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One hundred and ninety-five mink sera randomly selected from 17 Danish mink farms were evaluated for the presence of Toxoplasma gondii antibodies in the latex agglutination test. Six (3%) sera contained T. gondii antibodies in titres of 1:64 or more. The estimated 3% prevalence means that 300,000 mink out of a total mink population of ten million might be infected with Toxoplasma gondii. This large number of possible sero-positive mink in Denmark indicates that there exists a potential risk of acquiring toxoplasmosis by pelting mink.

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.

To obtain information on the prevalence of antibodies against Toxoplasma gondii in pigs in Austria, 4697 blood samples from pigs were collected in the years 1982 and 1992 and tested by an indirect fluorescence antibody test. The results of the studies show that due to modern fattening systems the prevalence of infections with T. gondii in slaughtered pigs has obviously decreased in Austria during the last 10 years. The investigations indicate a significant difference in the rate of infection of pigs between 1982 (13.7%) and 1992 (0.9%). Additionally, the prevalence of T. gondii antibodies in breeding sows (1982, 43.4%; 1992, 4.3%) was higher than that in fattening pigs (1982, 12.2%; 1992, 0.8%).

The unusual occurrence, protein manifestations, and often devastating consequences of toxoplasmosis in patients with cancer emphasize the need for clinical acumen in the diagnosis and management of this disorder. Toxoplasmosis in patients with cancer has most commonly been described in association with Hodgkin's disease. It has also been reported, usually in the setting of treatment with antineoplastic agents, in patients with other lymphoproliferative disorders, hematologic malignancies, and solid tumors. In this review, among patients for whom the diagnosis was made early enough to begin specific treatment, conditions of 68% improved; this finding was in marked contrast to the severe morbidity and mortality observed for untreated individuals. The high mortality in the untreated group reflects the general debilitation and severe immunocompromise of these patients. Therefore, although toxoplasmosis contributed to a poor prognosis, it was not necessarily always the proximate cause of death.

The objective of this study was to assess the risk of toxoplasmosis in HIV-positive subjects as a basis for primary prophylaxis. A retrospective chart review of 400 consecutive patients was carried out and clinical and laboratory markers at first presentation and follow-up data on the occurrence of toxoplasmosis were recorded. Independent variables were identified, laboratory parameters were stratified, and estimates for the risk of toxoplasmosis and the impact of different variables on its occurrence were made using conventional statistical methods. An increased risk of toxoplasmosis was strongly associated with a positive Toxoplasma gondii IgG EIA in conjunction with a CD4+ cell cont below 0.15/nl (the estimated risk of toxoplasmosis was 20% and 35% after 12 and 24 months, respectively) or a history of one or more opportunistic infections (the estimated risk was 12% and 30% after 12 and 24 months, respectively). Toxoplasma gondii-seropositive patients with CD4+ cell counts below 0.15/nl and those with antecedent opportunistic infections are most likely to develop toxoplasmosis and thus might benefit from primary prophylaxis. The risk of disease probably outweighs the risk of medication in these subjects. Prospective clinical trials are needed to define the optimal choice of drugs.

The profile of toxoplasmosis was studied among the inhabitants of two different localities in Dakahlia in relation to age, sex, occupation and contact with animals and/or birds. The total percentage of seropositive Toxoplasma antibodies using Dot-ELISA was 23.8%. The seropositivity rate was higher among the inhabitants of the village particularly in those in contact with farm animals. The results are discussed.

The population biology of Toxoplasma gondii is reviewed in the context of how its complex life cycle might be responsible for the current picture and how a knowledge of the population structure may have an impact on the thinking of both clinician and researcher. Published results already clearly indicate that the population can be divided into two distinct groups that are genetically and biologically distinct. The more virulent group, as defined by their LD50 in mice, is apparently a single, clonal line. The biological and clinical implications of the existence of such a group are discussed.

