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Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease.

PURPOSE: To update clinical information about ocular toxoplasmosis. Part I reviews information about prevalence of disease, sources of infection, relation of ocular disease to time of Toxoplasma gondii infection (congenital vs. postnatally acquired), and course of disease. DESIGN: Literature review. METHODS: Selected articles from the medical literature, information from recent scientific meetings, and the author's personal experiences were reviewed critically in preparation for the LX Edward Jackson Memorial Lecture. RESULTS: The prevalence of T. gondii infection varies geographically and increases with age; in the United States, the overall proportion is 22.5%. The proportion of infected individuals in the United States who have had episodes of ocular toxoplasmosis is unknown, but may be approximately 2%. Prevalence of ocular involvement is substantially greater in other parts of the world, including southern Brazil. In addition to undercooked meat and unwashed vegetables, drinking water contaminated with oocysts may be an important source of infection in some settings. In contrast to traditional teaching, evidence suggests that most individuals with ocular toxoplasmosis were infected postnatally. Ocular lesions may first develop many years after T. gondii infection. The risk of recurrent ocular disease appears to be greater during the first year after an episode of toxoplasmic retinochoroiditis than during subsequent years. CONCLUSIONS: Reassessment of older publications in the light of recent observations provides a richer understanding of ocular toxoplasmosis, although knowledge about the disease remains incomplete. A better understanding of the clinical characteristics and course of ocular toxoplasmosis will have important implications for developing more effective prevention and treatment strategies.

Adolescent↗

Survey of ophthalmologists about ocular toxoplasmosis.

PURPOSE: To investigate the number of patient visits to ophthalmologists in the United States that are associated with ocular toxoplasmosis, and to assess ophthalmologists' knowledge and treatment practices with regard to the disease. DESIGN: Written survey. METHODS: A random sample of 1000 US ophthalmologists was surveyed by mail in early 2002 by a questionnaire that was developed to collect information about physician demographics, and with regard to toxoplasmosis, number of patients seen, management practices, and knowledge about pathogenesis and risk factors. RESULTS: Among 478 respondents (48%), 261 (55%) indicated that they had seen one or more patients thought to have active toxoplasmic retinochoroiditis in the prior 2 years, and 445 (93%) indicated that they had seen one or more patients with inactive retinochoroidal scars thought to be inactive toxoplasmosis in the prior 2 years. There was a diversity of opinions regarding topics, including the timing of infection and risk factors for ocular involvement. Many ophthalmologists expressed uncertainty about questions regarding the disease. CONCLUSIONS: Ocular toxoplasmosis is associated with a substantial number of patient visits in the United States each year. A variable understanding of the disease indicates a need for continuing medical education regarding ocular toxoplasmosis.

Chorioretinitis↗

Incidence of toxoplasmosis in 5532 pregnant women in Crete, Greece: management of 185 cases at risk.

OBJECTIVES: To study the incidence of toxoplasmosis in pregnant women in Crete and to test a designed protocol for handling those at risk of delivering congenitally infected infants. STUDY DESIGN: Pregnant women were screened serologically over a period of 5 years. Cases with suspected acute toxoplasmosis were treated, peripheral blood (PB), and amniotic fluid (AF) tested by polymerase chain reaction (PCR) and culture, and fetuses monitored by ultrasonography. The absence of congenital infection in infants was confirmed by serology and clinical evaluation. RESULTS: Of the 5532 pregnant women followed, 70.57% remained seronegative, 29.45% were seropositive, and there was direct evidence of seroconversion in six cases. Acute toxoplasmosis was suspected in 185 cases, maternal parasitemia was detected in five cases and positive amniotic fluid in one case. Congenital infection was excluded in all infants followed, based on the absence of ultrasound findings in utero, lack of clinical symptoms at birth, negative Western blotting (WB) at birth and 3 months later, and descending serology for a year. CONCLUSION: Overall, 29.45% of the pregnant women followed were seropositive, 3.3% with suspected acute toxoplasmosis, and in 0.02% cases there was evidence of maternofetal transmission. The protocol tested allowed differentiation between acute and latent toxoplasmosis, safe management of the cases at risk and assisted in avoidance of unwarranted pregnancy terminations.

