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Clindamycin therapy of cerebral toxoplasmosis in an AIDS patient.

A 47-year-old patient with AIDS and cerebral toxoplasmosis was treated with sulfadiazine pyrimethamine for 5 days. After developing a severe rash his regimen was changed to clindamycin 600 mg q 6 h intravenously and pyrimethamine 25 mg daily, given for 37 days. This resulted in improvement of clinical symptoms and complete resolution of CT scan abnormalities. Clindamycin combined with pyrimethamine may be a useful alternative therapy for cerebral toxoplasmosis in patients who can not tolerate sulfonamides.

Acquired Immunodeficiency Syndrome↗

Intracerebral toxoplasmosis in patients with acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) is a recently described T-cell deficiency predisposing patients to a spectrum of opportunistic infections. Kaposi's sarcoma, and other neoplasms. It appears primarily among homosexual males and intravenous drug abusers, but is now being observed in other groups as well. The authors describe six adult patients with AIDS who developed intracranial toxoplasmosis. In four patients, diagnosis was made by brain biopsy, and in one by serology. These patients received a 90-day course of therapy with sulfadiazine, pyrimethamine, or both when tolerated, and improved neurologically. In one patient, the brain biopsy was nondiagnostic and the organism was identified at autopsy. On computerized tomographic and pathological follow-up studies the organism appeared to be eradicated by therapy. Early aggressive diagnostic study and prompt institution of therapy are imperative for reversal of neurological deficits. Despite cure of toxoplasmosis, the prognosis in patients with AIDS is poor; the mortality in this series was 67%. Isolation precautions should be taken by those caring for such patients.

Acquired Immunodeficiency Syndrome↗

Electron microscopic diagnosis of cerebral toxoplasmosis. Case report.

Rapid and specific diagnosis of infections involving patients with acquired immunodeficiency syndrome (AIDS) is imperative. Toxoplasmosis is one of the most frequent causes of central nervous system disease in these patients. The authors present a case of cerebral toxoplasmosis in an AIDS patient, diagnosed by electron microscopy of brain biopsy tissue using rapid techniques.

Acquired Immunodeficiency Syndrome↗

Isolated toxoplasmosis of the thoracic spinal cord in a patient with acquired immunodeficiency syndrome. Case report.

Toxoplasmosis and lymphoma are the two most common causes of intraparenchymal cerebral mass lesions in patients with acquired immunodeficiency syndrome (AIDS). The clinical and radiographic features of the intracranial lesions have been well described. Because of the high frequency of toxoplasmosis in the AIDS population, common therapy for patients presenting with intracranial mass lesions consists of an empirical trial of anti-Toxoplasma chemotherapy, with biopsy reserved for cases demonstrating features considered to be more consistent with lymphoma, or for lesions that do not improve despite adequate anti-Toxoplasma treatment. A similar treatment algorithm does not exist for intramedullary lesions of the spinal cord. The authors describe a patient who presented with paraparesis resulting from an isolated thoracic intramedullary lesion. An open biopsy of the lesion revealed characteristic structures containing Toxoplasma tachyzoites. The clinical and radiographic presentation of the lesion is discussed, the available literature is reviewed, and a treatment strategy for spinal cord lesions in AIDS patients is proposed.

Acquired Immunodeficiency Syndrome↗

Genetic divergence of Toxoplasma gondii strains associated with ocular toxoplasmosis, Brazil.

Previous studies have shown a high prevalence of toxoplasmosis and the frequent occurrence of ocular disease in Brazil. To identify the genotypes of parasite strains associated with ocular disease, we compared 25 clinical and animal isolates of Toxoplasma gondii from Brazil to previously characterized clonal lineages from North America and Europe. Multilocus nested polymerase chain reaction analysis was combined with direct sequencing of a polymorphic intron to classify strains by phylogenetic methods. The genotypes of T. gondii strains isolated from Brazil were highly divergent when compared to the previously described clonal lineages. Several new predominant genotypes were identified from different regions of Brazil, including 2 small outbreaks attributable to foodborne or waterborne infection. These findings show that the genetic makeup of T. gondii is more complex than previously recognized and suggest that unique or divergent genotypes may contribute to different clinical outcomes of toxoplasmosis in different localities.

