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We report the vertical transmission of congenital toxoplasmosis from a chronically infected immunocompetent woman to her child. On the background of published knowledge in this field, vertical transmission must have developed after maternal reinfection or reactivation of the preexisting disease.
A 16-year-old female patient, who had undergone bone marrow transplantation 35 days earlier, presented with dry cough, dyspnea, and fever for 4 days. Chest radiography showed poorly-defined bilateral opacities. High-resolution CT revealed bilateral ground glass opacities with superimposed septal thickening and intralobular linear opacities. Laboratory results were nonspecific and empiric treatment with multiple drugs was initiated. The patient had no response to therapy and died 12 days after the admission. At autopsy the patient had disseminated toxoplasmosis with involvement of the central nervous system, myocardium, bone marrow, and lungs.
PURPOSE OF REVIEW: The purpose of this review is to update the latest information on a long-recognized infectious disease, ocular toxoplasmosis. RECENT FINDINGS: Topics include how the disease is acquired, how to make a clinical diagnosis, and what laboratory tests to order when the diagnosis is not clear. New insights into the genetic make-up of the parasite and new treatment alternatives are discussed. SUMMARY: Recent findings are updated on the epidemiologic status of the disease, methods for correct diagnosis of unusual presentations, and alternative therapies.
The clinical and diagnostic findings in 20 cases of toxoplasmosis associated with the Acquired Immune Deficiency Syndrome (AIDS) were investigated in a prospective study of patients in south-east England. Individual details were recorded by a standardised questionnaire incorporating an evaluation of initial presentation, radiological findings, therapy and clinical progression. Toxoplasma serology was performed by reference assays and the presence of the parasite in tissue was sought by culture, histological examination and specific DNA detection. Clinical findings at presentation and results of radiological investigation were comparable with previously published experience from the USA. In contrast, sampling of the cerebrospinal fluid was rarely performed and was found to be of little clinical value. Examination of tissue samples was diagnostic when available, but was not performed routinely. Sulphonamide plus pyrimethamine was the treatment of choice in most cases and response to therapy was satisfactory, although a high incidence of toxicity was recorded.
We report a 59-year-old woman with severe dermatomyositis in association with high serum toxoplasma antibody titres who was successfully treated with pyrimethamine and sulphadiazine. This case supports an aetiological role for toxoplasmosis in the pathogenesis of some cases of dermatomyositis.
Treatment with an anti-IL-4 monoclonal antibody protected susceptible C57BL/6 mice against challenge with an avirulent strain of T. gondii. Antibody therapy with 100 micrograms on days 0 and 7 post infection resulted in 100% survival of C57/BL6 mice infected orally. Survival was dose-dependent. Treatment prolonged parasitaemia but did not alter tissue parasite load. Increased serum IgG2a and IFN-gamma levels, together with low levels of IgG1, in mice treated with anti-IL-4 or an isotype control, indicated a trend towards a predominant Th1 response in all survivors. The persistence of an IgE response after treatment suggests that endogenous IL-4 was only partly neutralized or that other factors can induce the production of IgE in murine toxoplasmosis.
Ocular toxoplasmosis is a local manifestation of systemic infection in which Toxoplasma spreads into the eye, affecting mainly the posterior segment of the eye. Reactivation of the initial retinal condition presumably results from the rupture of quiescent parasitic cysts lying adjacent to pre-existing scars and may secondarily involve the choroid (leading to retinochoroiditis). Although the molecular mechanisms underlying host-parasite interaction are largely unknown, toxoplasmic retinochoroiditis usually remains a local event, and does not necessarily evoke a detectable systemic immune response. Local immunotolerance mechanisms may likewise confound attempts to confirm the clinical diagnosis by serology. Aqueous humour may be analysed for the presence of parasite DNA or of specific antibodies, but the DNA burden therein is low, and a more definite confirmation would require risky puncturing of the vitreous. Laboratory confirmation of the diagnosis is also frustrated by marked individual differences in the time elapsing between the onset of clinical symptoms and the activation of specific antibody production, resulting in a high proportion of false negative results. Whether a delay in the onset of local specific antibody production reflects immunotolerance in cases of congenital - but not obviously in those of acquired - infection remains an open question, but it could account for a relatively low confirmation rate in laboratory tests for local antibody production. Against this background, current diagnostic strategies need to be re-evaluated with a view to future improvements.
