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PubMed1993

Cognitive disorders in children.

Cognitive disorders affect thinking and perceptual processes and the acquisition of knowledge and new information. They have an enormous societal impact because special educational resources are required, and independent living often cannot be achieved. Learning problems may lead to behavioral disorders in the home and community. The pathogenesis of most mild and moderate cognitive disorders is poorly understood. Severe cognitive impairment is usually accompanied by somatic abnormalities, and an etiology can be identified in many cases. Specific treatments are available for disorders such as cogenital hypothyroidism, some metabolic acidurias, and congenital toxoplasmosis. Other disorders affecting cognition such as fetal alcohol syndrome, maternal cocaine and heroin exposure, HIV encephalopathy, and prematurity require aggressive prevention and education to reduce their occurrence. The recent advances in molecular genetics offer a faster and better method of diagnosing fragile X syndrome, now recognized as the most common inheritable cause of mental retardation. In the future, DNA analysis may elucidate the basis of many other cognitive disorders.

Asthma↗
PubMed1991

Current status of food-borne parasitic zoonoses in the United States.

Although not a major public health problem, food-borne parasitic zoonoses in the United States are the cause of numerous diseases that occur widely in the population. The most common food-borne parasitic diseases in the United States are trichinosis, toxoplasmosis, taeniasis/cysticercosis, diphyllobothriasis, and anisakiasis. Since 1947, when the US Public Health Service began to record statistics on trichinosis cases in humans, the numbers of reported cases in the United States have declined markedly, from an average of about 400 with 10-15 deaths reported each year in the late 1940s, to an average of 57 per year with three deaths overall in the 5 years 1982-1986. Each year throughout the world, Toxoplasma gondii infects millions of persons, who contract it either by eating raw or poorly cooked meat from infected animals such as hogs or sheep or by ingesting soil contaminated with cat feces. In the United States between 400 and 10,000 infants are born each year with congenital toxoplasmosis. Toxoplasmic encephalitis, marked by dementia and seizures, has become the most commonly recognized cause of central nervous system opportunistic infection in AIDS patients. Intestinal taeniid tapeworm infection acquired in the United States is almost entirely caused by Taenia saginata, the beef tapeworm. Neurocysticercosis, caused by larvae of the pork tapeworm Taenia solium, is diagnosed in hundreds of persons in the United States every year. Nearly all patients are immigrants or travelers from Mexico and other disease-endemic areas. Diphyllobothriasis and anisakiasis both have increased in recent years in association with increasing popularity of raw fish dishes. Adequate prevention and control of food-borne parasitic zoonoses require continued and improved programs to educate consumers, producers and medical practitioners.

Animals↗
PubMed1982

Frequency of toxoplasmosis in the appearance of congenital hydrocephalus.

Thirty-eight children with signs of hydrocephalus have been tested for toxoplasmosis. On the basis of clinical data, including roentgenographical and ophthalmological findings, and serological data (Sabin-Feldman and IgM-IFA tests), congenital toxoplasmosis was confirmed in 15 (39%) infants. The diagnosis was established by demonstration of the persistence of Toxoplasma antibodies. In 13 (34%) infants aged 1 to 3 months there was not enough serological data and these were placed in a group of cases with "suspected congenital toxoplasmosis." Ten children with negative serology for toxoplasmosis and with hydrocephalus were considered not to be infected.

Child, Preschool↗
PubMed2005

Parasitic infections in Malaysia: changing and challenges.