A 37-year-old woman with chronic myelogenous leukemia underwent allogeneic bone marrow transplantation with CD8-depleted marrow from an HLA-identical sister. On day 43 post-transplant, the patient developed a headache and became lethargic and tremulous. Magnetic resonance imaging (MRI) of the brain showed abnormal meningeal and superficial parenchymal enhancement anteriorly. The spinal fluid had an elevated protein level with normal glucose and a neutrophilic pleocytosis. At autopsy, Toxoplasma meningoencephalitis was seen. On review of the literature, headache and confusion at 1-2 months post-transplant are common presenting signs of central nervous system toxoplasmosis. The predominance of neutrophils in the spinal fluid in this patient probably reflects the meningeal component of the infection and is an unusual finding. The presentation of toxoplasmosis in marrow transplant recipients is quite pleomorphic, and a definite diagnosis is difficult to obtain antemortem. Empiric therapy with pyrimethamine and sulfadiazine should be considered for marrow transplant recipients with neurologic deficits for which there is no other apparent etiology.

Because of renewed interest in parasitic diseases, increasing numbers of persons in clinical and research laboratories have the potential for exposure to parasites and therefore are at risk for acquiring parasitic infections. In this review of laboratory-acquired parasitic infections, we concentrate on protozoan diseases that frequently have been reported to be laboratory acquired: malaria, leishmaniasis, trypanosomiasis (American and African), and toxoplasmosis. These diseases can be severe, even fatal, and may be difficult to diagnose. Many laboratorians who have acquired these diseases did not recall having had an accident. Of those with recognized accidents, needlestick injuries were the most common. Laboratories should have established protocols for handling specimens that may contain viable organisms and for responding to laboratory accidents.

Among all organ transplantations, those of heart or heart-lung carry the greatest risk of toxoplasmosis. The disease is observed mainly when the donor is seropositive and the recipient seronegative. In these mismatched couples the risk may be as high as 57 percent. Cardiac tissue transplants are responsible for most contaminations. A subclinical serological reactivation can be observed in seropositive recipients. Patent forms are associated with seroconversion in seronegative subjects. Toxoplasmosis is often severe with multivisceral foci; interstitial pneumonia is possible. The serological diagnosis is easy in cases with significant antibody movements, but it may be difficult if the titre is low or stable. The parasitological diagnosis rests on the isolation of toxoplasma in blood, cerebrospinal fluid, bronchoalveolar lavage fluid and cardiac or cerebral biopsy. Immune defence against toxoplasmosis is primarily cellular, with lymphocytosis and inversion of the CD4/CD8 ratio. Macrophages play a crucial role. Interferon-gamma is the major mediator of cellular resistance. In spite of its immunosuppressive action, cyclosporin clearly has an antiparasitic action in vitro and in vivo. A cytomegalovirus infection might facilitate toxoplasma reactivation. Prevention of toxoplasmosis in transplant recipients includes systematic serology of the recipient and, if possible, the donor, detection of mismatched couples and systematic treatment with pyrimethamine of recipients at risk (in seronegative recipients, this drug has reduced the risk from 57 to 14 percent). Cyclosporin should be used as immunosuppressant in preference to other drugs of this kind. Corticosteroids administered in rejections increase the risk of toxoplasmosis.

Toxoplasmosis may cause serious problems after organ transplantation. For treatment of active infection, pyrimethamine combined with a sulfonamide is recommended. During oral sulfadiazine therapy, a significant decrease in cyclosporine concentrations was observed in three heart transplant recipients. This interaction has not been reported previously.

We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty-four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases.

Toxoplasmosis is one of the major opportunistic infections observed in France in 15 to 37 percent of HIV-infected patients. Its main manifestation is encephalitis. Other, less frequent manifestations are chorioretinitis, pneumonia or disseminated toxoplasmosis. The conventional treatment is a combination of pyrimethamine 50-75 mg/day and sulfadiazine 6-8 g/day. Acute therapy should be pursued for at least 3 weeks or until optimal response is achieved, i.e. 6 to 8 weeks in most cases. The pyrimethamine-clindamycin combination in doses of at least 2.4 g/day is a possible alternative. Other drugs are being studied, but there is still a need for new drugs active against the parasite, that could be used in humans. In HIV-infected patients treatment should be maintained lifelong to prevent relapses. Maintenance regimens use the same drugs as acute therapy but in lower doses. The main field of research is primary prophylaxis of toxoplasmosis in HIV-infected patients.