Clinical Protocols↗

Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis.

OBJECTIVE: To compare the efficacy of the classic treatment of ocular toxoplasmosis (pyrimethamine, sulfadiazine, and prednisolone) with a regimen consisting of trimethoprim/sulfamethoxazole (co-trimoxazole) plus prednisolone. DESIGN: Prospective randomized single-blind clinical trial. PARTICIPANTS: Fifty-nine patients with active ocular toxoplasmosis were randomly assigned to 2 treatment groups: 29 were treated with pyrimethamine/sulfadiazine, and 30 patients received trimethoprim/sulfamethoxazole. INTERVENTION: Treatment consisted of 6 weeks' treatment with antibiotics plus steroids. Antitoxoplasmosis antibodies (immunoglobulin M [IgM] and IgG) were measured using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Changes in retinochoroidal lesion size after 6 weeks' treatment, visual acuity (VA) before and after intervention, adverse drug reactions during follow-up, and rate of recurrence. RESULTS: Active toxoplasmosis retinochoroiditis resolved in all patients over 6 weeks' treatment, with no significant difference in mean reduction of retinochoroidal lesion size between the 2 treatment groups (61% reduction in the classic treatment group and 59% in the trimethoprim/sulfamethoxazole group, P = 0.75). Similarly, no significant difference was found in VA after treatment between the 2 groups (mean VAs after treatment were 0.12 logarithm of the minimum angle of resolution [logMAR] [20/25] in the classic treatment group and 0.09 logMAR [20/25] in the trimethoprim/sulfamethoxazole group, P = 0.56). Adverse effects were similar in both groups, with one patient in each suffering from any significant drug side effects. The overall recurrence rate after 24 months' follow-up was 10.16%, with no significant difference between the treatment groups (P = 0.64). CONCLUSIONS: Drug efficacies in terms of reduction in retinal lesion size and improvement in VA were similar in a regimen of trimethoprim/sulfamethoxazole and the classic treatment of ocular toxoplasmosis with pyrimethamine and sulfadiazine. Therapy with trimethoprim/sulfamethoxazole seems to be an acceptable alternative for the treatment of ocular toxoplasmosis.

Adolescent↗

Prenatal diagnosis of congenital toxoplasmosis: a multicenter evaluation of different diagnostic parameters.

OBJECTIVE: Our purpose was to evaluate different methods of diagnosing congenital toxoplasmosis prenatally by amniocentesis and cordocentesis. STUDY DESIGN: In a retrospective multicenter study, we investigated consecutive women who had seroconversion for Toxoplasma gondii during pregnancy and who underwent either amniocentesis or cordocentesis or both to obtain a prenatal diagnosis of fetal toxoplasmosis. Data were obtained from 122 patients recruited in 6 different European Toxoplasma reference centers. Infants born to these mothers were followed up until 1 year of age to confirm or exclude congenital toxoplasmosis. Sensitivity, specificity, positive predictive value, and negative predictive value were measured for the following parameters: (1) detection of the parasite in amniotic fluid by mouse inoculation, (2) detection of the parasite in amniotic fluid by in vitro cell culture, (3) detection of Toxoplasma deoxyribonucleic acid in amniotic fluid by a polymerase chain reaction assay, (4) detection of the parasite in fetal blood by mouse inoculation, (5) detection of specific immunoglobulin M antibodies in fetal blood, and (6) detection of specific immunoglobulin A antibodies in fetal blood. RESULTS: The polymerase chain reaction test performed on amniotic fluid had the highest level of sensitivity (81%) and also a high level of specificity (96%). The combination of the polymerase chain reaction test and mouse inoculation of amniotic fluid increased sensitivity to 91%. The sensitivity of immunoglobulins M and A in fetal blood was 47% and 38%, respectively. In congenitally infected fetuses a negative correlation was observed between positive serologic parameters and gestational age at the time of maternal infection and at prenatal diagnosis. CONCLUSION: Congenital toxoplasmosis is best predicted by prenatal examination with the combination of T gondii polymerase chain reaction and mouse inoculation of amniotic fluid. The role of cordocentesis in the diagnosis of congenital toxoplasmosis is limited.

