. The prevalences of serum antibodies to Toxoplasma gondii in the study and control groups were 22% and 9%, respectively. Children with one of the three neurological disorders were significantly more likely to have IgG antibodies to T. gondii (relative risk, 2.5; P = .03). The relative risk of seropositivity was remarkably high (7.1) among children with nerve deafness (P = .01). Large-scale prospective cohort studies of pregnant women are needed to substantiate the impact of congenital toxoplasmosis on the neurological diseases of childhood in Israel.

Adolescent↗
PubMed1996

Toxoplasmosis of the spinal cord in a patient with AIDS: case report and review.

We present the case of a patient whose acute myelopathy almost completely resolved with empirical therapy for toxoplasmosis, and we review thirteen previously reported cases of myelopathy thought to have been caused by Toxoplasma gondii in patients with AIDS. The most common symptoms and abnormal physical findings were motor loss (usually paraparesis), bilateral sensory loss, urinary bladder dysfunction, and local pain. The majority of patients had magnetic resonance images that showed abnormalities of the spinal cord and brain in association with positive serology for Toxoplasma. Therapy for toxoplasmosis, when administered soon after the onset of symptoms, has resulted in clinical and radiographic improvement in the conditions of patients with toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1980

Antigenemia in recently acquired acute toxoplasmosis.

An enzyme-linked immunosorbent assay (ELISA), designed to detect low concentrations of antigens of Toxoplasma gondii, was used to determine whether antigenemia is present in patients with recently acquired acute toxoplasmosis. The ELISA detected antigenemia in 15 (65.2%) of 23 sera from 22 patients with recently acquired acute toxoplasmosis. Antigenemia was not detected in sera from 28 normal (seronegative for antibodies to Toxoplasma) individuals or from 55 individuals chronically infected with T. gondii. Sera from 13 individuals who were not infected with Toxoplasma but who had circulating rheumatoid factor were positive with normal and Toxoplasma-infected rabbit IgG but not with the F(ab)2 fractions. Sera from each of the 15 patients in the acute phase of infection did react with the F(ab)2 fraction of Toxoplasma-infected rabbit IgG but not with the F(ab)2 fraction of normal rabbit IgG. In preliminary studies, toxoplasma antigens were also detected in amniotic fluid and cerebrospinal fluid of newborns with congenital toxoplasmosis.

Acute Disease↗
PubMed1994

Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis.

Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.

Animals↗
PubMed2006

Roles of the small intestine for induction of toll-like receptor 4-mediated innate resistance in naturally acquired murine toxoplasmosis.

Peroral infection of Toxoplasma gondii is thought to reflect the typical infection route of naturally acquired toxoplasmosis in humans. We have investigated possible differential roles of toll-like receptor 2 (TLR2) and TLR4 in host defense against naturally acquired murine toxoplasmosis. After peroral inoculation of T. gondii ME49 cysts, TLR4-deficient C3H/HeJ mice were more susceptible to infection than wild-type (WT) C3H/HeN mice, as shown by increased cyst number and low production of cytokines, which are the key factors in protective immunity. When mice were inoculated by intra-peritoneal inoculation of T. gondii, there were no significant differences in the number of brain cysts and cytokine productions between C3H/HeJ and C3H/HeN mice. Histopathologic examination revealed severe inflammation in the small intestine of C3H/HeJ (TLR4-deficient) mice, while an increased number of TLR4-positive mononuclear cells was found in C3H/HeN (WT) mice. To confirm these phenomena, TLR2(-/-) or TLR4(-/-) mice were infected perorally with T. gondii cysts. TLR4(-/-) mice were more susceptible to infection compared with TLR2(-/-) and C57BL/6 mice. Nuclear factor-kappa B activation through TLR4 agonistic activity of T. gondii ME49 was demonstrated by luciferase assay using stably expressing mouse (m) TLR2 or mTLR4/mMD-2 transfectants. We demonstrate here for the first time that innate immune recognition by TLR4 is involved in protective mechanisms against peroral infection with T. gondii ME49. These results suggest that the small intestine plays an important role in the induction of innate immunity in naturally acquired toxoplasmosis.