Animals↗

Seroprevalence of toxoplasmosis in the residents of Cheju island, Korea.

This study was performed to evaluate the epidemiological status of toxoplasmosis among the residents of Cheju island. The sera of local students from 18 high schools (boys 2110, girls 2460) and those of adults (474 admitted to Cheju Chungang General Hospital) were collected and checked for the IgG antibody titers against Toxoplasma gondii. Serum samples collected from both the students and adults showed sero-positive rate of 5.5% and 12.9%, respectively. Although the rates were not significantly different between the sexes (5.4% for the boys and 5.5% for the girls attending school), the geographical difference showed a significant difference between the urban (4.6-6.9%) and rural areas (5.6-8.8%) (p < 0.05). Based on the high positive rates, it should be necessary to control toxoplasmosis in Cheju island.

Adolescent↗

Cytokine and antibody responses of reactivated murine toxoplasmosis upon administration of dexamathasone.

Toxoplasma gondii has been shown to result in life-threatening encephalitis in immunocompromised patients after reactivation of dormant parasites. In order to obtain information on immune responses related to this phenomenon, BALB/c mice were infected with 25 cysts of the 76K strain of T. gondii, then, treated orally with dexamethasone (Toxo/Dexa-treated group) in order to reactivate the chronic toxoplasmosis. None of the T. gondii-infected mice died during the experimental periods, whereas the Toxo/Dexa-treated mice evidenced a significant attenuation of survival periods. Toxoplasma-specific IgG2a, IgA and IgM titers in sera were significantly depressed in the Toxo/Dexa-treated mice; however, the IgG1 sera titers were similar to those seen in the Toxoplasma-infected mice. The percentages of CD4+ and CD8 alpha + T cells in the Toxo/Dexa-treated mice were significantly reduced 2 weeks after dexamethasone treatment. IFN-gamma and IL-10 production levels in the Toxo/Dexa-treated mice were depressed significantly, whereas IL-4 production was increased temporarily. The expression levels of the Toxoplasma-specific P30 and B1 genes were found to have been increased in the Toxo/Dexa-treated mice in comparison with the Toxoplasmainfected mice. Collectively, the findings of this study demonstrate that reactivation of murine toxoplasmosis as the result of dexamethasone treatment induced a depression in Th1 immune responses, whereas Th2 immune responses were not significantly influenced.

Animals↗

Congenital toxoplasmosis associated with acquired oculomotor nerve (CN III) palsy.

A nine-week-old Caucasian male presented with right ptosis and right exotropia due to a third cranial nerve palsy. Symmetrical macular lesions and a paramacular hyperpigmented lesion with overlying vitreous cells in the left eye were compatible with congenital toxoplasmosis. Computer tomography demonstrated calcifications in the periventricular and midbrain regions where the oculomotor nerve exits the brainstem. The diagnosis was confirmed by the toxoplasma indirect fluorescent antibody titer greater than 1:2048 for the infant and greater than 1:512 for the mother. Treatment was instituted with pyrimethamine, sulfadiazine and folinic acid. Neurologic sequelae included a right hemiparesis, infantile seizures, and generalized developmental delay. A Mueller's muscle resection (RUL) combined with 9-mm recession of the right lateral rectus and 7-mm resection of the right medial rectus muscles produced minimal ptosis and right exotropia one year later. the child now prefers to fix with the right eye and a vertical nystagmus is evident in the left eye. To our knowledge this is the first reported case of an infant with noncomitant strabismus due to congenital toxoplasma cranial nerve involvement. The finding of an acquired third cranial nerve palsy accompanied by progressive neurologic sequelae warrants consideration of congenital toxoplasmosis.