Ocular toxoplasmosis (OT) can occur in the children of mothers infected with Toxoplasma gondii during pregnancy. It is not limited to the congenitally infected, but can also occur following adult-acquired infection or as a result of disease reactivation in immune-compromised and pregnant individuals. Many aspects of immune privilege in the eye, including constitutive TGF-beta expression and reduced MHC class 1 expression, would appear at first to favour parasite survival. Conversely, many of the mechanisms that control parasite multiplication in other anatomical sites, such as nitric oxide expression, IFN-gamma and TNF-alpha, are known to disrupt immune privilege and are associated with ocular damage. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction we review the pathogenesis of OT in the murine model.
Natural killer (NK) activity against Toxoplasma gondii tachyzoites and tumour cells during acute toxoplasmosis was investigated using a single-cell NK assay. During the course of infection the percentage of lymphocytes binding tachyzoites and tumour cells did not vary significantly and NK activity was enhanced due to an increase in the specific cytolytic capacity per cell. To determine whether regulatory mechanisms mediated by cytokines might explain the increased NK activity, the kinetics of interleukin-2 (IL-2) and interferon (IFN) production and the correlation between their concentrations and the level of NK activity were analysed at the same time. As the infection progressed NK activity increased in spite of the fact that IL-2 production decreased (except for a small increase during the first day of infection). However, IFN production increased gradually in close temporal and quantitative association with the overall increase in NK activity. These results suggest that T. gondii, via its ability to produce interferon, enhances NK activity against itself and other cells.
A 9-year-old female, domestic short hair cat was presented with sudden onset of polyuria/polydipsia, and hundreds of cutaneous nodules. Prior to referral, the cat had had four skin nodules that were treated with steroids. The four skin nodules then multiplied to form more than 100 ulcerated and nonulcerated nodules located all over the trunk. Clinical evaluation revealed hypothermia and respiratory distress. Cytology from both skin nodules and bronchoalveolar lavage showed macrophages and small organisms whose shape and size were indicative of Toxoplasma spp., or similar organisms. Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) serology results were negative. The cat was seropositive for Toxoplasma (IgG 1 : 640) and Neospora (1 : 80) infections. The cat died soon after referral. Necropsy revealed pyothorax, necrotic/purulent pneumonia, haemorrhagic spots on kidneys and mesentery. Histopathology from skin nodules showed diffuse, deep necrotic dermatitis/panniculitis, vasculitis and disseminated free and grouped protozoa. The parasites were found in lungs, spleen, kidneys and liver. Immunohistochemistry on skin tissue with anti-Toxoplasma gondii and Neospora caninum antibodies gave positive results with both. Electron microscopy showed single and grouped tachyzoites with morphological features of T. gondii, often within macrophages. Samples of cutaneous nodules and bronchoalveolar fluid were examined by a polymerase chain reaction (PCR) assay for detecting apicomplexa coccidia. PCR results were consistent only with T. gondii infection. Therefore, immunohistochemistry positivity for N. caninum was considered a cross-reaction and a diagnosis of cutaneous and visceral toxoplasmosis was made.
Nine patients with cutaneous toxoplasmosis had slowly regressing erythema-multiforme-like eruptions or lichenoid, papulonodular and purpurictelangiectatic disorders. The most common histologic finding was subacute histiolymphocytic perivasculitis with frequent demonstration of the parasite. Another group of patients showed similar clinical and histological findings, but the parasite was not evidenced in these.
In total, 171 students from a boarding school in Izmir, Turkey, with mild and non-specific symptoms of toxoplasmosis, were screened during September-October 2002. All 171 students were seropositive for Toxoplasma gondii IgG and IgM. Of 43 students tested, 40 (93%) had low IgG avidity. None showed evidence of ophthalmic involvement. The data suggest that T. gondii may spread rapidly in close living conditions, possibly following exposure to cat litter. This is the largest recent outbreak of toxoplamosis described in the medical literature.