Animals↗
PubMed1998

Use of ketolides in combination with other drugs to treat experimental toxoplasmosis.

Because combination therapy is required to treat human toxoplasmosis, we examined combinations of the ketolides HMR 3004 and HMR 3647 with atovaquone, clindamycin or sulphadiazine in a murine model of toxoplasmosis. An oral dose of 50 mg/kg/day of HMR 3004 protected 30% of mice lethally infected with Toxoplasma gondii. The same dose protected 100% of infected mice when administered in combination with non-protective doses of atovaquone, clindamycin or sulphadiazine. Similar results were noted with 25 mg/kg/day of HMR 3647. These results demonstrate that these drug combinations are highly effective for treating toxoplasmosis in mice.

Animals↗
PubMed1983

Toxoplasmosis infection associated with eating undercooked venison.

Toxoplasmosis infection was documented in one Alabama and two South Carolina deer hunters in 1980. All three cases were acutely ill and required hospitalization. Physical findings included fever, leukopenia, and abnormal liver function tests. Two of the three patients showed infiltrates on chest x-ray. All three hunters had recently consumed raw or nearly raw venison and lacked other known risk factors for toxoplasmosis such as cat contact or eating other undercooked meats. In a serosurvey and questionnaire of 62 wildlife workers who regularly handled deer viscera, an association between seropositivity to Toxoplasma gondii and a history of eating raw or rare venison was found (p less than 0.05), but no significant association was found between seropositivity and any other risk factors. Eating inadequately cooked venison may represent an important vehicle of human toxoplasmosis infection.

Acute Disease↗
PubMed2005

Clinical validation of a western blot assay for congenital toxoplasmosis and newborn screening in a hospital in Armenia (Quindio) Colombia.

Congenital Toxoplasma infection can only be discovered or prevented by the appropriate serological screening and subsequent treatment of the mother and her offspring. In Colombia, there is no obligatory Toxoplasma screening for pregnant women and both the reporting and follow-up of congenital toxoplasmosis cases is limited, thereby is a public health problem that have no been addressed by health authorities. The aim of this study was to investigate the occurrence of congenital toxoplasmosis in a public hospital from Armenia, Colombia. A total of 200 serum samples of cord blood were collected. We applied a western blot assay (ID Blot DPC Diagnostics, US) for Toxoplasma IgG, IgM and IgA antibodies that was validated in a cohort of children with confirmed presence or absence of congenital infection. The sensitivity of western blot assay was 91 per cent and the specificity was 100 per cent. In the cord blood samples, we found one infected child that died at day 4 of life and his infection was confirmed by PCR of the B1 specific Toxoplasma gene on brain biopsy. This results show a high prevalence (0.5 per cent, IC95 per cent 0.2-0.8) of Toxoplasma infection in Colombian newborns. Thus, we recommend additional studies to determine the cost-effectiveness of a newborn screening program for congenital toxoplasmosis in other settings in Colombia.

Blotting, Western↗
PubMed1995

Early biopsy versus empiric treatment with delayed biopsy of non-responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis.

OBJECTIVE: To construct and evaluate a decision analytic model of proposed management strategies for HIV-infected patients presenting with cerebral mass lesions, radiographically compatible with toxoplasmosis, lymphoma, or other etiologies, assuming knowledge of Toxoplasma antibody status in serum. METHODS: Using decision analysis, we evaluated two management strategies, for patients found to be either Toxoplasma-seropositive or -negative, for whom an initial choice was made for early brain biopsy (EB) or for empiric therapy with delayed biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage of patients alive at 12 months. Model variables included predictive value of toxoplasmosis serology, probabilities of treatment response and death within 14-21 days conditional on correct diagnosis, probability of operative death, probabilities of non-diagnostic brain biopsy conditional both on correct diagnosis and prior treatment. RESULTS: One and two-way sensitivity analyses, by Toxoplasma serostatus, led to the following conclusions (1) for Toxoplasma-seropositive patients, ETDB gives nearly equivalent outcomes to EB of all patients; (2) for Toxoplasma-seronegative patients, although both strategies have equivalent outcomes under baseline assumptions, EB is preferred if there are even small survival advantages for early versus delayed diagnosis of lymphoma or other conditions, or if risk of death within 14-21 days of ET exceeds 10% when correct diagnosis is not toxoplasmosis. CONCLUSION: Under plausible assumptions, Toxoplasma-seronegative patients will benefit from an early biopsy strategy.

