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PubMed1988

Epidemiology of toxoplasmosis among pregnant women in the Paris area.

A survey was performed using a sample of pregnant women selected at one of the biggest test centres in the Paris area. These women were serologically screened for toxoplasmosis between October 1981 and September 1983 (according to the prevention protocol for congenital toxoplasmosis established by the French health ministry). The prevalence rate of specific antibodies for toxoplasmosis was estimated from the 1074 women who were tested for the first time during the study. The prevalence rate among pregnant women in the Paris area was derived by direct standardization according to age and geographical origin. A standardized prevalence rate of 71% +/- 4% among French women, of 51.4% +/- 5% among immigrant women and a global adjusted prevalence rate of 67.3% +/- 3% for pregnant women in the Paris area was found. An incidence rate of 1.6% was estimated for the 2216 non-immune pregnant women included in the sample. There is no significant difference between the probabilities of seroconversion among French and immigrant women (2.3% +/- 1% and 1.6% +/- 0.8% respectively). Comparison of the data with previous study results show a decrease in the prevalence rate of specific antibodies for toxoplasmosis in the Paris area over the last 20 years that cannot be explained by changes in age and geographical origin. No data were available to support an aetiological hypothesis for a decrease in toxoplasma transmission to humans. Since immigration and a decrease in toxoplasma transmission to humans has led to a larger population of women at risk of infection during pregnancy in France, it is therefore important to perform studies to investigate risk factors and markers of acquired toxoplasmosis during pregnancy in order to improve the prevention of congenital toxoplasmosis.

Adolescent↗

PubMed1999

Immunoglobulin G avidity in diagnosis of toxoplasmic lymphadenopathy and ocular toxoplasmosis.

Traditional serological techniques have some limitations in evaluating the duration of Toxoplasma gondii infection in pregnant women, patients with lymphadenopathy, and older children suspected of having congenital toxoplasmosis. In these three groups of patients, two variants of T. gondii immunoglobulin G (IgG) avidity tests were used: an EIA Kit (Labsystems) and a noncommercial enzyme-linked immunosorbent assay specially elaborated in the laboratory. The avidity of specific IgG in sera from 23 patients with a known recently acquired infection (mainly pregnant women) was low (less than 30%), whereas that in sera from 19 patients with toxoplasmic lymphadenopathy of 3 weeks to 6 months in duration (mean, 8.3 weeks) covered a large range (between 0.2 and 57.8%; mean, 25. 7%); high avidity results were observed for 10 of 19 patients (52. 6%). The large range of IgG avidity in patients with toxoplasmic lymphadenopathy suggests various durations of infection in these patients, with a tendency for a chronic phase of toxoplasmosis. According to the avidity marker, five patients with lymphadenopathy for less than 3 months did not have a recent Toxoplasma infection. In 6 of 19 patients with lymphadenopathy (31.6%), low IgG avidity values persisted until 5 months after the first serological examination. In all four patients with a documented chronic course of Toxoplasma infection (6 months to 8 years after the first positive serology), high IgG avidity values were observed. Among sera from 10 children and young immunocompetent adults suspected of having ocular reactivation of congenital toxoplasmosis, all had high IgG avidity values (over 40%), suggesting congenitally acquired ocular infection rather than noncongenital infection. In conclusion, the avidity of IgG is a valuable marker of recent toxoplasmosis in pregnant women, suggests the duration of invasion in patients with lymphadenopathy, and may be helpful for differentiation between reactivation of congenital infection and recently acquired ocular toxoplasmosis in immunocompetent patients. A low IgG avidity does not always identify a recent case of toxoplasmosis, but a high IgG avidity can exclude primary infections of less than 5 months' duration.

Adult↗

PubMed1994

Value of PCR for evaluating occurrence of parasitemia in immunocompromised patients with cerebral and extracerebral toxoplasmosis.