Blepharoptosis↗

Evidence for a compartmentalized B cell response as characterized by IgG epitope specificity in human ocular toxoplasmosis.

Infectious agents in the eye induce both a local and a systemic humoral immune response. Previously, differences in Ag recognition were observed between systemic and ocular derived IgG of patients with ocular toxoplasmosis. This finding implied a nonrandom distribution of IgG-producing B cells in the inflamed eye. In the present study, we compared the intraocular and systemic B cell responses of patients with ocular toxoplasmosis to a single Toxoplasma gondii Ag. Two series of C-terminally deleted recombinant T. gondii GRA-2 proteins were constructed to delineate IgG B cell epitopes of paired ocular and serum samples. Differences in epitope region recognition between the ocular and systemic compartment were detected in 9 of 13 patients. The difference in distribution of GRA-2 epitopes between paired samples is indicative of a local GRA-2 specific B cell population functionally different from the systemic GRA-2-specific B cell population. Our results suggest a selective activation of a subset of B cells locally in nonlymphoid tissue.

Adolescent↗

Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines.

Virulence in Toxoplasma gondii is strongly influenced by the genotype of the parasite. Type I strains uniformly cause rapid death in mice regardless of the host genotype or the challenge dose. In contrast, the outcome of infections with type II strains is highly dependent on the challenge dose and the genotype of the host. To understand the basis of acute virulence in toxoplasmosis, we compared low and high doses of the RH strain (type I) and the ME49/PTG strain (type II) of T. gondii in outbred mice. Differences in virulence were reflected in only modestly different growth rates in vivo, and both strains disseminated widely to different tissues. The key difference in the virulent RH strain was the ability to reach high tissue burdens rapidly following a low dose challenge. Lethal infections caused by type I (RH) or type II (PTG) strain infections were accompanied by extremely elevated levels of Th1 cytokines in the serum, including IFN-gamma, TNF-alpha, IL-12, and IL-18. Extensive liver damage and lymphoid degeneration accompanied the elevated levels of cytokines produced during lethal infection. Increased time of survival following lethal infection with the RH strain was provided by neutralization of IL-18, but not TNF-alpha or IFN-gamma. Nonlethal infections with a low dose of type II PTG strain parasites were characterized by a modest induction of Th1 cytokines that led to control of infection and minimal damage to host tissues. Our findings establish that overstimulation of immune responses that are normally necessary for protection is an important feature of acute toxoplasmosis.

Acute Disease↗

The induction and kinetics of antigen-specific CD8 T cells are defined by the stage specificity and compartmentalization of the antigen in murine toxoplasmosis.

Toxoplasma gondii forms different life stages, fast-replicating tachyzoites and slow-growing bradyzoites, in mammalian hosts. CD8 T cells are of crucial importance in toxoplasmosis, but it is unknown which parasite stage is recognized by CD8 T cells. To analyze stage-specific CD8 T cell responses, we generated various recombinant Toxoplasma gondii expressing the heterologous Ag beta-galactosidase (beta-gal) and studied whether 1) secreted or cytoplasmic Ags and 2) tachyzoites or bradyzoites, which persist intracerebrally, induce CD8 T cells. We monitored the frequencies and kinetics of beta-gal-specific CD8 T cells in infected mice by MHC class I tetramer staining. Upon oral infection of B6C (H-2(bxd)) mice, only beta-gal-secreting tachyzoites induced beta-gal-specific CD8 T cells. However, upon secondary infection of mice that had received a primary infection with tachyzoites secreting beta-gal, beta-gal-secreting tachyzoites and bradyzoites transiently increased the frequency of intracerebral beta-gal-specific CD8 T cells. Frequencies of splenic and cerebral beta-gal-specific CD8 T cells peaked at day 23 after infection, thereafter persisting at high levels in the brain but declining in the spleen. Splenic and cerebral beta-gal-specific CD8 T cells produced IFN-gamma and were cytolytic upon specific restimulation. Thus, compartmentalization and stage specificity of an Ag determine the induction of CD8 T cells in toxoplasmosis.