In this study we evaluated the release of some mediators of inflammatory reactions such as histamine (H), leukotriene B4 (LTB4), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in the cerebrospinal fluid (CSF) of 15 patients with acquired immunodeficiency syndrome (AIDS), eight with opportunistic infections of the central nervous system (CNS) and seven without HIV-related neurological pathology, and of 25 HIV-negative control subjects with other neurological diseases. The cerebrospinal LTB4 level was increased in all the AIDS patients (mean 348 pg/ml); the control group revealed normal levels of LTB4 in the CSF (mean 63.2 pg/ml). The PGD2 level in the HIV-positive (mean 264 pg/ml) patients was higher than of the control subjects (mean 50 pg/ml), while low LTC4 levels were found both in the HIV-positive and control groups. We did not find any significant concentration of H in the CSF of either the HIV-positive or the control subjects. These findings may be due to the presence of chronic HIV infection or to the opportunistic infections of the CNS that so often occur in the latest stages of the disease.

In patients with acquired immunodeficiency syndrome (AIDS), toxoplasmosis almost exclusively involves the central nervous system (CNS), and extra-CNS organ infection is rare. We report a case of Toxoplasma gondii colitis in a patient with AIDS characterized by the following: 1) onset of diarrhea was simultaneous with disseminated toxoplasmosis; 2) T. gondii was found in colonic biopsies, whereas other infectious causes of diarrhea had been ruled out; 3) diarrhea was cured by anti-Toxoplasma therapy.

Toxoplasmosis is usually asymptomatic in pregnant women but poses a risk of severe effects on the fetus. One to eight of every 1,000 pregnant women become infected, and the infection is transmitted to the fetus in approximately 40 percent of these cases. The risk of transmission rises with increasing gestational age at the time of initial infection. Congenital infection with toxoplasmosis may lead to serious sequelae, such as blindness, mental retardation, neurologic deficits and deafness. Prevention of morbidity from toxoplasmosis depends on prevention of the infection in pregnant women, plus early recognition and aggressive treatment of maternal infections.

Toxoplasma gondii has long been recognized as a potential cause of severe disease in the congenitally infected infant and the immunocompromised host. This report describes three children with toxoplasmosis after heart transplantation and reviews the cases of 18 adult recipients of cardiac transplants (reported in the English-language literature) who developed toxoplasmosis postoperatively. Onset of disease was within the first 6 1/2 months following transplantation. Severity ranged from asymptomatic seroconversion to myocardial infiltration or disseminated neurological disease and death. Only one patient was known to be seropositive for antibody to T. gondii prior to transplantation. Transmission was most likely via the donor organ. Seronegative patients who receive organs from seropositive donors are at high risk for serious disease; prophylactic strategies need to be developed.

Encephalitis occupies a large part in the neurological complications of HIV infection. It is frequent and in most cases of poor prognosis. Some cases of encephalitis are directly related to HIV while others are caused by an opportunistic infection. Among the former is the acute encephalitis coincident with seroconversion, which is exceptional and spontaneously regressive, and the subacute encephalitis better known as HIV encephalopathy which has a constantly pernicious course ending in subcortical dementia lethal within a few months. Some cases of opportunistic encephalitis are associated with a virus: a Papovavirus is responsible for progressive multifocal leucoencephalopathy where mental deterioration is combined with focal symptoms, both resulting in death in less than 6 months. Cytomegalovirus is responsible for an encephalitis that is frequently found on pathological examination but is usually subclinical. Anecdotic cases of toxoplasmic encephalitis have been reported. Finally, emphasis should be placed on the frequency of encephalitis-associated pathologies with all possible combinations, the most common being HIV encephalitis with another encephalitis and/or focal ou multifocal infectious or tumoral processes.