PCR was used to evaluate the occurrence of Toxoplasma gondii parasitemia by detection of the B1 gene in blood samples in two groups of immunosuppressed patients (148 subjects) suspected of having cerebral or extracerebral infection, respectively. Group I consisted of 52 patients with AIDS with suspected cerebral toxoplasmosis. The diagnosis was clinically proven in 15 cases. Parasitemia was detected by PCR in only two of these patients (13.3%), both showing evidence of disseminated infection. Group II consisted of 96 immunocompromised patients, either with AIDS or receiving iatrogenic immunosuppressive therapy. Of these patients, 65 (34 with AIDS and 31 others) showed abnormalities only in chest radiography and were first screened for the presence of Toxoplasma DNA in bronchoalveolar lavage fluid. Blood was then analyzed when the parasite was detected in the bronchoalveolar lavage fluid. The remaining 31 subjects (22 with AIDS and 9 others) were suspected of having extracerebral, pulmonary, or disseminated toxoplasmosis, and blood was studied directly in these cases. Among the nine patients with clinically diagnosed extracerebral infection in group II, the parasite was detected by PCR in the blood of five patients (55.5%), all having pulmonary toxoplasmosis. If all patients with clinical manifestations of extracerebral toxoplasmosis (from both groups) who had not received antitoxoplasma therapy when the samples were collected are considered, PCR detected parasitemia in seven of the nine cases (77.8%). The present study indicates that examination of blood by PCR may be valuable in cases of extracerebral toxoplasmosis because of the disseminated nature of the disease. Since most cases of cerebral toxoplasmosis result from the local reactivation of latent brain cysts, detection of parasitemia by PCR is useful only in cases associated with severe cerebral infection or dissemination of this disease.

Acquired Immunodeficiency Syndrome↗

PubMed1995

HLA typing in congenital toxoplasmosis.

HLA-A, HLA-B, HLA-C, and HLA-D typing was performed in 47 mothers of patients suffering from ocular toxoplasmosis to investigate whether an immunogenetic predisposition exists for developing congenital toxoplasmosis in their offspring. No significant association between any HLA antigen was observed in the mothers of patients with ocular toxoplasmosis, although a total absence of the HLA-B51 antigen was found in this group. HLA-A, HLA-B, and HLA-C typing was also performed in their children (52 patients with ocular toxoplasmosis), to investigate a possible relation between the severity of ocular toxoplasmosis and an eventual immunogenetic factor. In the patients with ocular toxoplasmosis an increased frequency of the HLA-Bw62 antigen was observed in correlation with severe ocular involvement.

Disease Susceptibility↗

PubMed1994

Management of toxoplasmosis.

Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent of toxoplasmosis, a widespread infection affecting various birds and mammals including humans. In immunocompetent hosts, the infection is usually asymptomatic and benign. Toxoplasmosis is either congenital or acquired. In general, prenatal therapy of congenital toxoplasmosis is beneficial in reducing the frequency of infant infection. Therapies are based primarily on spiramycin because of the relative lack of toxicity and high concentrations achieved in the placenta. Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is directed at preventing the occurrence of retinochoroiditis as a late sequel to congenital infection. The standard treatment for acquired toxoplasmosis in both immunocompetent and immunodeficient patients is the synergistic combination of pyrimethamine and sulphonamides. Toxoplasmic encephalitis is the most common manifestation of acquired toxoplasmosis in immunocompromised patients and if not treated is fatal. However, because of toxicity, the therapeutic efficacy of pyrimethamine-sulphonamide combinations may be seriously limited in immunodeficient patients. A number of novel and less toxic agents are being currently studied in clinical settings, including macrolide antibiotics (clindamycin, clarithromycin and azithromycin) and atovaquone, as well as some older anti-infective drugs such as cotrimoxazole (trimethoprim/sulfamethoxazole). Maintenance or prophylactic therapy is essential in many patients with acquired immunodeficiency syndrome (AIDS) where toxoplasmosis is most often the result of a pre-existent latent infection.

Anti-Infective Agents↗

PubMed1992

Congenital toxoplasmosis: is screening desirable?