Biopsy↗
PubMed1996

Varicella infection and toxoplasmosis in pregnancy.

Varicella occurring in pregnancy can be dangerous for the fetus, the mother, and the newborn. The fetus may experience multiple system damage. The mother and newborn are at increased risk for varicella pneumonia with a 9% and 20% fatality rate, respectively. The recent introduction of the varicella vaccine will affect the occurrence of gestational infection. Toxoplasmosis is rarely dangerous for the pregnant woman, yet the fetus and newborn may be at risk for chorioretinitis, hydrocephalus, intracranial calcifications, and convulsions. The greatest challenge in the management of toxoplasmosis in pregnancy is diagnosis of the asymptomatic newborn before damage occurs. Strategies to prevent toxoplasmosis should be taught to every pregnant woman as part of parental care.

Chickenpox↗
PubMed1994

Extracerebral toxoplasmosis in patients infected with HIV. A French National Survey.

A French nationwide survey of extracerebral toxoplasmosis (ECT) in HIV-infected patients was performed between January 1990 and September 1992. All French hospitals were surveyed, and all but a few responded. Data collected included epidemiologic, clinical, and biologic features; therapy; and outcome. During the 33-month survey, 199 cases were collected. The prevalence of ECT in patients with AIDS can be estimated at 1.5%-2%. Age, sex, and HIV risk factors were similar to those of the general AIDS population in France. Extracerebral toxoplasmosis appeared mainly in HIV-infected patients with advanced immunosuppression: the mean CD4+ lymphocyte count was 57/mm3(+/- 99). The localizations observed were: eyes (50% of patients); lung (26%); disseminated (at least 2 extracerebral visceral localizations) (11.5%); peripheral blood (acute febrile syndrome with isolated positive parasitemia) (3%); heart (3%); bone marrow (3%); bladder (1%); and isolated cases of rhinopharynx, skin, liver, lymph nodes, conus medullaris, and pericardium. In this survey, muscular and pancreatic localizations were always associated with other extracerebral localizations. A cerebral localization was diagnosed in 41% of cases. Serologic data provided little information. Ocular fundus examination, bronchoalveolar lavage, tissue biopsy, and search for parasitemia were the main diagnostic procedures. Treatment was the same as for cerebral toxoplasmosis. A clinical response was observed in 64% of cases; 19% relapsed. Death occurred in 106 (53%) cases and was related to ECT in 34% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1990

Prenatal diagnosis of congenital toxoplasmosis.

Prenatal diagnosis of congenital toxoplasmosis was attempted in 50 pregnant women at risk for giving birth to an affected child. Fifteen of these patients seroconverted during pregnancy and 35 had a high initial antibody level in their first serum sample. Prenatal diagnosis consisted of a combination of ultrasound screening, amniocentesis, and funipuncture at about 20 weeks' gestation. Diagnosis of congenital toxoplasmosis was based on a positive toxoplasma culture of amniotic fluid or fetal blood and on the presence of specific immunoglobulin M antibodies in fetal blood. In addition, alterations in fetal hematology, cellular immunology, and fetal liver tests were indicative of infection. Fetal infection was detected in six fetuses; two died in utero as a consequence of the infection and four were born after 37 weeks' gestation. Despite antibiotic treatment with pyrimethamine and sulfadiazine, one child has internal hydrocephalus and chorioretinitis and another has unilateral chorioretinitis. In the two other children, the disease is still subclinical. Of the 44 children born after a negative prenatal diagnosis, 35 have reached the age of 1 year; toxoplasma antibodies have disappeared in all of them. Investigation of the remaining nine children showed a decrease in toxoplasma antibodies, suggesting that none of them are affected. Prenatal diagnosis was never associated with fetal loss, and premature delivery occurred in only two cases. We conclude that prenatal diagnosis of congenital toxoplasmosis is safe and reliable.