The morbidity of cytomegalovirus (CMV) infection and toxoplasmosis was evaluated in 75 heart transplant recipients. Among the 73 patients who survived more than one week after transplantation, 16 (22%) acquired primary CMV infection and 30 (41%) had evidence of secondary infection. All CMV seronegative recipients receiving hearts from seropositive donors developed CMV infection. The majority of infections (42/46) occurred during the first 4 months after transplantation. Overall, the incidence of symptomatic CMV disease was 44%. The infections were generally mild and only 1 death was attributed to primary CMV disease complicated by bacterial septicaemia and multiple organ failure. The severity of CMV disease was greatest among those with primary infection. There were 3 cases of toxoplasmosis. Two patients were toxoplasma seronegative before transplantation and developed clinical and serological signs of infection 2-3 months after transplantation despite receiving organs from seronegative donors. Of toxoplasma seronegative recipients receiving allografts from seropositive donors 3/4 were prophylactically treated with pyrimethamine for 6 weeks. None developed clinical or serological signs of toxoplasmosis while one patient who received trimethoprim-sulfamethoxazole had a subclinical infection.

1. Toxoplasma gondii is a ubiquitous, obligate intracellular parasite of worldwide distribution. In humans, the parasite exists in two forms: the tachyzoite is the rapidly multiplying stage of the parasite which actively invades host cells and represents the principal pathogenic form at the acute phase of the disease; the bradyzoite is the form which multiplies slowly in host cells, resulting in the formation of cysts which persist in tissues. Several antigenic components have been identified, some of which are characteristic for each parasitic stage; particularly, in tachyzoites, the 30 kDa membrane protein represents up to 5% of the total protein content. 2. Toxoplasma infection in humans is usually asymptomatic because of effective immunity involving antibodies, T cells and cytokines. Activated macrophages, CD4 and CD8 lymphocytes and cytokines, such IFN gamma, play a major role in the control of acute infection and the maintenance of infection at the chronic stage. The alteration of immune functions, as observed in congenitally infected children and in HIV-infected patients, may induce the recrudescence of previously latent toxoplasmosis, in relation to disruption of the cyst form of the parasite. The resulting reactivation is responsible for life-threatening infections which are frequently manifested as toxoplasmic encephalitis. 3. In this review, the parasite and immunological factors participating in the pathogenesis of the lesions associated with acute, chronic and reactivated toxoplasmosis are presented.

Human serological profiles, and feline serological and fecal profiles were used to study the epidemiology of toxoplasmosis in Santa Clara County, California. The prevalence of human toxoplasmosis was determined to be 42.9% in a test population of 147 women. The prevalence of feline toxoplasmosis was indicated to be 34.8% based on serological analysis of 158 felines. Of 107 cats tested, 6.5% were shedding Toxoplasma gondii - like oocysts in their feces. Statistical analyses of questionnaire data indicated that the major infection sources for seropositive humans in this study were: (1) eating rare-medium cooked beef; (2) exposure to cats; and (3) working in an outside garden. Of these three sources, gardening represented the least risk. The data from questionnaires with reference to age, residence, and eating and toilet habits of owned felines were evaluated and found to show no significant statistical correlation with seropositivity. The infection sources for seropositive felines could not be determined. The plausible significance of feline-human interaction, human consumption of infected meat, and gardening habits is stressed.

Over the past 20 years allogeneic bone marrow transplantation has been increasingly utilized in the treatment of acute and chronic leukemias, aplastic anemia, severe forms of thalassemia, immunodeficiency syndromes and metabolic disorders due to a lack of specific enzymes in the monocyte-macrophage system. Despite the overall success of this approach and besides the so-called classic complications arising from the toxicity of the conditioning regimen, occurrence of GVH disease and interstitial pneumonitis, there are other less common complications which have been reported mainly by teams transplanting on a large number of patients. With only a limited experience, concerning 60 patients with transplants between May 1987 and May 1991, we have seen some unusual complications such as toxoplasma encephalitis, myasthenia gravis and aseptic bone necrosis, which may give rise to difficult diagnostic and therapeutic decisions.