A total of 1,885 blood and stool samples of four main protozoan parasitic infections were retrospectively reviewed from January, 2000 to April, 2004. Eleven of the 1,350 stool samples were shown positive for Cryptosporidium and Giardia infections; one of the 5 cases was clinically diagnosed as gastrointestinal cryptosporidiosis, while 6 cases were giardiasis. In patients with giardiasis, children were among the high-risk groups, making up 66.7% of these patients. The common presenting signs and symptoms were: diarrhea (83.3%), loss of appetite (83.3%), lethargy (83.3%), fever (66.7%), nausea/vomiting (50.0%), abdominal pain (16.7%), dehydration (16.7%) and rigor and chills (16.7%). Metronidazole was the drug of choice and was given to all symptomatic patients (83.3%). For the blood samples, 28 of the 92 peripheral smears for Plasmodium spp infection were diagnosed as malaria. The age range was from 4 to 57, with a median of 32.5 years. The sex ratio (M:F) was 3.6:1, while the age group of 30-44 years was the most commonly affected in both sexes. The majority of patients were foreigners (60.7%) and non-professional (39%). Plasmodium vivax (71%) infection was the most common pathogen found in these patients, along with a history of traveling to an endemic area of malaria (31%). The predominant presenting signs and symptoms were: fever (27%), rigor and chills (24%), nausea/vomiting (15%) and headache (8%). Chloroquine and primaquine was the most common anti-malarial regimen used (78.6%) in these patients. The seroprevalence of toxoplasmosis in different groups was 258/443 (58%): seropositive for IgG 143 (32.3%); IgM 67 (15%); and IgG + IgM 48 (10.8%). The age range was from 1 to 85, with a mean of 34 (+/- SD 16.6) years. The predominant age group was 21 to 40 years (126; 28.4%). The sex ratio (M:F) was 1.2:1. Subjects were predominantly male (142; 32%) and the Malay (117; 26.4%). Of these, 32 cases were clinically diagnosed with ocular toxoplasmosis. The range of age was from 10 to 56 years with a mean of 30.5 (+/- SD 12.05) years. The sex ratio (M:F) was 1:1.7. The majority were in the age group of 21 to 40 years, female (20; 62.5%), and Malay (17; 53%). They were also single (16; 50%), unemployed (12; 37%), and resided outside Kuala Lumpur (21; 65.6%). The more common clinical presentations were blurring of vision (25; 78%), floaters (10; 31%) and pain in the eye (7; 22%). We found that funduscopic examination (100%) and seropositivity for anti-Toxoplasma antibodies (93.7%) were the main reasons for investigation. Choroidoretinitis was the most common clinical diagnosis (69%), while clindamycin was the most frequently used antimicrobial in all cases. Among HIV-infected patients, 10 cases were diagnosed as AIDS-related toxoplasmic encephalitis (TE) (9 were active and 1 had relapse TE). In addition, 1 case was confirmed as congenital toxoplasmosis.

Adolescent↗
PubMed1988

Human toxoplasmosis in Somalia. Prevalence of Toxoplasma antibodies in a village in the lower Scebelli region and in Mogadishu.

The acquisition of Toxoplasma antibodies in various age groups was studied in 2 populations in Somalia, inhabitants of a village in the southern part of the country and residents in Mogadishu. The overall prevalence of antibodies was 56% in the village and 40% in Mogadishu. In both populations, antibodies were acquired early in life. At the age of 10 years, 44% of the villagers and 31% of the Mogadishu children were seropositive. In Europe and the USA the highest rate of antibody acquisition has been recorded in young adults. This difference may indicate different routes of transmission. In Europe and the USA Toxoplasma is transmitted mainly by the ingestion of undercooked pork or lamb. Undercooked meat is seldom consumed in Somalia, and pork not at all. However, the soil in Somalia is heavily contaminated with cat faeces and the humid climate in the southern part of the country may contribute to long survival of oocysts. In the villages all household activities are performed on the ground and in Mogadishu children play mainly outdoors on the ground. It therefore seems that conditions in Somalia favour transmission by oocysts rather than by infected meat. The early acquisition of antibodies in Somalia suggests that infection during pregnancy and, therefore, congenital toxoplasmosis are rare.

Adolescent↗
PubMed2002

VIDAS test for avidity of Toxoplasma-specific immunoglobulin G for confirmatory testing of pregnant women.