Amniotic Fluid↗
PubMed2000

Neonatal screening for congenital toxoplasmosis in the Poznań region of Poland by analysis of Toxoplasma gondii-specific IgM antibodies eluted from filter paper blood spots.

OBJECTIVES: The aims of the study were to determine the prevalence of congenital toxoplasmosis at birth in the Poznań region of Poland, the value of the serologic examination of filter paper blood specimens collected from newborns for the diagnosis of congenital Toxoplasma infection and the duration of anti-Toxoplasma-specific IgM antibodies in infants' sera. MATERIALS AND METHODS: All neonates born in the maternity wards of the University Hospital of Gynaecology and Obstetrics in Poznań and in 10 selected obstetrics wards in the district hospitals were included. Blood samples were collected on filter paper cards, between the first and sixth day of life, screened for anti-Toxoplasma-specific IgM antibodies by an immunocapture enzyme-linked immunosorbent assay and if positive further analyzed for specific IgG and IgA antibodies. RESULTS: Between June, 1996, and October, 1998, filter paper samples from 27,516 liveborn infants were tested, which constituted approximately 75% of all births and 83% of liveborn neonates from the Poznań region. Anti-T. gondii-specific IgM antibodies were found in 13 newborns, equivalent to a prevalence of Toxoplasma-specific IgM in newborns of 1 per 2,117 liveborn children (0.47 per 1,000) or 1 per 870 children (1.15 per 1,000) born to seronegative women at risk of primary T. gondii infection during pregnancy. We identified two congenitally infected infants who were IgM-negative at birth, had a classic triad of clinical symptoms during the first year of life and had high levels of specific IgG. The birth prevalence of congenital toxoplasmosis in the Poznań region was at least 1 per 1,834 live births (0.55 per 1,000) or 1 per 754 live neonates born to seronegative women (1.33 per 1,000). The sensitivity of the IgM assay on eluate from filter paper was not more than 86.7%, and the mean duration of IgM detectable by enzyme-linked immunosorbent assay in serum samples was the first 4.8 weeks of life. CONCLUSION: In Poland the screening for congenital toxoplasmosis detecting one case per each 2,000 live births could be considered for inclusion in existing national neonatal screening programs for phenylketonuria and congenital hypothyroidism.

Animals↗
PubMed1988

Congenital toxoplasmosis in an infant with hydrops fetalis.

We have described an infant born with severe hydrops fetalis due to congenital toxoplasmosis. Although uncommon, toxoplasmosis should be considered in the differential diagnosis of hydrops fetalis, particularly when the preliminary clinical work-up suggests a nonimmunologic basis for the hydrops. Although the clinical outcome in an infant as severely affected as this one will remain poor, the therapy for toxoplasmosis has improved over the years, and with quick diagnosis of the disease, a less severely affected infant may have a better prognosis.

Animals↗
PubMed2001

Spinal toxoplasmic arachnoiditis associated with osteoid formation: a rare presentation of toxoplasmosis.

STUDY DESIGN: An extremely rare presentation of an isolated spinal toxoplasmic arachnoiditis is described. OBJECTIVE: To draw attention to the fact that spinal arachnoid membranes may be a potential reservoir for Toxoplasma gondii. SUMMARY OF BACKGROUND DATA: Central nervous system toxoplasmosis is a common manifestation in patients who are immunodeficient. Reports on the spinal toxoplasmosis are rare and focused on spinal cord involvement. METHODS: An adult patient presented with symptoms of spastic paraparesis that had begun 13 years before admission. Thoracic spinal magnetic resonance imaging showed small lesions in posterior subarachnoid space at Th7-Th8. A Th7-Th8 laminectomy was performed. Intradural-extramedullary lesions were excised. RESULTS: Clinical, immunologic, and pathologic examinations showed adhesive spinal arachnoiditis associated with osteoid formation caused by past toxoplasmic infection. There was no impairment of the immunologic defense system. CONCLUSION: Where no causative factor is found in serious spinal adhesive arachnoiditis, the possibility of spinal toxoplasmosis should also be investigated.