Toxoplasmosis is usually diagnosed in the clinical laboratory by detecting antibodies to Toxoplasma gondii, and only rarely by isolating the parasites. A number of serologic tests are used; each has its own advantages and disadvantages. The methods of diagnosis and their interpretations differ for each clinical category of infection.

A 41-year-old woman with acute myelomonocytic leukemia in remission died of a rapidly progressive necrotizing pneumonia while in the recovery phase following consolidation chemotherapy. Autopsy revealed disseminated toxoplasmosis. Although this syndrome has been well described to present as a neurologic complication in certain immunocompromised patients, it is rare in acute leukemia, and non-neurologic presentations are even more unusual. This case emphasizes the need to be suspicious of toxoplasmosis in immunocompromised patients even in the absence of neurologic signs or symptoms.

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.

In three cases of acute disseminated toxoplasmosis developing soon after renal (two patients) or hepatorenal (one patient) transplantation, Toxoplasma gondii trophozoites were visualized on Giemsa-stained smears of bronchoalveolar lavage fluid. Trophozoites were also found in bone marrow smears in one instance. Seroconversion occurred late in two cases and was not detected before the patient's death in the third. These observations underline the potential of bronchoalveolar lavage as a diagnostic procedure for disseminated toxoplasmosis.

Neurological complications may occur even before immunosuppression is clinically observed, and can thus reveal HIV infection. Aseptic meningitis, subacute encephalitis, vacuolar myelopathy, inflammatory myopathy, and different types of polyneuropathies seem to be associated with HIV, but their pathogenesis has only recently begun to be understood. These complications must be distinguished from opportunistic infections and from intra-cerebral tumors with which they often coexist. The Sixth International Conference on AIDS in San Francisco has defined the extent and limits of our present knowledge, and has given new directions for research in this last, but not least important chapter of modern neurology.

A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis.

The risk of toxoplasmic encephalitis complicating AIDS appears largely limited to those HIV-infected patients with serologic evidence of past Toxoplasma gondii infection and low CD4 lymphocyte counts. The Community Programs for Clinical Research on AIDS has initiated a randomized, placebo-controlled trial to determine if clindamycin or pyrimethamine prophylactic regimens are effective and safe in preventing toxoplasmic encephalitis.

To assess potential interactions of multiple drug regimens administered to patients with AIDS for toxicity and efficacy, we reviewed the charts of 35 patients on maintenance therapy for toxoplasmosis. Seven relapses of toxoplasmosis occurred in 6 of 35 (17%) patients, and seven episodes of pneumocystosis occurred in 6 of 35 (17%) patients. Four relapses of toxoplasmosis and 5 relapses of pneumocystosis were seen in 20 patients treated with pyrimethamine/clindamycin; 2 relapses of toxoplasmosis and 2 relapses of pneumocystosis were seen in 11 patients treated with pyrimethamine alone, and 1 relapse of toxoplasmosis was seen in 13 patients treated with pyrimethamine/sulfadiazine. Adverse effects were related to pyrimethamine in 10 patients, to clindamycin in 7 patients, and to sulfadiazine in 8 patients. These results must be compared with those of prospective trials to determine the efficacy and safety of various maintenance regimens.

Through the European Network in the Treatment of AIDS, a multicenter trial is being conducted to compare the efficacy and safety of pyrimethamine (50 mg/day) plus clindamycin (2.4 g/day) with the regimen of pyrimethamine (50 mg/day) and sulfadiazine (4.0 g/day) for induction and maintenance treatment of toxoplasmic encephalitis. By 1 September 1990, 281 patients had been randomized to enter the study. Preliminary data show that 77% of the 148 patients evaluated showed a complete response or improvement with minor sequelae during therapy. Twenty percent of the patients deteriorated. This was due to toxoplasmosis in only 10% of the patients. Side-effects were common in all patients regardless of treatment regimen and consisted mainly of rash (52 cases), fever (31 cases), diarrhea (17 cases) and nausea (12 cases). The final analysis should be available by the middle of 1991.