Because congenital toxoplasmosis is almost solely the result of maternal infection acquired during gestation, it is critical to determine whether infection during pregnancy has occurred. In the United States, definitive diagnosis of the acute infection and the time of its occurrence have been compromised by a lack of systematic screening and the fact that only a single serum sample is submitted for testing. In studies in Europe, and depending on the method used, the demonstration of high-avidity immunoglobulin G (IgG) toxoplasma antibodies has been shown to exclude infection having occurred in the first 3 to 5 months of pregnancy. We investigated the usefulness of determining the avidity of IgG toxoplasma antibodies with a VIDAS kit (herein referred to as the VIDAS Toxo-IgG avidity kit, the VIDAS kit essentially rules out acute infection having occurred within the 4 prior months) in the setting of a reference serology laboratory in the United States. Sera (132 samples) from 132 women in the first 16 weeks of pregnancy were chosen because at least one test in the toxoplasma serological profile (TSP) suggested or was equivocal for a recently acquired infection. High-avidity antibodies were demonstrated in 75% of 99 sera positive with the IgM enzyme-linked immunosorbent assay (ELISA) and 31.3% of 16 sera with acute TSP results. A significant percentage of sera with equivocal results wtih the IgM ELISA or TSP also had high-avidity test results. Of 39 women for whom treatment with spiramycin had been suggested to attempt to prevent congenital transmission, 19 (48.7%) had high-avidity antibodies. These findings highlight the value of the VIDAS IgG avidity kit when used in combination with the TSP to exclude recent infection, especially when only a single serum sample is available.

Acute Disease↗
PubMed1991

Anti-toxoplasma antibodies in healthy adults and in different patient categories.

This study analyzes the anti-toxoplasma sero-titres and prevalence rates in normal healthy adults and in patients presenting with different symptom-complexes. The study was based on sera from 80 normal healthy adults and 2,185 patient sera samples from 2,032 patients (from various clinics and hospitals in Singapore) being investigated for the diagnosis or exclusion of toxoplasmosis, over a 42-month study period. About 15% of the healthy adults were found to have low IgG antibody titres (1:64 to 1:256), while 3.8% had high IgG titres (1:1024 or higher). Interestingly, among the patients investigated for toxoplasmosis: i) more than 20% of those presenting with lymphadenopathy (usually cervical) had antibody titres more than or equal to 1:1024; ii) more than half of all patients with an antibody titre of 1:4096, and more than three-quarters of all patients with a titre exceeding 1:4096 had presented with lymphadenopathy; iii) about 20% of those presenting with ocular symptoms had low antibody titres of 1:64 or 1:256, whereas 7% had higher titres. Malay (p less than 0.01) and Indian (p less than 0.05) patients had significantly higher seropositive rates than the Chinese. In particular, the Malays (p less than 0.00001) and Indians (p less than 0.01) had significantly higher incidence of low-positive titres (1:64, 1:256); conversely the Chinese patients had a significantly higher (p less than 0.01) incidence of high-positive titres (1:4096 or higher). Finally, the epidemiology and clinical profiles of patients presenting with acute toxoplasmic lymphadenitis are contrasted with that of patients presenting with ocular manifestations of congenital toxoplasmosis.

Adult↗
PubMed2004

[Diagnostic kits in parasitology: which controls?].