Adult↗
PubMed2003

Ocular manifestations of toxoplasmosis.

PURPOSE OF REVIEW: The concepts of toxoplasmosis and its ocular manifestations in humans have thoroughly changed in the past 3 years. This review addresses new epidemiologic data, specifically the occurrence of ocular disease in postnatal infections, and puts the changed views on the frequency and pathogenesis of toxoplasmic ocular manifestations into historical perspective. RECENT FINDINGS: Newly described clinical presentations are discussed together with their recent diagnostic possibilities. The new data on congenital or postnatal acquisition of infection and their importance for ocular involvement are presented as well as the high prevalence of 79% of recurrent disease in ocular toxoplasmosis, which cannot be prevented by short-term treatments. Recently published analyses of literature showed, unexpectedly, the lack of efficacy of short-term treatments for ocular disease as well as of the long-term prenatal treatments on fetal transmission rate and the severity of congenital disease. SUMMARY: The recent guidelines for treatment are included together with the up-to-date recommendations for the treatment of ocular toxoplasmosis in the immunosuppressed host.

Africa, Western↗
PubMed1992

Evaluation of a recombinant antigen ELISA for the diagnosis of acute toxoplasmosis and comparison with traditional antigen ELISAs.

An evaluation of five ELISA methods for the diagnosis of acute toxoplasmosis was undertaken by comparing a laboratory-produced ELISA employing two recombinant Toxoplasma gondii polypeptides as antigen with a laboratory-produced ELISA and three commercially available ELISAs employing traditional parasite antigen preparations derived from whole tachyzoites. With a panel of 75 sera from patients who showed either serological and clinical evidence of acute toxoplasmosis, or of diseases caused by other infectious agents, or from patients who showed no evidence of infectious disease, the ELISAs gave overall positive predictive values of 81.6-100%, negative predictive values of 87.8-100%, sensitivities of 81.3-100%, and specificities of 83.7-100%. No two ELISAs gave identical results with all sera tested. In total, the ELISA based on the two recombinant T. gondii polypeptides appeared to be the most specific ELISA in this comparison, showing positive predictive values and specificities of 100% for all groups of patients tested. The overall negative predictive value for this ELISA was 87.8% and the sensitivity was 81.3%. Therefore, the ELISA based on recombinant antigen appears to be a promising advance in the serological diagnosis of acute toxoplasmosis.

Acute Disease↗
PubMed2006

Toxoplasmosis-associated hemophagocytic syndrome in renal transplantation.

Toxoplasmosis is an infrequent, often difficult to diagnose and potentially lethal disease in kidney transplant recipients. Among reported cases, a few were associated with hemophagocytic syndrome (HPS), a rare condition characterized by widespread proliferation of macrophages phagocytizing blood elements, accompanied by fever and pancytopenia. We report here the case of a patient who received a Toxoplasma gondii positive kidney allograft and developed invasive toxoplasmosis 10 days after surgery, with high fever, skin rash, arthralgias, and renal failure, followed by pneumonia, anemia, thrombocytopenia, liver dysfunction, and encephalitis. Mislead by the absence of Toxoplasma on blood smears, alveolar fluid, renal graft biopsy, and negative brain computed tomography, confusion with serum sickness, and simultaneous herpetic infection, we failed to make the right diagnosis and the patient died with septic shock 11 days later. An HPS was revealed by a late bone marrow analysis. This may well be the fourth case ever reported of toxoplasmosis-associated HPS in renal transplant recipients.

Adult↗