Amniocentesis↗

The epidemiologic association of Fuchs' heterochromic iridocyclitis and ocular toxoplasmosis.

Between January 1983 and July 1987, I examined 25 patients at the Department of Ophthalmology, West Virginia University, who had the anterior segment characteristics of Fuchs' heterochromic iridocyclitis. Of these patients, 16 had fundus lesions suggestive of ocular toxoplasmosis. Of these 16 patients, 13 had a positive serologic test for toxoplasmosis, two patients were not tested, and one patient had a negative test at 1:16. The remaining nine patients with Fuchs' heterochromic iridocyclitis had no fundus lesions suggestive of toxoplasmosis. A chart review of 792 consecutive patients at the Retinal Unit, West Virginia University, during a six-month period disclosed that 24 of 590 patients (4%) had chorioretinal scars suggestive of toxoplasmosis. I concluded from these data that in at least one subgroup of patients with Fuchs' heterochromic iridocyclitis there is a significant association with the chorioretinal scars of toxoplasmosis (P less than .01), and this is suggestive of a causal relationship.

Adult↗

Differences between intraocular and serum antibody responses in patients with ocular toxoplasmosis.

PURPOSE: To investigate the antigen specificity of the intraocular anti-Toxoplasma gondii antibody response in patients with ocular toxoplasmosis. METHODS: Paired ocular fluid and serum samples were collected from 13 patients with active ocular toxoplasmosis. Serum IgM anti-T. gondii antibodies were tested to distinguish recently-acquired from chronic infection. Anti-T. gondii IgG specificity was analyzed by immunoblotting using a crude T. gondii extract. RESULTS: Two of the 13 patients tested were IgM positive and considered to have acquired ocular toxoplasmosis. The antibody specificity in ocular fluid and serum of these two patients was similar, whereas in the patients with presumed chronic disease, marked differences could be observed. Most ocular fluid samples contained antibodies that stained a 28-kD antigen more intensely than did antibodies from paired serum samples. Using absorption and elution experiments, we demonstrated that this 28-kD protein was identical to the GRA-2 antigen, which is expressed in both the tachyzoite and the bradyzoite stages of the parasite. CONCLUSIONS: Our results show that the intraocular T. gondii antibody response of patients with recurrent ocular toxoplasmosis differs from the systemic response. This finding may have implications for our understanding of the immunopathogenesis of ocular toxoplasmosis and could be employed to improve diagnosis of the disease.

Adult↗

Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team.

BACKGROUND: Outbreaks of toxoplasmosis are recognised infrequently. In March, 1995, a sudden increase of serologically diagnosed cases of acute toxoplasmosis was noted in the Greater Victoria area of British Columbia, Canada. Concurrently, but independently, seven cases of acute toxoplasma retinitis were diagnosed against a background of no cases in the previous 5 years. METHODS: Cases were defined by serological testing, clinical presentation, and residence in Greater Victoria. A screening programme for women who were or had been pregnant was started. Geographical mapping of cases, and case-control studies of symptomatic cases and of women enrolled in the screening programme were done. FINDINGS: 100 individuals aged 6 to 83 years met the definition for an acute, outbreak-related case. 94 resided in Greater Victoria and six had visited it; 19 had retinitis, 51 had lymphadenopathy, four others had symptoms consistent with toxoplasmosis, seven had other symptoms, 18 were symptom-free, and one would not provide information. 36 (0.9%) of 3812 screened pregnant and postnatal women were cases. Excess cases were not detected outside Greater Victoria and no conventional source of toxoplasmosis was implicated. Mapping studies of cases and of the screened women, and both case-control studies showed significant associations between acute infection and residence in the distribution system of one reservoir supplying water to Greater Victoria (ORs or RRs: 3.53, 3.05, 8.27, and 5.42, respectively). The epidemic curve appeared bimodal, with peaks in December, 1994, and March, 1995, that were preceded by increased rainfall and turbidity in the implicated reservoir. INTERPRETATION: A municipal water system that uses unfiltered, chloraminated surface water was the likely source of this large community-wide outbreak of toxoplasmosis.