The development of new diagnostic tools particularly for some parasitic "neglected diseases", is slowed or even hindered by limited resources assigned for basic and applied research in public institution and private sector. Even if the time-line and costs needed for developing a new In Vitro Diagnostic (IVD) test are generally lower compared to vaccines or new drugs, industry is poorly engaged in investing resources due to the perception of limited markets. To accelerate the development of diagnostics for the world's most deadly diseases, the World Health Organization's (WHO) Special Programme for Research and Training in Tropical Diseases (TDR), the United Nations Development Programme, the World Bank and the Gates Foundation, last year launched a new initiative, FIND (Foundation for Innovative New Diagnostics, www.finddiagnostics.org). The aim is to "apply the latest biotechnology innovations to develop and validate affordable diagnostic tests for diseases of the developing world". Ideally, a new diagnostic test should be accurately evaluated prior to use in medical practice. The first step would be a pre-clinical evaluation, an analytic study to determine its laboratory performance. A crucial point in this phase is the calibration of reagents (antigens, antibodies, DNA probes, etc.) against a standard reference preparation. WHO, through the WHO International Laboratories for Biological Standards, "provides International Biological Reference Preparations which serve as reference sources of defined biological activity expressed in an internationally agreed unit" (www.who.int/biologicals/IBRP/index.htm). Standardization allows "comparison of biological measurements worldwide" and ensures the reliability of diagnostic procedures. These preparations are generally intended for use in the characterization of the activity of secondary reference preparations (regional, national or in-house working standards). Unfortunately, international reference standards for parasitic diseases are not available at present, except for Toxoplasma antibodies. The first international standard reagent for Anti-Toxoplasma Serum was established in 1968 and at present, an international standard reference serum, Anti-toxoplasma serum, human TOXM is available at the National Institute for Biological Standards and Control (NIBSC) in UK. Several collaborative, multicenter studies were carried out to assess the performance of different methods and commercial tests for the diagnosis of toxoplasmosis, by providing to participating laboratories a panel of well-defined sera to be tested. A four-phase process following well-accepted methodological standards for the development of diagnostics, analogous to those internationally accepted for drugs and vaccines was recently proposed. The pre-clinical evaluation, the analytic study to assess sensitivity, specificity, predictive values in laboratory (phase I), should be followed by a proof of principle study to distinguish diseased from healthy persons in easily accessible populations (phase II). The evaluation of test performance in populations of intended use (phase III), and finally the delineation of cost-effectiveness and societal impact of new tests in comparison with existing tools (phase IV) should complete the validation procedure. In this context, national regulatory agencies play a major role in pre-market approval and post-market surveillance of IVDs. The European Community in 1998 approved a directive (Directive 98/79/EC) which rules the marketing of IVD medical devices, in order to harmonise the performance levels and standards in European countries. But, among IVDs for parasitic diseases, only those to detect congenital toxoplasmosis are submitted to defined procedures to provide the verification of products before their placing on the market and the surveillance after their marketing by a notified body, which perform appropriate examinations, tests and inspections to production facilities to verify if the device meets the requirements of the directive. In U.S.A., the Food and Drug Administration (FDA), through the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), provides a comprehensive and regulatory activity for IVDs through pre-market evaluation and post-market surveillance. In developing countries, the scarcity of resources limits the procedures through which the national control authority can assure safety, quality and efficacy of products marketed, both imported and locally manufactured.

Animals↗
PubMed1993

[Acquired cerebral toxoplasmosis in an non-immunosuppressed child].

BACKGROUND: Postnatally acquired toxoplasmosis is relatively common as an unapparent infection. When there are severe clinical manifestations such as encephalitis, pneumonia and myocarditis, the patient should be checked for immunocompetence deficiencies. CASE REPORT: A two-year old girl living in French Guyana suffered from acute respiratory distress due to interstitial pneumonia plus pericarditis that was treated by closed pericardial aspiration. Palsies of four limbs and chorioretinitis gradually appeared. The CSF protein content was elevated, 1 g/l, but the number of cells was normal. Serologic tests indicated a recent toxoplasma infection; she was given sulfadoxine, pyrimethamine and spiramycin. Her neurologic condition and the persistent antibodies, indicating active disease, led to her transfer to our Department 3 months after the onset of the disease. The CSF contained 47 cells/mm3 and 0.8 g/l proteins. Measurement of both IgM and IgG classes of toxoplasma antibodies showed persistent high titers in the blood and CSF. The CT scan showed numerous calcifications in the brain and hypodense areas in the frontal and parietal lobes. The MRI showed extensive changes. The severity of the disease in this girl led us to study her immune system. It was normal. The girl was given 6-week treatments with pyrimethamine-sulfadiazine for 2 years. This treatment stabilized the disease, but her titers of toxoplasma antibodies remained high. CONCLUSION: The initial clinical presentation of the disease in this patient and persistent high titers of toxoplasma antibodies, especially of the IgM class, argue against the possibility of congenital toxoplasmosis and favor the diagnosis of acquired disease in a patient who has no immune deficiency.