Maccario et al. described, in 1987, the case of an HIV-positive patient whose psychotic symptomatology was the expression of right centrum semi-ovale lesion. We report the case of a patient who suffered a sudden delirium, expression of a probable right lenticular cerebral toxoplasmosis. This 35-year-old male homosexual, who had no psychiatric history, suddenly developed in November 1988 the following psychiatric signs: he started to walk back and forth incessantly, he had the impression that he was the subject of the conversations of the passers-by, that all the posters and notices refer to him, and that he was God. He was admitted in a psychiatric department where the symptoms were progressively curbed by neuroleptics (cyamemazine 75 mg, and haloperidol 15 mg). The episode was not questioned by the patient, but attributed to bad eating habits. HIV-positivity had been discovered a year later (during systematic screening). A computerized tomographic (CT) scan performed subsequently to this delirium was interpreted as normal. Four weeks later the patient was referred to us. The psychiatric condition was stabilized in spite of a certain aggressiveness and the probable persistence of an underlying delirium state. Laboratory examinations showed the following: blood count revealed leukopenia (2.2 G/l) and thrombocytopenia (135 G/l; OKT4/OKT8 ratio was 0.08; CSF: normal; sputum culture evidenced the presence of pneumocystis carinii; EEG were normal. Neuropsychological symptoms concerned in particular a lack of concentration during the different tests with a definitive wavering of attention. Lexical retrieval was poor whatever the topic proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

There are several protozoan infections that cause relatively benign illness in normal individuals but result in severe disease manifestations in patients with AIDS. These diseases include Pneumocystis carinii pneumonia, CNS toxoplasmosis, cryptosporidiosis, and isosporiasis. Pneumocystis carinii pneumonia (PCP) caused by Pneumocystis carinii, is the most common opportunistic infection in AIDS. It is seen in more than 80% of individuals with this syndrome. Although historically classified as a protozoan, this organism shares many biochemical characteristics with fungi. The onset of PCP may be insidious, and cough and dyspnea are the most common presenting symptoms. Auscultation of the lungs is often unremarkable, but diffuse infiltrates are commonly seen on chest radiographs. The diagnosis of PCP can be confirmed by identifying the organism on specimens obtained by sputum induction or bronchoalveolar lavage. Trimethaprim-sulfamethoxazole is the treatment of choice but is unfortunately associated with leukopenia and rash in many individuals. Both trimethaprim-sulfamethoxazole and aerosolized pentamidine are used prophylactically in patients at high risk for initial or relapsing infection. The appropriate use of these agents has resulted in improved survival for AIDS patients with PCP. Toxoplasmosis, due to Toxoplasma gondii, affects the central nervous system in patients with AIDS. Headache is a common presenting symptom, and both seizures and paresis can occur. A diagnosis of toxoplasmosis is strongly suspected in symptomatic individuals with ringed mass lesions noted on head CT. Patients with this condition are treated with a combination of sulfadiazine, pyrimethamine, and folinic acid. Cryptosporidiosis and isosporiasis are coccidian protozoan diseases that can result in severe, acute, and chronic diarrhea in immunocompromised individuals. Cryptosporidiosis is the more common of the two and is caused by an unknown species of the genus crytosporidium. Isosporiasis is due to infection with Isospora belli. Dehydration and weight loss are a common result of infection with either agent. A definitive diagnosis can be made by examining an acid fast stain of a diarrheal stool specimen and demonstrating oocysts that are specific for each of these organisms. Fluid replacement and general supportive care are essential in the treatment of both of these diseases. Spiramycin is an unproven treatment modality that is often used in patients with cryptosporidiosis. Isosporiasis responds to initial therapy with trimethaprim-sulfamethoxazole, followed by prophylaxis with pyrimethamine. The adoption of safe sexual practices that minimize fecal-oral contamination should decrease the future prevalence of these diseases and other enteric parasitic infections.