Adolescent↗

Extracerebral toxoplasmosis in AIDS. Histological and immunohistological findings based on 80 autopsy cases.

Despite the great amount of literature concerning toxoplasmic encephalitis in AIDS patients, little is known about extracerebral toxoplasmosis. Therefore we conducted a study of 80 autopsy cases to estimate the frequency of extracerebral toxoplasmosis. A control group of 50 cases was completely negative for all markers applied. In 35 of the 80 AIDS-cases (43.7%), organisms could be detected. In 13 cases (16.2%) there was an extracerebral toxoplasmosis; 4 cases (5%) showed only extracerebral involvement and in 9 cases (11.2%), extracerebral toxoplasmosis occurred in combination with cerebral manifestations. In 22 cases (27.5%), only cerebral toxoplasmosis was found. The following organs were involved: cardiac muscle (15%), lungs (6.2%), liver (5%), pancreas (5%), gastrointestinal tract (6.2%), adrenal glands (5%), lymph nodes (5%) and testis (3.7%). In individual cases further organs, not mentioned above, were involved. Pseudocysts could be demonstrated within necroses and inflammatory foci by conventional staining, whereas trophozoites became apparent only immunohistologically.

Acquired Immunodeficiency Syndrome↗

Extracerebral toxoplasmosis in the acquired immunodeficiency syndrome (AIDS).

Although Toxoplasma gondii frequently causes lesions of the central nervous system in AIDS, the exact incidence of extracerebral toxoplasmosis in these immunodepressed patients remains difficult to determine. Isolation of the parasite outside the central nervous system is rarely performed ante mortem, and most diagnoses of extracerebral toxoplasmosis are made post mortem. This article describes 23 cases of extracerebral toxoplasmosis diagnosed between 1987 and 1991 in an autopsy series of 170 patients infected with the human immunodeficiency virus (HIV). Ante mortem diagnosis of extracerebral involvement was affirmed in 4 of these 23 patients by identification of trophozoites in bronchoalveolar lavage fluid (2 cases), a surgical pulmonary biopsy specimen, and a bladder biopsy. Clinical and paraclinical findings suggested cardiac involvement in 4 other patients. Post mortem examination demonstrated disseminated toxoplasmosis in 18 cases and extracerebral monovisceral involvement in 5 cases. Extracerebral toxoplasmosis was directly responsible for the death of 6 patients. The most frequent extracerebral sites of Toxoplasma gondii involvement were the heart (21/23 cases; 91%), the lungs (14/23 cases; 61%) and the pancreas (6/23 cases; 26%). The tissular consequences of toxoplasmic involvement varied considerably, from formation of pseudocysts or cysts without any surrounding inflammatory reaction to necrotic lesions rich in neutrophilic polynuclear cells containing numerous free parasites. Immunoperoxidase study using antitoxoplasmic antibodies contributed to the diagnosis of 8 extracerebral localizations. Electron microscopy examination of a surgical lung biopsy and myocardial specimens (2 cases) demonstrated the ultrastructural characteristics of Toxoplasma gondii trophozoites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Toxoplasmosis in Pallas' cats (Otocolobus manul) raised in captivity.

Manuls or Pallas' cats (Felis manul, syn. Otocolobus manul) are endangered wild cats from Central Asia kept and bred in many zoos. Despite good breeding success young cats frequently die from acute toxoplasmosis. From 1998 to 2002, a breeding pair in the Schönbrunn Zoo in Vienna, Austria, gave birth to 24 kittens; 58 % of kittens died between the 2nd and the 14th week of life, mostly due to acute toxoplasmosis. The epidemiology of toxoplasmosis in Pallas' cats was examined and a control strategy to protect the kittens from fatal toxoplasmosis was developed. One 12-week-old kitten from a litter of 6 born in 2001 died of generalized toxoplasmosis. This kitten had shed T. gondii oocysts that were bioassayed in mice. Toxoplasma gondii was isolated in tissue culture inoculated with tissues of these mice. The surviving animals were immediately treated with clindamycin for 16 weeks; they acquired a natural infection and seroconverted by the end of this time without clinical signs.