Child, Preschool↗
PubMed1992

Fuchs' heterochromic iridocyclitis is not associated with ocular toxoplasmosis.

To analyze the association between Fuchs' heterochromic iridocyclitis (FHI) and toxoplasmosis, we performed ocular examinations and used various specific laboratory tests to establish a role for Toxoplasma gondii in the pathogenesis of FHI. Results were compared with those for other types of uveitis and healthy controls. Of the 88 patients with FHI, nine (10.2%) had toxoplasmosislike scars, but an association could not be proved by the indirect immunofluorescence antibody test or enzyme-linked immunosorbent assay, or by a test for cellular immunity to Toxoplasma antigen. Analysis of aqueous humor samples for Toxoplasma antibodies in patients with FHI also yielded negative results. On the basis of the negative results of these laboratory tests, we concluded that FHI is not associated with ocular toxoplasmosis.

Adolescent↗
PubMed1999

Toxoplasma gondii in primary rat CNS cells: differential contribution of neurons, astrocytes, and microglial cells for the intracerebral development and stage differentiation.

The central nervous system (CNS) of the intermediate host plays a central role in the lifelong persistence of Toxoplasma gondii as well as in the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised patients. In order to analyze the parasite-host interaction within the CNS, the host cell invasion, the intracellular replication, and the stage conversion from tachyzoites to bradyzoites was investigated in mixed cultures of dissociated CNS cells from cortices of Wistar rat embryos. Two days post infection (p.i.) with T. gondii tachyzoites, intracellular parasites were detected within neurons, astrocytes, and microglial cells as assessed by double immunofluorescence and confocal microscopy. Quantitative analyses revealed that approximately 10% of neurons and astrocytes were infected with T. gondii, while 30% of the microglial cells harbored intracellular parasites. However, the replication of T. gondii within microglial cells was considerably diminished, since 93% of the parasitophorous vacuoles (PV) contained only one to two parasites which often appeared degenerated. This toxoplasmacidal activity was not abrogated after treatment with NO synthase inhibitors or neutralization of IFN-gamma production. In contrast, 30% of the PV in neurons and astrocytes harbored clearly proliferating parasites with at least four to eight parasites per vacuole. Four days p.i. with tachyzoites of T. gondii, bradyzoites were detected within neurons, astrocytes, and microglial cells of untreated cell cultures. However, the majority of bradyzoite-containing vacuoles were located in neurons. Spontaneous differentiation to the bradyzoite stage was not inhibited after addition of NO synthase inhibitors or neutralization of IFN-gamma. In conclusion, our results indicate that intracerebral replication of T. gondii as well as spontaneous conversion from the tachyzoite to the bradyzoite stage is sustained predominantly by neurons and astrocytes, whereas microglial cells may effectively inhibit parasitic growth within the CNS.

Animals↗
PubMed1993

An unusual dural arteriovenous fistula in an infant.

Dural arteriovenous fistula, (AVF), a rare entity, presents most commonly in adults. An 11-month-old boy presented with symptoms of congenital toxoplasmosis associated with an extensive dural AVF of the torcular Herophili and bilateral occlusion of the transverse and sigmoid sinuses. His intracranial venous drainage had become rerouted via the cavernous sinuses to the ophthalmic veins. The relationship of toxoplasmosis and sinus thrombosis to the pathogenesis of dural AVF and their clinical and radiological features are discussed.

Cerebral Angiography↗
PubMed1985

The influence of congenital Toxoplasma infection on the spontaneous running activity of mice.

Home-cage running-wheel activity of mice congenitally infected with Toxoplasma was recorded over 24 days. Infected mice were consistently more active than uninfected controls over the entire testing period. This finding extends previous studies and indicates that such increased activity levels occur not only in novel but also in familiar environments, and suggests that congenital toxoplasmosis tends to render mice "hyperactive'. If such behavioural alterations occur in wild mice, it is likely that infected mouse intermediate hosts would be more susceptible to predation by cats, the definitive hosts of Toxoplasma.

Animals↗