Toxoplasmosis, a disease caused by the parasite Toxoplasma gondii, is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity and even death. Moreover, there is increasing awareness that congenital toxoplasmosis can cause blindness, epilepsy and other abnormalities in children and adults. Congenital toxoplasmosis can only be prevented by giving information on how to avoid the infection during pregnancy or by routine serologic screening of pregnant women to identify a recent toxoplasma infection that would allow a timely decision for antibiotic treatment and prenatal diagnosis. Advice to pregnant women to apply hygienic measures during pregnancy can reduce with 63% the toxoplasma infection rate during pregnancy and should therefore become standard obstetrical care. Adequate serological screening for toxoplasmosis is possible and allows selection of patients at high risk for delivering a congenitally infected child. Prenatal diagnosis is accurate in diagnosing correctly infected fetuses around the 20th week of gestation. Whether or not serologic screening for toxoplasmosis should be combined with primary prevention will depend on the incidence of congenital toxoplasmosis in a given geographic area.

Female↗

PubMed1992

Neonatal screening for congenital toxoplasmosis in Denmark: presentation of the design of a prospective study.

The design of a two year prospective study of 45,000 mothers and their newborn children aiming at determining the incidence of congenital toxoplasmosis in Denmark is presented. Toxoplasma IgG antibodies in a bloodspot from the newborn, routinely collected on filterpaper (the Guthrie card), and IgG antibodies in a stored serum sample from the mother collected in the first trimester are compared. Seroconversion identify mothers infected with T. gondii during pregnancy and identify newborn children at risk of congenital toxoplasmosis. All children at risk will be treated and followed until congenital toxoplasmosis is verified or excluded. Children with verified congenital toxoplasmosis will be followed clinically and the effectiveness of the treatment will be evaluated. The study design allows determination of the materno-fetal transmission rate in untreated pregnancies, and will furthermore allow a good estimate of the incidence of congenital toxoplasmosis in Denmark. In addition we hope that the diagnosis and treatment of cases of subclinical toxoplasmosis will prevent chorioretinitis and minor cerebral disorders later in life. Of 6355 pregnancies tested during the first 3 month of the study, 14 cases of maternal seroconversions have been diagnosed. Only one child had detectable toxoplasma specific IgM antibodies at birth.

Antibodies, Protozoan↗

PubMed2000

Preventing congenital toxoplasmosis.

SCOPE OF THE PROBLEM: Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Acute infections in pregnant women can be transmitted to the fetus and cause severe illness (e.g., mental retardation, blindness, and epilepsy). An estimated 400-4,000 cases of congenital toxoplasmosis occur each year in the United States. Of the 750 deaths attributed to toxoplasmosis each year, 375 (50%) are believed to be caused by eating contaminated meat, making toxoplasmosis the third leading cause of foodborne deaths in this country. ETIOLOGIC FACTORS: Toxoplasma can be transmitted to humans by three principal routes: a) ingestion of raw or inadequately cooked infected meat; b) ingestion of oocysts, an environmentally resistant form of the organism that cats pass in their feces, with exposure of humans occurring through exposure to cat litter or soil (e.g., from gardening or unwashed fruits or vegetables); and c) a newly infected pregnant woman passing the infection to her unborn fetus. RECOMMENDATIONSFOR PREVENTION: Toxoplasma infection can be prevented in large part by a) cooking meat to a safe temperature (i.e., one sufficient to kill Toxoplasma); b) peeling or thoroughly washing fruits and vegetables before eating; c) cleaning cooking surfaces and utensils afterthey have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables; d) pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly; and e) not feeding raw or undercooked meat to cats and keeping cats inside to prevent acquisition of Toxoplasma by eating infected prey. RESEARCH AGENDA: Priorities for research were discussed at a national workshop sponsored by CDC in September 1998 and include a) improving estimates of the burden of toxoplasmosis, b) improving diagnostic tests to determine when a person becomes infected with Toxoplasma, and c) determining the applicability of national screening programs. CONCLUSION: Many cases of congenital toxoplasmosis can be prevented. Specific measures can be taken by women and their health-care providers to decrease the risk for infection during pregnancy and prevent severe illness in newborn infants.

Female↗

PubMed1988

Recognition of Toxoplasma gondii excreted and secreted antigens by human sera from acquired and congenital toxoplasmosis: identification of markers of acute and chronic infection.