Fourteen patients with AIDS and toxoplasmic encephalitis, who could not be treated with the standard regimen of pyrimethamine and a sulfonamide due to a previous history of bone marrow suppression and severe allergic reactions to sulfonamides, were treated with oral clindamycin and pyrimethamine. All 14 patients received a 100 mg loading dose of pyrimethamine orally followed by 50 mg/day plus clindamycin orally (600-900 mg q8h). The duration of primary treatment ranged from 6 to 8 weeks. All patients also received folinic acid (15 mg/day orally). Maintenance therapy consisted of 25 mg/day of pyrimethamine and clindamycin (300 mg q6h or 450 mg q8h). A complete or partial clinical or neuroradiological response was observed in all patients at the end of two months of primary therapy. Ten of 14 patients showed complete resolution of clinical signs, and 8 of 14 patients showed complete resolution of neuroradiologic signs. All 14 patients continued the maintenance regimen, and although there were no relapses, symptoms that had not resolved by the end of the second month of acute therapy tended to remain unchanged.

The interim results are presented of an ongoing large-scale, prospective, randomized study to determine the potential role of clindamycin in the treatment of toxoplasmic encephalitis. Patients were seropositive for Toxoplasma gondii antibodies and had clinical signs compatible with toxoplasmic encephalitis. Data was available on 33 patients, 15 of whom received pyrimethamine p.o./clindamycin i.v. and then p.o., and 18 of whom received pyrimethamine p.o./sulfadiazine p.o. The interim evaluation did not reveal a remarkable difference between the two regimens in the clinical or radiologic response. Adverse reactions to both regimens were common and frequently multiple, there being more adverse gastrointestinal reactions in patients on pyrimethamine/clindamycin and more adverse hematological reactions in those on pyrimethamine/sulfadiazine.

Compound 566C80, 2-[trans-4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone, was studied for its in vitro and in vivo activities against Toxoplasma gondii. Replication within human foreskin fibroblasts of tachyzoites of seven different strains, five of them isolated from AIDS patients, was inhibited by concentrations as low as 4.8 x 10(-9) M. In vivo, a dose of 100 mg/kg of body weight per day, administered by gavage for 10 days, protected 100% of mice against death due to infection with five different strains of T. gondii, including the highly virulent RH strain. A dose of 50 mg/kg/day protected at least 80% of mice infected with the same inoculum, and a dose as low as 9.3 mg/kg/day protected 40 to 60% of mice. Treatment with 50 mg/kg/day for 30 days completely eradicated parasites from mice infected with four of five strains of T. gondii. 566C80 was active in vitro against the cyst stage of T. gondii at concentrations of 50 to 100 micrograms/ml. In vivo activity against this form of T. gondii was examined in mice infected for 6 weeks with strain ME49 and then treated orally with 100 mg of 566C80 per kg per day for 8 weeks. Treated mice sacrificed at 2-week intervals revealed a steady decline in the numbers of cysts in their brains compared with untreated controls. In addition, mortality as well as clinical signs of brain infection was absent from treated mice, whereas control mice had a high mortality rate and showed clinical signs of central nervous system infection. These results reveal remarkable in vitro and in vivo activities of 566C80 against T. gondii.

Cerebral blood flow (CBF) was evaluated by gamma camera 99mTc-HMPAO SPECT in 11 patients with AIDS-related neurotoxoplasmosis and correlated with neurological findings and the results of CT and MRI. Evident CBF abnormalities were observed in all patients with involvement of at least two cerebral lobes. In 10 patients the abnormalities were bilateral and in 8 patients basal ganglia were involved; no specific hypoperfusion pattern was however evident. Focal lesions were found in 7 patients by CT (sensitivity: 63.6%) and in 10 patients by MRI (sensitivity: 90.9%). It may be concluded that neurotoxoplasmosis in AIDS patients is associated with a high prevalence of focal cortical and subcortical hypoperfusion but that the scintigraphic findings are not specific; that HMPAO SPECT may show focal hypoperfusion in patients with normal CT studies and/or non-focal MRI abnormalities; that the hypoperfusion may be more extensive than the corresponding MRI lesion(s) and that it may be present even in areas with normal MRI signals; and that more experience and longitudinal studies are needed to assess the possible impact of HMPAO SPECT on follow-up and therapy monitoring.