Groups of mice were given an intraperitoneal injection of one of six monoclonal antibodies to Toxoplasma gondii, a mixture of equal amounts of five monoclonal antibodies to T. gondii, or the murine myeloma protein MOPC 21, and challenged with either a highly virulent or moderately virulent parasite strain. Two monoclonal antibodies (FMC 19 and FMC 22) conferred total protection against the moderately virulent challenge, with all mice surviving, whereas 90% of control mice died. FMC 19 and FMC 22 also conferred significant protection against the highly virulent challenge as indicated by a prolonged mean time to death (MTD) of immunized compared with control groups of mice. One monoclonal antibody (FMC 23) and the mixture of five antibodies gave significant protection against the moderately virulent challenge only. Passive immunization with dilutions of FMC 22 antibody indicated that the lowest serum titer needed to confer significant protection to mice against a moderately virulent Toxoplasma challenge was 1/640. Mice challenged with highly virulent tachyzoites that had been preincubated with FMC 22 had a significantly longer MTD than mice challenged with highly virulent tachyzoites that had been preincubated with MOPC 21 or phosphate buffered saline, pH 7.2 (PBS). Immunoprecipitation and autoradiography of radiolabeled tachyzoites confirmed that FMC 19 was directed against a 35,000 molecular weight (mol. wt.) antigen and FMC 22 was directed against a 14,000 mol. wt. fraction. The potential for use of single antigens as protective immunogens in preventing toxoplasmosis is raised.
Toxoplasma gondii was found in tissues of a six-year-old female Pallas cat (Felis manul) from the Milwaukee County Zoo. Toxoplasma gondii meronts (types D and E), gamonts, and oocysts were present in the epithelium of the small intestine. Numerous unsporulated oocysts were present in the intestinal lumen. The cat died of acute, overwhelming toxoplasmosis. Necrotic enteritis, multifocal necrotizing granulomatous hepatitis, and pneumonia were the prominent lesions.
We report a newborn with typical lesions of congenital toxoplasmosis. Retrospectively, the time of infection could be located to or even before conception. A diagnostic work-up should be performed in every newborn whose mother presents persistent high antibody titers against toxoplasma during pregnancy.
Lactating mother mice were infected with an avirulent strain of Toxoplasma gondii. When the milk from these mice was exposed to HCl, it was found that some of the parasites present were "acid-resistant" cystozoites. Hence there is an obvious risk of acquiring toxoplasmosis by consuming milk from infected donors.
Ewes were inoculated orally with 1500 Toxoplasma gondii oocysts at 6 to 14 weeks of pregnancy. Abortions occurred at 26 to 55 days after inoculation, and maternal serum T. gondii antibody titres did not peak/plateau until 20 to 103 days after inoculation, usually after abortion occurred. Serums or body fluids from unautolysed foetuses aborted at 35 days or more after maternal inoculation, contained significant levels of Toxoplasma antibodies as determined by the indirect fluorescent-antibody test. It was considered that foetal serology was a quick and efficient method of diagnosing congenital toxoplasmosis in sheep on a flock basis.
Thirteen Tammar wallabies (Macropus eugenii) were dosed orally with 500, 1000 or 10,000 oocysts of Toxoplasma gondii, as part of a vaccination trial. Eleven animals died of acute toxoplasmosis 9 to 15 days after challenge. The lesions were similar in all animals, consisting of foci of necrosis and inflammation in the intestines, lymphoid tissue, adrenal cortex, heart, skeletal muscle and brain, and severe generalised pulmonary congestion and oedema. Free and intracellular tachyzoites of Toxoplasma were associated with the lesions. The remaining 2 animals had shown no signs of disease when euthanased four months after challenge. Small, focal, non-suppurative inflammatory lesions were seen in brain, heart and skeletal muscle of these animals and chronic Toxoplasma infection was confirmed by mouse inoculation.