While the serological response to somatic antigens of Toxoplasma gondii is currently analysed, little information is available on the antibody response to the antigens excreted and secreted by tachyzoïtes (ESA). This serological study is focused on the immune response towards these antigens which were released by the parasites in cell-free culture medium. Human sera corresponding to 'acute', 'subacute' and 'chronic' acquired infection and sera from infected newborns and from their mothers were analysed by radio-immunoprecipitation with 35S methionine-labelled ESA and with radio-iodinated membrane antigens followed by polyacrylamide gel electrophoresis. In chronic toxoplasmosis, IgG antibodies recognized among ESA major 108, 97, 86, 60, 57, 42, 39 and 28.5 kD antigens; the 108-97 kD doublets and the 28.5 kD antigen seemed characteristic of the chronic phase of toxoplasmosis. In acute infection, IgM antibodies to the 97 kD antigen, the first to appear, seem to contitute good markers of early acute infection. The comparative study of antibody response to membrane antigens showed that, in chronic toxoplasmosis, human sera recognized four antigens of 43, 35, 30 and 22 kD and that, in acute toxoplasmosis, they first recognized the 43 and 30 kD antigens. The serological evolution in congenital toxoplasmosis was the same as in acquired infection. In some cases, the serological profile of the newborn was different from that of his mother, with an additional antibody response to a 170 kD antigen. This study demonstrates in human toxoplasmosis an early, intense and characteristic antibody response against ESA, suggesting that the use of these antigens could lead in the future to improved diagnostic tests.

Acute Disease↗

PubMed1995

[Congenital toxoplasmosis: transmission to the fetus of a pre-pregnancy maternal infection].

It has been established that maternal immunity developing before conception protects the fetus from congenital toxoplasmosis. We observed a case of congenital toxoplasmosis consecutive to a maternal toxoplasma infection that had preceded pregnancy. A woman with normal immune system developed toxoplasmosis 2 months before conceiving. No treatment was given to this prepregnancy seroconverted patient. At 25 weeks of amenorrhoea, the ultrasound examination showed a fetal cerebral ventricular dilatation. Amniocentesis and cordocentesis showed fetal toxoplasmosis infection. Fetopathologic examination confirmed the diagnosis of cerebral toxoplasmosis. The pathophysiology of maternal-fetal toxoplasma transmission and the role played by maternal immunodeficiency are discussed. This exceptional case-report showed the difficulties of the management in patients with 3-month pre-pregnancy toxoplasmosis and its practical implications.

Abortion, Therapeutic↗

PubMed1997

Does human toxoplasmosis involve an imbalance in T1/T2 cytokines?

The T1 (interferon-gamma, interleukin-12, interleukin-2) and T2 (interleukin-4, interleukin-10, interleukin-6) cytokine groups constitute two polar responses of the immune system. The T1 group is a predominantly cellular response, while the T2 group response is mainly humoral. The hypothesis forwarded here links these subgroups of induced cytokines to the various clinical forms of human toxoplasmosis. Ocular toxoplasmosis in immunocompetent patients could be attributed to a T1 hyper-response, whereas congenital toxoplasmosis, toxoplasmic encephalitis (in immunodeficient patients) and active chronic toxoplasmosis (with persistent lymphadenophathy) would be characterized by a predominantly T2 response. Confirmation that this kind of immunological imbalance effectively underlies the various clinical forms of toxoplasmosis would open the way for a new range of treatments based on immunomodulation.

Animals↗

PubMed2006

Analysis of the utility of diffusion-weighted MRI and apparent diffusion coefficient values in distinguishing central nervous system toxoplasmosis from lymphoma.