Animals↗

STAT1 plays a critical role in the regulation of antimicrobial effector mechanisms, but not in the development of Th1-type responses during toxoplasmosis.

The production of IFN-gamma by T cells and the ability of this cytokine to activate the transcription factor STAT1 are implicated in the activation of antimicrobial mechanisms required for resistance to intracellular pathogens. In addition, recent studies have suggested that the ability of STAT1 to inhibit the activation of STAT4 prevents the development of Th1 responses. However, other studies suggest that STAT1 is required to enhance the expression of T-bet, a transcription factor that promotes Th1 responses. To address the role of STAT1 in resistance to T. gondii, Stat1-/- mice were infected with this pathogen, and their response to infection was assessed. Although Stat1-/- mice produced normal serum levels of IL-12 and IFN-gamma, these mice were unable to control parasite replication and rapidly succumbed to this infection. Susceptibility to toxoplasmosis was associated with an inability to up-regulate MHC expression on macrophages, defects in NO production, and the inability to up-regulate some of the IFN-inducible GTPase family of proteins, molecules associated with antitoxoplasma activity. Analysis of T cell responses revealed that STAT1 was not required for the development of a Th1 response, but was required for the infection-induced up-regulation of T-bet. Together these studies suggest that during toxoplasmosis the major role of STAT1 is not in the development of protective T cell responses, but, rather, STAT1 is important in the development of antimicrobial effector mechanisms.

Animals↗

IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12.

IL-23 and IL-12 are heterodimeric cytokines which share the p40 subunit, but which have unique second subunits, IL-23p19 and IL-12p35. Since p40 is required for the development of the Th1 type response necessary for resistance to Toxoplasma gondii, studies were performed to assess the role of IL-23 in resistance to this pathogen. Increased levels of IL-23 were detected in mice infected with T. gondii and in vitro stimulation of dendritic cells with this pathogen resulted in increased levels of mRNA for this cytokine. To address the role of IL-23 in resistance to T. gondii, mice lacking the p40 subunit (common to IL-12 and IL-23) and mice that lack IL-12 p35 (specific for IL-12) were infected and their responses were compared. These studies revealed that p40(-/-) mice rapidly succumbed to toxoplasmosis, while p35(-/-) mice displayed enhanced resistance though they eventually succumbed to this infection. In addition, the administration of IL-23 to p40(-/-) mice infected with T. gondii resulted in a decreased parasite burden and enhanced resistance. However, the enhanced resistance of p35(-/-) mice or p40(-/-) mice treated with IL-23 was not associated with increased production of IFN-gamma. When IL-23p19(-/-) mice were infected with T. gondii these mice developed normal T cell responses and controlled parasite replication to the same extent as wild-type mice. Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection.

Acute Disease↗

Outbreak of ocular toxoplasmosis in Coimbatore, India.

Toxoplasma gondii is a protozoan parasite that infects up to a third of the world's population. Infection is mainly acquired by ingestion of food that is contaminated with oocysts. We report an outbreak of ocular toxoplasmosis, which is an acute acquired type rather than reactivation of congenital toxoplasmosis. Our preliminary investigation points to municipal water contamination. This outbreak only proves the need of an effective public health system and health education in curtailing any outbreak.

Adolescent↗

Seroepidemiological survey of toxoplasmosis in La Guadeloupe, French West Indies.