Animals↗

Risk factors for toxoplasmosis in pregnant women in Kent, United Kingdom.

The aim of this study was to establish the relative importance of various risk factors for toxoplasmosis in a United Kingdom antenatal population. Toxoplasma immune status was determined by an immunoassay and linked to a questionnaire exploring dietary and environmental exposure to toxoplasmosis. The overall seroprevalence found was 9.1% (172/1897). A significantly higher seroprevalence was associated with rural location of the childhood home, childhood home in Europe excluding the United Kingdom, feeding a dog raw meat and increased age. A non-significant higher prevalence of toxoplasmosis was observed in women who had lived with a cat or kitten as a child. In contrast to recent European studies only weak associations between diet and toxoplasmosis were found. Gardening activity was not associated with seropositivity but a non-significant lower seroprevalence was seen in gardeners who always wore gloves. This study confirms that toxoplasma prevalence in the United Kingdom has continued to decline since the 1960s. The increasing seroprevalence with age found in this study, highlights the continuing need to educate women of childbearing age about the risk factors for toxoplasmosis.

Adult↗

Anti-toxoplasma serotitres in ocular toxoplasmosis.

Serological studies are one of the important diagnostic tools used in the investigation of uveitis. This study was based on anti-toxoplasma serotitres obtained from 80 normal healthy adults and 122 patients investigated for ocular toxoplasmosis over a 42 month period. Fifteen per cent of normal healthy sera were found to have low titres (1:64 to 1:256), while 3.8% had high titres (1:1024 or higher). Thirty five eyes of 29 patients had presumed ocular toxoplasmosis based on clinical features and a typical fundal appearance. 89.6% of clinically positive ocular toxoplasmosis were found to have titres ranging from 1:64 to 1:4096. Among the suspected ocular toxoplasmosis cases with a serotitre more than or equal to 1:256, at least 77% had clinical ocular toxoplasmosis.

Adolescent↗

Human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBL SCID) models of toxoplasmosis.

Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu-PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice had low titre T. gondii-specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n-glucolyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.

Acute Disease↗

[Experimental models of toxoplasmosis. Pharmacological applications].

Toxoplasma gondii is an ubiquitous protozoan parasite causing severe or life-threatening infections in immunocompromised patients and in congenitally infected infants. Animal models have been extensively used to describe the pathology of infection and to identify new effective drugs for the treatment of congenital infections, chrorioretinitis and toxoplasmic encephalitis. Although inherent differences between man and animal can reduce the relevance of data obtained experimentally, animal models have greatly improved our knowledge on the various aspects of toxoplasmosis. Toxoplasma infection can be easily obtained in most laboratory animals, with exception of rats which are partially resistant. According to the strain used, the resulting infection may be acute, subacute or chronic, and can be monitored either by the survival of animals, the histopathological examination of lesions or, preferably, by titration of parasites in infected tissues using subinoculation to mice or tissue culture. This latter method has proved particularly useful to describe the kinetics of infection in host tissues and to assess the efficacy of drugs, according to their pharmacokinetics and tissue distribution. The relevance of results obtained in animal models of congenital toxoplasmosis and of chrorioretinitis is more questionable, due to the marked differences between the mode of infection in humans and in animals. Experiments performed in primates provided valuable informations for the management of therapy of congenital toxoplasmosis but were of limited interest for ocular toxoplasmosis. The pathogeny of toxoplasmic encephalitis is still poorly understood, and no experimental model is fully satisfactory to produce focal encephalitic lesions as observed in immunocompromised humans. Acute infections with highly virulent strains induce disseminated infection with major pulmonary and brain involvement, and thus can be used to assess the efficacity of drugs in these tissues. Direct inoculation of tachyzoites into brain tissue can induce focal encephalitis but this model is of difficult use for large scale studies. Although cellular immunity is mainly responsible for the control of toxoplasmosis at the chronic stage, administration of immunosuppressive drugs does not usually result in focal brain reactivation; such reactivation can only be obtained using antibodies against CD8 and CD4 T lymphocytes or interferon gamma. Another experimental approach is the use of genetically immunodeficient animals: these models are of limited interest for pharmacological research since infection of nude or T depleted mice usually results in a dissemination of infection; however, using these models it could be clearly demonstrated that immunity plays a major adjunctive role in the control of acute infection. Concurrent infections between viruses and parasites is a common feature in immunocompromised patients and especially during AIDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.