INTRODUCTION: Toxoplasmosis and lymphoma are common lesions of the central nervous system in patients with AIDS. It is often difficult to distinguish between these lesions both clinically and radiographically. Previous research has demonstrated restricted diffusion within cerebral lymphomas and bacterial abscesses. However, little work has been done to evaluate the diffusion characteristics of toxoplasmosis lesions. This study was designed to explore further the utility of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps and values in making the distinction between toxoplasmosis and lymphoma. METHODS: The magnetic resonance imaging (MRI) studies of 36 patients, including 22 with toxoplasmosis (all of whom had AIDS) and 14 with lymphoma (8 of whom had AIDS), at two institutions were reviewed retrospectively. The characteristics of the lesions on DWI were evaluated, and the ADC ratios of the lesions were calculated and compared. RESULTS: There was significant overlap of the ADC ratios of toxoplasma and lymphoma, most notably in the intermediate (1.0-1.6) range. There was variability in ADC ratios even among different lesions in the same patient. In only a minority of the lymphoma patients were the ADC ratios low enough to suggest the correct diagnosis. CONCLUSION: Our study showed that toxoplasmosis exhibits a wide spectrum of diffusion characteristics with ADC ratios which have significant overlap with those of lymphoma. Therefore, in the majority of patients, ADC ratios are not definitive in making the distinction between toxoplasmosis and lymphoma.

AIDS-Related Opportunistic Infections↗

PubMed1992

An unusually high prevalence of ocular toxoplasmosis in southern Brazil.

Because of the frequency of ocular toxoplasmosis and its occurrence in multiple siblings in southern Brazil, a population-based household survey was performed to better understand the epidemiologic characteristics of the disease in this region. Of 1,042 individuals examined, 184 (17.7%) were deemed to have ocular toxoplasmosis on the basis of conservative assessment of ophthalmic findings. Of those with ocular toxoplasmosis, 183 (99.5%) had specific IgG antibodies, compared with only 140 of 181 age-matched control subjects (77.4%; P less than .001). The prevalence of ocular toxoplasmosis was 0.9% in 1- to 8-year-olds, 4.3% in 9- to 12-year-olds, 14.3% in 13- to 16-year-olds, and 21.3% (95% confidence interval, 18.6% to 24.2%) in all individuals 13 years or older. The prevalence of ocular toxoplasmosis in this population was more than 30 times higher than previous estimates for the same condition elsewhere. The low prevalence in the young children we studied supplements previous data suggesting that, in this population, ocular toxoplasmosis is a sequela of postnatal rather than congenital infection.

Adolescent↗

PubMed1999

Intraocular anti-Toxoplasma gondii IgA antibody production in patients with ocular toxoplasmosis.

PURPOSE: To investigate the immunoglobulin classes associated with the intraocular anti-Toxoplasma gondii antibody response during clinical ocular toxoplasmosis and to determine which immunoglobulin class is most helpful in the diagnosis of this disease. METHODS: Paired serum and intraocular fluid samples from 155 patients who had uveitis were tested for intraocular anti-T. gondii IgG, IgA, and IgM antibody production. The presence of T. gondii DNA was determined by polymerase chain reaction. Patients were divided into two groups, based on the initial clinical diagnosis; group 1 included 78 patients with presumed ocular toxoplasmosis, and group 2 included 77 patients with uveitis that was not clinically suspected to be ocular toxoplasmosis. Samples from 27 nonuveitis patients who underwent intraocular surgery were used as control subjects. The final diagnosis was based on the clinical course and interpretation of laboratory tests. RESULTS: A final diagnosis of ocular toxoplasmosis was made in 88 of 155 patients (group 1, 68; group 2, 20). Among these patients, 65% had intraocular IgG production, 52% had intraocular IgA production, 37.5% had both IgG and IgA production, 27% had IgG production only, and 15% had IgA production only. Of the 13 patients tested, only one had intraocular IgM production. Intraocular IgA could not be detected in patients who had final diagnoses other than ocular toxoplasmosis or in control subjects. A positive polymerase chain reaction combined with a test that was positive for intraocular IgG production had a sensitivity of 77%, which increased to 91% after the detection of intraocular IgA production was added. CONCLUSIONS: Immunoglobulin G is the major class involved in the humoral immune response against the T. gondii parasite, followed by IgA. The determination of IgA production is useful as an additional test in the diagnosis of ocular toxoplasmosis.

Adolescent↗

PubMed1999

Recurrent ocular disease in postnatally acquired toxoplasmosis.