A random survey of 1% of the total population of La Guadeloupe, French West Indies, for toxoplasmosis was carried out. Blood specimens from 3,238 individuals were collected on filter paper strips and tested for Toxoplasma antibodies by the fluorescent antibody technique. Sixty percent were positive. A gradual increase in positivity with increasing age, and high prevalence in children (50% in the 6- to 10-year age group) were observed. No differences were found among the different ethnic groups, nor among persons in different occupations. Economic status showed a highly negative correlation with antibody prevalence rates. The infection rate was not higher in individuals who consumed raw or undercooked meat, and no differences in antibody prevalence related to the sources of meat were observed. The seropositivity rates varied over a wide range (40-76%) according to the locality; higher Toxoplasma antibody rates were found in areas with higher rainfall, and toxoplasmosis prevalence rates correlated positively with mean annual rainfall but not with altitude or with rural or urban residence. A significant difference was observed between seropositivity rates when people living in houses with or without cats were compared. A higher prevalence of hookworm and Strongyloides infections--considered as evidence of closer contact with moist soil--were found in children with Toxoplasma antibodies than in age-adjusted control children without such antibodies. These results provide evidence that meat plays a negligible role in the transmission of Toxoplasma to man, and support the hypothesis that oocysts shed in cat feces are the almost exclusive mode of human infection in Guadeloupe.

Adolescent↗

Cross-reactivity between antibodies in the sera of individuals with leishmaniasis, toxoplasmosis, and Chagas' disease and antigens of the blood-stage forms of Plasmodium falciparum determined by indirect immunofluorescence.

Seroepidemiologic studies using the indirect immunofluorescent antibody test (IFAT) are valuable in malaria control programs in identifying local foci of malaria, in diagnosing malaria in asymptomatic, low-parasitemia blood donors in nonendemic countries, in detecting imported malaria and preventing its introduction into new areas, and in excluding recurrent fever from causes other than malaria. Because other diseases may occur in areas where malaria is prevalent, the aim of this work, using the IFAT, was to determine the frequency of cross-reactions between blood-stage antigens of Plasmodium falciparum and antibodies present in the serum of individuals with leishmaniasis, toxoplasmosis and Chagas' disease. Since malaria transmission does not occur in the study area (State of Minas Gerais, Brazil) where these other diseases are present, we studied sera from individuals living in this area who had never been in the areas endemic for malaria in the Amazon region. Positive reactivity of sera with blood malaria antigens evaluated by IFAT at dilutions > or = 1:40 was detected in 19 (38%) of 50 individuals with cutaneous leishmaniasis, five (62%) of eight individuals with visceral leishmaniasis, 14 (32%) of 44 individuals with Chagas' disease, four (11%) of 36 individuals with toxoplasmosis, and in none of the 14 uninfected controls. All 23 of the control malaria sera from the endemic area (State of Mato Grosso, Brazil) were positive at high dilutions. We found no correlation between titers of the IFAT with malaria and the specific antigens used for serodiagnosis of the other protozoan infections studied. At dilutions of 1:20 and 1:40, the sensitivity of the IFAT test was 100% and specificity was 52% and 72%, respectively. At a dilution of 1:80, the sensitivity was 86% and the specificity was 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diagnosis of naturally occurring toxoplasmosis by bronchoalveolar lavage in a cat.

A 5-year-old cat presented with a history of fever and respiratory distress of 7 days' duration. The cat did not respond to initial symptomatic treatment. Through use of a bronchoalveolar lavage (BAL) technique, the diagnosis of toxoplasmosis was obtained rapidly without evidence of adverse effects to the cat. Antemortem diagnosis of naturally occurring active Toxoplasma gondii infection can be difficult in cats. Identification of organisms obtained by BAL may be beneficial in the diagnosis of feline toxoplasmosis.

Animals↗

Central-nervous-system toxoplasmosis in homosexual men and parenteral drug abusers.

Central-nervous-system toxoplasmosis developed in 7 of 269 patients with the acquired immunodeficiency syndrome reported to the New York City Health Department through July 1982. Focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis, and detectable IgG antibody to Toxoplasma gondii were common; but IgG titers of 1:1024 or more, IgM antibody to T. gondii, and positive open brain biopsies were uncommon. Serologic findings suggested that the disease resulted from recrudescent rather than primary infection. Four of five patients improved when treated with sulfonamides and pyrimethamine, but 2 had relapses. An aggressive diagnostic approach and sometimes even empiric therapy are warranted when central-nervous-system toxoplasmosis is suspected in a seropositive patient with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