BACKGROUND AND METHODS: Toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with the acquired immunodeficiency syndrome (AIDS). To investigate its clinical course, we reviewed the records of 115 patients with AIDS and central nervous system toxoplasmosis treated at San Francisco General Hospital between 1981 and 1990. RESULTS: The most common presenting symptoms were headache (in 55 percent), confusion (52 percent), and fever (47 percent). Focal neurologic deficits were present in 79 patients (69 percent). The median CD4 cell count at presentation was 50 per cubic millimeter (50 x 10(6) per liter). Thirteen of 80 patients with clinical toxoplasmosis (16 percent) and 4 of 18 patients with pathologically proved disease (22 percent) had undetectable antitoxoplasma IgG antibodies by indirect immunofluorescence assay. Of 103 patients, 94 (91 percent) had enhancing lesions on CT. Single lesions were seen in 28 of 103 patients (27 percent) on CT, and such lesions were seen in 3 of 21 patients (14 percent) on magnetic resonance imaging. Over 90 percent of patients who eventually had clinical and radiographic improvement had evidence of improvement by day 14 of therapy. Adverse drug reactions occurred in 71 patients (62 percent) and led to a change in therapy in 50 patients (43 percent). Among the patients who survived a first episode of toxoplasmosis, the median survival was 265 days. CONCLUSIONS: Toxoplasmosis occurs in advanced stages of human immunodeficiency virus infection, and the absence of antitoxoplasma antibodies on immunofluorescence assay does not exclude the diagnosis. The clinical and radiographic response to therapy is usually rapid, but treatment is frequently limited by adverse drug effects.

AIDS-Related Opportunistic Infections↗

Punctate outer retinal toxoplasmosis in an HIV-positive child.

PURPOSE: To discover whether the outer layer of the retina can be the site for toxoplasmosis in AIDS patients. METHODS: An HIV-positive child, who previously had a normal ocular examination, was reexamined three months later. This examination showed outer retinal lesions compatible with toxoplasmosis and positive IgM and IgG titers specific for that organism, despite the small drop in the CD4 count. RESULTS: During the first examination, the antibodies for toxoplasmosis were negative. At the three-months follow-up, the anti-toxoplasmosis antibodies were positive and the rest of the workup was negative, suggesting a strong correlation with the patient's fundus pattern. CONCLUSION: We describe a case of punctate outer retinal toxoplasmosis uveitis, which has been previously associated with immunocompetent hosts. We, however, believe that it can be seen in immunocompromised patients as well.

Child↗

CCR5 delta32 deletion and reduced risk of toxoplasmosis in persons infected with human immunodeficiency virus type 1. The SEROCO-HEMOCO-SEROGEST Study Groups.

This study attempted to determine whether the CCR5 Delta32 deletion affected progression to certain first AIDS-defining illnesses in human immunodeficiency virus type 1-infected patients enrolled in the French SEROCO/HEMOCO/SEROGEST cohorts. Toxoplasmosis onset as a first AIDS-defining illness was significantly delayed in 253 heterozygous patients, compared with 1404 wild type patients. The relative risk of toxoplasmosis associated with heterozygosity was 0. 39 (95% confidence interval, 0.16-0.96) after adjustment for age, CD4 cell count, and primary specific prophylaxis. A nonsignificant protective trend was observed with regard to the onset of mycobacterial, cytomegalovirus, and herpesvirus diseases, but these events were less frequent than toxoplasmosis. Progression to other conditions (e.g., wasting, non-Hodgkin's lymphoma, Kaposi's sarcoma) was similar in the 2 groups as was the frequency of toxoplasmosis as a subsequent AIDS-defining illness. As chemokines are involved in numerous infectious processes, the Delta32 deletion could delay progression to certain opportunistic infections such as toxoplasmosis.

AIDS-Related Opportunistic Infections↗