PURPOSE: Although recurrences are typical of congenital toxoplasmosis, the long-term ocular manifestations in postnatally acquired toxoplasmosis have never been systematically studied. We report on the ocular manifestations complicating the chronic phase of postnatally acquired toxoplasmosis. METHODS: Review of the clinical data of 14 patients who presented with active ocular toxoplasmosis not associated with scars and who had serologic characteristics of recently acquired systemic toxoplasmosis. RESULTS: Mean follow-up was 4.6 years. Recurrent ocular disease developed in eight (57%) of 14 cases. The number of patients with recurrences increased with the follow-up time: four (29%) of 14 during the first year of follow-up; eight (57%) of 14 during the second year; and eight of nine during the third follow-up year. No risk factors for the development of recurrences were identified. Satellite lesions developed in five of eight patients with recurrences, whereas lesions not adjacent to old scars, located in areas of previously unaffected retina, developed in three patients. CONCLUSIONS: In postnatally acquired toxoplasmosis, frequent recurrences of ocular disease can be seen during the chronic phase of infection.

Adolescent↗

PubMed1997

Prenatal screening for toxoplasmosis.

OBJECTIVE: To evaluate the merits of screening for toxoplasmosis in all pregnant women. METHODS: We used decision analysis to compare three strategies for the antepartum management of congenital toxoplasmosis: 1) no testing for congenital toxoplasmosis; 2) current practice, which is to perform targeted screening in cases of incidental abnormalities noted on ultrasound; and 3) universal serologic screening of pregnant women followed by amniocentesis to diagnose fetal infection in cases of maternal seroconversion. For each of the three strategies, we considered the two available treatment options: intrauterine antiparasitic treatment or pregnancy termination. RESULTS: Universal screening reduced the total number of cases of congenital toxoplasmosis compared with no testing or targeted screening. However, compared with no testing, universal screening with medical treatment resulted in 18.5 additional pregnancy losses for each case of toxoplasmosis avoided. If infected pregnancies underwent termination, universal screening resulted in 12.1 additional pregnancy losses for each case avoided. CONCLUSION: Maternal screening reduces the number of cases of disease, but at a substantial clinical cost. The rarity of the disease and limitations in diagnosis and therapy limit the effectiveness of screening strategies. The risks associated with amniocentesis are particularly important. Universal maternal screening for congenital toxoplasmosis should not be performed.

Decision Support Techniques↗

PubMed2004

MVA ROP2 vaccinia virus recombinant as a vaccine candidate for toxoplasmosis.

Toxoplasma gondii is the aetiological agent of toxoplasmosis and is the most frequent and best known of the parasitic diseases. In the United States, a serological survey from the Third National Health and Nutrition Examination Survey found that an estimated 23% of adolescents and adults have laboratory evidence of infection with T. gondii. Although toxoplasmosis is asymptomatic or shows self-limited symptoms in adults, in pregnant women infections can cause severe health problems to the fetus if the parasites are transmitted. Also, in immunodeficient patients, chronic infection with T. gondii can reactivate and produce encephalitis, which is frequently lethal. In addition, in veterinary medicine, T. gondii infection is of economic importance due to abortion and neonatal loss in sheep and goats. Recently, the development of vaccines against toxoplasmosis has progressed considerably. The live attenuated S48 strain of Toxoplasma has been broadly used for veterinary purposes. DNA vaccines containing the full-length of SAG1/P30, ROP2 or ROP1 genes have proved to be a promising candidate to induce protection against toxoplasmosis. Viral vectors have proved to be the best candidates for vaccination in different diseases. A recombinant Herpes virus carrying the ROP2 gene is able to induce protective immunity in cats. In the present work we describe the potential of the MVA ROP2 recombinant vaccinia virus as a vaccine against toxoplasmosis. MVA ROP2 induces antibodies against the ROP2 protein in similar amount and types as the thermo-sensible strain ts-4 of T. gondii, which is able to fully protect mice against challenge with the virulent RH strain of T. gondii. Also, the life-span of mice is increased in MVA ROP2 vaccinated animals. We conclude that MVA ROP2 vaccine can possibly generate an immune response, which could be useful in protection against toxoplasmosis.

Animals↗

PubMed1993

Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group.

BACKGROUND: Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis. METHODS: We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter). RESULTS: In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.

AIDS-Related Complex↗